Drugs in Renal Placement Book

Drugs in Renal Replacement Therapy A Guide to Clinical Practice

The printing of the English version of this book has been sponsored by an educational grant from Fresenius Medical Care Deutschland GmbH. All rights are reserved by the author and publisher, including the rights of reprinting, reproduction in any form and translation. No part of this book may be reproduced, stored in a retrieval system or transmitted, in any form or by means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher.

First edition: September 2012

European Dialysis and Transplant Nurses Association/ European Renal Care Association (EDTNA/ERCA) Pilatusstrase 35, Postfach 3052, 6002 Luzern, Switzerland www.edtnaerca.org

ISBN: 978-84-615-9447-4

D.L.: M-25225-2012

Layout, Binding and Printing: Imprenta Tomás Hermanos Río Manzanares, 42-44 · E28970 Humanes de Madrid Madrid - Spain www.tomashermanos.com Acknowledgements

5 The original version of this handbook “Fármacos en Terapia Renal Sustitutiva – Guía de Práctica Clínica” was produced for the 19th EDTNA/ERCA Spanish Seminar, celebrated in June 2011 and was organised by nurses of the Nephrology Department at Hospital del Mar in Barcelona (Spain). The initiative to edit this handbook received encouragement and support from Mrs Núria Pujolar (Head Nurse of Nephrology & Cardiology Departments, Hospital del Mar & LOC President), Dr. Julio Pascual (Chief of Nephrology Department and Kidney Transplantation Programme, Hospital del Mar) and Dr. Esther Salas (Chief of Pharmacy Departments for Parc de Salut Mar).

Authors (nurses) Yessica Advincula, Pilar Anglada, Mª Carmen Barragan, Indalecia Bosqué, Anna Calleja, Yolanda Castillo, Isabel Cherrail, Marta Cortés, Marisol Fernández, Tai Mooi Ho, Yolanda Pérez, Mª Cinta Picart, Mercedes Soto, Martina Vilarrasa.

Authors (hospital pharmacists) José Alfonso del Villar, Mónica Marín.

Reviewers (nephrologists) Francesc Barbosa, Higini Cao, Silvia Collado, Marisa Mir, Anna Oliveras, Julio Pascual, Josep Mª Puig, Laia Sans.

Reviewer (hospital pharmacist) Esther Salas

Illustrations (auxiliary nurse) Laia Fontdevila

Co-ordinator (EDTNA/ERCA Publication Co-ordinator) María Cruz Casal

The printing of this handbook in Spanish was financed by the 19th EDTNA/ERCA Spanish Seminar funds. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Acknowledgements

The translation to English and the publication of “Drugs in Renal Replacement Therapy – A Guide to Clinical Practice” was an initiative of EDTNA/ERCA. On behalf of EDTNA/ERCA and as Coordinator for this edition of the handbook, I would like to express my gratitude to Jitka Pancirová and María Cruz Casal (Executive Members) for their support. My sincere thanks also go to each and every one of the translators and reviewers for their unconditional collaboration and hard work in making this handbook in English a reality. A big thank-you to ALL!

Translators (alphabetical order):

-- María Cruz Casal, RN. EDTNA/ERCA Publication Co-ordinator. Laboratorio Nefrología, H.U. 12 de Octubre, Madrid, Spain.

-- Antonio Cervera Barajas, RN, MSc Clinical Trials. Unidad de Diálisis, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

-- Juan Luis Chaín de la Bastida, RN. Servicio de Nefropediatría, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

-- José Luis Cobo Sánchez, RN, MSc Nursing. Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.

-- Anna Junque Jiménez, RN. Servei de Nefrologia, Consorci Sanitari de Terrassa, Hospital de Terrassa. Terrassa, Barcelona, Spain. Acknowledgments

-- Cristina Mendías Benítez, RN. Servicio de Nefrología, Clínica Santa Isabel, Sevilla, Spain.

-- Beatriz Mirabet Sáez, RN, PG Dip Social Development. Servicio de Nefrología, Consorcio Hospital General Universitario de Valencia, Spain.

Reviewers (alphabetical order):

-- Lesley Bennett, RN, RM, BA, MSc (Anaemia). EDTNA/ERCA Anaemia Consultant. Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.

-- Adrian Coleman, MRPharmS, Diploma in Clinical Pharmacy Practice, Independent Prescriber. Renal Pharmacist, Kent and Canterbury Hospital, Canterbury, Kent, UK.

-- Karen Jenkins, RN, PG Dip HE, MSc Health and Social Care (Nursing). EDTNA/ERCA Chronic Kidney Disease Consultant. Kent Kidney Care Centre, East Kent Hospitals University, NHS Foundation Trust, Canterbury, Kent, UK.

-- Raymond Trevitt, RN, MSc. Renal and Urology Outpatients, Royal London Hospital, Barts Health NHS Trust, London, UK.

Tai Mooi Ho, RN, RM. EDTNA/ERCA Project Co-ordinator. Servei de Nefrologia, Hospital del Mar, Barcelona, Spain.

Table of Contents Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Prologue ...... 15

María Cruz Casal

Abbreviation List ...... 21

1. Basics of Pharmacokinetics and Pharmacodynamics ...... 27 Antonio Cervera Barajas

2. Safe Administration of Medications ...... 39 Tai Mooi Ho

3a. Pharmacological Adherence ...... 57 Tai Mooi Ho

3b. Patient Education in Pharmacological Treatment after Kidney Transplantation ...... 67 José Luis Cobo Sánchez Table of Contents

4. Influence of the Use of Herbal Plants in Renal Replacement Therapy ...... 77 Anna Junque Jiménez

Drug Sheets How to use Drug sheets ...... 100

Drug Sheets

Analgesics (Beatriz Mirabet Sáez) ...... 102

Antacids and Antiulcer Drugs (Beatriz Mirabet Sáez) ...... 109

Antianaemics (Beatriz Mirabet Sáez) ...... 112

Anticoagulation Therapy (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 116

Antiemetics (Beatriz Mirabet Sáez) ...... 118

Antihyperuricaemic Agents (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 119

Anti-infectious Therapy (Beatriz Mirabet Sáez) ...... 121

Antiplatelet Agents (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 130

Cardiotonic Drugs (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 131 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

CKD - Mineral and Bone Disorder Therapy (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 132

Colony Stimulating Factor (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 139

Corticosteroids (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 140

Diuretics and Antihypertensive Drugs (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 141

Immunosuppressants (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 155

Laxatives (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 160

Lipid-lowering Agents (Juan Luis Chaín de la Bastida & Cristina Mendías Benítez) ...... 162

Oral Antidiabetic Drugs and Insulin (Beatriz Mirabet Sáez) ...... 165

Recommendations in the Administration of Specific Drugs: ...... 171

Anti-infectious Therapy in Peritoneal Dialysis ...... 172 Table of Contents

Erythropoiesis-stimulating Agents ...... 176

Iron Sucrose ...... 177

Insulin ...... 177

Hepatitis B vaccine ...... 179

Appendix References, Journals & Useful websites ...... 183

Index of Drugs ...... 189

Prologue Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Prologue Kidney disease is a set of clinical syndromes. From its early stages, patients begin drug therapy as well as making lifestyle changes to alleviate possible symptoms and decelerate the disease progression to chronic kidney disease. In its more advanced stages, drug therapy is not enough and it is necessary to include renal replacement therapy (RRT), such as, haemodialysis, peritoneal dialysis or kidney transplantation. Dialysis patients and those who have received a kidney transplant often require therapeutic regimens that include an extensive list of medications. Literature reviews1,2 and clinical experience show that errors can occur in pharmacological treatment with administration being the most common mistake. Within the hospital environment, the process of medical treatment activity involves different disciplines. It starts with the prescription of a drug by the physician, then the dispensing of the corresponding drug by the pharmacist, followed by its reception, preparation and administration by the nursing staff. Each of these steps includes a series of sequential activities that require scientific, technical and ethical knowledge in order to meet the basic criteria of safety, timeliness and reliability. It is a task that competes within itself, each within its own sphere of responsibility and competence. The scientific aspect is comprised of the knowledge of pharmacodynamics (drug action on the organism, including the interactions both with the receptor and the mechanisms of the therapeutic and toxic effects) and pharmacokinetics (the body’s action on the drug, including its absorption mechanism, distribution, metabolism, elimination, clearance, half-life, maximum and minimum concentrations, and therapeutic concentration monitoring, among others). Prologue

In Chapter One, there is a brief description of these processes, as well as the main changes in a patient with RRT. Included in the technical aspect are the processes related to storage, dispensing, reception and return of medicines, preparation, storage and programming. Each of these processes has a specific standard to be met within strict compliance to medical treatment, consistent with each individual patient’s needs and the measures required to identify risks and prevent complications. Chapter Two discusses these technical aspects within the safe administration of drug treatments and Chapter Three reviews the importance of pharmaceutical adherence. Also, due to a rise in the use of non-pharmacologic therapies, Chapter Four raises the issue of medicinal plants and their possible effects on a patient with RRT. Within the ethical aspect, the nursing staff is not only compelled to perform the actions ordered, but they also have the duty to safeguard the ethical principles based on excellence in professional practice. The administration of medicine by nurses requires: knowledge of the clinical status of the patient, the generic and trade names of a drug, the primary as well as side effects of the drug, the presentation and concentration of said drug, the minimum and maximum therapeutic dosages and half-life of the drug in the blood system. They must also be aware of the metabolic rate and how the body eventually eliminates the medication, possible drug reactions to other medications the patient is receiving, along with the requirements for conservation of both the physical and chemical qualities of the drug. Additionally, they must know the rules related to medication prescription, medication record and management. Therefore, this Guide contains a series of user-friendly tables that contain all of these key aspects. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

With this handbook, the Editors of “Drugs in Renal Replacement Therapy – A Guide to Clinical Practice” provide us with a solid tool and updated knowledge of the most commonly used drug treatments in the care of patients who require RRT. Undoubtedly, this Guide will help achieve the primary objective of safeguarding the patient by preventing medication errors and providing the quality of care that every patient deserves.

María Cruz Casal EDTNA/ERCA Publications Coordinator Prologue

References 1. Brady AM, Malone AM, Fleming S. A literature review of the individual and systems factors that contribute to medication errors in nursing practice. Journal of Nursing Management. 2009; 17(6):679-697. 2. Ledger S, Choma G. Medication reconciliation in hemodialysis patients. CANNT Journal. 2008; 18(4):41-43.

Abbreviations Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

22 Abbreviation List ACEI: angiotensin-converting enzyme inhibitor Adm: administer/administered/administration Amp: ampoule ASA: acetylsalicylic acid - Aspirin BP: blood pressure CAD: coronary artery disease Cap: capsule CBC: complete blood count CD3: cluster of differentiation 3 (immunology) CHF: congestive heart failure CKD: chronic kidney disease CMV: cytomegalovirus CNS: central nervous system CK: creatine kinase (CPK: creatine phosphokinase) CTx: chemotherapy CVD: cardiovascular disease CsA: ciclosporin DM: diabetes mellitus EC: enteric coated eGFR: estimated glomerular filtration rate EPSE: extrapyridamal side effect ESRD: end stage renal disease Abbreviations

Fe: iron 23 5D: refers to advanced chronic kidney disease in stage 5 dialysis GI: gastrointestinal HD: haemodialysis HR: heart rate HTN: arterial hypertension HypoTN: arterial hypotension IG: immunoglobulin IM: intramuscular INR: International Normalized Ratio (serves to monitor blood coagulation time in patients being treated with oral anticoagulants; normal value is 2.0 to 3.0). IV: intravenous LF: liver failure LMWH: low-molecular-weight heparin MAINT: maintenance MAOI: monoamine oxidase inhibitor Max: maximum Min: minute MIU: million international unit MMF: mycophenolate mofetil NS: normal saline (NaCl 0.9%) NSAID: non-steroidal anti-inflammatory drug OAD: oral antidiabetic drug Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

24 OTC: over the counter PCP: pneumocystis carinii pneumonia PIs: protease inhibitors PO: oral POM: prescription-only medication PPIs: proton pump inhibitors PR: rectal PRN: as needed (pro re nata in Latin) RF: renal failure Rx: treatment SC: subcutaneous Sec: second SGOT: serum glutamic oxaloacetic transaminase SL: sublingual SLE: systemic lupus erythematosus SSRI: selective serotonin reuptake inhibitor Synd: syndrome Tab: tablet TD: therapeutic dosage TOP: topical Tx: transplant Wk: week Abbreviations

Basics of Pharmacokinetics and Pharmacodynamics Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

28 29

Learning objectives: • To acquire knowledge of the main pharmacokinetic processes and its alteration in patients with renal failure or dialysis • To understand the effects of drug response (pharmacodynamic) in renal failure

PHARMACOKINETICS Once administered, a drug must undergo 4 processes until it is removed from the organism: absorption, distribution, metabolism and elimination. Absorption involves the passage of drug from its site of administration to the blood. Distribution is its passage from blood to tissues and cells, where it produces the effect. Metabolism is the change experienced by the drug

Oral Administration IV / IM / SC (tablet, capsule...) Tissues Pharmacological Administration Place of action effect

Distribution GI Mucosa

Excretion Plasma Urine, Liver Free Drug bound sweat, drug to plasma stools... Absorption proteins

Metabolism

Diagram 1: Pharmacokinetic Processes Basics of Pharmacokinetics and Pharmacodynamics

28 to facilitate its elimination. Finally, elimination is the removal of 29 drug and/or its metabolites from the organism (see Diagram 1).

a. Absorption: in order for a drug to be absorbed it must pass through a series of physiological barriers to reach the bloodstream (intestinal wall, portal system, liver, and finally the systemic circulation). Below is a list of factors that can affect how a drug is absorbed into the blood system: • Particle size: smaller particle size enhances the absorption of drugs. • Lipophilicity: the structure of cell membranes is lipid, therefore, lipid-soluble drugs (non-polar or non- ionised) pass through easily, while the water-soluble drugs (polar or ionised) pass across with difficulty. For example, aminoglycoside antibiotics are polar molecules that do not pass through the membranes (intestinal cells) and therefore are not absorbed by the oral route. • Absorption environment: sometimes drugs can be inactivated by gastric acid pH, as in the case of insulin which cannot be administered orally. Omeprazole (a medication used to reduce stomach acid) is also inactivated by an acidic environment. It is therefore formulated with an acid resistant coating known as an enteric coating. The enteric coating is removed by an alkaline environment releasing the drug in the small intestine where it is best absorbed. Co-administration of any medication that can increase gastric pH may remove this coating prematurely and cause the drug to be released incorrectly. An enteric coating can also be used to protect the stomach from drugs that can cause irritation such as aspirin or prednisolone. Tablets and capsules with an enteric Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

30 coating should not be crushed, as it will destroy this 31 protection. • pH of molecule: drugs that are weak acids will be more likely to be absorbed in the stomach where as drugs that are weak bases are more likely to be absorbed in the small intestine. Again co-administration of any medication that can alter the stomachs pH may cause the drug not to be absorbed. • Mucosal surface area: the presence of food or the existence of malabsorption may affect the proportion of drug absorbed. Bioavailability is the fraction of drug reaching the systemic circulation. Bioavailability of 50% means that only half of the administered dose will reach the systemic circulation. Intravenous administration is characterized by a 100% bioavailability. The time it takes for the drug from its administration until the expected effect occurs is known as latency. This time depends mainly on the route of administration. In the intravenous route, the drug has a directly access into the bloodstream (no absorption) so the latency is much lower than in other routes (requiring absorption).

b. Distribution: once the drug has been absorbed, it is distributed according to its ability to diffuse across membranes. Distribution is not uniform all over the organism. There are highly vascularized organs (liver, kidneys, heart) that the drug can reach with ease, while there are organs which are less well perfused such as the subcutaneous tissue which will be harder for a drug to reach therapeutic levels in. Furthermore, there are some membranes that play an important role in the diffusion of drugs. The blood-brain barrier is formed by a wall that hinders the passage of small and large lipophobic molecules, however, the placenta can be easily crossed by many drugs and can cause tetratogenic effects in foetus. Basics of Pharmacokinetics and Pharmacodynamics

30 Drugs are distributed in the blood in free form or bound to 31 plasma proteins, primarily albumin. The free fraction is the active one, which can be distributed and easily removed. The volume of distribution (Vd) of a drug is the volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Drugs with a high Vd have a higher tissue distribution (e.g. digoxin), while those with decreased Vd, are mostly found in blood and extracellular space (e.g. aminoglycosides). This parameter is very useful for dosing.

c. Metabolism: some drugs are eliminated unchanged by the body. However, most of them must undergo a series of changes that enhance their elimination from the organism. These products are called metabolites. Depending on the activity of the metabolites, they can be: • Inactive: most of the time when drug undergoes a transformation, it is inactivated. • Active: some metabolites show some activity, same as the drug administered, thus prolonging the effect of the drug (e.g. benzodiazepines). Sometimes, the drug administered does not present any activity initially, but once metabolised is activated. These drugs are called pro-drugs (e.g. captopril). • Toxic: some metabolites can be toxic to the organism (e.g. metabolites of paracetamol, sodium nitroprusside).

Metabolism occurs in different organs, however, the liver is the organ that has more processing capacity (e.g. oxidation, hydrolysis, conjugation). Reactions by cytochrome p450 (enzymes responsible for oxidation and biotransformation of a large number of drugs) can be induced or inhibited depending on the administration of other medications. These interactions may decrease drug effect and/or Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

32 produce side effects, so it may be necessary to adjust the 33 dosage of the drug affected.

d. Elimination: most of the drugs (original or metabolites) are excreted by the kidneys. Renal excretion occurs by glomerular filtration or by elimination by secretion in to the renal tubule. Other routes of elimination (less important) are gallbladder, saliva, sweat or breast milk. The elimination of drugs by renal replacement therapy (haemodialysis, peritoneal dialysis, ultrafiltration, haemo- perfusion) depends on the characteristics of each drug. Therefore, when using these techniques, dosage adjustments and time of administration of each drug should be consulted, as there will be drugs that will not need a change in dosage, others will need dosage to be decreased and others will need to be given post-procedure to compensate the deletion.

Differences in patients with chronic kidney disease (CKD) and/or dialysis. Patients with CKD or receiving dialysis may have a number of characteristics that may affect the pharmacokinetics of drugs:

Absorption: • The presence of urea decreases the absorption of drugs, because these patients often have nausea, vomiting, and gastroparesis. • Sometimes there is an increase in the concentration of gastric ammonia, which can neutralise the stomach acid. The dissolution of some drugs requires an acidic environment and hence its absorption may be incomplete (e.g. iron salts, folic acid and flucloxacillin). • The use of antacids containing aluminum and phosphate binders containing calcium, magnesium Basics of Pharmacokinetics and Pharmacodynamics

32 and sevelamer can chelate other drugs, decreasing 33 their absorption.

Distribution: • These patients can suffer from proteinuria and/ or malnutrition and consequently may have hypoalbuminemia. Therefore, the free fraction of drug (not bound to albumin) is increased. The presence of uraemia and altered acid-base balance may also lead to alterations in drug binding to albumin. It should be remembered that the extra renal clearance only removes the 'free' unbound drug. • There is a reduction in the Vd of the highly protein bound drugs due to reduced affinity to albumin (increased free fraction). • CKD may affect Vd: alterations of body water content, acidosis, hypocalcemia, anaemia, drug binding to tissues and albumin. In dialysis patients (especially patients with significant inter-dialysis weight gain) changes in pre-dialysis and post-dialysis have implications in drug concentration and consequently in its effect.

Metabolism: • A large number of drugs are metabolized in the liver, so the presence of CKD does not usually affect the dosage. However, those metabolised by reduction, hydrolysis or acetylation, require lower doses because uraemia may alter these processes.

Elimination: • Drugs that are eliminated primarily by renal excretion, will require dosage adjustments in both CKD and dialysis. However, those drugs whose renal clearance is less than 20-30% may not require dose adjustments. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

34 • Drug metabolism mainly occurs in the liver, however, 35 the majority of the metabolites formed will be eliminated by renal excretion and may require dose adjustments (e.g. opiates). • There are a number of factors that may affect the elimination of drugs in dialysis: a. The drug itself: molecular weight, electric charge, protein binding, Vd, water solubility, adsorption to the dialysis membrane or extra renal clearance. b. Depending on the dialysis membrane: effective surface degree of hydraulic permeability, pore size, electric charge, adsorption capacity, biocompatibi- lity, etc. c. Depending on the dialysis technique: duration and frequency of dialysis, blood flow, dialysate flow and temperature, chemical composition of the bath, diffusive or convective technique, etc.

Pharmacodynamics The pharmacological action of a drug occurs when it interacts with the receptor. The intensity of the response depends on the dose administered, its receptor affinity and the pharmacokinetic processes discussed above. When a drug binds to a receptor and performs an activity it is considered to be an agonist, while if it binds to the receptor but has no activity it is considered to be an antagonist. The pharmacological activity of the latter is due to interference in the activity of endogenous molecules. However, to the same concentration of a drug there are differences in treatment response among different individuals (inter-individual variability). Furthermore, this difference may also occur in the same individual (intra-individual variability). Basics of Pharmacokinetics and Pharmacodynamics

34 The change in the number of receptors or their function, either 35 by physiological processes (aging) or pathological (disease) may be one of the reasons for this variability. Kidney failure is a factor that can alter the pharmacological effect of drugs (other than the effect on the concentrations of the drug): • High concentrations of urea alter the sensitivity of the drugs to their receptors. Examples include sedatives, anxiolytics, hypnotics and some analgesics. • Acid-base changes and some electrolytes can alter the activity and/or toxicity of anti-arrhythmic drugs and digoxin. • Sometimes the drug cannot have access to the site of action, such as some urinary tract antibiotics, osmotic and thiazide diuretics. • Drug requires some form of metabolic transformation which seems to be affected by renal failure, such as 1 α-hydroxylated cholecalciferol and insulin metabolism • Some adverse effects are potentiated by renal failure such as hyperkalaemia due to distal diuretics in patients with elevated creatinine. • Overload of any component of the drug, such as Na+ in effervescent tablets. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

36 References 37 1. Bennett WM, Golper TA. Uso de fármacos en la Insuficiencia Renal. In: Llach F, Valderrábano F. Insuficiencia Renal Crónica: diálisis y Trasplante Renal. 2nd ed. Madrid: Norma Eds; 1997. p1327-1353. 2. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmaco- dynamics Concepts and Applications Hardbound. 4th ed. Phila- delphia: Lippincot Williams & Wilkins; 2011. 3. Winters ME. Basic Clinical Pharmacokinetics. Applied Therapeutics. 5th Ed. Baltimore: Lippincot Williams & Wilkins; 2009. 4. http://bibliotecas.saludextremadura.com/portal/hic/06_2007_ farmacos_funcion_renal.pdf (accessed 3 Feb 2011). 5. http://www.dep19.san.gva.es/farmacia/New_eGFT%20carpeta/ AjustesDosis%20IR.pdf (accessed 6 Dec 2010). 6. http://www.docentes.utonet.edu.bo/mterang/wp-content/uploads/ cap11_copy1[1].pdf (accessed 19 Oct 2011 - updated). 7. de la Prada Alvarez FJ. Prescripción farmacológica en la enfermedad renal. Available from: http://www.elcomprimido.com/INFORMED/PDC_HUSD_Curso10_ Prescripcionfarmacologicaenlaenfermedadrenal.ppt (accessed 3 Feb 2011). 8. Valsecia M, Malgor L. Utilización de fármacos en insuficiencia renal. Available from: http://www.med.unne.edu.ar/catedras/ farmacologia/temas_farma/volumen5/11_rinion.pdf (accessed 6 Dec 2010). 9. Antonio Javier Carcas Sansuán AJ, Frías Iniesta J. Situaciones patológicas que modifican la respuesta a los fármacos: Insuficiencia renal e insuficiencia hepática. Available from: http:// www.normon.es/media/manual_8/capitulo_27.pdf (accessed 3 Feb 2011).

Additional reading:

-- Ashley C, Morlidge C. Introduction to renal therapeutics. London: Pharmaceutical Press; 2008. -- Ashley C, Currie A. The renal drug handbook 3rd edition. London: Radcliffe Publishing Ltd.; 2009. Basics of Pharmacokinetics and Pharmacodynamics

36 37

Safe Administration of Medications Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

40 Learning Objectives: 41 • To demonstrate and raise awareness about the adverse impact of errors related to medication administration • To increase and enhance knowledge about processes and strategies to ensure safe drug administration • To increase knowledge regarding the management of drugs in the context of renal replacement therapy (RRT)

Introduction Patient safety has become a priority for health systems in developed countries1,2,3,4. It is therefore recommended that healthcare organizations should foster a safety culture in staff and care delivery processes5,6,7. Several epidemiological studies have shown that the same practice to improve the health of people, can simultaneously be a potential source of damage, with medication errors (ME) being one of the leading preventable causes3, 4, 8. ME is any error occurring in the process system regarding the use of drugs (drug- use-system error). The National Coordinating Council for Medication Error Reporting and Prevention defines ME as “any preventable event that may harm the patient or lead to an inappropriate use of drugs when they are under the control of health professionals, the patient or consumer. These incidents may be related to professional practice, products, procedures or systems, including errors in prescription, communication, Safe Administration of Medications

labelling, packaging, naming, preparation, dispensing, distribution, administration, education, monitoring and use”9. In Spain, it is estimated that 4.7% - 5.3% of hospital admissions are caused by ME, with an average cost per stay of 3,000 40 41 EUR10. According to a report produced by the Committee on Quality of Health Care in America Institute of Medicine, ME cause more than 7,000 deaths annually and adverse events to 2% of patients, increasing hospital costs to $4,700 for every related admission4. Furthermore, a recent report on drug safety concluded that each year it produces about 1.5 million of preventable ME, resulting in a total cost of $3.5 billon11. The 2003 Commonwealth Fund Survey revealed that 11% of patients in the UK reported having received the wrong medication on an occasion12. Most ME are due to mistakes in prescribing, dispensing or drug administration, the latter being the most common13,14.

Nursing and Drug Administration The most frequent errors associated with drug administration are15,16:

• Wrong drug. • Incorrect dosage. • Omitted dose/drug. • Incorrect route of administration (with/without food, whole/parted tablet, incompatibility with other drugs, e.g. antacids).

Other reasons for error include17,18,19:

• Interruption in activity (phone calls, people, patients who require attention). • Increased workload (staff shortage, patient’s complicated condition). Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

• Newly qualified professional (lack of experience or unfamiliar with the patient’s clinical history). • Tired professional due to long working hours.

42 As a wide range of drugs are used, their name can easily be 43 confused both verbally and in writing, as they sound alike or have very similar spellings (e.g. amiloride and amlodipine)20. Abbreviations, symbols and dose expressions can also be associated with ME21. Medication administration is an integral part of the nursing role and there is a tendency to think that the responsibility rests solely on this group of professionals22, albeit other professionals are also involved in the process, for example, pharmacists in dispensing medications and medical staff in prescribing the drugs to be administered. Moreover, some studies focused on factors contributing to drug errors in being limited to nurses23,24. For decades, as a measure in the prevention of ME, nurses have followed the rule of ‘5-rights’ in the administration of medication: right dose, right drug, right patient, right route and right time25. Table 1 summarizes the key points of this rule. However, there are authors who insist that relying only on the rule of ‘5-rights’ is insufficient26, 27, as ME are produced both in the process of prescribing (39%) and administration (38%)28. For this reason, Cook proposed an additional six rights for nurses in the safe administration of medication29 (see Table 2). Safe Administration of Medications

Check if the prescribed dose is appropriate. Verify the Right mathematical calculation of dose and infusion rate, if dose applicable. Double-check for any unusual doses. Calculate correctly the fraction to be administrated (vial, syrup...). 42 43 Identify the drug while removing it out of the container, while Right preparing it and before administering it (some have similar drug name and aspects) and check its expiry date.

Right Identify the patient by his/her full name, preferably patient requesting him/her to tell us (if possible).

Check the prescribed route. If this is not specified, consult. Right Verify if the drug has special administration indications (e.g. route dilution, time of administration).

Right Take particular care in the administration of drugs that time require a strict dosing interval or time.

Table 1: Key Points of the Rule of ‘5 rights’ in the Administration of Medication

Right to have legible and complete medical orders. Right to have correct dispensing of medications. Right to have easy access to updated drug information. Right to have policies for safe administration of medications.

Right to have an optimal system and environment to administer drugs safely.

Right to participate in the identification and prevention of errors in the system.

Table 2: Administration of Medications - The 6 Rights for Nurses

MacDonald stressed that the rule of ‘5-rights’ was implemented at a time when the paradigm in healthcare provision alluded to only an individual professional (and not to the whole system) being responsible in the event of any kind of error in care delivery27. Later, it became evident that this paradigm was not Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

beneficial nor a solution at all to address this problem in health care. This concept was criticized for preventing professionals from reporting the errors that occurred, rendering it impossible to discover and analyse the causes of errors in order to 44 develop better preventative strategies4. 45 The promotion of a safety culture is essential to ensure quality of care, as this is one of the key components to a safe, effective, patient-centred, without delay, efficient and equitable healthcare3,4,5. Strategies have been introduced to promote the safe administration of drugs. For example, the Nursing and Midwifery Council in the UK and the Ontario College of Nursing developed standardized practice guidelines to safeguard patient safety30, 31. The guidelines specify steps to be performed by the nurse in such activity, thus minimizing the risk of errors and in turn accounting for individual responsibility. The following is an overview of the procedures in the guidelines:

1. Assessment: • Prior to administering medications, the nurse should assess the following: -- Age -- Sex -- Weight -- Vital signs -- Blood test results -- History of drug allergies/intolerance plus any previous history of adverse reactions

• Know the therapeutic dose of the drug to be administered, units of dosage that is presented and how to convert them if necessary. Safe Administration of Medications

• Check for possible drug interactions or foods that may interfere with drug absorption. • Verify that the patient does not take any medications that are not prescribed. 44 45 2. Planning • Check correct storage (temperature, light) and expiry date of the drug. • Obtain informed consent from the patient or legal guardian before administering the first dose of any medication. • Check the prescription. Should there be any doubt, the nurse should consult the prescriber (this may be a doctor, nurse or pharmacist). • Wash hands adequately before preparing and administering medications. Repeat washing at the end of the activity (remember to use alcohol gel in between patients). • If the drug requires to be reconstituted, it should be labelled correctly as soon as it is reconstituted.

3. Implementation • Check that the prescription matches the patient’s data, confirming patient’s name and date of birth. • Know the generic and the trade name of the drug, primary and secondary effects, presentation and concentration, minimum and maximum therapeutic dose, half-life, metabolism and elimination of the drug, synergy and antagonism with the other drugs that the patient is receiving. • Administer all medications using antiseptic techniques, following the protocol of each centre and monitoring the patient, if required. • Double-check with other professionals in cases of rarely used drug and dosage. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

• Ensure that the patient takes the medication administered. • Record that the medication has been administered.

46 4. Evaluation 47 • Evaluate continuously the effectiveness of the drug administered, documenting the results and taking the appropriate actions if needed.

All medication administered to a patient should be prescribed by a qualified prescriber and clearly hand written or electronically prescribed. Only in real emergencies should a verbal order be accepted and a written prescription should always follow. The drug chart should be signed as soon as the drug is administered. If for some reason the drug has not been administered or is administered later, this should be stated on the chart and in the nursing notes, specifying the reason. In cases of ‘PRN’ (as needed) medication, should it be administered, the reason and outcome must be documented in the patient’s chart. Any side effects observed, must be recorded. Some drugs require greater control of vital signs. For example: • Digoxin – control heart rate. Do not administer if less than 60 beats/min. This event should be documented and the physician should be notified. • Hypotensive drugs - control of blood pressure. • Narcotics - control of respiratory rate. • Hypoglycaemic drugs//insulin – control of blood sugar levels.

There are factors that can modify pharmacological action: • Physiological: administration site, sex, weight, individual absorption and elimination capacity, patient’s pathology and state of consciousness. Safe Administration of Medications

• External: the way drug is prepared for administration, interaction with other drugs, administration schedule (chronopharmacology) and tolerance. • Routes of administration: oral (PO), sublingual (SL), 46 parenteral (IV, IM, SC and intradermal), topical, ocular, 47 aural/otic and rectal. In RRT, the commonly used routes are PO and IV.

The PO route is the most comfortable, safe and economic. Precaution should be taken in terms of interactions with other drugs or food, which can alter drug efficacy and safety; it is not advisable to alter the medication (crush tablets, open capsules). The long-acting drugs if parted or crushed will lose this ability. Other points to note: • If the medication should be taken with food or on an empty stomach (1 or 2 hours before or after meals). • Avoid PO administration in unconscious patients (risk of aspiration and gastrointestinal disturbances). • In the SL route, the oral mucosa is highly vascularised and facilitates rapid absorption of some medications. Fluid should not be given immediately after administration by this route. In the IV route, it should be remembered that the effect of the drug is more rapid and intense, because the drug is injected directly into the bloodstream. The following points should be applied: • Use sterile technique for placement of IV access (risk of infection). • Check IV route patency prior to administration of drug • Respect the time of infusion; if in dilution, ensure fluid compatibility, the amount and the equipment used are appropriate. In cases when the drug infusion rate must be accurate (parenteral nutrition, immunosuppressants, potassium, heparin) use a Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

continuous infusion pump. Label the bag with the drug name, dosage, patient’s name, date and time. Do not keep infusions over 24 hours. • Unless specifically prescribed, do not mix two 48 medications in the same infusion bag/bottle because, 49 should there be a reaction, this would impede the identification of the causative drug. • At the end of infusion, ‘flush’ the line with sterile normal saline. The amount will vary depending on whether the IV route is peripheral or central.

The IM route is rarely used in haemodialysis patients, except in exceptional cases (e.g. vaccination against hepatitis B). In these patients, if they receive heparin during the procedure, this route is not recommended before and after the session (risk of bruising at injection site). As mentioned, stress, fatigue and insufficient human resources or a high staff turnover increase the risk of ME. Therefore, professionals must be alert in these situations. Human error is a possibility regardless of level of competence. It is essential that any errors in the administration of drugs to be recorded and the procedure established by each institution for drug errors be followed. Notification of errors enables a root cause analysis to be carried out which can result in improvements in medication management processes and avoidance of repeated incidents.

Other measures/models in the prevention of ME Working Groups stressed that errors are caused by deficiency in safety in the health care process and that the administration of drugs requires a multidisciplinary and cooperative strategy4. Therefore new improved strategies and models are proposed4,7: • Unidosage dispensing system. Safe Administration of Medications

• Introducing technology -- ‘Intelligent’ infusing pumps -- Computerized Physician Order Entry (CPOE)

48 -- Bar Code Medication Administration (BCMA) 49

• Patient-Centred Care Patient-centred care is defined by the U.S. Institute of Medicine as “providing care that is respectful and responsive to the preferences, needs and values of each patient, and ensuring that patient values guide all clinical decisions”. In recent years, the concept of this model of care has gained prominence as a key objective in the healthcare system32,33. The participation of the patient and family in his/her care is a critical component of patient-centred care and is a condition that helps to ensure a safe healthcare delivery34,35.

• Medication Reconciliation Medication Reconciliation is an initiative that began in the U.S. and involves the entire multidisciplinary healthcare team in the prevention of ME, which often occurs with the transition of care (admission, transfer and discharge)36. This initiative recommends the following processes: -- Create a more complete and accurate list of medications that the patient is taking and note the last dose. For example, the named nurse creates a medication history upon receiving the patient on admission37. -- Compare this list to the prescription made by the physician at admission, in order to identify any discrepancies. Should there be any, notify the physician to make the appropriate changes. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

-- Inform the patient and family/caregiver(s) about the current drug treatment. This approach allows the patient/carer to increase his/her knowledge about the medications, improve adherence and reduce 50 ME. 51 -- Compare the medication history with the physician’s orders for transfer or discharge to ensure that both reconcile.

Patient and family/carer education Using an understandable language to the patient and/or the family/carer, to: • Encourage the habit of knowing the drugs to be taken and check that the medication and the dose of usual treatment are correct, especially upon hospital admission and discharge. • Consult the corresponding medical staff or nurse regarding any question that may arise about the medication being prescribed. • Notify the physician or nurse, as soon as possible, if there is intolerance to the drug or any side effect. • Keep a current record of the pharmacological treatment and take it along to every clinic visit and in case of admission.

Considerations in the context of RRT. For example: • Right time: pay special attention to the administration of medications that requires strict dosing interval (e.g. immunosuppressants, insulin and antibiotics) or to be given at a certain time (e.g. circadian rhythm, relation to meals and relationship to dialysis). Some drugs lose their effectiveness in dialysis. Therefore, they have to be given post-dialysis. Safe Administration of Medications

• Correct dose: take into account the eGFR to adjust dosage of certain drugs in patients undergoing dialysis and to assess blood levels of some immunosuppressive agents to administer the proper dosage. 50 • Precaution should be taken when administering 51 antihypertensive drugs before a haemodialysis session. In general, this is not recommended within 2 hours before the start of the session. Patient’s blood pressure should be checked post-dialysis, before giving this group of drugs (to avoid hypotension). • Do not give laxatives before dialysis. • Perform pre-HD blood glucose control in diabetics by using the cannulated needle line to obtain blood sample, thus minimising needle-sticks being performed to the patient.

For more information, please refer to drug data sheets.

Conclusion The inherent responsibility of any nurse is to ensure patient safety in the course of their healthcare profession. Although there are criticisms about the shortcomings of the rule of ‘5-rights’ in the administration of medications, it is still useful to achieve a safe procedure if combined with the latest available measures/models, and in addition to follow the relevant guidelines in our daily practice. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

References 1. Agencia de Calidad del Sistema Nacional de Salud. Plan de Calidad para el Sistema Nacional de Salud. Madrid: Ministerio de Sanidad y Consumo; abril 2007. 52 2. NHS. Seven steps to patient safety in general practice. National 53 Patient Safety Agency; 2006. Available from: http://www.nrls. npsa.nhs.uk/resources/collections/seven-steps-to-patient- safety/?entryid45=59804 3. Fifty-fifth World Health Assembly - Quality of care: patient safety. http://apps.who.int/gb/archive/pdf_files/WHA55/ewha5518.pdf (accessed Dec 2010). 4. Kohn LT, Corrigan JM, Donaldson MS. To Err Is Human: Building a Safer Healthcare System. Washington, DC: National Academy Press; 2000. 5. Expert Group on Safe Medication Practices. Creation of a better medication safety culture in Europe: Building up safe medication practices. 2006. http://www.coe.int/t/e/social_cohesion/socsp/ Medication%20safety%20culture%20report%20E.pdf (accessed Dec 2010). 6. Safe Use Initiative: Collaborating to Reduce Preventable Harm from Medications. U.S. Department of Health and Human Services. Food and Drug Administration; Nov. 2009. http://www.fda.gov/downloads/ Drugs/DrugSafety/UCM188961.pdf (accessed Dec 2010). 7. Otero MJ. Nuevas iniciativas para mejorar la seguridad de la utilización de los medicamentos en los hospitales. Rev Esp Salud Pública. 2004; 78: 323-339. 8. Otero MJ, Martín R, Santos B, Puigventós F, Delgado O. Seguridad de medicamentos. Importancia del proceso de selección de medicamentos en la prevención de errores de medicación. Farm Hosp. 2003;4:264-270. 9. National Coordinating Council for Medication Error Reporting and Prevention. NCCMERP Taxonomy of medication errors, 1998. http://www.nccmerp.org/aboutmederrors.htm (accessed Dec 2010). 10. Otero MJ, Alonso P, Martín R, Valverde MP, Dominguez-Gil A. Analysis of preventable adverse drug events (ADEs) leading to hospital admission: incidence, categorization and cost. 36th ASHP Midyear Clinical Meeting and Exhibits, December 2-6, 2001, New Orleans (LA). 11. Institute of Medicine. Preventing medication errors. http://www.iom. edu/Reports/2006/Preventing-Medication-Errors_Quality-Chasm_ Series.aspx Safe Administration of Medications

12. Schoen C, DesRoches C, Downey D. The Canadian Health Care System: views and experiences of adults with health problems. The Commonwealth Fund; 2003. http://www.commonwealthfund.org/usr_ doc/canada52003_db_641.pdf?section=4039 (accessed Dec 2010). 13. Brady AM, Malone AM, Fleming S. A literature review of the individual 52 and systems factors that contribute to medication errors in nursing 53 practice. Journal of Nursing Management. 2009; 17(6):679-697. 14. Ledger S, Choma G. Medication reconciliation in hemodialysis patients. CANNT Journal. 2008; 18(4):41-43. 15. Otero MJ, Codina C, Tamés MJ, Pérez M en representación del grupo de trabajo Ruiz-Jarabo. Errores de medicación: estandarización de la terminología y clasificación. Resultados de la Beca Ruiz-Jarabo 2000. 2000. Farm Hosp. 2 0 0 3 ; 2 7 : 1 3 7 - 1 4 9 . http://www.ismp-espana.org/ficheros/Fichero24.pdf (accessed 5 Nov 2010). 16. Vidal Miquel A, Baldrich Andreu MJ, Arcos Palomino C, Sacrest Güell R. Errores en la administración de medicamentos por vía oral en dos centros sociosanitarios. Farmacia Hospitalaria. 2002; 26(5): 287- 293. 17. Nichols P, Copeland TS, Craib IA, Paul Hopkins P, Bruce DG. Learning from error: identifying contributory causes of medication errors in an Australian hospital. MJA. 2008; 188 (5): 276-279. http://www.mja. com.au/public/issues/188_05_030308/nic10159_fm.html (accessed Dec 2010). 18. Tang FI, Sheu SJ, Yu S, Wei IL, Chen CH. Nurses relate the contributing factors involved in medication errors. J Clin Nurs. 2007;16(3):447-457. 19. Biron AD, Loiselle CG, Lavoie-Tremblay M. Work interruptions and their contribution to medication administration errors: an evidence review. Worldviews Evid Based Nurs. 2009;6(2):70-86. Epub 2009 Apr 29. 20. Institute for Safe Medication Practices. ISMP’s List of Confused Drug Name. http://www.ismp.org/Tools/confuseddrugnaME.pdf (accessed Dec 2010). 21. Otero MJ, Martín R, Domínguez-Gil A. Abreviaturas, símbolos y expresiones de dosis asociados a errores de medicación. Farm Hosp. 2004; 28: 141-144. 22. Pepper G. Errors in drug administration by nurses. Am J Health Syst Pharm. 1995;52:390-395. 23. Pape T. Searching for the final answer: factors contributing to medication administration errors. Journal of Continuing Education in Nursing. 2001;32(4):152-160. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

24. Preston R. Drug errors and patient safety: the need for a change in practice. British Journal of Nursing. 2004;13(2): 72-78. 25. Kron T. Stepping beyond the 5 rights of administering drugs. Am J Nurs.1962;62(7):62-63.

54 26. Institute for Safe Medication Practices. The five rights: a destination 55 without a map. http://www.ismp.org/newsletters/acutecare/ articles/20070125.asp (accessed Dec 2010). 27. MacDonald M. Patient Safety: Examining the Adequacy of the 5 Rights of medication Administration. Clinical Nurse Specialist. 2010; 24(4):196-201. 28. Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drug events. ADE prevention study group. JAMA. 1995;279:1200- 1205. 29. Cook M. Nurses’ six rights for safe medication administration. Mass Nurse. 1999; 69(6):2-5. 30. Nursing and Midwifery Council. Standards for medicines management. 2007. http://www.nmc-uk.org/Documents/Standards/ nmcStandardsForMedicinesManagementBooklet.pdf (accessed Dec 2010). 31. College of Nurses of Ontario Practice Standard: Medication, Revised 2008. http://www.cno.org/Global/docs/prac/41007_Medication.pdf (accessed 2 Jan 2011). 32. Donaldson L. Expert patients usher in a new era of opportunity for the NHS. BMJ. 2003;326(7402):1279-1280. 33. Jacob J. Voice of the patient: the essence of patient-centered care. Crit Care Nurs Clin North Am. 2010;22(2):227-232. 34. Macdonald M. The role of the hospitalized patient in medication administration safety. Patient Saf Qual Healthc. 2009;6(3):28-31. 35. Fredericks JE, Bunting RF Jr. Implementation of a patient-friendly medication schedule to improve patient safety within a healthcare system. J Healthc Risk Manag. 2010;29(4):22-27. 36. The Joint Commission. Medication reconciliation. Sentinel event alert, Issue 35. 2006. http://www.jointcommission.org/SentinelEvents/ SentinelEventAlert/sea_35.htm. 37. Ketchum K, Grass CA, Padwojski A. Medication reconciliation: verifying medication orders and clarifying discrepancies should be standard practice. Am J Nurs. 2005;05:78-9, 81-2, 84-5. Safe Administration of Medications

Useful websites: -- http://www.ismp-espana.org/publicaciones/ (accessed 5 Nov 2010). -- http://www.nrls.npsa.nhs.uk/resources/collections/seven-steps-to- patient-safety/ (accessed 2 Jan 2011). 54 55 -- http://www.nrls.npsa.nhs.uk/EasySiteWeb/GatewayLink. aspx?alId=59970 (accessed 2 Jan 2011). -- www.npsa.nhs.uk/

Pharmacological 57 Adherence Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Learning Objectives: • To understand the correlation between pharmacological adherence and patient safety

58 • To increase knowledge of the factors associated with 59 poor/lack of adherence to prescribed treatment • To identify strategies that can be implemented to improve patient’s pharmacological adherence

Introduction Therapeutic adherence (therapeutic compliance) is defined by the World Health Organization as “the extent to which the conduct of a person (whether in taking a medication, following a diet or executing changes in lifestyle) corresponds to the advice given by a health professional”1. The words ‘adherence’ and ‘compliance’ are often used interchangeably. However, in current healthcare the preferred recommended term to use is, ‘adherence’ because ‘compliance’ implies to following precisely the instructions indicated by the healthcare professional, with an undertone that any failure to follow the instructions will be solely the patient’s fault. On the other hand, the term ‘adherence’ is considered not to be associated with blame as an endpoint in patients not taking their drugs as prescribed. The concept of this word accepts that patients make rational decisions based on their own beliefs and experiences2. It is an approach which is more consistent with the concept of patient- centred care3. Pharmacological Adherence

Oral medication constitutes a key component in the patients’ therapeutic regimen1. Lack of adherence can be costly and harmful often leading to the patient being admitted due to adverse effects and/or deterioration of the disease1,4. Non- adherent behaviour is universal, varying in rates5 and being more prevalent in chronic diseases6,7,8.

Pharmacological adherence in the context of renal 58 replacement therapy (RRT) 59 Patients who dialyse usually have an extensive number of medications which they need to take daily to manage their multiple associated pathologies9,10. Lack of adherence to complex pharmacological treatment is a well-known problem in this patient group, which can result in increased morbidity and mortality11. Schmid et al conducted a systematic literature review of MEDLINE and PubMed (1971 - 2008) and concluded that the rate of non-adherence to oral medications was 3% - 80%, noting that the use of phosphate binders was the most common12. Among those transplanted, it was estimated that non- adherence was between 16% and 55%13. As we can appreciate, this group of patients has to follow a complicated and long-term immunosuppressive regimen. Moreover, they often also need concomitant treatment for conditions such as diabetes, hypertension and dyslipidaemia. In order to maintain the functioning of graft, they need regular medical follow-up which involves frequent visits to the hospital. Adherence to immunosuppressive drugs has been identified as an important behaviour to prevent graft rejection14. The importance of adequate treatment adherence has been shown in numerous studies. Takemoto et al in their study indicated that lack of pharmacological adherence in renal transplant recipients is associated with negative results15. Failure to follow correctly the immunosuppressive regimen may lead to several complications such as acute and chronic graft rejection, Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

decreased kidney function that ends up with the return to dialysis or death16,17. In clinical practice, it is found that inadequate adherence behaviour can manifest itself in several ways: • Difficulties in initiating treatment. • Inadequate adherence to treatment indicated, which may occur as errors in omission, dosage, time, drug 60 (error in taking one or other drugs). 61 • Suspension or premature discontinuation of treatment. • Absence of changes in lifestyle habits required to prevent disease complications. • Absenteeism in follow-up visits. • Practice of self-medicating with OTC drugs or alternative treatment.

Factors associated with such behaviour are many. There is extensive literature on it. The following Tables include some of the above mentioned factors and strategies to overcome non-adherence1,2,18,19 (see Table 1 and Table 2, respectively). Pharmacological Adherence

Age, gender, culture and ethnicity, Demographic/socio-economic marital status, education level, factors religion, employment status, perceived economic situation.

Health beliefs and behaviour, depression, smoking/alcohol/ toxic drug, presence or absence Patient/disease related factors of symptoms, chronicity, time in dialysis, previous experience of 60 transplant. 61

Pill burden, complexity of regimen, size and taste of the drug, side Treatment related factors effects of medication, cost of the drugs prescribed.

Professional/healthcare system Patient-professional relationship, related factors lack of medical insurance.

Table 1: Factors associated with poor/lack of pharmacological adherence

Address the subject with an empathetic attitude, promoting an effective communication and a trusting relationship with the patient.

Give explanation and educate the patient about the negative impact of non-adherence.

Establish treatment objectives.

Involve the patient and family/carer in the taking of medicines and in self- management.

Provide continuous education on the health condition and the treatment.

Promote patient motivation and enhance adequate behaviour toward the prescribed treatment.

Evaluate the possibility of reducing the complexity of treatment.

Detect cognitive deterioration.

Table 2: Strategies to improve pharmacological adherence Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

A study analysing the behaviours or factors associated with success in treatment adherence in renal transplant identified the following strategies20: • Creating methods to prevent forgetfulness in taking medication, e.g. leaving the drugs in a visible or fixed place, or close to other objects that were used regularly. • Organizing a medication plan (a system to remember 62 63 when each drug needs to be replenished and have extra pills in the wallet/purse, if necessary). • Obtaining the medications was not a problem because the participants had insurance coverage and also used the generic brands that were relatively cheaper. Some commented that the fact of buying the medications usually at the same pharmacy was convenient. Some acquired their medications monthly through telephone orders or Internet. • Establishing and maintaining routines is one of the characteristics identified. These patients, who have been transplanted many years ago (26 to 36), believed that the formation of habit is a key success in adherence. • Developing skills in this context through time and experience, e.g. having a supply of medications at work, making a list in order to bring enough medication (more than is needed) when travelling and always having a specific toilet bag for this use.

There is no single effective intervention to bring about changes in patient’s behaviour; the most effective is the use of combined strategies21: • Patient education. • Empowerment skills. • Self-reward. Pharmacological Adherence

• Social support. • Close monitoring. • Communication.

Conclusion Up to date, interventions designed to improve adherence have had limited success. However, in view of the potentially harmful 62 consequences, inadequate pharmacological adherence 63 deserves attention and action. Nurses can enhance their role in the assessment, education, strategic planning and implementation of self-care (patient self-management) to promote adherence. In clinical practice, nurses are responsible for providing education about the prescribed treatment, especially prior to discharge. In this activity, special attention should be paid to enhance patient understanding and self- management within their personal context, thus facilitating long-term adherence. According to experts, the most effective interventions to improve adherence are those that focus in motivating patients in self-management as objective22,23. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

References 1. Sabate E. Adherence to Long-Term Therapies: Evidence for Action. Geneva, Switzerland: World Health Organization; 2003. 2. Wells H. Promoting adherence in renal transplant patients. Hospital Pharmacist. 2004;11:69-71. 3. Jacob J. Voice of the patient: the essence of patient-centred care. Crit Care Nurs Clin North Am. 2010;22(2):227-232. 4. Dunbar-Jacob J, Mortimer-Stephens MK. Treatment adherence in 64 chronic disease. J Clin Epidemiol. 2001;54(1):S57-60. 65 5. Horne R, Weinman J, Barber N, Elliott RA, Morgan M. Concordance, Adherence and Compliance in Medicine Taking: A conceptual map and research priorities. London: National Co-ordinating Centre for NHS Service Delivery and Organisation R&D; 2005. 6. Holley JL, DeVore CC. Why all prescribed medications are not taken: results from a survey of chronic dialysis patients. Adv Perit Dial. 2006;22:162-6. 7. Osamor PE, Owumi BE. Factors associated with treatment compliance in hypertension in southwest Nigeria. J Health Popul Nutr. 2011;29(6):619-28. 8. Rubin RR. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med. 2005;118 Suppl 5A:27S-34S. 9. Chiu Y-W, Teitelbaum I, Misra M, de Leon EM, Adzize T, Mehrotra R. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin J Am Soc Nephrol. 2009;4(6):1089-1096. 10. Manley HJ, Garvin CG, Drayer DK, et al. Medication prescribing patterns in ambulatory haemodialysis patients: comparisons of USRDS to a large not-for-profit dialysis provider. Nephrol Dial Transplant. 2004;19(7):1842-1848. 11. O’Brien ME. Compliance behavior and long-term maintenance dialysis. Am J Kidney Dis. 1990;15(3):209-214. 12. Schmid H, Hartmann B, Schiffl H. Adherence to prescribed oral medication in adult patients undergoing chronic hemodialysis: a critical review of the literature. Eur J Med Res. 2009;14(5):185-190. 13. Chisholm MA. Issues of adherence to immunosuppressant therapy after solid-organ transplantation. Drugs. 2002;62(4):567-575. 14. Desmyttere A, Dobbels F, Cleemput I, De Geest S. Noncompliance with immunosuppressive regimen in organ transplantation: is it worth worrying about? Acta Gastroenterol Belgica. 2005;68(3):347-352. Pharmacological Adherence

15. Takemoto SK, Pinsky BW, Schnitzler MA, et al. A retrospective analysis of immunosuppression compliance, dose reduction and discontinuation in kidney transplant recipients. Am J Transplant. 2007;7(12):2704-2711. 16. De Geest S, Borgermans L, Gemoets H, et al. Incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in renal transplant recipients. Transplantation. 1995;59(3):340-347. 17. Shoskes DA, Avelino L, Barba L, Sender M. Patient death or renal graft loss within 3 yr of transplantation in a county hospital: importance 64 of poor initial graft function. Clin Transplant. 1997;11(6):618-622. 65 18. Browne T, Merighi JR. Barriers to Adult Hemodialysis Patients’ Self- Management of Oral Medications. American Journal of Kidney diseases. 2010;56(3):547-557. 19. Gellad WF, Grenard J, McGlynn EA. A review of barriers to medication adherence: a framework for driving policy options. RAND Corporation. 2009. http://www.rand.org/pubs/technical_ reports/2009/RAND_TR765.pdf (accessed 5 March 2011). 20. Ruppar TM, Russell CL. Medication adherence in successful kidney transplant recipients. Prog Transplant. 2009;19(2):167-172. 21. McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to medication prescriptions. Journal of the American Medical Association. 2002; 288(22):2868–2883. 22. Tattersall R. The expert patient: a new approach to chronic disease management for the 21st century. Clin Med. 2002; 2:227-229. 23. Costantini L. Compliance, adherence, and self-management: is a paradigm shift possible for chronic kidney disease clients? CANNT J. 2006;16(4):22-26.

Additional reading -- Denhaerynck K, Steiger J, Bock A, Schäfer-Keller P, Köfer S, Thannberger N, De Geest S. Prevalence and Risk Factors of Non- Adherence with Immunosuppressive Medication in Kidney Transplant Patients. Am J Transplant. 2007; 7(1):108–116. Accessed at: http:// onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2006.01611.x/full -- Fine RN, Becker Y, De Geest S, Eisen H, Ettenger R, Evans R, Rudow DL, McKay D, Neu A, Nevins T, Reyes J, Wray J, Dobbels F. Nonadherence Consensus Conference Summary Report. Am J Transplant. 2009;9(1):35–41. Accessed at: http://onlinelibrary.wiley. com/doi/10.1111/ajt.2008.9.issue-1/issuetoc

Patient Education in

Pharmacological 67 Treatment after Kidney Transplantation Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

IntroducTIOn

Education in pharmacological treatment following kidney transplantation is an important aspect of nursing care. When the patient is first discharged from hospital he/she should have acquired sufficient knowledge about taking medication and self-management to prevent complications. Therefore, each unit will have a specific strategy to provide post-transplant education, including support for the patient and family/ caregiver. 68 69 The following is an example of a descriptive plan for education in pharmacological treatment (this will be developed according to the nursing intervention system used by each centre): Patient Education in Pharmacological Treatment after Kidney Transplantation

. 1 : may : bear in mind : if the patient Attitude/belief/perception influence pharmacological treatment adherence or non- adherence. Patient should show interest in the given information. Note : Nurse records her nursing in findings and assessment care plan/clinical pathways. Illiteracy : discuss with the family the need to include a family member/carer in the education process. Foreign origin does not sufficiently speak the local language, linguistic support resources should be utilised (e.g. a family member who knows the language or professional interpreter/cultural mediator services if available within the hospital). Psychological state that anxiety and fear can interfere understand to ability patient’s with R ationales/Expected esults

68 69 To achieve an effective education, it is achieve an effective To Literacy/academic education levels Native language. In case patient is of foreign origin, verify if the patient understands local language, and if he/she knows how to read it. Cognitive level Eye-sight and hearing ability Psychological state (e.g. anxiety and fear) Attitude/beliefs/perception, in their cultural context, on the taking of medication. ------The nurse introduces herself to the patient and, during the preparation procedures for kidney transplant (Tx), makes an initial assessment of the patient: Patient is informed that during hospitalisation, he/ she will receive education on treatment. Self- management is emphasized (depending on the amount of information already received at pre- transplant clinic, this may include a brief discussion surrounding rationale). Note: essential that throughout the process, there is good coordination and communication between medical and nurses from all shifts. staff Guidelines for Education

ransplant D ays (approximate) Pre-transplant: patient preparation Kidney T Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Patient’s interest is evaluated. (For Patient’s example, if patient is responsive and participative by listening and asking appropriate/coherent questions). After this initial period, Note : each responsible nurse should continuously provide the patient with maximum information about This the prescribed medication. is done each time medication administered. R ationales/Expected esults

70 71 . 2 It is essential that the prescribed dose taken - do not miss a dose This is because Blood tests are needed daily. initially immunosuppressive dosages will vary according to the drug levels in blood. Check if fasting is required and inform patient. Importance of personal hygiene to reduce the risk of infection. - - - The drug regimen is explained to the patient, in simple terms and adapted to individual needs. Emphasis is placed on the importance of adhering to the regimen to prevent rejection, explaining that medicines are called immunosuppressants and Also stress on: to be taken forever. : To achieve effective communication among achieve effective To Note : shifts, each nurse responsible for the patient should document the education given and assessment competence. of patient’s Following the transplant the patient’s general Following the transplant patient’s condition is evaluated, and education continues. learning style is At the same time, patient’s assessed in order to adopt appropriate educational intervention Guidelines for Education ransplant D ays Within 48 hours after (approximate) transplantation Kidney T Patient Education in Pharmacological Treatment after Kidney Transplantation To repeat the names of To prescribed drugs and function for each one. express their understanding To of the importance immunosuppressive drugs/ communicate any difficulties they have with the learning process. verbalize their doubts and/or To related concerns. - - - To feedback questions, the patient To is able: If it is confirmed that the patient has the habit of self-medicating or using alternative therapies, they should be told of the importance in communicating this with their doctor/nurse in order to assess whether they can combine this Tx drug practice safely with the regimen.

70 71 Patient recognition of the name each drug, associates its function and possible side effects. Patient knowledge of the schedule and way that each drug should be taken (fasting/with food) to obtain the best effect. Patient adherence to prescribed dosage. - - - Medication knowledge is reinforced, in order to enhance: After each stage, feedback with the patient to assess their degree of understanding the explanations provided. Also, explain to the patient that should there be any such as vomiting or diarrhoea, they side effects as should inform the healthcare team immediately, this can alter the absorption of administered drug dose. Give the patient/carer written information which includes the main points of drug treatment and post- transplant self-management. During the education process, it is also worthwhile to find out if the patient has a self-medicating habit (i.e. taking over-the-counter medication) or uses any alternative/ traditional therapy. Between transplantation 48-72 hours after Drugs in Renal Replacement Therapy: A Guide to Clinical Practice R ationales/Expected esults Patient is able to recognize the immunosuppressants. Patient is able to explain why it should be taken at specific times and what to do if vomiting or diarrhoea occurs. If patient expresses doubts, the corresponding process in educational intervention should be reinforced, with an empathetic attitude and patience, providing support material (e.g. written information with illustrations / drawings).

72 73 Explain that should they forget any dosage, advice; and that if should seek medical/nurse’s there are more than four hours before the next dose, they should then take the missed dose. any interactions between drugs; advise Avoid that drugs should not be mixed on individual’s initiative (e.g. tacrolimus and ibuprofen; the latter is nephrotoxic). Be aware of foods that can interfere with the absorption of drugs (e.g. tacrolimus should be taken in fasting state, 1 hour before or 2-3 hours after meal and greasy foods lower the absorption of this drug). Inform the transplant team if another healthcare professional has prescribed any medication. - - - - Guidelines for Education The patient is instructed to administer the medication supervised by the nurse. Key Points for patients to remember: Patient’s nearest family member/caregiver is Patient’s also engaged to participate in gaining previously transmitted knowledge in order to give the patient support and help when required.

ransplant D ays Between (approximate) 4-5th day after transplantation Kidney T Patient Education in Pharmacological Treatment after Kidney Transplantation At this stage, the patient is able to self-manage his medication regimen, under the nurse’s supervision. The patient demonstrates complete independence and has enough confidence in performing this activity. Note : Give the patient a record of current drug treatment with their full name and clinical history Explain to them that it number. should be taken to each follow-up This is to facilitate visit at clinic. medication modification as indicated by blood-test results condition, thus and patient’s avoiding possible errors in drugs administration.

72 73 Keeping the medication in order, clean and dry, clean and dry, Keeping the medication in order, away from points of light, heat or humidity so as not to lose its effectiveness. Not changing or adding medication in the boxes and discarding the empty ones to avoid errors. Replacing the drugs before they run out along all medicines if they go on holiday, Taking in case they cannot get supplies from that location. Informing their dentist that they are transplanted, in case a technique or medication prescribed by the dentist may cause an interaction. - - - - - The above process is repeated and reinforced. In addition, the patient is told importance of: transplantation From 6th day after Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Patient expresses their understanding and feels competent in self-management. Patient knows which day is scheduled for the next blood-test so as to be in fasting, and to take the appropriate immunosuppressants after venepuncture is performed. As it is understood, if Note: education is provided to a family member/caregiver from the beginning, then the evaluation and expected outcomes will relate to this person. R ationales/Expected esults

74 75 Knowing the name, dosage and schedule of each drug. Keeping in mind the name of their doctor and nurse, and to refer them for any further facilitate this, To consultation that they may need. the corresponding names and contact phone number are given. by Knowing how to communicate effectively phone with healthcare professional: introduce himself/herself by full name, clinical history After name. number and responsible physician’s that, explain the reason for call. Attending all follow-up visits, and if unable to attend to telephone the indicated person reschedule the appointment. - - - - Guidelines for Education The patient is reminded of the importance of: ransplant D ays At discharge (approximate) Kidney T Patient Education in Pharmacological Treatment after Kidney Transplantation

References

1. Andreu L, Force E. La Enfermería y el Trasplante de Órganos. 2. Cox S, Thomas N, Liossatou A. Giving Choice Through Timely Education: How to Set Up and Implement Education Programmes for CKD. In: Jenkins K, Mahon A (eds). Chronic Kidney Disease (Stages 4-5) - A Guide to Clinical practice. Madrid: EDTNA/ERCA; 2008. p29- 30.

Additional Reading • Chamney Melissa. In: Ray Trevitt (ed). Renal Transplantation - A Guide to Clinical Practice. Madrid: EDTNA/ERCA; 2009. p59-73. • Prendergast MB, Gaston RS. Optimizing Medication Adherence: An Ongoing Opportunity To Improve Outcomes After Kidney Transplan- 74 tation. Clin J Am Soc Nephrol. 2010;5(7):1305-1311. Accessed at 75 http://cjasn.asnjournals.org/content/5/7/1305.full.pdf+html

Influence of the Use of Herbal Plants in Renal Replacement Therapy 77 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Learning objectives • To be aware of the use of traditional treatments/ medicinal plants by some patients • To know the side effects/incompatibilities of some traditional remedies in the context of renal replacement therapy

Introduction The evolution of pharmacological treatment has led to great improvements in the fight against diseases in the last two centuries. However, it has been accompanied, unfortunately, 78 79 with a number of adverse effects caused by potent new drugs. This situation, along with the desire to cure illness with minimal risk, has prompted people of the developed countries to pursue the almost forgotten knowledge (‘grandmother’s remedies’) for less aggressive treatments. The increase in tourism to countries with more ‘exotic’ cultures has contributed to the incorporation of therapies and remedies into our society as valid alternatives. The migratory flow towards Europe from developing countries is clearly changing our traditional environment, introducing curative practices from cultures with other philosophical and practical systems about disease and healing. This produces a phenomenon of acculturation in both directions. Consequent to international migratory flows, the presence of patients from other cultures who need some level of healthcare attention in our healthcare settings is becoming increasingly common1. This poses a challenge for healthcare professionals Influence of the Use of Herbal Plants in Renal Replacement Therapy

to acquire knowledge about the particular needs of people from other communities who are now fellow citizens. In spite of the popular opinion that alternative/complementary remedies lack side effects, reality demonstrates that plant species (or compounds) do have adverse effects on biological systems, including the renal system2,3. Patients might use a variety of treatments, among which is the so-called natural therapy, without the healthcare professional being aware of it (due to the fact that generally patients are not being questioned about it). The processes of prescribing, dispensing and administration of registered pharmaceutical products must take into account any herbal remedies which patients are taking. In these cases there is the risk of interactions between the different types of treatments that, as a whole, can be harmful to the patient. 78 In addition, dialysis patients often have polypharmacy due to 79 their multiple pathologies such as heart disease, hypertension and metabolic disorders (e.g. diabetes, dyslipidaemia, gout, bone mineral balance disorders) whose treatment can be altered by concomitant use of alternative remedies. Moreover, in the case of transplant patients, immunosuppressive drugs are known to cause or exacerbate hypertension, type 2 diabetes and dyslipidaemia. A point that should not be forgotten is the potential hydroelectrolytic disorder produced by plant species used as a laxative, with positive or negative effects on diuresis. In those cases when fluid restriction is required, the volume provided by herbal teas (the most common administration route) should be taken into account. The healthcare professional should routinely ask the patient about the use of traditional medicine and/or health practices. An exploration into the potential consequences/interactions of the use of alternative remedies will help to orientate the type Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

of therapy that may be used and to rule out those that are not recommended (or totally contraindicated) for the renal patient.

Medicinal plants in patients with nephropathies Table 1 summarizes the adverse effects/contraindications and precautions to be taken regarding the possible use of medicinal plants in patients with chronic kidney disease (CKD).

80 81 Influence of the Use of Herbal Plants in Renal Replacement Therapy O bservations Monitoring Monitoring Monitoring Monitoring Monitoring Monitoring Monitoring Monitoring Affectation Renal dysfunction, hydroelectrolytic imbalance. Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Acute tubular necrosis, intersticial fibrosis. Anticoagulant action. Hyperthyroidism. Urinary retention (atropinic alkaloids). Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect 80 81 Botanic name Barosma betulina (Rutaceae) Cytisus scoparius (Fabaceae/Leguminosae) Fucus vesiculosus Ascoohyllum nodosum (Fucaceae) Arctostaphylos uva-ursi (Ericaceae) Atropa belladona (Solanaceae) Atractylodes macrocephala (Asteraceae/Compositae) Asparagus officinalis (Liliaceae) Agrimonia eupatoria A. pilosa (Rosaceae) Common name B u ch BROOM BLADDER WRACK (*) KELPWARE BEARBERRY BANEWORT ATRACTYLODIS ASPARAGUS AGRIMONY 1: Medicinal Plants and Effects on Renal Function Table Drugs in Renal Replacement Therapy: A Guide to Clinical Practice O bservations Monitoring Monitoring Monitoring Monitoring Observation Observation Monitoring Monitoring Monitoring Monitoring Affectation Affectation Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Renal dysfunction, hydroelectrolytic imbalance. Diuretic + potentiates the of diuretics. effect Urinary retention (atropinic alkaloids). Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect 82 83

Botanic name Galium aparine (Rubiaceae) Rehmannia glutinosa (Scrofulariaceae) Taraxacum dens-leonis Taraxacum officinale T. (Asteraceae/Compositae) Cucumis sativa (Cucurbitaceae) Agropyrum repens (Poaceae/Gramineae) Datura estramonio (Solanaceae) Houttuynia cordata (Saururaceae) Centaurium erytraea (Gentianaceae) Chelidonium majus (Papaveraceae) Ruscus aculeatus (Liliaceae) Common name GOOSEGRASS ‘DI HUANG’ DANDELION CUCUMBER COUCHGRASS COMMON THORNAPPLE COMMON CHAMELEON cao’ ‘Yuxing CENTAURY CELANDINE BUTCHER’S BROOM Influence of the Use of Herbal Plants in Renal Replacement Therapy Monitoring Monitoring Monitoring Monitoring Monitoring Monitoring Observation Observation Observation Monitoring Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Renal dysfunction, hydroelectrolytic imbalance. Photosensitization. Diuretic (studies in rats) of + potentiates effect diuretics. Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Urinary retention (atropinic alkaloids). Diuretic + potentiates the of diuretics. effect 82 83 Viola tricolor Viola (Violaceae) Allium cepa (Liliaceae) Levisticum officinale Apiaceae/Umbelliferae Lavandula officinalis (Labiatae) Larix americana (Pinaceae) Alchemilla spp. (Rosaceae) Hydrangea paniculata (Saxifragaceae)) Echysetum arvens (Echysetaceae) Hyosciamus niger (Solanaceae) Chimaphila umbellata (Ericaceae) PANSY ONION LOVAGE LAVENDER LARCH LADY’S MANTLE HYDRANGEA HORSETAIL HENBANE GROUND HOLLY Drugs in Renal Replacement Therapy: A Guide to Clinical Practice O bservations Monitoring Observation Monitoring Monitoring Monitoring Monitoring Liver function test Monitoring Monitoring Monitoring Affectation Affectation Diuretic + potentiates the of diuretics. effect Urinary retention (atropinic alkaloids). Diuretic + potentiates the of diuretics. effect Renal dysfunction, hydroelectrolytic imbalance. Diuretic + potentiates the of diuretics. effect Renal dysfunction, hydroelectrolytic imbalance. Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. Bladder effect contraction (Seeds). Diuretic + potentiates the of diuretics. C ontains effect tubocurarine. 84 85

Botanic name Rosmarinus officinalis (Labiatae) Rhododendrum molle (Ericaceae) Senecio spp (Compositae) Populus spp. (Salicaceae) Adonis vernalis (Ranunculaceae) Mentha pulegium (Lamiaceae/Labiatae) Levisticum officinale Apiaceae/Umbelliferae Petroselinum crispum (Umbelliferae) Chondodendron tomentosum (Menispermaceae) Common name ROSEMARY RHODODENDRON RAGWORT POPLAR PHEASANT’S EYE PENNYROYAL OIL OIL PENNYROYAL PELLITORY PARSLEY PAREIRA ROOT PAREIRA Influence of the Use of Herbal Plants in Renal Replacement Therapy Observation Monitoring Very little information Very available: avoid. Liver function test Monitoring Liver function test Observación Monitoring Monitoring Monitoring Irritation of urinary tract (short duration). Diuretic + potentiates the of diuretics. effect Renal dysfunction, hydroelectrolytic imbalance. Irritation of oral mucosa. Renal dysfunction, hydroelectrolytic imbalance. Retención urinaria (alcaloides atropínicos). Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect Diuretic + potentiates the of diuretics. effect 84 85

Nasturtium officinale (Brassicaceae) Alisma plantago (Alismaceae) Rumex acetosa (Poligonaceae) Saponaria rubrae S. officinalis (Caryophyllaceae) Capsella bursa-pastori (Cruciferae) Sassafras officinale (Lauraceae) Smilax officinalis Herniarica glabra (Cariophyllaceae) WATERCRESS WATER PLANTAIN WATER SORREL SOAPWORT SHEPHERD’S PURSE SASSAFRAS BARK SARSAPARILLA ROOT SARSAPARILLA RUPTURE WORT Drugs in Renal Replacement Therapy: A Guide to Clinical Practice O bservaciones Monitoring Monitoring Observation: Renal stones? Monitoring Liver function test C oagulation screening Monitoring - to keep a close watch on the possible undesired Afectación Observation Renal dysfunction, hydroelectrolytic imbalance. Renal dysfunction, hydroelectrolytic imbalance. CNS toxicity (thujone). Renal dysfunction, hydroelectrolytic imbalance. Renal dysfunction, hydroelectrolytic imbalance. papillary ↓ renal flow, necrosis (Salicin). Anticoagulant action. Diuretic + potentiates the of diuretics. effect 86 87

Nombre botánico Rumex patientia R. crispus (Poligonaceae) Artemisia absinthium (Asteraceae/Compositae) Oxalis acetosella (Oxalidaceae) Salix alba (Salicaceae) Daucus carota (Umbelliferae) - it is advisable to perform periodical analysis monitor renal function. Nombre común YELLOW DOCK WORMWOOD WOOD SORREL WILLOW BARK WILD CARROT effects described for this plant specie. (*) As Kelp: Alga. The expression refers to several species: Laminaria digitata, L. japonica (Laminariáceae), Fucus y Ascophyllum. All of them contain Ascophyllum. Alga. The expression refers to several species: Laminaria digitata, L. japonica (Laminariáceae), Fucus y As Kelp: (*) iodine, and can produce hypo or hyperthyroidism. They may contain arsenic. have been used as a source of iodine in gynaecology to widen the cervical canal to facilitate labour. Nota: Monitoring Influence of the Use of Herbal Plants in Renal Replacement Therapy O bservations CO LA Cola spp. (Sterculiaceae) Not approved by the German C ommission E, due to safety issues (***) Avoid Potentially unsafe (*) Avoid Avoid MATE Ilex paraguayensis (Aquifoliaceae) Affectation Nephrotoxicity. Cystitis. Nephrotoxicity. Interstitial nephritis. Renal dysfunction. Fibrosing interstitial nephritis (**). Interstitial nephritis. Renal fibrosis.

86 ) 87 COCOA, CHOCOLATE Theobroma cacao ( Sterculiaceae Botanic Name Citrullus colocynth Colocyntis vulgaris (Cucurbitaceae) Uncaria tomentosa U. guianensis (Rubiaceae) Colchicum autumnale (Liliaceae) Stephania tetrandra ‘fang-ji’ + Stephania tetrandra ‘fang-ji’ Magnolia officinale Aristolochia pistolochia spp (Aristolochiaceae)

TEA Camelia sinensis (Cameliaceae) Common Name COFFEE Coffea arabica (Rubiaceae) COLOCYNTH CAT’S CLAW CAT’S AUTUMN CROCUS ASSOCIATION of CHINESE ASSOCIATION HERBS for weight loss ARISTOLOCHIA It should be remembered that common plant species used in the household possess more or less noteworthy diuretic effects. This is the case of drinks with xanthin 3). bases Table Furthermore, some plant species are nephrotoxic (see (see 2). Table 2: Drinks with Xanthin Bases Table 3: Plant species with renal toxicity Table Drugs in Renal Replacement Therapy: A Guide to Clinical Practice O bservations Not approved by the German C ommission E, due to safety issues (***) Not approved by the German C ommission E, due to safety issues (***) Toxic: avoid. Toxic: + complete blood LFT count Potentially unsafe (*) Avoid Potentially unsafe (*) Affectation Renal dysfunction (short duration). Nephrotoxicity. Nephrotoxicity. Renal dysfunction, hydroelectrolytic imbalance. Hepatotoxicity. Bone marrow depression. Hypernatraemia, hypokalaemia, pseudo- hyperaldosteronism, oedema, alkalosis, HTN. Renal dysfunction (in prolonged use or overdosage). Hypokalaemia. 88 89

Botanic Name Smilax ornata S. Asper (Smilacaceae) Ruta graveolens (Rutaceae) Podophyllum peltatum Podophyllum emodi (Berberidaceae) Glycyrrhiza spp. (Fabaceae/Leguminosae) Juniperus communis (Cupresaceae) Gossypium hirsutum (Malvaceae) Common Name SARSAPARILLA ROOT ROOT SARSAPARILLA RUE MAYAPPLE LICORICE ROOT JUNIPER COTTON Influence of the Use of Herbal Plants in Renal Replacement Therapy 5 . 4 Renal Effects CKD stages 3-5 Potentially unsafe (*) Not recommended: Acute tubular necrosis. Action Neuro- and nephrotoxic. Renal dysfunction. 88 89 Stimulates intestinal motility due to irritation. Botanic Name Averrhoa carambola Averrhoa (Oxalidaceae) Barbarea vulgaris (Cruciferae) Aloe vera (Liliaceae) Laxative / cathartic ALOES STARFRUIT WINTERCRESS (***) Blumenthal M. 1998 Fetrow CW. Avila JR. 1999 Avila (*) Fetrow CW. (**) Described as ‘Chinese herbal nephropathy’, it was observed in Belgium 1993, with about ten people affected. It considered to be caused by the inadvertent substitution of Stephania for ‘fang-ji’, a plant specie of Aristolochia which contains a potent nephrotoxins, aristolochic acid inadvertent substitution of Stephania for ‘fang-ji’, a plant specie As an additional precaution, the effects caused by some plant species must be followed with special attention, especially those used as laxatives, or ‘drastics’ sometimes (maximum and referred rapid to effect), whose as irritant ‘cathartics’ action on produce the copious diarrhoeas intestinal that, jeopardises indirectly, renal mucosa function due to can the consequent 4). Table hydroelectrolytic imbalance (see 4: Plants with strong laxative effect Table Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Electrolyte loss in high doses. Electrolyte loss in high doses. Intense electrolyte loss in high doses. Renal dysfunction. Intense electrolyte loss in high doses. Electrolyte loss in high doses. Not recommended. Frequent electrolyte loss in high doses. Electrolyte loss in high doses.

90 91 Stimulates intestinal motility due to irritation (anthraquinones). Stimulates intestinal motility due to irritation (anthraquinones). Intestinal irritant (drastic). Laxative effect. Cathartic (drastic). Stimulates intestinal motility due to irritation. Stimulates intestinal motility due to irritation (anthraquinones). Stimulates intestinal motility due to irritation (anthraquinones). Rhamnus frangula (Rhamnaceae) Rhamnus prusiana (Rhamnaceae) Ricinus comunis (Euphorbiaceae) Hydrastis canadensis (Ranunculaceae) Exagonium purga (Convolvulaceae) Menispermum canadense (Menispermaceae) Rheum officinale (Polygonaceae) Cassia angustifolia (Fabaceae) BUCKTHORN BARK C AS ARA OIL, BEANS CASTOR GOLDEN SEAL ROOT JALAP MOONSEED R H UBARB SENNA Influence of the Use of Herbal Plants in Renal Replacement Therapy

Renal transplant patients and immunosupression therapy: interactions with medicinal plants Patients with renal transplants receive immunosuppressant medication to avoid rejection of the graft. Clinical evidence has shown interaction between some medicinal plants and immunosuppressant drugs, this can be specified in two major aspects: • Plant species that possess immunosuppressive effects (positive or negative) altering the outcome of immunosuppressant drugs.

• Plant species that alter the pharmacokinetics of immunosuppressant drugs, modifying plasma levels to an extent which is below or above those therapeutically desired or producing collateral interactions.

90 In such cases an appropriate action involves either to 91 monitor the immunosuppressant levels or, clearly, to avoid the concomitant administration of a medicinal plant with immunosuppressive effects. The following two tables (5 and 6) summarize the information on these aspects: Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

immunosuppressants) (Do not administer with GINSENG Panax ginseng (Araliaceae) • Immunomodulating effect (+/-)

92 93

transplants) C LAW T ’s Immunostimulant effect (Papilionaceae) C A Uncaria tomentosa (Rubiaceae) ECHINACEA Echinacea spp. (Compositae) GARLIC Allium sativum (Liliaceae) ALFALFA Medicago sativa (Not advisable for people with • • • •

immunosuppressants) (Do not administer with Immunosuppressory effect BITTER MELON Momordica charantia(*) (Cucurbitaceae) SINOMENION Sinomenion acutum (Menispermaceae) TRIPTERYGIUM / Tripterygium ‘lei-gong-teng’ wilfordii (Celastraceae) • • • 5: Medicinal Plants with modulating effect on immunity Table (*) Possesses marked hypoglycaemic action. Influence of the Use of Herbal Plants in Renal Replacement Therapy O bservations Do not use concomitantly. Do not use concomitantly. Monitor blood glucose. Do not use concomitantly. Monitor blood glucose. Do not use concomitantly. Do not use concomitantly.

92 93 Interactions with immunosppressants ↑ levels of CsA Antagonizes hyperglycaemia caused by: Steroids C sA Tacrolimus Sirolimus MMF ↑ levels of CsA ↓ levels of: C sA Tacrolimus Sirolimus Potentiates HTN due to: Steroids C sA Tacrolimus Sirolimus MMF

SINICA Plant species AVENS GeumChiloense (Rosaceae) BITTER MELON / BITTER GOURD Momordica Charantia (Cucurbitaceae) BITTER ORANGE Citrus Ausantium (Rutaceae) CONEFLOWER Echinacea Spp (Compositae) (‘Ma huang’) (Gnetaceae) EPHEDRA 6: Medicinal plants that interact with immunosuppressants Table Drugs in Renal Replacement Therapy: A Guide to Clinical Practice O bservations Do not use concomitantly. Monitor blood glucose. Do not use concomitantly. Do not use concomitantly.

94 95 - Renal stones - Natural urinary antiseptics - Urinary pH modifiers - Uricaemia Interactions with immunosppressants Antagonizes hyperglycaemia caused by: Steroids C sA Tacrolimus Sirolimus MMF ↓ levels of: C sA Tacrolimus Potentiates HTN Alteration in response to steroids

Plant species GINKGO BILOBA Ginkoaceae HYPERICUM PERFORATUM (Hypericaceae) LICORICE Glycirrhiza Glabra (Fabaceae/Leguminosae) Summary It is important to remember that special care has to be taken with alternative medicines and where possible advocate avoidance of all alternative medicines (or aliments) that may cause disorder of: - Blood pressure - Cardiovascular function - Liver function - Glycaemia Influence of the Use of Herbal Plants in Renal Replacement Therapy

References

1. Del Villar JA, Melo E. Guía de Plantas medicinales del Magreb. Establecimiento de una conexión intercultural. Barcelona: Cuadernos de la Fundación Dr. Antonio Esteve. Nº 18; 2010. 2. Ernst E. Risks associated with complementary therapies. In Dukes MNG, Aronson JK (eds.) Meyler’s Side Effects of Drugs. 14th ed. Amsterdam, the Netherlands: Elsevier Science; 2000. p1649-1681. 3. Aronson JK. Meyler’s Side Effects of Drugs. The International Encyclopedia of Adverse Drug Reactions and Interactions. Amsterdam: Elsevier Science & Technology; 2000. 4. Reginster F, Jadoul M, Ypersele de Sttribhou C. Chinese herbs nephropathy presentation, natural history and fate alter tr.ansplantation. Nephrol Dial Transplant 1997;12:81-85. 5. Moyses Neto M, Silva GEB, Costa RS, Vieira Neto OM, Garcia- Cairasco N, Lopes NP, Haendchen PFC, Silveira C, Mendes AR, Filho RR, Dantas M. Star fruit: simultaneous neurotoxic and nephrotoxic effects in people with previously normal renal function. NDT Plus. 2009; 2: 485–488. http://ckj.oxfordjournals.org/content/2/6/485.full. pdf (accessed 19 Jan 2012). 94 95 The information contained in the tables has been elaborated from:

• Blumenthal M (ed). The complete Commission E Monographs. Boston: Integrative Medicine Communications; 1998. • Bruneton J. Plantes toxiques. Végétaux dangereux pour l’homme et les animaux. Paris: Technique & Documentation; 2008. • Tomás E, Farriols A, Cantarell C, Juárez JC. Interacciones entre plantas medicinales y fármacos inmunodepresores. Medicina Clínica. 2006; 27:177-184. • Ernst E. The Desktop Guide to Complementary and Alternative Medicine. London: Harcourt Publishers Limited; 2001. • Fetrow CW, Avila JR. Professional’s Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp.; 1999. • Font i Quer P. Plantas Medicinales. El Dioscórides Renovado. Barcelona: Editorial Labor; 1992. • Jellin JM, Gregory PJ, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 12th ed. Stockton, CA: Therapeutic Research Faculty; 2009. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

• Paris RR, Moyse M. Précis de Matière Médicale. Paris: Masson & Cie.;1967. • Philp B. Herbal-drug Interactions and Adverse Effects. New York: McGraw-Hill; 2004. • Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia: Hanley & Belfus, Inc.; 2002. • San Martín R. Farmacognosia con Farmacodinamia. Barcelona: Editorial Científico – Médica; 1968. • Baxter K. Stockley’s Drug Interactions. London: Pharmaceutical Press; 2008. • Tayler VE. Herbs of Choice. The Therapeutic Use of Phytomedicines. New York: Pharmaceutical Products Press; 1994. • Natural Medicines Comprehensive Database. Available at: www.naturaldatabase.com (accessed 6 Feb 2011).

96 97 Influence of the Use of Herbal Plants in Renal Replacement Therapy

96 97

Drug Sheets

99 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

How to use the Drug Sheets

The medicines included in the Drug Sheets are those commonly used in RRT (in view of the variation in the European drug market and brand names, only those currently licenced in the UK are cited as reference).

• Each sheet is developed in table format for easy reference.

• Each table contains the following headings: -- Group - stating the class of drug, with a brief explanation of its action/indication.

-- Active ingredient (Brand name) - arranged within each group/subgroup in alphabetical order according to the active substance (INN: International Non- proprietary Name).

100 -- Administration Route (Available Formulations) 101 and Therapeutic Dosage (TD indicating minimal dose – maximum dose/24 hours. For example, amlodipine TD: 5 – 10 mg/24h. This is only a guideline; dosage should be adjusted in each case, depending on patient’s characteristics and indication or, in some cases, according to local policy.

-- Principal Side Effects - these are included either due to frequency or clinical relevance. -- Contraindications/Precautions/Observations this section includes considerations to be taken by nurses. Where more information or specific Drug Sheets

considerations are required, consultation is available in ‘Recommendations in the Administration of Specific Drugs’.

Note: To reduce text density, repeatedly used words are abbreviated (e.g. administer, administration, administered are abbreviated to “adm” – refer to Abbreviation List) or represented by symbols (e.g. increases/raises is represented by ↑; decreases/lowers by ↓; more than by > and less than by <).

100 101 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Cautions: see dexketoprofen. Use with caution in eGFR <50 ml/min. Not recommended for use in eGFR <20 ml/min. IM : intragluteal injection (into the upper outer quadrant of buttock). PR : adm at night. Not recommended to be given with tacrolimus or sirolimus (nephrotoxicity). Use cautiously in eGFR <50 ml/min. Not recommended for use in eGFR <20 ml/min. PO: adm with foods (gastric irritation). Principal S ide E ffects GI disorders. Peptic ulceration. HTN. RF. Oedema. GI disorders. Peptic ulceration. HTN. RF. Oedema.

102 103 Gel. Sup 100 mg. Tabs 12.5 mg, Tabs 50 mg. Tab PO : 50 mg/8-12h. Amp 75mg. 75 mg/12-24h. Administration R oute (Available Formulations) (Available 25 mg. Sachets 25 mg. Caps 75 mg, 100 mg. and T herapeutic Dosage P O : T D: P O : IM: P R : P: TO T D: IM: Max dose via any route = 150 mg/day. PO: 25 mg/8h. Max 75 mg/day; reduced to max 50 mg/day in elderly.

(Brand Name) Active Ingredient

Dexketoprofen (Keral) Diclofenac Arthrotec, (Voltarol, Dyloject, and different generic and different brands)

To treat mild to moderate pain. moderate to mild treat To

roup roup G

Non-steroidal anti-inflammatory drugs drugs anti-inflammatory Non-steroidal (NSAIDs): ANAL GES IC S Drug Sheets every 6 hours. every 6 hours. Do not use more than 4 g in 24 hours. eGFR 10-50 ml/min: eGFR <10 ml/min: Cautions: see dexketoprofen. Not recommended for use in eGFR <20 ml/min. Use with caution in eGFR <50 ml/min. GI disorders. Peptic ulceration. HTN. RF. Oedema. Hepatotoxicity in overdose.

102 103 Tabs 200 mg, Tabs 500 mg, Tabs Sups 60 mg, 200-800 mg 6-8h 500 mg-1 g/6h (Max 1g. 125 mg, 250 500 mg, 1000 mg 400 mg. 800 mg retard. Tab Oral suspension 100 mg/5ml. 650 mg, 1g. P O : T D: P O : IV: P R : T D: (Max 2.4 g/day). 4 g/day). See Observations.

Ibuprofen (Calprofen, Cuprofen, Fenbid, Ibuleve, Brufen, Nurofen and different generic brands) Paracetamol (Panadol, Perfalgan and generic brands) different

To treat mild to moderate pain. moderate to mild treat To

(NSAIDs):

Paracetamol Non-steroidal anti-inflammatory drugs drugs anti-inflammatory Non-steroidal Drugs in Renal Replacement Therapy: A Guide to Clinical Practice 75% of normal dose.* 50 % of normal dose.* Contraindications/ Precautions / O bservations Use cautiously with: - Other analgesics, narcotics, anxyolitics, antihistamines (↑sedative action). Anticholinergics (paralytic ileus). - - Bupropion or iodinated contrasts (risk of convulsion). interval). - Droperidol (↑ QT - MAOI (HypoTN, respiratory depression). eGFR 10-50 ml/min: eGFR <10 ml/min: dose and titrate *(start with lowest effective according to response). 10% Active metabolites accumulates in RF. codeine converted to morphine sulphate. Principal S ide E ffects Constipation. GI disorders. Rash. Drowsiness. Confusion. Respiratory depression. Dependence, withdrawal syndr. Urinary retention.

104 105 Tabs 15, 30, 60 mg. Tabs 30 - 60 mg/6h. 60 mg/ml. Administration R oute (Available Formulations) (Available and T herapeutic Dosage P O : IM: T D: See Observations. Oral Solution 25 mg/5ml. (Brand Name) Active Ingredient

Codeine (Codeine Phosphate)

To treat chronic and severe pain. severe and chronic treat To

roup roup G

piates: O Drug Sheets smooth skin areas (torso, upper Use cautiously with/in: - CYP3A4 inhibitors (amiodarone, azole, diltiazem, clarithromycin, darunavir, atazanavir, verapamil): enhancement dronedarone, ritonavir, effects. - SSRI (e.g. citalopram, escitalopram, duloxetine, fluoxetine): serotonin synd. place under the tongue, in deepest area Tab: Allow to dissolve, do not chew of the mouth. a glass of water before adm to Take or split. promote hydration of the oral mucosa. Transdermal: arm). Press for 30 sec. Do not cut the patches. applying Avoid After application, wash hands. another patch in the same area of skin until at least after a Wk. No dose reduction required in RF as majority are dose according to Titrate inactive metabolites. dose. Start with lowest effective effect. Constipation. GI disorders. Rash. Drowsiness. Confusion. Respiratory depression. Dependence, withdrawal synd. Urinary retention.

104 105 ransdermal: Tabs suckable/ P O : Tabs sublingual 200 µg, 400 600 800 µg, 1200 µg. 0.05 µg /ml. S C/IV: T 12 µg/hour patch, 25 µg/hour patch, 50 µg/hour patch, 75 µg/hour patch, 100 µg/hour patch. T D: individualized for each patient. There is no specific In RF: recommendation but ↓ doses are advisable.

Fentanyl (Durogesic DTrans, Actiq Effentora, and generic brands) different

To treat chronic and severe pain. severe and chronic treat To

piates: O Drugs in Renal Replacement Therapy: A Guide to Clinical Practice 75 % of the usual dose.* avoid if possible or use 50 % Contraindications/ Precautions / O bservations Use cautiously with: - Bupropion or iodinated contrasts (risk of convulsions). - MAOI (HypoTN, respiratory depression). - CNS depressants. Do not confuse modified release (MR) forms with quick release forms. Do not use MR preparations in severe RF. In RF adjust dose: eGFR 10-50 ml/min: eGFR <10 ml/min: of the usual dose.* dose and titrate *(start with lowest effective according to response). Morphine- Active metabolites accumulate in RF. 6-glucoronide (active metabolite) half-life approx 50 hours (major accumulator and responsible for toxicity). Metabolites can be removed by dialysis. Principal S ide E ffects Constipation. GI disorders. Rash. Drowsiness. Confusion. Respiratory depression. Dependence, withdrawal synd. Urinary retention.

106 107 Caps 10 mg, 30 individualized for Administration R oute (Available Formulations) (Available and T herapeutic Dosage P O : Amp 1% (10 mg/1ml), S C: 2% (40 mg/2 ml). T D: each patient. See Observations. 60 mg, 100 200 mg. 5 mg, 10 Tabs. 15 mg, 20 30 60 mg, 100 200 mg. (Brand Name) Active Ingredient

Morphine (Oramorph, Sevredol, continus, Zomorph) MST

To treat chronic and severe pain. severe and chronic treat To

roup roup G

piates: O Drug Sheets

dilute to 1 mg/ml in NS, Dextrose 5% Majority of metabolites are inactive and do not Preferred opiate of choice accumulate in RF. in RF. The active drug (oxycodone) will still accumulate in RF therefore titrate dose cautiously. Do not use MR preparations in severe RF. Normal dosing: dose - Start with lowest effective and titrate according to response. - Usual starting dose: 2.5-5 mg, 4-6 hourly. SC bolus: use 10 mg/ml concentration. Starting dose: 5 mg. Repeat 4 hourly PRN. SC infusion: starting dose of 7.5 mg/day in opioid naïve patients, titrating gradually according to symptom control. IV bolus: dilute to 1 mg/ml in NS, Dextrose 5% Adm 1-10 mg slowly over or water for injections. 1-2 min. IV infusion: or water for injections. Starting dose: 2 mg/hour. The MR form of tab should not be broken, chewed, or crushed (could lead to a faster release and absorption of drug, potentiating toxicity). HypoTN. Confusion, hallucination. Respiratory depression. Dependence, withdrawal synd. GI disorders. Constipation. Urinary retention.

106 107 10 mg/1ml. doses are Caps 5 mg, 10 ↓ 20 mg. 5 mg, 10 Tabs MR 15 mg, 20 30 40 mg, 60 80 120 mg, Oral suspensions 5 mg/5ml or 10 mg/1ml. P O : S C/IV: TD: individualized for each patient. There is no In RF: specific recommendation but advisable.

Oxycodone (Oxycontin, Oxynorm)

To treat chronic and severe pain. severe and chronic treat To

piates: O Drugs in Renal Replacement Therapy: A Guide to Clinical Practice slow adm. (2-3 min). Contraindications/ Precautions / O bservations Not advisable due to side effects (see list). Not advisable due to side effects effects not reversed by naloxone. Toxic Not dialysed. Use Cautiously with MAOI (HypoTN, respiratory depression). eGFR <50 ml/min: 75-100 % of the usual dose /6 h. repeated dosing. Avoid eGFR <20 ml/min: avoid if possible. Slow adm. Use cautiously with: - CsA, bupropion, teofiline, SSRI, quinolones, MAOI, neuroleptics, tricyclic antidepressant, carbapenems, interferons, foscarnet, cloroquine, iodinated contrasts (risk of convulsions). - Linezolid, ergot alkaloids, sumatriptan ( risk of serotonin synd). Do not use MR preparations in severe RF. eGFR >20 ml/min: 50-100 mg 6 hourly; Max 400 mg/day. eGFR <20 ml/min: 50 mg 8 hourly and titrate according to response. PO: with or without food. IV: Principal S ide E ffects See morphine. Cardiac abnormalities. Norpethidine main metabolite is neurotoxic and accumulates in RF. See morphine. Dizziness. Sedation. Euphoria. Nausea. Dry mouth.

108 109 Amp 100 mg. Cap 50 mg. 50-100 mg/ 50-100 mg/6-8h. Administration R oute (Available Formulations) (Available Tabs retard 50 mg, Tabs 75 mg, 100 150 200 mg, 300 mg. Oral solution 100 mg/ml. and T herapeutic Dosage S C/ IM/ IV: T D: P O : IV/IM/ S C: Amp 100 mg/2ml. T D: 1-3 times/24h. See observations. (Brand Name) Active Ingredient ramadol

Pethidine (Generic brands) T (Zamadol, Zydol and generic brands) different

Note: Opiate antagonist - Naloxone IV: 0.4 - 2 mg given every 2 minutes to a max of 10 mg and review patient’s condition. 0.4 - 2 mg given every minutes to a max of 10 and review patient’s Note: Opiate antagonist - Naloxone IV:

roup roup G To treat chronic and severe pain. severe and chronic treat To

piates: O Drug Sheets ↓ to 75%. ↓ to 50-100%. : bolus (at least 2 min); infusion hours. Avoid adm with tizanidine and in patients Avoid porphyria. PO : single dose at bedtime or in 2 divided doses (morning and evening) with or without food. Do not swallow the chewable tablets without The liotabs should be placed under the chewing. tongue to be dissolved without swallowing saliva. PO : see famotidine. IM : undissolved. IV If eGFR 10-50 ml/min: If eGFR <10 ml/min: In HD: adm 150 mg post-HD. Nausea, vomiting, abdominal pain. Diarrhoea/constipation, It can cause mood swings, confusion, depression, irritability, hallucinations and/ or insomnia in elderly patients with RF.

108 ↓ dose 109 ↓ dose is Tabs 10 mg, Tabs 75 mg, Tabs 10-80 mg/day. Amp 50 mg. : 50 mg/6-8h. 20 mg, 40 mg. 150 mg, 300 mg. recommended ( or ↓ interval of adm). P O : T D: In R F: P O : IV: T D: PO : 75- 300 mg/24h. IV Famotidine (Pepcid) R anitidine (Zantac and different generic brands)

ACID S AND AN T I U LC ER D RUGS induced by histamine. GI injury prevention. injury GI histamine. by induced

H2 receptor antagonists: receptor H2 ↓ gastric acid secretion by blocking gastric stimulation stimulation gastric blocking by secretion acid gastric ↓ AN T Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

lower dose. Contraindications/ Precautions / O bservations ½ hour before breakfast. Not recommended to be given with atazanavir and nelfinavir. Use cautiously with clopidogrel. Recently associated with acute interstitial nephritis. eGFR <30 ml/min: PO: see omeprazole. Not recommended to be given with atazanavir and nelfinavir. Recently associated with acute interstitial nephritis PO : see omeprazole. Adm in the morning on an empty stomach, Principal S ide E ffects Headache. Constipation. Abdominal pain. Nausea, vomiting and flatulence. Hyponatraemia.

110 111 herapeutic Dosage T herapeutic Sachets 10 mg. Comp 15 mg, 20-40 mg/24h. 30 mg/24h. Administration R oute (Available Formulations) (Available 30 mg. and P O : 10 mg, 20 40 mg. Tab T D: P O : T D: (Brand Name) Active Ingredient

E someprazole (Nexium) Lansoprazole (Zoton and different generic brands)

tion and treatment of GI injury. GI of treatment and tion Preven lumen. gastric the to ion hydrogen of transport final the

roup roup G Inhibit acid secretion in the stomach, joining the proton pump in gastric parietal cell, inhibiting inhibiting cell, parietal gastric in pump proton the joining stomach, the in secretion acid Inhibit

Proton-pump inhibitors inhibitors Proton-pump (PPIs): Drug Sheets dissolve in 100 ml Dextrose 5% solution or : dissolved in 100 ml Dextrose 5% or NS - Not recommended to be given with atazanavir Precaution with clopidogrel. and nelfinavir. Recently associated with acute interstitial nephritis. PO : one dose, in the morning, swallowing capsules whole. Do not split or chew. IV slow infusion (20-30 min). Not recommended to be given with atazanavir and nelfinavir. PO : see omeprazole. IV: NS. Not recommended to be given with atazanavir and nelfinavir. Adm on an empty PO : see omeprazole. stomach. Headache. Constipation. Abdominal pain. Nausea, vomiting and flatulence. Hyponatraemia.

110 111 10-20 mg/24h. CapS 10 mg, 20 Comp 20 mg, 10 mg, Tabs 20-40 mg/24h. 20-40 mg/24h. Vial 40 mg. Vial Amp 40 mg. mg, 40 mg. 40 mg. 20 mg. P O : IV: T D: P O : IV: T D: P O : T D:

O meprazole (Losec and different generic brands) Pantoprazole (Protium and different generic brands) R abeprazole (Pariet)

of hydrogen ion to the gastric lumen. Prevention and treatment of GI injury. GI of treatment and Prevention lumen. gastric the to ion hydrogen of

in gastric parietal cell, inhibiting the final transport transport final the inhibiting cell, parietal gastric in pump proton the joining stomach, the in secretion acid Inhibit Proton-pump inhibitors: Proton-pump Drugs in Renal Replacement Therapy: A Guide to Clinical Practice ↑ absorption of Fe. Contraindications/ Precautions / O bservations Ascorbic acid Antacids (calcium, magnesium, aluminium), vegetarian food (rich in phosphates, phytates and tea ↓ absorption. and oxalates), milk, coffee of NSAIDs. ↑ the irritant effect It can interfere with the absorption of quinolones, tetracyclines, levodopa, methyldopa, thyroid hormones, penicillin. Adm 4 hours before or after quinolones. Adm without chewing & with sufficient water. Preferably on an empty stomach (1 hour before or 2 hours after meals) ( ↑ absorption of Fe). If GI disorders, adm with food and/or low doses and adjusted as tolerated The amp form can be adm directly or dissolved in water. In case of constipation, encourage high-fibre diet. Principal S ide E ffects GI disorders. Constipation. Darkening of the faeces. Rash.

112 113 Tabs 210 mg Tabs herapeutic Dosage T herapeutic 100 mg Fe – 200 300 mg – 300 mg Tabs 200 mg Tabs

200 mg – Administration R oute (Available Formulations) (Available (35 mg Fe). (65 mg Fe), 300 (65 mg Fe). and P O : Syrup 140 mg/5ml (45 mg Fe). T D: P O : T D: P O : T D: Fe/day. 1800 mg/24h. 600 mg/daily. 600 mg/daily. (68 mg Fe), 322 (100 mg Fe). Caps 305 mg (100 Fe), A metal essential for the formation of haemoglobin (oxygen-carrying protein to tissues). A Iron: (Brand Name) Active Ingredient

Ferrous fumarate Fersamal, Galfer) (Fersaday, Ferrous gluconate generic (Different brands) Ferrous sulphate generic (Different brands)

roup roup G Oral Iron II Iron Oral AN T IANA E MIC S Drug Sheets ↓ risk of max dose is 20 ml (1000 mg See Page 177. dissolve dose <200 mg in 50 ml . Dissolve in NS and adm immediately. , preferably in infusion (to HypoTN). Dilute only in NS and adm at once. This can be given as a single bolus of 200 mg over 10 minutes (undiluted). Max 600 mg/Wk. Adm schedule: IV only IV only In IV infusion: NS, dose 200-499 mg in 100 ml NS and to be adm in > 6 min; dissolve doses of 500 to 1000 mg in 250 ml NS and adm at least 15 min. do not dilute For reasons of stability, concentrations <2 mg /ml. In bolus injection: iron). In HD: adm undiluted, in haemodialyzer venous line. Max dose is 200 mg/Wk. See oral Fe. Exanthema. Reaction at the puncture site. Musculoskeletal pain/ myalgia. Hypophosphataemia. ↑ liver enzymes. HypoTN. Headache. Metallic taste. Anaphylaxis. Discomfort at the puncture area. GI disorders. Metalalic taste. Headache. Arthralgia. HypoTN.

112 113 100-1000 mg/Wk. 100-200 mg/ Vial 500 mg. Vial Amp 100 mg. IV: T D: IV: T D: 3 times/Wk.

Ferric carboxymaltose (Ferinject) Iron sucrose (Venofer) Parenteral Iron Parenteral Drugs in Renal Replacement Therapy: A Guide to Clinical Practice adm/15 days. See Page 176. Contraindications/ Precautions / O bservations Use cautiously in: - Coronary artery disease, peripheral arterial disease, carotid artery disease or stroke. - Patients who cannot receive antithrombotic therapy. - Uncontrolled HTN. is diagnosed therapy must be If PRCA switch to another discontinued, and DO NOT recombinant erythropoietic protein. HD patients: IV Non HD patients: SC in the abdomen, arm or thigh. In correction phase: phase: adm monthly. In MAINT Adm schedule: Follow local guidelines to adjust dosing as Hb rises, maintaining Hb levels at: •10-12 g/dl (NICE guidelines – UK). g/dl (KDOQI guidelines). •11-12 Principal S ide E ffects Generalised skin reactions at the puncture site. Flu-like symptoms, headache, arthralgia. HypoTN. access Vascular thrombosis. Neutralising anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA).

114 115 Prefilled syringes herapeutic Dosage T herapeutic Administration R oute (Available Formulations) (Available Prefilled S C/IV: syringes 1000 UI, 2000 3000 UI, 4000 5000 UI, 6000 8000 UI, 10000 UI. 10000 UI, Viales 40000 UI. and S C/IV: 10 µg, 15 20 30 µg, 40 50 60 µg, 80 100 130 µg, 150 300 µg, 500 µg. Pre-filled pen (SureClick) 20 µg, 40 µg, 60 80 100 µg, 130 150 300 µg, 500 µg. (Brand Name) Active Ingredient

Darbepoetin alfa (Aranesp) Erythropoietin alpha (Eprex, Binocrit)

They stimulate the bone marrow to produce red blood cells. cells. blood red produce to marrow bone the stimulate They

roup roup G Used to treat anaemia in CKD, besides other conditions (e.g. chemotherapy). chemotherapy). (e.g. conditions other besides CKD, in anaemia treat to Used

Erythropoiesis-stimulating agents Erythropoiesis-stimulating (ESAs): Drug Sheets adm/15 days. See Page 176. Use cautiously in: - Coronary artery disease, peripheral arterial disease, carotid artery disease or stroke. - Patients who cannot receive antithrombotic therapy. - Uncontrolled HTN. is diagnosed therapy must be If PRCA switch to another discontinued, and DO NOT recombinant erythropoietic protein. HD patients: IV Non HD patients: SC in the abdomen, arm or thigh. In correction phase: phase: adm monthly. In MAINT Adm schedule: Follow local guidelines to adjust dosing as Hb rises, maintaining Hb levels at: •10-12 g/dl (NICE guidelines – UK). g/dl (KDOQI guidelines). •11-12 Generalised skin reactions at the puncture site. Flu-like symptoms, headache, arthralgia. HypoTN. access Vascular thrombosis. Neutralising anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA).

114 115 Prefilled syringes Prefilled syringes S C/IV: S C/IV: 500 UI, 1000 2000 UI, 3000 4000 UI, 5000 6000 UI. 30 µ g, 50 75 µ g, 100 150 200 µ g.

Erythropoietin beta (NeoRecormon) Methoxy polyethylene glycol-epoetin beta (Mircera)

stimulate the bone marrow to produce red blood cells. cells. blood red produce to marrow bone the stimulate

Used to treat anaemia in CKD, besides other conditions (e.g. chemotherapy). They They chemotherapy). (e.g. conditions other besides CKD, in anaemia treat to Used

: agents Erythropoiesis-stimulating (ESAs) Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Capecitabine or 5-FU, enhances cytotoxic effect. Adm post-HD (dialyzed). Contraindicated in active bleeding or risk of bleeding. Use cautiously in LF. is enhanced by: oral anticoagulants, fibrinolytic Its effect agents, NSAIDs, alprostadil. Adm 1% strength: infusion controlled by using infusing pump. guideline: 3000-5000 units with a maintenance dose between 1000-2000 units/h until 30 or 60 min before the end of HD, heparinization graft. If catheter, AV or AVF when the access is is maintained throughout HD. Important: follow the protocol of each unit. In some cases HD sessions may be carried out without heparin (patient actively bleeding or about to undergo a high bleeding risk procedure) 5% strength: reserved exclusively for the sealing of HD catheter. Dilute in NS. adm IM. Do NOT Principal S ide E ffects Fever or rash (rarely). Bleeding gums, nose, urine and/ or faeces. Osteoporosis in long- term Rx. Alteration of liver enzymes. Thrombocytopenia. Allergic skin reactions. Alopecia on prolonged use. Hyperkalaemia.

116 117 herapeutic Dosage T herapeutic Tab 5 mg. Tab 5-15 mg/24h. Follow the protocol Vials Vials Administration R oute (Available Formulations) (Available IV: and P O : T D: 1% (5000 units/5ml), 5% (25000 units/5ml). T D: of each unit. T I O N H ER APY (Brand Name) Active Ingredient

Folic acid generic (Different brands) Heparin sodium

of clotting of the extracorporeal circuit during the session. session. the during circuit extracorporeal the of clotting of

roup roup G ther O ↓ the possibility possibility the to used is it HD In III. antithrombin activating

Heparin : Inhibits thrombin and fibrin formation by by formation fibrin and thrombin Inhibits : AN T IC O A GU LA Drug Sheets Do not interchange (they differ in their Do not interchange (they differ manufacturing process and dosing). Caution if risk of bleeding, coagulation disorders, severe uncontrolled hypoTN, hypertensive or LF, diabetic retinopathy. ↑ risk of bleeding in Rx with aspirin, NSAIDs, oral anticoagulants, IV glucocorticoids, platelet aggregation inhibitors. In HD adm through the arterial port of extracorporeal circuit at the beginning of session. Dosing schedule for maintenance of extracorporeal circuit is dependent on local unit protocol. Thrombocytopenia. Haemorrhages. ↑ Liver enzymes. Hyperkalaemia. Alopecia.

116 117 Pre-filled syringes. Adjust dose in RF. S C: T D: See observations.

inzaparin

LM W H (low molecular weight heparin): Bemiparin (Zibor) Dalteparin (Fragmin) E noxaparin (Clexane) T (Innnohep)

clotting of the extracorporeal circuit during the session. the during circuit extracorporeal the of clotting

Heparin: ↓ the possibility of of possibility the to used is it HD In III. in antithromb activating by formation fibrin and thrombin Inhibits Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

dilute in 50 ml NS or Dextrose 5% (dose >8 mg) in at least 15 min. Contraindications/ Precautions / O bservations Not recommended to be given with neuroleptics, phenothiazines, antidopaminergic: risk of extrapyramidal reactions. Risk of convulsion with tramadol. No dose reduction required in RF. Patients with ESRD may be at an ↑risk of EPSE. Adm ½ hour before meals. IV bolus: (dose <10 mg) in 1-2 min. IV infusion: solution and adm in 15 min. Not recommended to be given with antiarrhythmic, droperidol, some quinolones, ziprasidone methadone, nilotinib, saquinavir, (↑ QT interval). (↑ QT PO: adm capsules whole. IV bolus: (doses <8 mg). IV infusion: Can be adm IM. Tx it is used to treat post-surgical Note: in vomiting. Principal S ide E ffects Headache, dizziness, fatigue, weakness, myalgia, constipation. Drowsiness, restlessness, dizziness. Insomnia. Diarrhoea. Muscle weakness. Rash.

118 119 Tabs 4 mg, 8 mg. Tabs Tab 10 mg. Tab PO/IV 10 mg/8-12h. Amps 4 mg, 8 mg. : IV 4-8 mg. Amp 10 mg/2ml. Administration R oute (Available Formulations) (Available See Observations. Oral solution 5 mg/5ml. and T herapeutic Dosage P O : IV: T D P O : IV: T D: See Observations. (Brand Name) Active Ingredient

Metoclopramide (Maxolon and other generic brands) O ndansetron (Ondemet, Zofran and other generic brands)

and the CNS that are involved in vomiting. in involved are that CNS the and

roup roup G

Antiemetics: Antiemetics: Antagonists of receptors in peripheral neurons neurons peripheral in receptors of Antagonists AN T I E M ET IC S Drug Sheets 200 mg – 300 mg/24h. 100 mg-200 mg/24h. 100 mg/24-48h. give as a total dose of 300 mg post- Contraindications/ Precautions / O bservations Avoid use with ACE inhibitors: risk of use with Avoid hypersensibility. concurrent use with azathioprine or Avoid 6-mercaptopurine. levels. Monitor CsA Adm after meals. If GI intolerance, adm in divided doses. eGFR 20-50 ml/min: eGFR 10-20 ml/min: eGFR <10ml/min: Dialyzable: HD, 3 x weekly. (Allopurinol can be given as a daily dose of 100 mg, up to 300 mg depending on uric acid levels On – the most common dose is 100 mg daily. dialysis days it should be taken after dialysis. Principal S ide E ffects Itching. Hypersensitivity. GI disorders. Tthrombocytopenia, agranulocytosis, aplastic anaemia.

118 119 Tabs 100 mg, Tabs See observations Administration R oute (Available Formulations) (Available 300 mg. and T herapeutic Dosage P O : T D: (Brand Name) Active Ingredient Allopurinol (Zyloric)

Antihyperuricaemic agents: (also known as antigout agents). These agents work to either correct overproduction or underexcretion Antihyperuricaemic agents: (also known as antigout agents).

roup roup G acid uric of synthesis the of Inhibitors of uric acid. Correct excess uric acid/urate in the body through different mechanisms, such as inhibition of enzymes involved in the creation of uric acid. Correct excess acid/urate in the body through different of crystals or forcing the excretion these substances. G roup: AN T IHYP ERUR ICA E MIC A GE N TS Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

: use with caution. 2 Contraindications/ Precautions / O bservations Recent information shows↑potential for an allergic reaction if the patient has RF or previous allergic reaction to allopurinol. Caution advised. concomitant use with azathioprine or Avoid 6-mercaptopurine. May↑levels of theophylline. Elimination↓if used with NSAIDs. Absorption↓with concurrent administration of antacids. Limited data in use patients with a eGFR below 30ml/min/1.73m Principal S ide E ffects Gout flares. Rash. GI disorders. Headache. Alteration in Liver function tests.

120 121 Tabs 80 mg, Tabs 80 mg daily, Administration R oute (Available Formulations) (Available 120 mg. and T herapeutic Dosage P O : T D: ↑to max 120 mg daily depending on uric acid levels. (Brand Name) Active Ingredient

Febuxostat (adenuric)

roup roup G acid uric of synthesis the of Inhibitors Drug Sheets 5- 6 mg/kg every 12 hours. 3-4 mg/kg every 24 hours. 3-5 mg/kg/24h. 2-3 mg/kg 24h. 2 mg/kg every 24-48 hours. 2 mg/kg 48–72h. dissolved in 50-200 ml NS or Dextrose 5% : dissolved in 50-200 ml NS or Dextrose 5% Contraindications/ Precautions / O bservations Use cautiously with vancomycin or CsA Use cautiously with vancomycin or CsA Adjust dose in RF. ( ↑ nephrotoxicity). eGFR 20-50 ml/min: eGFR 10-20 ml/min: eGFR <10 ml/min: serum levels should be less than 5 mg/L. Trough IV: solution and infuse in 30 min. Use cautiously with vancomycin or CsA Adjust dose in ( ↑ nephrotoxicity). Gentamicin dosing in RF. eGFR 30-70 ml/min: eGFR 10-30 ml/min: eGFR <10 ml/min: Gentamicin pre-dose trough levels should be less than 2 mg/L. IV solution and infuse in 30 min. Principal S ide E ffects Nephrotoxicity. Ototoxicity. Neuromuscular blockade, unsteady gait.

120 121 See Observations. See Observations. Vials 125 mg, Vials 20 mg, 40 Vials Administration R oute (Available Formulations) (Available 250 mg, 500 mg. 80 mg. and T herapeutic Dosage IV: T D: IV: T D: (Cydomicin, (Brand Name) Active Ingredient

Amikacin (Amikin and other generic brands) G entamicin Genticin, Gentisone and other generic brands)

roup roup G Aminoglycosides Note: For anti-infectious therapy in peritoneal dialysis, refer to the International Society of Peritoneal Dialysis (ISPD) Guideline s/Recommendations (see Page 172 ). APY AN T I-INF E C I OUS H ER APY Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

250-500 mg 12 hourly dilute in 250 ml NS or Dextrose 5% solution adm in 1-3 hours (no bolus or IM). Contraindications/ Precautions / O bservations Use cautiously with amiodarone, haloperidol, interval). methadone, saquinavir (↑ QT It does not alter levels of CNI. Adm single daily dose 1 hour before food or Cautions: Amiodarone, haloperidol, methadone, - interval). saquinavir (↑ QT - ↑ levels of CNI, sirolimus, everolimus, carbamazepine, statins, colchicine and salmeterol. of acenocoumarol and - ↑ anticoagulant effect warfarin. In eGFR <30 ml/min: (increased nausea with higher doses). PO: with or without food. If GI disorders, adm with food. IV: and adm in 60 min (no bolus or IM). 2 hours after food. IV: Principal S ide E ffects Epigastric pain. GI disorders.

122 123 250-500 mg/24h. 250-500 mg/12h. Tab 500 mg. Tab 250 mg, Tabs Vial 500 mg. Vial 500 mg. Vial Administration R oute (Available Formulations) (Available Sachets 250 mg, 500 mg. Suspension 200 mg/5ml. 500 mg. Suspension 125 mg/5 ml, 250 mg/5 ml. and T herapeutic Dosage P O : IV: T D: P O : IV: T D: (Brand Name) Active Ingredient

Azithromycin (Zithromax and other generic brands) Clarithromycin (Klaricid and other generic brands)

roup roup G Macrolides Drug Sheets

250-500 mg stat, then 50% 250-500 mg stat, then adm/24h. adm in 30-60 min, using major veins (to avoid 125 mg every 12-24 hours. eGFR <10: 250-500 mg stat, then 125 every 24-48 hours. Adm 2 hours before or after Fe salts, antacids, sucralfate. PO: adm whole, without chewing, with or food. Use cautiously with iodinated contrasts (risk of interval). convulsion) and saquinavir (↑QT ↑ Levels of teofiline. ↑ risk of tendinitis with corticosteroids. ↑ anticoagulant effect. Adm 2 hours before or after Fe salts, antacids, sucralfate. PO: adm 2 hours before or after meals (faster absorption). In HD: 500 mg/24h (post-HD). IV: irritation). In HD: 400 mg/24h post-HD. Adjust dose, if: eGFR 20-50 ml/min: of stat dose every 24 hours. eGFR 10-20 ml/min: Cautions: see ciprofloxacin. If eGFR <30 ml/min: Adm whole, without chewing, with or food. GI disorders. Spontaneous tendon rupture. Muscle weakness. Psychosis. Pseudomembranous colitis. Stevens-Johnson Synd. Insomnia.

122 123 Tabs 250 mg, Tabs 250 mg, Tabs 400 mg. Tab 250-750 mg/12 h. 250-500 mg/12-24h. 400 mg/12-24h. 25-50 mg/24h. Bag 500 mg/100 ml. 500 mg, 750 mg. Tabs 250 mg, 500 mg, 750 mg. P O : IV: T D: P O : IV: T D: P O : T D: See Observations. See Observations. See Observations.

Ciprofloxacin (Ciproxin and other generic brands) Levofloxacin and (Tavanic other generic brands) Norfloxacin (Utinor) Quinolones Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

0.5 -1 g every 12-24 hours. 0.5 -1g every 24-48 hours. 400 mg/12h x 3 days and 400 mg/12h x 3 days and 0.5-1g every 48-96 hours. (tissue necrosis). rapid injection 3-5 min or dissolve in 50-100 ml Contraindications/ Precautions / O bservations Use cautiously with tacrolimus and sirolimus (risk nephrotoxicity). Adjust according to levels. IV dosing in RF: eGFR 20-50 ml/min: eGFR 10-20 ml/min: eGFR <10 ml/min: dissolve in 200 ml NS or Dextrose 5% IV: solution. Slow infusion (> 60 min). eGFR 20-50 ml/min: continue 400 mg/24h. eGFR 10-20 ml/min: continue 200-400 mg every 24-48h. eGFR <10: 400 mg/12h x 3 days and continue 200- 400 mg every 48-72h. IV: NS or Dextrose 5% solution and infuse in 30 min. Do N OT adm IM CK Wkly checks and monitor signs of myopathy onset. Dissolve in 50-100 ml NS (incompatible with Dextrose 5% solution). Slow adm (30 min). Principal S ide E ffects Nephrotoxicity. Ototoxicity. peripheral phlebitis, Via local tissue necrosis if extravasation. Red man synd (erythema on the face and upper chest). Pseudomembranous colitis Reaction at the injection site. Nausea, constipation/ diarrhoea. Headache. Muscle pain or weakness, numbness or tingling. ↑ CK.

124 125 Vials 200 mg, Vials 3-12 mg/kg/day 3-12 mg/kg/day 4-6 mg/kg/24h. Vials 500 mg, 1 g. Vials 350 mg, Vials Administration R oute (Available Formulations) (Available 400 mg. 500 mg. (according to indication and RF). See Observations. (according to indication and RF). See Observations. If eGFR <30 ml/min: 4-6 mg/kg /48h. and T herapeutic Dosage IV/IM: T D: IV: T D: IV: T D: (Brand Name) Active Ingredient

eicoplanin

T (Targocid) Vancomycin and other (Vancocin generic brands) Daptomycin (Cubicin)

roup roup G Glycopeptides Lipopeptides Drug Sheets dose as in normal RF. 50% dose; anticoagulant effect. ↑ dilute each 5ml Co-trimoxazole strong solution : adm in 30-120 min. Use cautiously with SSRI (serotonin synd risk). PO: adm with or without food. IV HD: eliminates 30% of drug (adm post-HD). ↓ levels C sA. eGFR 15-30 ml/min: 50% of dose; PCP: 60 mg/kg/12h for 3 days then 30 mg/kg/12h. eGFR <15 ml/min: 30 mg/kg/12h (only to be given if HD PCP facilities are available). Ensure adequate hydration during Rx to ↓ toxicity. PO: can be adm after meals to ↓ GI disorders. IV: with 125 ml NS or Dextrose 5%. If fluid restricted dilute 5 ml to 75 Dextrose 5% and adm over 1 hour. Dissolve in 100 ml NS and adm 30-60 min. eGFR 30-50 ml/min: liver ↑ GI disorders. Metallic taste. Convulsion (if previous history). Optic and peripheral neuropathy. Oral and vaginal candidiasis. Nausea, vomiting, thrombocytopenia, headache, pruritus, rash, dizziness, Rash, hives. Photosensitivity. Nausea, vomiting. enzymes, amylase, urea.

124 125

Tab 600 mg. Tab Tabs 400/80 mg, Tabs 600 mg/12h. 100 mg (loading 800/160 mg/12h. Bag 600 mg/300 ml. 50 mg Vial 800/160 mg. Suspension 100 mg/5ml. 800/160 mg. P O : IV: T D: IV: T D: P O : IV: T D: dose) and continue 50 mg/12h. See Observations.

rimethoprim)

Linezolid (Zyvox) Tigecycline (Tygacil) Co-trimoxazole (association S ulfamethoxazole/ T (Septrin and other generic brands)

xazolidinones O Glycylcyclines ulphonamides S Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations All β-lactam antibiotics are contraindicated in patients with a history of allergic reactions to any of these antibiotics. drug allergy history should be enquired Patient’s before therapy is begun. it is not Imipenem > CNS irritant capacity, recommended in neurological patients. liver enzymes. Principal S ide E ffects Allergic reactions. Infusion phlebitis. Eosinophilia. Headache, dizziness. Diarrhoea, nausea, abdominal pain. ↑ Convulsion (primarily imipenem). Superinfection (e.g. candidiasis).

126 R oute 127 Varies according Varies herapeutic Dosage T herapeutic Varies according Varies Administration (Available Formulations) (Available to drug. and P O /IV: T D: to drug. (Brand Name) Active Ingredient Amoxicillin Ampicillin Co-amoxiclav Piperacillin+Tazobactam Doripenem Ertapenem Imipenem Meropenem Cefazolin Cefotaxime Ceftazidime Cefuroxime Aztreonam

1.-Penicillin: 2.-Carbapenems: 3.-Cefalosporins: 4.-Monobactams

roup roup G Βeta-Lactam Drug Sheets ↓ GI disorders. adm post-HD. adm in 30-60 min. anticoagulant effect. and lithium. levels of CsA Avoid alcoholic drink. Avoid ↑ ↑ PO: adm with food to IV: Dialyzed: Shake the bottle before removing each dose. Withold in the mouth (rinse) for max time before swallowing. If poor tolerance, do not swallow. GI disorders. Headache, dizziness. Dry mouth, metallic taste. Thrombophlebitis. Convulsions. Leucopenia, neutropenia, thrombocytopenia. GI disorders (rare).

126 127

Tab 250 mg. Tab Suspension 1 spoonful /6-12h. Bag 500 mg/100 ml. : : 500 mg/8h. PO : 200-500 mg/8-12h (as indicated). IV Oral solution 200 mg/5ml. 100.000 U/ml. P O : IV: T D P O : T D:

Metronidazole (Flagyl, Norzol and other generic brands) Nystatin (Nystan)

treatment of mild oral/esophageal candidiasis. oral/esophageal mild of treatment

Nitroimidazoles

Antifungal: It is used in Tx for the prevention and/or and/or prevention the for Tx in used is It Drugs in Renal Replacement Therapy: A Guide to Clinical Practice 5-10 mg/kg/12h. 5-10 mg/kg/24h. dose as in normal RF. 2.5-5 mg/kg/24h. both concentrations. ↑ Zoster: 800 mg every 8-12 hours. Zoster: 400-800 mg every 12 hours. 5 mg/kg/8h. Dissolve in 100ml NS and adm Contraindications/ Precautions / O bservations ↓ Nitrofurantoin levels with risk of convulsion. adjust dose: In RF, IV: If eGFR 25-50 ml/min: If eGFR 10-25 ml/min: If eGFR <10 ml/min: PO: If eGFR 25-50 ml/min: Use cautiously in patients with history of epilepsy, Use cautiously in patients with history of epilepsy, dehydration or RF. If taking MMF, If eGFR 10-25 ml/min: Simplex: 200 mg 3-4 times a day. If eGFR <10 ml/min: Simplex: 200 mg every 12 hours. Main metabolite 9-carboxymethomethylguanine accumulates in RF causing neurotoxic side effects. Maintain adequate hydration. Maintenance guidelines: PO: 200-800 mg x 5 times/day (4h intervals) 5 days. IV: in 1 hour. liver enzymes. Principal S ide E ffects ↑ ↓ RF. GI disorders. Phlebitis, inflammation perfusion area.

128 R oute 129

Dosage and T herapeutic Tabs 200 mg, Tabs Amp 250 mg/Vial Amp 250 mg/Vial : See Observations. Administration (Available Formulations) (Available 500 mg/vial. 400 mg, 800 mg. Suspension 400 mg/5ml. P O : IV: T D (Brand Name) Active Ingredient

Aciclovir (Zovirax and other generic brands)

varicella-zoster).

roup roup G

Antivirals: Antivirals: Treatment of human herpes (herpes simplex, herpes zoster and and zoster herpes simplex, (herpes herpes human of Treatment Drug Sheets See Page 179. 2.5 mg/kg/12h. 2.5 mg/kg/24h. 450 mg/12h. 450 mg/24h. 450 mg/48h. 450 mg/24h. 450 mg/48h. 450 mg twice/Wk. 1.25 mg/kg/24h. dissolve with 100ml NS and adm in ≥1h. hydration during Tx. hydration during Contraindicated in severe acute febrile synd. Not contraindicated in minor infections. Do NOT adm if leucopenia. Do NOT Use of gloves. Advisable to use veins of good calibre. ↑ If eGFR 25-50 ml/min: If eGFR 10-25 ml/min: If eGFR <10 ml/min: Give dose post HD on dialysis days IV: Dialyzed 50% → adm post-HD. Use of gloves. Prodrug of ganciclovir Precaution: dosing: Induction/Treatment If eGFR 40-59 ml/min: If eGFR 25-39 ml/min: If eGFR 10-24 ml/min: MAINT/Prophylaxis dosing: If eGFR 40-59 ml/min: If eGFR 25-39 ml/min: If eGFR 10-24 ml/min: adm in HD. Do NOT PO: adm with food. If possible, vaccinate patients before starting RRT, because response depends on stage of CKD. schedule: Vaccination Phlebitis and pain in Infusion site. Leucopenia, thrombocytopenia, anaemia. GI disorders. Allergic reactions. Leucopenia, thrombocytopenia, anaemia. Local reactions at the injection site (pain, erythema, induration). Flu-like symptoms. (Rarely: severe anaphylactic reaction). µ g.

128 129

Vial 40 µ g/ml. Vial Tab 450 mg. Tab Initial dose: 900 mg/12h-24h. Vial 500 mg. Vial Solution 250 mg/5ml. IV: T D: P O : T D: IM/ S C: 5 mg/kg/12h. dosage: MAINT 5 mg/kg/24h. See Observations. Syringe pre-filled 20

G anciclovir (Cymevene, Virgan) Valganciclovir (Valcyte) Hepatitis B recombinant vaccine, adsorbed (Ambirix, HBvaxPRO, Engerix, Fendrix)

vaccine transplanted patients. transplanted

Antiviral drugs: drugs: Antiviral B Hepatitis Prevention and/or Rx, CMV infection in in infection CMV Rx, and/or Prevention Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Potentiates the effect of anticoagulants. Potentiates the effect Use cautiously with: sirolimus, diuretics (nephrotoxicity). -Tacrolimus, of oral Acenocumarol (potentiates the effect - anticoagulants). Acetazolamide (metabolic acidosis). - - Heparin (bruises). Adm at the same time every day: lunch/dinner. Use cautiously with omeprazole, esomeprazole, efavirenz, etravirine, azoles, fluoxetine, isoniazid, of clopidogrel). oxcarbazepine (↓effect Suspend 5 days before any operation, according to medical indication. Adm at the same time every day. Principal S ide E ffects GI disorders. Headache, dizziness, flushing face. Diarrhoea. Tachycardia. Myalgia. GI disorders. Peptic ulceration. Unusual bruising or bleeding. Bleeding, haematological problems. GI disorders.

130 R oute 131

Tab 100 mg. Tab 75-300 mg/24h. 75 mg dispersible 75 mg, Tabs 75 mg/24h (loading 100 mg/6-8h or Administration and T herapeutic Dosage (Available Formulations) (Available for MR preparation 200 mg/12h. T D: tabs, 300 mg dispersible tabs. 75 mg EC tabs, 300 EC tabs. 300 mg. P O : T D: P O : T D: P O : dosage 300 mg). 200 mg modified release caps. (Brand Name) Active Ingredient A GE N TS TE L ET

Acetylsalicylic Acid Acetylsalicylic (Aspirin, Nu-Seals Aspirin) Clopidogrel (Plavix) Dipyridamole (Persantin)

leads to blood platelet aggregation, thus inhibiting thrombus formation. thrombus inhibiting thus aggregation, platelet blood to leads

roup roup G

Platelet aggregation inhibitors: aggregation Platelet Antagonise the mechanism that that mechanism the Antagonise AN T IPLA Drug Sheets 60 bpm, ↑ 125-250 µg/24h. 62.5 µg/24-48h. digoxin levels.

↑ do not give & consult if effect of sildenafil. effect Contraindications/ Precautions / O bservations nauseas/vomits. adjust dosage: In RF, eGFR 10-50 ml/min: eGFR <10 ml/min: Check levels 6 hours post-dose. Monitor level if digoxin toxicity suspected. Normal therapeutic range: 0.8-2 nanograms/ml. Patients with impaired renal function may show signs of toxicity even though levels within desired therapeutic range. Not eliminated by HD. Transdermal: Allow a free period of at least 8 hours (night). - - Rotate area of application. Amiodarone Control H R : (possible Use cautiously in HD: monitor BP hypoTN). ↑ Principal S ide E ffects HypoTN. Headache. Tachycardia. Flushing. Skin reactions. Anorexia. GI disorders. fatigue, apathy, Debility, headache. Impaired vision. Depression, psychosis. Bradycardia, arrhythmia.

R oute 130 131 Patches

Tab 62.5 µg, Tab 62.5 µg-250 µg/24- Tabs 0.3 mg. Tabs Amp 250 µg/1ml. 5 mg/5ml. 0.3-4 mg/h. ransdermal: Administration and T herapeutic Dosage (Available Formulations) (Available Spray 0.4 mg/dose. 125 µg, 250 µg. Oral solution 50 µg/1ml. 5 mg, 10 15 mg. P O : IV: T D: S L: T IV: T D: Spray: 1-2 doses PRN. SL Transdermal: 1 patch/24h. IV: 48h (according to levels in blood). PRN. Tab SL: 1 (Brand Name) Active Ingredient

Digoxin (Lanoxin, Lanoxin-PG) Glyceryl Trinitrate GTN300, (Nitro-Dur, Suscard)

paroxysmal supraventricular tachycardia. supraventricular paroxysmal pectoris. angina of attacks prevent to

roup roup G To treat CHF, atrial fibrillation and and fibrillation atrial CHF, treat To Used dilator. muscle smooth vascular

Digitalis: Nitro-glycerine: a is It (NTG) NIC D RUGS CA R DI OTO Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Contraindications/ Precautions / O bservations 3 months. Suspend if aluminium levels in blood is (60 µ g/L). >2.2 µ mol/L KDOQI guidelines recommend its use as phosphate binder in rescue therapy for refractory hyperphosphataemia, only during 4 Wks. Monitoring plasma levels of aluminum every Contraindicated in hypercalcaemia. Use cautiously in patients treated with digoxin (risk of arrhythmias if hypercalcaemia). It interferes with the absorption of tetracyclines and zinc. Recommended max dose of 1500 mg elemental Ca/24h.

Principal S ide E ffects Encephalopathy, Encephalopathy, osteomalasia, myopathy, hypoparathyroidism, anaemia resistant to erythropoiesis stimulating agents. Constipation. GI disorders. Hypersensitivity. Pruritus. Hypercalcaemia.

132 R oute 133 Cap 475 mg. Caps/tabs: 500 mg, According to plasma According to Administration and T herapeutic Dosage (Available Formulations) (Available 667 mg. 1000 P O : T D: P O : T D: phosphorus levels of the patient *. plasma calcium and phosphorus levels of the patient *. (Brand Name) Active Ingredient

Aluminium hydroxide (Alu-Cap) Calcium acetate (Phoslo, Phosex)

H: T iP calcium: 2-9 times the upper limit of assay used. assay of limit upper the times 2-9 mmol/L. 2.1-2.6 or mg/dl 8.5-10.5

erum erum S phosphorus: erum S for: levels target treatment (2009), GO KDI *

2.5-4.5 mg/dl or 0.81-1.45 mmol/L. mmol/L. 0.81-1.45 or mg/dl 2.5-4.5 roup roup G

Indicated in hyperphosphataemia associated with CKD. Nursing Intervention: Dietary education (diet low in phosphorus). phosphorus). in low (diet education Dietary Intervention: Nursing CKD. with associated hyperphosphataemia in Indicated

↓ absorption weak basic gastric pH (may Use cautiously with sodium polystyrene sulfonate (systemic alkalosis; acetazolamide, ascorbic acid, topiramate, triamterene saquinavir, (> nephrolithiasis incidence). It interferes with the absorption of tetracyclines, quinolones, bisphosphonates, phenytoin, Fe Adm 2 hours before or 4-6 salts, levothyroxine. hours later. Do not adm together with antacids. The amount of elemental Risk of hypercalcaemia. Ca is 500 mg/tab (4 tabs provide 2000 mg of elemental Ca). drugs). Interferes with the absorption of tetracyclines - adm 2 hours before or after. Adm with or Swallowing without chewing. immediately after meals, dividing the daily dosage between meals. ↑ GI disorders. Risk of hypercalcaemia. GI disorders.

132 133 Tabs 1.25 g, 1.5 g. Tabs 500 mg, Tabs <1500 mg/24h 750-3000 mg/ Sachets 2.5 g, 3 g. 750 mg, 1000 mg. P O : T D: P O : T D: (according to plasmatic calcium and phosphorus levels of the patient – see KDIGO treatment target levels*). day (according to phosphorus levels of the patient *).

(Adcal, Cacit, Calceos, Calcichew) Calcium carbonate Lanthanum carbonate (Fosrenol)

H: T iP calcium: erum S phosphorus: 2-9 times the upper limit of assay used. assay of limit upper the times 2-9 mmol/L. 2.1-2.6 or mg/dl 8.5-10.5 mmol/L. 0.81-1.45 or mg/dl 2.5-4.5

erum erum S for: levels target treatment (2009), GO KDI * phosphorus). in low (diet education Dietary Intervention: Nursing CKD. with associated

Phosphate binders: Phosphate They combine with dietary phosphate to form compounds which are then excreted in the faeces. Indicated in hyperphosphataemia hyperphosphataemia in Indicated faeces. the in excreted then are which compounds form to phosphate dietary with combine They Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

KDIGO redefines the treatment of hyperphosphataemia in patients with CKD

Parameter K/DOQI (2003)1 KDIGO (2009)2

Serum 3.5–5.5 mg/dL 2.5–4.5 mg/dL phosphorus 1.13–1.78 mmol/L Towards 0.81–1.45 mmol/L

8.4–9.5 mg/dL 8.5–10.5 mg/dL Serum calcium 2.1–2.37 mmol/L 2.1–2.6 mmol/L

Daily intake of 1,500 mg elemental calcium –

< 55 mg2/dL2 Ca x P product < 4.48 mmol2/L2 –

2–9 times the 150–300 pg/mL iPTH upper normal limit 18.5–33 pmol/L of assay used

KDIGO targets call for more rigid phosphate lowering and tolerate higher calcium and PTH levels

provides effective serum phosphorus control in all respects of KDIGO

134 135

Literature References 1. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease Am J Kidney Dis 2003, 42 (4), Suppl 3. 2. KDIGO Guideline for Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD) Kidney Int 2009; 76, Suppl 113. OsvaRen® abbreviated prescribing information OsvaRen® 435 mg / 235 mg film-coated tablets. Composition: Each film-coated tablet contains: Calcium acetate, 435.00 mg equivalent to 110 mg calcium and magnesium carbonate, heavy 235.00 mg equivalent to 60 mg magnesium. Excipients: Tablet core: Starch, pregelatinised, from maize, maize starch, sucrose, gelatine, croscarmellose sodium, magnesium stearate. Film coating: Castor oil, refined, hypromellose.Indications: Treatment of hyperphosphataemia associated with chronic renal insufficiency in patients undergoing dialysis (haemodialysis, peritoneal dialysis).Contraindications: OsvaRen® is contraindicated in patients with: Hypophosphataemia, Hypercalcaemia with or without clinical symptoms, e.g. as a result of an overdose of vitamin D, a paraneoplastic syndrome (bronchial carcinoma, breast cancer, renal cell carcinoma, plasmacytoma), bone metastases, sarcoidosis or immobilisation osteoporosis; Elevated serum magnesium levels of more than 2 mmol/l, and/or symptoms of hypermagnesaemia; AV-block III°; Myasthenia gravis; Hypersensitivity to the active substances or to any of the excipients. Side effects: Very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Gastrointestinal disorders: Common: Soft stools, gastrointestinal irritation like nausea, anorexia, sensation of fullness, belching and constipation, diarrhoea. Metabolism and nutrition disorders: Common: Hypercalcaemia either asymptomatic or symptomatic, asymptomatic hypermagnesaemia. Uncommon: Moderate to severe symptomatic hypercalcaemia, symptomatic hypermagnesaemia. Very rare: Hyperkalaemia, magnesium-induced osteal mineralisation disturbances. Special warning: Contains sodium (not more than 5.6 mg per each film coated tablet) and sucrose. Read the package leaflet before use.Supply classification: Prescription only medicine. Fresenius Medical Care Nephrologica Deutschland GmbH. 61346 Bad Homburg v.d.H., Germany. Date: February 2010. The names of this medicinal product in the Member States of the EEA are as follows: B: Renepho, Other countries: OsvaRen®. OsvaRen® has received marketing authorisations in: A, B, CY, CZ, D, DK, E, EST, F, FIN, GB, GR, H, I, IRL, IS, L, LT, LV, M, N, NL, P, PL, S, SK, SLO, SRB (status: February 2010). The registration procedure for other countries is currently in progress.

Contact: Fresenius Medical Care Deutschland GmbH · Renal Pharma Else-Kröner-Straße 1 · 61352 Bad Homburg v. d. H. · Germany Phone: +49 (0) 6172-609-0 · Fax: +49 (0) 6172-609-5638 [email protected] · www.fmc-renalpharma.com Drug Sheets Contraindications/ Precautions / O bservations Contraindicated in hypophosphataemia, hypercalcaemia with or without clinical symptoms, and hypermagnesaemia > 2.0 mmol/L. The tab should not be crushed Adm with meals. or chewed. Adm 2 hours before or 3 after certain oral drugs (to prevent drug interactions). Principal S ide E ffects GI disorders. Risk of hypercalcaemia. Asymptomatic hypermagnesaemia.

134 R oute 135 until 12 tabs, ↑ Tab 435 mg/235 mg Tab 3 to 10 tab/day. It 3 to 10 tab/day. Administration and T herapeutic Dosage (Available Formulations) (Available according to plasmatic phosphorus levels of the patient *. film-coated. P O : T D: can be (Brand Name) Active Ingredient

Calcium acetate with magnesium carbonate (OsvaRen)

H: T iP calcium: erum S 2-9 times the upper limit of assay used. assay of limit upper the times 2-9 mmol/L. 2.1-2.6 or mg/dl 8.5-10.5

erum phosphorus: erum S for: levels target treatment (2009), GO KDI *

mmol/L. 0.81-1.45 or mg/dl 2.5-4.5 roup roup G

phosphorus). in low (diet education Dietary Intervention: Nursing CKD. with associated hyperphosphataemia in Indicated

Phosphate binders: Phosphate They combine with dietary phosphate to form compounds which are then excreted in the faeces. faeces. the in excreted then are which compounds form to phosphate dietary with combine They Drugs in Renal Replacement Therapy: A Guide to Clinical Practice ↓ exchange capacity of K+ content). ↑ absorption of ciprofloxacin. Contraindications/ Precautions / O bservations Contraindicated in intestinal obstruction. Be aware that it can bind fat-soluble vitamins (A, D, E and K) contained in ingested food, thus interfering with their absorption. Interferes with absorption of tetracycline, levothyroxine and digoxin. Use cautiously with antacids and cationic Al or Ca) due to risk of laxatives (Mg hydroxide, metabolic alkalosis or the resin. yoghurt. Do not sugar water, Dissolve in water, adm with juices ( Not recommended in patients <18 years. The tabs should be swallowed Adm with meals. The sachets, dissolved in whole without chewing. 60 ml of water. ↑ Sodium resonium: contraindicated in hypernatraemic patients. Principal S ide E ffects GI disorders. ↓ cholesterol (LDL-C and total). GI disorders.

136 R oute 137 Sachets 15 g, Tab 800 mg. Tab powder suspension.

Administration and T herapeutic Dosage (Available Formulations) (Available Sachets 2.4 g P O : T D: P O /P R : T D: P O : T D: powder suspension. 1-2 tabs or sachets /3 (800 - 7200 times-day. mg), according to phosphorus levels of the patient *. 15-60 g, 3 or 4 doses/ with meals. day, 15-60 g, 3-4 doses/day, with meals. (Brand Name) Active Ingredient

S evelamer (Renagel, Renvela) Calcium Polystyrene S ulphonate (Calcium Resonium) Sodium Polystyrene S ulphonate (Sodium Resonium)

Ion exchange resins. exchange Ion

Phosphate binders Phosphate roup roup G

resin: Potassium-removing Drug Sheets

in bolus, through HD access at any time of Use cautiously in patients treated with digoxin (risk of arrhythmias if hypercalcaemia). increases. Monitor and adjust levels as Ca/P Do not administer concurrently with other D, or derivatives. derivatives of Vit Doses are adjusted according to stage of CKD and metabolism Ca/ P/ PTH. Use cautiously in patients treated with digoxin (risk of arrhythmia if hypercalcaemia). Caution with phosphates or drugs related vitamin D (risk of hypercalcaemia and ↑ production of CaXP). One of the excipients (propylene glycol) of heparin. neutralizes the effect PO: adm with or without foods. Do not more than 1 dose/24h. IV: dialysis. Upset stomach. Headache. Myalgia, weakness. Xerostomia, polydipsia. chills. Fever, Arrhythmia. Pruritus. Hypercalcaemia. Rash, pruritus. Bone and muscle pain. Fever. Polydipsia, Xerostomia. ↓ weight. Constipation. Headache. Insomnia.

136 137 Caps 0.25 µ g, Caps 0.25 µ g, Caps 1 µ g, 2 1-2 µ g/24h or 5 µ g/ml. Vial 0.5 µ g, 1 Caps 0.25 0.5 µ g, 1 g. Drops 2 µ g/ml (1 ml = 20 Drops). 0.50 µ g. 4 µ g. Amps 1 µ g/0.5ml, 2 µ g/1ml. See observations. Amps 1 µ g/1ml, 2 µ g/ml. See observations. P O : IV: P O : IV: P O : IV: T D: 2-4 µ g/3 times/Wk. Doses are adjusted according to stage of CKD and Ca/P/ PTH metabolism.

Alfacalcidol (One-Alpha) Calcitriol (Rocaltrol, Calcijex) Paricalcitol (Zemplar)

associated with CKD. with associated

Active metabolites of Vit. D: D: Vit. of metabolites Active Prevention and treatment of secondary hyperparathyroidism hyperparathyroidism secondary of treatment and Prevention Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

↓ activity). Contraindications/ Precautions / O bservations ↓ serum calcium. In GFR <30 ml/min do not give infusion at a rate faster than 20 mg/60 min. Do not adm as IV bolus. It should be diluted in NS and adm by slow IV infusion. Assess RF before each dose. Check serum calcium, previous before adm as can cause parathyroidectomy, hypocalcaemia. Be aware that it can take up to 72 hours Not recommended to be given with pimozide (toxicity), tamoxifen ( Caution with CYP3A4 inhibitors ( ↓ dose of cinacalcet). ↓ cinacalcet levels due to induction of Tobacco CYP1A2 (adjust dosage if patient starts or stops smoking during Rx). Do not use as Rx for hyperparathyroidism if patient has

138 R oute 139 Tabs 30 mg, 60 Tabs

Amp 15 mg/ml. Administration and T herapeutic Dosage (Available Formulations) (Available IV: P O : 90 mg. T D: T D: 30-90 mg/Kg by slow infusion dependent on indication and serum calcium. 30-180 mg/24h. (Brand Name) Active Ingredient

Disodium Pamidronate Cinacalcet (Mimpara)

osteoclast activity. osteoclast with CKD in dialysis. in CKD with

↑ with associated conditions roup roup G hyperparathyroidism in patients patients in hyperparathyroidism

Calcimimetic: Calcimimetic: To treat treat To Biphosphonates: Biphosphonates: To treat treat To Drug Sheets diluted in Dextrose 5% solution (incompatible reconstituted with the solvent and dilute in Contraindications/ Precautions / O bservations Monitor CBC and platelet count at regular intervals during therapy. Adjust dose to maintain neutrophil counts >1.5 x 109/L. IV: with NS). Monitor CBC and platelet count at regular intervals during therapy. SC: reconstituted with the solvent and adm immediately. IV: NS (PVC bags or glass bottle) in Dextrose 5% solution (glass bottle). It should be stored at 2-8°C in the carton provided (protection from light). Do not shake (causes aggregation and inactivation of the drug). Principal S ide E ffects Bone pain. Splenomegaly. ↑ liver enzymes, thrombocytopenia and leukocytosis. Headache. Asthenia. Haematuria.

138 R oute 139 Amps 105 µg, Prefilled syringes 10 µg /kg/24h. 6 mg fixed-dose. Pre-filled syringe 5 μg/kg/24h. Vial 0.3 mg. Vial Administration and T herapeutic Dosage (Available Formulations) (Available IV: S C: 300 µg, 480 µg T D: S C/IV: T D: S C: T D:

6 mg. 263 µg. TOR T IN G FAC (Brand Name) Active Ingredient

Filgrastim (Neupogen, Ratiograstim) Lenograstim (Granocyte) Pegfilgrastim (Neulasta)

of committed progenitor cells. progenitor committed of

roup roup G Haematopoietic stimulants that help the proliferation and differentiation differentiation and proliferation the help that stimulants Haematopoietic Granulocytic colony stimulating factors: stimulating colony Granulocytic NY ST IM U LA C O L NY Drugs in Renal Replacement Therapy: A Guide to Clinical Practice ↓ possible GI disorders. Contraindications/ Precautions / O bservations Use cautiously with bupropion (risk of seizures), quinolones (risk of tendinitis). Do not expose to the sun and protect skin. Monitor for possible hyperglycaemia. In diabetic patients, readjust hypoglycaemic Rx regimen. Remember that it lessen the immune response, thus producing new infections, activating opportunistic microorganisms and manifestation of latent infections. May mask signs of existing or developing infection. Recommended not to be vaccinated if high doses are being taken or prior consultation with the nephrologist. PO : adm with food to ↓ the dosage gradually to prevent acute adenocortical failure. ↓ Principal S ide E ffects Hyperglycaemias, diabetes mellitus. Cushing Synd, electrolyte disturbances, > infection risk, bone density (risk of fractures), ↓ muscle mass. CNS disorders (e.g. headache, insomnia, nervousness). Hirsutism. slow Skin atrophy, wound healing. Cataracts, glaucoma.

140 R oute 141

Tabs 2mg, 4 mg, Tabs Plain tabs 1 mg, individualized individualized Vials 40 mg, 125 Vials Administration and T herapeutic Dosage (Available Formulations) (Available 5 mg, 25 mg. EC tabs 2.5 mg, 5 mg. 500 mg, 1 g. according to indication. according to indication. P O : IV: T D: P O : T D: 16 mg, 100 mg. (Brand Name) Active Ingredient

Methylprednisolone (Solu-medrone, Medrone) Prednisolone (Deltacortril)

status, cerebral oedema & spinal cord injury. cord spinal & oedema cerebral status,

roup roup G have other applications such as in anaphylactic shock, acute asthma asthma acute shock, anaphylactic in as such applications other have

Corticosteroids: Used in the treatment of transplant rejection. They They rejection. transplant of treatment the in Used C ORT IC OSTERO ID S Drug Sheets . 2 and 2 Contraindications/ Precautions / O bservations Often used in combination with a loop diuretic resistant oedema. Monitor electrolytes closely. Contraindicated in eGFR <30 ml/min/1.73m Use cautiously in impaired renal function, as it can be aggravated. Risk of hypokalaemia. Adm a single daily dose. Can be used in patients with eGFR <30 ml/min/1.73 m anuria. Tx, it can be used on alternate days (long half-life). In Adm only with breakfast. Principal S ide E ffects Hypokalaemia. action. Vasodilator

140 R oute 141 Tab 50 mg. Tab 2.5 mg. Tab 5 mg. Tab 25-50 mg/ 24h. 2.5 mg/24h. 2.5-5 mg/24-48h. Administration and T herapeutic Dosage (Available Formulations) (Available P O : T D: P O : Slow release tab 1.5 mg. T D: P O : T D: 1.5 mg SR/24h. (Brand Name) Active Ingredient

Chlortalidone (Hygroton) Indapamide (Natrilix, Natrilix SR, Ethibide XL) Metolazone (Metenix 5)

- remove excess water and decrease renal reabsorption of Na+ and Cl- of the body, ↓ resistance to blood flow in the vessels - remove excess water and decrease renal reabsorption of Na+ Cl- the body, of Na+ and Cl and Na+ of and urine output. urine and

: roup roup G ub S ↑ excretion excretion nephron; the of tubules convoluted distal in

hiazides: T inhibit reabsorption of sodium and chloride chloride and sodium of reabsorption inhibit thereby producing a decrease in BP. G roup Diuretics and AN T IHYP ERTE N S IV E D RUGS DI URET IC S and Drugs in Renal Replacement Therapy: A Guide to Clinical Practice slow bolus, max 40 mg in 1-2 min. Infusion: start with Contraindications/ Precautions / O bservations Contraindicated in anuria. Use cautiously with aminoglycosides ( ↑ nephrotoxicity); amiodarone, dronedarone, pimozide, droperidol interval). ( ↑ QT In Tx: adm low dosage (risk of ↑ lipids, hyperuricaemia and hyokalaemia). Adm in fasting (1 hour before or 2 hours after meals) the In whole, without chewing & with the right amount of Tab In case of intolerance, adm with meals. water. IV: depending on 0.1 mg/min and gradually ↑ every ½ hour, the response (max 4 mg/min). Dilute in NS or Dextrose 5% solution. Use opaque giving set (photosensitivity). IM: used only when PO or IV route is not possible. Contraindicated in anuria. Use cautiously with aminoglycosides ( ↑ nephrotoxicity); amiodarone, dronedarone, pimozide, droperidol interval). ( ↑ QT In Tx: adm low dosage (risk of ↑ lipids, hyperuricaemia and hyokalaemia). Adm in fasting (1 hour before or 2 hours after meals) the tab in whole, without chewing & with the right amount of In case of intolerance, adm with meals. water.

Principal S ide E ffects Muscle cramps and weakness. Orthostatic hypoTN, dizziness, hearing difficulties, confusion, headache, blurred vision, agitation. Thirst, vomiting, stomach upset, constipation. ↑ Ac. Uric, ↑ triglycerides, ↑ cholesterol and serum calcium.

142 R oute 143 Tabs 20 mg, 40 Tabs 1mg, 5 mg. Tabs Amps 20 mg, 50 0.5 mg/1ml. 1-5 mg/24h. 80-1500 mg/24h. Administration and T herapeutic Dosage (Available Formulations) (Available 250 mg. 500 mg. Liquid: 40 mg/5ml. Liquid: 1 mg/5ml. P O : IV: T D: PO: 20-500 mg/day in divided doses. IV: P O : IV: T D: PO: 1-10 mg daily. IV: (Brand Name) Active Ingredient

Furosemide (Lasix). Bumetanide (Burinex)

It acts at the luminal face of the epithelial cells by inhibiting co-transport. inhibiting by cells epithelial the of face luminal the at acts It

roup roup G ub S Henlé. The drug eliminates both positive and negative free water production. production. water free negative and positive both eliminates drug The Henlé.

Loop Diuretics: Diuretics: Loop Inhibits sodium and chloride reabsorption at the Loop of of Loop the at reabsorption chloride and sodium Inhibits Drug Sheets Cautions: see furosemide. Long-term Rx: regular monitoring of electrolyte balance, plasma glucose, uric acid, creatinine and lipids levels. Adm tabs with a little amount of water. Adm a single dose (extended-release). Manufacturer does not recommend use in moderate – severe RF. no dose If used in moderate – severe RF, reduction is necessary but strict monitoring of potassium levels is recommended. Risk of hyperkalaemia. Adm once a day. Dyspepsia, nausea, vomiting, headache, weakness, cramps, thirst, hypovolemia, hypoTN. Hyperglycaemia, hypokalaemia, hyperuricaemia. Impotence. Extended-release form: drowsiness, polyuria, nocturia. Hyperkalaemia. Dizziness, hypoTN. Nausea. Diarrhoea. Rash.

142 143 Tabs 2.5 mg, 5 Tabs 25 mg, 50 mg. Tabs 10-40 mg/24h. 25-50 mg/24h. 10 mg. P O : T D: P O : T D:

orasemide

T (Torem) E plerenone (Inspra)

cortical collecting duct and the terminal portion of the distal tubule. distal the of portion terminal the and duct collecting cortical

Loop Diuretics Loop without promoting potassium loss. Antagonize the effects of aldosterone in the the in aldosterone of effects the Antagonize loss. potassium promoting without

Potassium-sparing diuretics: Potassium-sparing ↑ loss of water and electrolytes electrolytes and water of loss Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Colchicine levels and/or toxicity). ↑ Contraindications/ Precautions / O bservations Contraindications: anuria and hyperkalaemia. Use cautiously with/in: amiloride, eplerenone, triamterene, Tacrolimus, - ARB (risk of hyperkalaemia and ACEI, arrhythmias). - Colchicine ( - Lithium (↑lithemia). - Acidosis. - DM. Risk of hyperkalaemia. Strict monitoring potassium levels are recommended Adm with food to enhance absorption.

K+, azotaemia, ↑ Principal S ide E ffects renal dysfunction, fever, renal dysfunction, fever, urticaria, erythematous cutaneous eruptions, agranulocytosis. Endocrine affectations: Endocrine affectations: In males: gynaecomastia, decreased libido, impotence. In females: irregular menses, breast pain and infertility. GI affectations: anorexia, vomiting, diarrhoea, gastritis, gastric ulcers, abdominal pain and bleeding. CNS affectations: headache, dizziness, mental confusion, ataxia. Others:

144 R oute 145 Tabs 25 mg, Tabs 12.5-400 mg/24h. Administration and T herapeutic Dosage (Available Formulations) (Available 100 mg. P O : T D: (Brand Name) Active Ingredient

S pironolactone (Aldactone)

portion of the distal tubule. distal the of portion

roup roup G ub S potassium loss. Antagonize the effects of aldosterone in the cortical collecting duct and the terminal terminal the and duct collecting cortical the in aldosterone of effects the Antagonize loss. potassium

Potassium-sparing diuretics: Potassium-sparing ↑ loss of water and electrolytes without promoting promoting without electrolytes and water of loss Drug Sheets ↓ dosage. 0.15 mg/kg diluted in 50 ml NS or Cautions: see atenolol. Adm preferably at the same time, with meals. Cautions: see atenolol. Start Rx with the lowest possible dosage. should be Tab Adm once a day (morning). swallowed whole with liquid and not chewed. Use cautiously with: verapamil saquinavir, - Diltiazem, atazanavir, (abnormal heart beat). Slow IV bolus: 2.5-10 mg as indicated, at 1 mg/min. Infusion: Dextrose 5% solution, adm slowly (20 min) and monitor vital signs. In case of HD, adm post-HD. If eGFR <35 ml/min: Tx, start with low doses, monitoring HR In and adjust dosage in patients with chronic nephropathy due to renal metabolisation. heart activity and BP, ↑ bronchial and myometrium ↓ heart activity and BP, Headache, dizziness, dyspnoea, lethargy, paresthesia, nausea, diarrhoea/constipation, postural hypoTN, lower extremity oedema. Bradycardia, worsening of HF. Dizziness, headache. Nausea, vomiting, diarrhoea/constipation. Asthenia, fatigue. Feeling of coldness or numbness in the extremities. HypoTN.

144 145 ↓ intraocular pressure. Tabs 25 mg, 50 mg, 1.25mg, Tabs 5mg. Tab 1.25-20 mg/24h. 1.25-20 mg/24h. 25-100 mg/24h. Amp 0.5 mg/ml. 100 mg. Syrup: 25 mg/5ml. 2.5 mg, 5 10 mg. P O : IV: T D: P O : T D: P O : T D: Atenolol (Tenormin) Bisoprolol (Cardicor) Nebivolol (Nebivolol, Nebilet)

: strength of the heartbeat). the of strength

Cardio selective: Cardio Selective for beta-1 receptors (control the frequency and and frequency the (control receptors beta-1 for Selective tones, inhibit liver glycogenolysis in hypoglycaemia, G roup of adrenaline on beta receptors in the body and Beta blockers - block the effects Drugs in Renal Replacement Therapy: A Guide to Clinical Practice : adm <1 mg/min. Contraindications/ Precautions / O bservations Use cautiously at the beginning of Rx, orthostatic hypoTN may occur and end up in syncope. Adm at night, or morning and evening, as a whole (extended-release forms), with or without food. Tx for their positive Increasingly being used in on metabolic profile. effects Cautions: see atenolol. adm before meals When adm several times daily, Adm the extended-release form and at bedtime. before breakfast or at night. once a day, Separate 2 hours the adm of salts containing Mg or Al ( ↓ absorption). IV In HD, adm post-HD. Principal S ide E ffects Fatigue and/or lassitude (often transient). Bradycardia. Cold extremities, Raynaud’s phenomenon. Sleep disorders, nightmares. Dizziness. Headache. Drowsiness. Palpitations, tachycardia. Urinary incontinence. Peripheral oedema.

146 R oute 147 Tabs 1mg, 2 mg, Tabs Tabs 10 mg, 40 mg. Tabs 10-320 mg/ 2-8 mg/24h. Amp 5 mg/5ml. Administration and T herapeutic Dosage (Available Formulations) (Available Tab extended-release Tab 160 mg. P O : IV: T D: P O : T D: day in divided doses (according to indication and presentation). Max 16mg/24 with plain release tabs. 4 mg. extended-release Tabs 4 mg, 8 mg.

(Brand Name) Active Ingredient

Propranolol (Inderal) Doxazosin (Cardura)

beta-2 (control smooth muscle function) muscle smooth (control beta-2 peripheral vascular resistance and BP. and resistance vascular peripheral

roup roup G ub S which vasodilatation, peripheral causing receptor, block both beta-1 receptors such as as such receptors beta-1 both block ↓

Alpha-adrenergic blockers: blockers: Alpha-adrenergic Block mainly noradrenalin noradrenalin mainly Block Non-cardio selective: Non-cardio Drug Sheets ↓ peripheral vascular Cautions: see amlodipine. Adm preferably in the morning, swallowed whole. Adm with or without meals. Cautions: see amlodipine. always at the same time, Adm once a day, Adm with or without preferably in the morning. food. Cautions: see amlodipine. Adm at least 15 min before meals. Use cautiously in CKD and with itraconazole (↑ negative inotropic effect). Tx, may cause gingival hypertrophy. In Hepatic metabolism. Long half-life. Adm with or without meals, in a single dose, always at the same time. If GI upset, adm with food. liver ↑ ↓ myocardial contractility and Headaches and oedema. Flushing, weakness, numbness, dizziness and palpitations (often dose- dependent). Nausea, digestive problems and gastric pain. Jaundice and enzymes.

146 147 Tabs 2.5 mg, Tabs 2 mg, 4 mg. Tab 10 mg, 20 mg. Tabs Tabs 5 mg, 10 mg. Tabs 5-10 mg/24h. 5-10 mg/24h. 2-4 mg/24h. 10-20 mg/24h. /blockers - prevent calcium entry into cells (blood vessels and cardiac muscle). 5 mg,10 mg. P O : T D: P O : T D: P O : T D: P O : T D:

Amlodipine (Istin) Felodipine (Plendil) Lacidipine (Motens) Lercanidipine (Zanidip)

vasodilatation and less action on the heart. the on action less and vasodilatation

Dihydropyridines: L-type calcium channel blockers, with powerful arterial arterial powerful with blockers, channel calcium L-type G roup: Calcium channel antagonists resistance due to vasodilation. Therefore the effect is ↓ muscle contraction, resulting in Therefore the effect Drugs in Renal Replacement Therapy: A Guide to Clinical Practice dilute to a final concentration of 0.1 mg/ml. Contraindications/ Precautions / O bservations Cautions: see amlodipine. IV: See amlodipine. Prolonged-release forms should be swallowed whole with fluid, without being parted or chewed. liver ↑ Principal S ide E ffects Headaches and oedema. Flushing, weakness, numbness, dizziness and palpitations (often dose- dependent). Nausea, digestive problems and gastric pain. Jaundice and enzymes.

148 R oute 149 10-90 mg/24h in Tabs 20 mg, 30 mg. Tabs Cap 5 mg, 10 mg. Amp 5 mg/5ml. : PO 20-40 mg/8h or : 3-15 mg/h. Administration and T herapeutic Dosage (Available Formulations) (Available 40 mg/12h (prolonged release) IV Tab prolonged release Tab 40 mg. Drops 20 mg/ml. prolonged-release Tab 20 mg, 30mg, 60mg. divided doses according to preparation used. P O : IV: T D P O : T D: (Brand Name) Active Ingredient

Nicardipine (Cardene) Nifedipine (Adalat, Coractan, Adipine and generic brands)

vasodilatation and less action on the heart. the on action less and vasodilatation

roup roup G ub S

Dihydropyridines: L-type calcium channel blockers, with powerful arterial arterial powerful with blockers, channel calcium L-type Drug Sheets conc. of ↑ concentration of verapamil). ↑ controlled by using an infusion pump. dilute in 20 ml NS or Dextrose 5% solution, slow infusion (2 min). The patient should be slow infusion (2 min). and ECG). monitored continuously (BP Cautions: see verapamil. Adm preferably before or during meals and at the same time every day. Prolonged-release forms should be adm whole, without chewing or parting. IV bolus: adm in 2 min. IV infusion: Use cautiously with: sirolimus, everolimus ( Tacrolimus, - IV: Do not crush the tabs. Avoid grapefruit juice. Avoid Do not crush the tabs. immunosuppressant). Amiodarone, beta-blockers (additive effects). - verapamil saquinavir, - Diltiazem, atazanavir, (abnormal heart beat). - Simvastatin ( Headache, dizziness. palpitations. AV-blocks, Oedema of the lower limbs. Malaise. Constipation. Dyspepsia. Gastric pain. Nausea. Rash and skin redness. Dizziness. Headache. Bradycardia. HypoTN.

148 149 Tab 60 mg. Tab 80 mg, Tabs/Caps PO: 60 mg/8-12h, Vial 25mg/4ml. Vial Amp 5 mg/2ml. 0.25 mg/kg in 2 min.. 5-10 mg Prolonged-release 90 mg, 120 180 mg, 200 240 mg, 300 mg. Suspensión oral 1g/5ml. 120 mg,180 mg, 240 mg. Syrup 50 mg/ml. P O : IV: T D: P O : IV: T D: 240-360 mg/24h (prolonged- release). IV: PO: 240-480 mg/day (in divided doses). IV: (see Observations).

Diltiazem (Dilzem, adizem, angitil) Verapamil (Securon, Univer)

reduce heart rate. heart reduce

No dihydropyridines: No

Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Adm every 12 hours, due to short half-life. certain patients with HF have a better Moreover, tolerance to adm in 2 doses. Adm regardless of meals. However, if there is an Adm regardless of meals. However, control, adm 1 hour before or 2 inadequate BP hours after meals. 1-3 hours post-adm. for hypotensive effect Watch Separate 2 hours the adm of salts containing Mg or Al ( ↓ absorption). Tx because it has a short half-life Rarely used in and requires 2 or 3 daily doses. Currently it is used only in hypertensive crisis. Adm tablets whole (not to be fractionated). Adm in a once-daily dosage at the same time every day. Adm in a once-daily dosage at the same time every day. Principal S ide E ffects Angioneurotic oedema. Coughing ( ↑ at night when lying). Hyperkalaemia. May cause RF. Headaches, dizziness, palpitations, flushing. GI disorders. Pruritus. Photosensitivity. Frequent urination.

150 151 5-20 mg/12h. Tabs 12.5 mg, Tabs 2.5 mg, 5 Tabs 10mg, 20 mg. Tab 5 mg, 10mg, Tabs 12.5-75 mg in 10-40 mg/24h. 10-80 mg/24h. Administration R oute and T herapeutic Dosage (Available Formulations) (Available 25 mg, 50mg. 10 mg, 20 mg. 15mg 20 mg. P O : T D: P O : T D: P O : T D: P O : T D: hypertensive crisis. (Brand Name) Active Ingredient

Captopril (Capoten) E nalapril (Innovace) Fosinopril (Fositens) Lisinopril (Zestril, Carace Plus)

enzyme. As a result, the blood vessels dilate with the resultant decrease in blood pressure. blood in decrease resultant the with dilate vessels blood the result, a As enzyme.

roup roup G ub S enzyme by blocking the formation of angiotensin II, which is formed from angiotensin I in the blood by the the by blood the in I angiotensin from formed is which II, angiotensin of formation the blocking by enzyme

Angiotensin-Converting Enzyme Inhibitors Enzyme Angiotensin-Converting (ACEI): They act on the angiotension-converting angiotension-converting the on act They (ACEI): G roup: Antihypertensive agents that act on the renin-angiotensin system. Drug Sheets Adm in a once-daily at the same time every day, Adm in a once-daily at the same time every day, before breakfast. Adm in a single daily dose at the same time, regardless of meals. In some patients, or when using ↑ dose, it may be advisable to fractionate the daily dosage in 2 doses. Adm in a single daily dose at the same time every regardless of meals. day, Adm in a once-daily dosage at the same time every day. Angioneurotic oedema. Coughing ( ↑ at night when lying). Hyperkalaemia. May cause RF. Headaches, dizziness, palpitations, flushing. GI disorders. Pruritus. Photosensitivity. Frequent urination.

150 151 Tabs 2 mg, 4 Tabs 5 mg, 20 Tabs 1.25 mg, Tabs/caps: Caps 2.5 mg, 2 4 - 8 mg/24h. 10-80 mg/24h. 2.5-10 mg/24h. 2 - 4 mg/24h. 8 mg. 40 mg. 2.5 mg, 5 10 mg. 4 mg. P O : T D: P O : T D: P O : T D: P O : T D:

randolapril

Perindopril (Coversyl) Quinapril (Acuprel) R amipril (Tritace) T (Gopten)

blood vessels dilate with the resultant decrease in blood pressure. blood in decrease resultant the with dilate vessels blood

blocking the formation of angiotensin II, which is formed from angiotensin I in the blood by the enzyme. As a result, the the result, a As enzyme. the by blood the in I angiotensin from formed is which II, angiotensin of formation the blocking

Angiotensin-Converting Enzyme Inhibitors Enzyme Angiotensin-Converting (ACEI): They act on the angiotension-converting enzyme by by enzyme angiotension-converting the on act They (ACEI): Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Indicated preferably in incipient and established nephropathy secondary to type 2 DM. Use cautiously with amiloride, spironolactone, triamterene (hyperkalaemia). ACE Caution when adm in conjunction with inhibitors in patients with kidney disease. Adm always at the same time, with or without food. Its max action occurs after several Wks of Rx. Do not cause Principal S ide E ffects coughing. Note: Hyperkalaemia. Deterioration of renal function. Orthostatic hypoTN, dizziness, vertigo, headache, fatigue. Rhinitis. Abdominal pain, diarrhoea, nausea, dyspepsia. Peripheral oedema. Leg cramps.

152 153 Tab 600 mg. Tab 75 mg, Tabs 12.5 mg, Tabs 10 mg, 20 Tabs 20 mg, 40 Tabs Tabs 40 mg, 80 mg, 2-32 mg/24h. 600-800 mg/24h. 150-300 mg/24h. 12.5-100 mg/24h. 10-40 mg/24h. 20-80 mg/24h. 20-120 mg/12h : Tabs 4 mg, 8 Tabs : Administration R oute and T herapeutic Dosage (Available Formulations) (Available 50 mg, 100 mg. 150 mg, 300 mg. 40 mg. 80 mg. 160 mg, 320 mg. P O T D: P O : T D: P O : T D: P O : T D: P O : T D: P O : T D: P O : T D: 16 mg, 32 mg. or 80-320 mg/24h (according to indication).

(Brand Name) Active Ingredient

elmisartan

Candesartan (Amias ) E prosartan Irbesartan (Aprovel.) Losartan (Cozaar) O lmesartan (Olmetec) T (Micardis) Valsartan (Diovan) (Teveten)

aldosterone, vasopressin and peripheral resistance. peripheral and vasopressin aldosterone, ↓ secretion, catecholamine ↓ thus

roup roup G ub S They are ATI receptor antagonists of angiotensin II and inhibit the rennin-angiotensin-aldosterone system, system, rennin-angiotensin-aldosterone the inhibit and II angiotensin of antagonists receptor ATI are They

: blockers receptor ngiotensin antagonists receptor II Angiotensin (ARBs) A or II) (ARAs Drug Sheets

Use cautiously. Contraindications: hypersensitivity to drug, active hepatic disease and previous therapy associated with liver disorders. Drug of choice in hypertensive patients planning hypertensive pregnant patients for pregnancy, and during breastfeeding. May interfere with lab tests for urinary uric and urinary acid, serum creatinine, SGOT catecholamines. In investigations: positive Coombs test, LE cells, positive tests for antinuclear antibody, abnormal liver-function tests rheumatoid factor, and rise in blood urea. For patients on HD, start with a low dose and ↑ as tolerated. serious risk of rebound Do not stop abruptly, HTN. Not recommended in Tx due to ↑ weight, fluid Not recommended in retention and rebound HTN. Caution with tricyclic antidepressants (risk of HTN). ensuring the highest Adm in divided doses daily, dose at bedtime. Headaches, dizziness. Dry mouth. Fatigue. Orthostatic hypoTN. Bradycardia. Headache, dizziness. Nasal congestion. GI disorders. Rash. Mild arthralgia, fatigue. Hepatitis, jaundice. Haemolytic anaemia. Light-headedness, sedation, mood or sleep disturbances, dizziness, vertigo, nausea, anorexia, headache, fatigue, bradycardia, pruritus and rash, dry mouth, oedema in lower extremities, dizziness, constipation. HypoTN.

152 µ g/ml. 153 µ g, 100 µ g - 100 Amp 150 Tabs 125 mg, Tabs 25 Tab 0.2 mg, Tabs 250-500 mg/8h. 50 Tab 0.2-0.6 mg/24h in 250 mg, 500 mg. 0.3 mg, 0.4 mg. P O : T D: P O : IM/ S C: T D: P O : T D: divided doses. /8-24h. Max 1.2mg/24h. 300 µ g.

Methyldopa (Aldomet) Clonidine (Catapres, Dixarit) Moxonidine (Physiotens)

sympathetic outflow from the CNS. the from outflow sympathetic ↓ turn in which receptors, alpha-adrenergic (CNS) central stimulating by BP ↓ which

rine, rine, norepineph alpha-methyl to metabolism its to due (probably system nervous central the on be to believed is action principal Its

Central action antiadrenergic: antiadrenergic: action Central They block the release of catecholamines. of release the block They Drugs in Renal Replacement Therapy: A Guide to Clinical Practice ↑ BP. Contraindications/ Precautions / O bservations Contraindications: known hypersensitivity to drug; idiopathic SLE; severe tachycardia, CAD and myocardial insufficiency; porphyria. In reduced RF start at lowest dose and titrate according to response. Rapid withdrawal may Withdraw drug gradually. cause a possible sudden IV/IM: use drug immediately after drawing through a needle into syringe. It changes colour after contact with metal. Discoloured solution should be discarded. PO: give dose in a regular relationship to ingestion of food for consistent response to Rx. Principal S ide E ffects Headache. Palpitations, tachycardia. Nausea, vomiting, diarrhoea, anorexia. Rheumatic mitral valve disease.

154 155 Amp 20 mg. Tabs 25 mg, 50 mg. Tabs 12.5-50 mg/6h-12h. Administration R oute and T herapeutic Dosage (Available Formulations) (Available P O : IV/IM: T D: (Brand Name) Active Ingredient

Hydralazine (Apresoline)

resulting in ↑ BP. It is used as an adjunct to other anti-hypertensive agents. anti-hypertensive other to adjunct an as used is It BP. ↑ in resulting

roup roup G

ther: ther: O This drug works by relaxing the smooth muscles of arteries and arterioles, arterioles, and arteries of muscles smooth the relaxing by works drug This Drug Sheets Not recommended to be given with iodinated contrast agents. Monitor RF and LF. and plasma levels of uric acid Monitor BP lipids. Blood glucose control. Use cautiously with: foscarnet (nephrotoxic). Adefovir, - levels). clarithromycin, azole (↑CsA - IP, - Everolimus, sirolimus (↑levels); statins, bosentan, levels). dronedarone, pimozide (↑CsA - Carbamazepine, rifampicin, trimethoprim, levels). orlistat (↓CsA - Colchicine (↑levels of both drugs). The capsules Adm always at the same time. The solution should be should be adm whole. smoothies, diluted preferably in juice, water, grapefruit Avoid lemonade, tonic or cola drinks. juice. Do not rinse the syringe; clean exterior with a dry cloth. Nephrotoxicity. HTA. Hyperglycaemia. Hypercholesterolaemia. Gingival hypertrophy. Hirsutism. Tremor. Increased risk of infections (bacterial, fungal, viral and parasitic infections / neoplasia (lymphoma and melanoma).

154 155 Caps 10 mg, 2-15 mg/kg/day, 2-15 mg/kg/day, Amps 50 mg/1ml, 250 mg/5ml. P O : IV: T D: in 2 divided doses, according to drug levels in blood. Important: perform blood test to determine levels of the drug. 25 mg, 50 100 mg. Oral solution 100 mg/ml.

Ciclosporin (CsA) (Sandimmun, Sandimmun Neoral) Other generic forms are available such as Capimune and Deximune. These are interchangeable. NOT

nephrotic syndrome, rheumatoid arthritis, psoriasis and atopic dermatitis. atopic and psoriasis arthritis, rheumatoid syndrome, nephrotic Immunosuppression in organ and bone marrow transplantation. Also useful for useful Also transplantation. marrow bone and organ in Immunosuppression G roup: Calcineurin inhibitors (CNI) IMM U N OSU PP RESS AN TS Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

only when the oral route is impossible. Adm only when the oral route is impossible. Contraindications/ Precautions / O bservations Do not confuse Advagraf and Prograf Do not confuse (extended-release vs standard-release). Use cautiously with: colistin, ASA, cidofovir, Amphotericin B, - ibuprofen, methotrexate, vancomycin (nephrotoxic). Amiloride, spironolactone, triamterene - (hyperkalaemia). - Dronedarone, haloperidol, methadone interval). (↑ QT Azole (↑tacrolimus levels). - and blood glucose. BP LF, Monitor RF, Adm should commence approx. 12 hours after Tx is completed. the Adm in fasting or at least 1 hour before 2-3 hours after ingestion of food. Fatty foods ↓ absorption. Adm always at the same time. IV: slow infusion during 24 hours. Never adm in bolus. Dilute to a concentration of 4-100 μg/ml. The max daily volume to be adm should between 20-500 ml. Important: perform blood test to determine levels of the drug. Principal S ide E ffects Nephrotoxicity. Tachycardia. Tremor. Anaemia. DM, HTN. Diarrhoea. Alopecia. ↑ risk of infections/ neoplasm.

156 R oute 157 Caps 0.5 mg, 1 Caps 0.5 mg, 1 PO: 0.1-0.2 mg/ Amp 5 mg/ml. Amp 5 mg/ml. 0.05-0.1 mg/kg/24h, Administration and T herapeutic Dosage (Available Formulations) (Available 5 mg. P O : IV: T D: P O : IV: T D: Kg/24h, adjust dosage according to drug levels in blood. PO: 0.1-0.2 mg/Kg/24h, divided in 2 doses/12h. IV: adjust dose according to drug levels in blood. 3 mg, 5 mg. (Brand Name) Active Ingredient

acrolimus acrolimus

T (Prograf: standard release - 12h). Generics are available = Adoport, Modigraf, these are NOT Vivadex interchangeable. T (Advagraf: extended- release - 24h).

formation of lymphokines. of formation

roup roup G rejection), the T cell activation, proliferation of B lymphocytes and the the and lymphocytes B of proliferation activation, cell T the rejection), Inhibit the formation of cytotoxic lymphocytes (responsible for graft graft for (responsible lymphocytes cytotoxic of formation the Inhibit Drug Sheets refer to local protocol regarding blood test reconstitute in Dextrose 5% solution to a to determine levels of the drug. Monitor complete blood count and biochemistry. PO: adm with or without food but always in the The tabs should not be crushed same way. (enteric coating). IV: concentration of 6 mg/ml and adm slow infusion (>2 hours), using a peripheral or central vein. Note: GI disorders. Haematological disorders. Neurological disorders. Headache. Cough. ↑ risk of infections / neoplasm. Leucopenia, thrombocytopenia.

156 157 Tabs 180 mg, Tabs Cap 250 mg. 720 mg/12h, Adjust 1 g/12h. Vial 500 mg. Vial adjust dose according to drug blood levels and tolerance. 360 mg. 500 mg. Tab Oral suspension 1g/5 ml. P O : T D: P O : IV: T D: dose according to drug levels in blood.

Mycophenolic acid (Myfortic) Mycophenolate mofetil (Cellcept) Generics are now available.

purines. Prophylaxis of acute renal transplant rejection. transplant renal acute of Prophylaxis purines.

Antiproliferative: Antiproliferative: Inhibit proliferation of T lymphocytes and B, affecting the synthesis of of synthesis the affecting B, and lymphocytes T of proliferation Inhibit Drugs in Renal Replacement Therapy: A Guide to Clinical Practice use the dosing syringe to draw Contraindications/ Precautions / O bservations CsA, PIs, azole, diltiazem, verapamil, dronedarone: ↑ everolimus levels. Monitor for development of secondary neoplasm. PO: adm with or without food, divided into 2 Do not part doses but always in the same way. the tabs (use dispersible tabs, if needed). Important: perform blood test to determine levels of the drug. Use cautiously with: - Amphotericin B, ASA, cidofovir, colistin, ibuprofen, methotrexate, vancomycin (nephrotoxic). - PIs, clarithromycin, azole (↑sirolimus levels). - Rifampicin (↓sirolimus levels). Monitor renal and hepatic functions. Oral solution: prescribed amount from the bottle, pour into a glass or plastic (no other material) with 60 ml of water or orange juice (not grapefruit other liquid). Shake once and adm. Fill the glass again with 120 ml of the same liquid, shake and drink. PO: adm with or without food but always in the same way. Important: perform blood test to determine levels of the drug. This should never be co-prescribed with a CNI such as ciclosporin or tacrolimus. Principal S ide E ffects Anaemia. Dyslipidaemia. Peripheral oedema. Myelotoxicity (leucopenia, anaemia, thrombocytopenia). Lymphocele. Delayed surgical wound healing.

158 R oute 159 : To minimise : To Tabs 0.25 mg, Tabs Tabs 0.5 mg, 1 Tabs 1.5-3 mg/day in 2-6 mg/24h. Administration and T herapeutic Dosage (Available Formulations) (Available 0.5 mg, 0.75 mg, 1 mg. 0.5 mg, 0.75 1 mg. Dispersible tabs 0.1 mg, 0.25 mg. 2 mg. Oral solution 5 mg/5ml. P O : T D: P O : T D: Note Adjust dose according to drug levels in blood. 2 doses. Adjust dose according to drug levels in blood. variability, adm 4 hours variability, dose, and after the CsA consistently either with or without food. (Brand Name) Active Ingredient

E verolimus Votubia) (Afinitor, S irolimus (Rapamune)

rescue severe rejection, preventing the progression of renal damage. renal of progression the preventing rejection, severe rescue

roup roup G

inhibitors: inhibitors: TOR M- Have antiproliferative effect. Inhibit protein synthesis. It is used as as used is It synthesis. protein Inhibit effect. antiproliferative Have Drug Sheets To have available medication for immediate use To in case of severe hypersensitivity. Tx. 1st dose 2 hours before Tx. 2nd dose 4 days after Reconstitute with 5 ml of sterile water for injection. Dilute in 50 ml or more of NS Adm in IV bolus or infusion Dextrose 5% solution. in 20-30 min. Premedication: antipyretic, antihistamine and corticosteroids. Do not adm as fast IV infusion or bolus. Dilute in NS or Dextrose 5% solution to a concentration of 1-4 mg/ml. Initiate at a rate of 50 mg/h for 30 min, then it can be ↑ at intervals of 50 mg/h every 30 min up to 400 mg/h. E nsure to have measures available treat anaphylaxis. Premedication: antipyretic, antihistamine, corticosteroids. Perform daily CD3 counts during Rx. Dilute in 500 ml NS or Dextrose 5% solution and adm only using a central vein and continuous infusion pump (1st >6 hours, the rest >4 hours). Hypersensitivity. Immunogenicity Hypersensitivity. Infusion-related reactions (hypoTN, rash, headache, fever, pruritus). Bronchospasm. Arrhythmias. Pheblitis. Allergy. chills. Fever, Leucopenia, thrombocytopenia. HTN or hypoTN.

158 159 20 mg 2 hours Dependent on local 1.25-2.5 mg/kg/24h. Vial 20 mg. Vial 100 mg/10ml, Vial Thymoglobuline: Vial 500 mg/50ml. 25 mg/5ml. Atege Vial 100 mg/5ml, 200 mg/10ml. IV: T D: IV: T D: IV: T D: before Tx and 20 mg before 4 days later. protocol.

Basiliximab (Simulect) R ituximab (Mabthera) Antithymocyte immunoglobulin (rabbit) (Thymoglobuline)

lymphocytes (mainly T lymphocytes) T (mainly lymphocytes

Prophylaxis of acute rejection in TX in rejection acute of Prophylaxis

derived from different B cell lines.Deplete lines.Deplete cell B different from derived

Monoclonal Antibodies: Monoclonal

Polyclonal ABs: ABs: Polyclonal ABs Drugs in Renal Replacement Therapy: A Guide to Clinical Practice appetite). Dissolve ↓ Contraindications/ Precautions / O bservations in water or juice, stir until mixture is uniform and adm At continuation, another glass of water immediately. of fluid should be taken About 1-2 L should be taken. controlling the during Rx, so it is more indicated in DP, plasmatic levels of K+. Caution: may interfere with absorption of some drugs used in conjunction with antidiarrhoeal drug due to risk of intestinal obstruction. It is not a laxative of choice in stage 5 CKD and dialysis. Adm ½ -1 hour before meals ( Use cautiously in diabetic patients. may appear on the 2nd or 3rd The laxative effect day after adm. If Rx is longer than 6 months, risk of hypokalaemia. Adm Adm in a single dose, preferably at breakfast. is recommended with meals to avoid nausea. juice or tea. It can be diluted with water, Nursing Intervention: provide strategies to avoid prolonged and uninterrupted use of laxatives: - Dialysis patients: recommend a lifestyle as active as possible. patients: reinforce lifestyle Transplant - modifications (high consumption of vegetables and fruits, regular practice of physical exercise and of water/day). intake of 1.5-2 L Principal S ide E ffects Flatulence, bloating, abdominal discomfort. Initially flatulence and fullness. GI disorders (rarely).

160 R oute 161 Sachets 3.5 g. 3.1-3.7 g/5ml 1-3 sachets/day. 15-40 ml/24h, Administration and T herapeutic Dosage (Available Formulations) (Available P O : P O : T D: T D: adjusted according to response. solution. (Brand Name) Active Ingredient Lactulose Ispaghula

T IV ES

roup roup G Laxatives: Treatment of constipation (bowels open < 3/wk). < open (bowels constipation of Treatment LAXA Drug Sheets Use cautiously in eGFR <30 ml/min or RRT Use cautiously in eGFR <30 ml/min or RRT (electrolyte imbalance). It can be adm at room temperature (attention in The patient should remain reclined on winter). the left side with legs folded to chest. Once introduced into the rectum, press container gently and continue to release the liquid inside. Inform the patient to stay in previous position until he/she feels an urge to defecate. If resistance is found at the time of introducing the tube into rectum, procedure should be discontinued as this may damage the rectum. Contraindicated in intestinal haemorrhage. Colostomy or ileostomy: can cause retention of fluid and electrolytes such as Na+ K+. Use cautiously in CKD or RRT. Do not take on a full stomach because it delays laxative effect. Adm is recommended in the morning due to rapid in 2-3 hours. effect Monitoring of Mg levels in blood is indicated. Contraindicated in acute haemorrhoidal crisis and haemorrhagic colitis. Introduce the whole length of cannula and press device while removing. Immediate effect between 2 and 20 min. Temporary Temporary hyperphosphataemia. Diarrhoea. Hypermagnesaemia. Slight rectal burning.

160 161 sachets 2.24 g, Enemas 133 ml Microenema 5 ml. Adjust dose 1 microenema/day 3.92 g. Oral Suspension 1g/5ml. P R : T D: P O : T D: P R : T D: 1-2, according to requirements. according to degree of RF. (max for 6 days). pack.

S odium acid phosphate with S odium phosphate (Fleet enema) Magnesium hydroxide and liquid paraffin (Milpar) Sodium Lauryl Sulfate, sodium acetate, sodium citrate (Micralax)

Laxatives: Laxatives: Treatment of constipation (bowels open < 3/wk). < open (bowels constipation of Treatment Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Contraindicated in undiagnosed acute abdominal pain and ano-rectal problems. Moisten the suppository with cold water before starts within 15-30 min. Do not insertion. Effect adm consecutively for more than 6 days. Not used in Tx. Not used in Contraindicated in eGFR <15 ml/min. If creat >1.5 or eGFR <60 ml/min, adjust dosage. gallbladder disease. Cautions: in RF and/or LF, of anticoagulants. Risk myopathy or ↑ effect rhabdomyolysis with statins. Adm preferably at the end of a meal (prolonged- release form at the end of dinner), without chewing. Cautions: see bezafibrate. Not recommended in advanced CKD or RRT, but in rare cases, it may be used with caution, controlling CK levels and adm the lowest possible dose. Principal S ide E ffects Irritation, sore anus. GI disorders (abdominal pain, nausea, vomiting, and diarrhoea). Rash, pruritus, urticaria. Photosensitivity. ↑ liver enzymes.

162 R oute 163 Tabs 200 mg, Tabs Caps 67 mg, suppository 4 g. See observations. See observations. Administration and T herapeutic Dosage (Available Formulations) (Available 400 mg. P R : P O : T D: P O : T D: 200 mg, 267 mg. 160 mg. Tab: (Brand Name) Active Ingredient

Glycerol (Generics available) Bezafibrate (Bezalip, Bezalip Mono) Fenofibrate (Lipantil, Supralip)

roup roup G Laxatives Fibrates: triglycerides and VLDL. and triglycerides ↓ mainly A GE N TS LIPID-L OWER IN G Drug Sheets

Cautions: see fenofibrate. Tx: 600 mg/24 hours or adm in 2 doses, In 30 min before breakfast and dinner, as max dosage. if eGFR <30 ml/min. Avoid Not used in Tx. Contraindicated in complete biliary obstruction, severe constipation, hyperchloraemia. Never give in dry form due to danger of causing oesophageal spasm or respiratory distress. Mix juice, milk, at least with 100 ml of liquid (water, soup, pudding) until well dispersed. Doses of 30 g given in 3 distributed doses. Do not adm other drugs orally 1 hour before and up to 4 hours after its adm. GI disorders (abdominal pain, nausea, vomiting, and diarrhoea). Rash, pruritus, urticaria. Photosensitivity. ↑ liver enzymes. GI disorders (vomiting, constipation, diarrhoea).

162 163 Tabs 300 mg, Tabs Oral suspensions

600 mg. 4 g. P O : T D: P O : T D: See observations. in several 4-36 g/day, doses.

Gemfibrozil (Lopid) Cholestyramine (Questran)

cholesterol level in blood. in level cholesterol

Fibrates: Fibrates: triglycerides and VLDL. VLDL. and triglycerides ↓ mainly

Anion exchange resin: resin: exchange Anion Reduces the the Reduces Drugs in Renal Replacement Therapy: A Guide to Clinical Practice up to 35% in ↓ Contraindications/ Precautions / O bservations Contraindicated in active liver disease or unexplained persistent ↑ liver enzymes, currently active myopathy (↑ in patients treated with macrolides, ciclosporin, fibrates, azole, niacin, IP, danazol). Concomitant Rx with antacids may Cautions: see atorvastatin. Doses of 40 mg and 80 mg/24 can be taken in divided doses every 12 hours. Caution when using dosage >40 mg/24h in eGFR monitoring CK levels. It is <30 ml/min or RRT, safer than other statins in CKD. plasma levels of atorvastatin. Adm every day at the same time (with or without food). It is advisable to take preferably in the evening or at bedtime as it is when cholesterol synthesized. If an ion exchange resin is given, adm 2 hours before or 4 hours after the resin. Principal S ide E ffects GI disorders (abdominal pain, nausea, vomiting, diarrhoea, fatigue). Headaches, blurred vision. Itching, rash. Insomnia. Myopathy. ↑ liver enzymes.

164 R oute 165 Caps 20 mg, Tabs 10 mg, 20 Tabs 10-80 mg/24h. 20-80 mg/24h. Administration and T herapeutic Dosage (Available Formulations) (Available 40 mg, 80 mg. P O : T D: P O : T D: 40 mg, 80 mg. (Brand Name) Active Ingredient

Atorvastatin (Lipitor) Fluvastatin (Lescol)

with statin. with

roup roup G Note: Patient should continue on cholesterol-lowering diet during treatment treatment during diet cholesterol-lowering on continue should Patient

tatins S : Reduce the values of LDL-C and total cholesterol in blood. blood. in cholesterol total and LDL-C of values the Reduce :

Drug Sheets ↑ risk of risk of ↑ : use normal dosing. : start with low dose and titrate Contraindications/ Precautions / O bservations Contraindicated in CKD stages 4, 5 and 5D. Not recommended for use in Adm during or after meals to reduce GI effects. eGFR <30 ml/min. eGFR >10 ml/min eGFR <10 ml/min according to response*. *Half-life prolonged therefore eGFR <50 ml/min: start with 20-40 mg daily and titrate according to response*. *Half life prolonged therefore hypoglycaemic episodes. Adm in a single dose the morning (except at is enhanced when The effect doses >10 mg). adm 30 min before breakfast. hypoglycaemic episodes. Adm in a single dose the morning, before or during breakfast. Doses greater than 160 mg should be given as a divided daily dose (twice day). Principal S ide E ffects Hypoglycaemia when combined with other OAD. Nausea, diarrhoea, lactic acidosis. Hypoglycaemia (> risk than other Sulphonylureas). GI disorders. disturbances Transient of vision (initially). Hypoglycaemia. GI disorders

164 R oute 165 Tabs 500 mg, Tabs 5 mg. Tab 30 mg (MR). Tabs Max dose 2 g/24h. 2.5-15 mg/24h. 30-120 mg/24h Administration and T herapeutic Dosage (Available Formulations) (Available 750 mg, 1 g. 850 mg. 500 mg, Tabs MR P O : T D: P O : T D: P O : T D: (MR) - usually avoided 40-320 mg/24h in RF. (plain release). Plain release 40 mg, 80 mg. (Brand Name) Active Ingredient

Metformin (Glucophage and other generic brands) G libenclamide (Glyburide and other generic brands) G liclazide (Diamicron, Zicron and other generic brands)

roup roup G Biguanide Sulphonylureas O ral antidiabetic drug ( AD) - used in adjunct to diet lower blood glucose with non-insulin-dependent type 2 DM. AL AN T IDIAB ET IC D RUGS and IN SU LIN OR AL Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations eGFR <50 ml/min: start with 1.25-2.5 mg daily and titrate according to response*. *Haf-life prolonged therefore ↑ risk of hypoglycaemic episodes. Adm in a single dose the morning, before or during breakfast. Not recommended for use with eGFR <25 ml/min. Contraindicated in stage 5D. Not recommended in patients with chronic disease, ulcerative intestinal disorders (Crohn’s colitis, severe diarrhoea, etc.). simultaneous adm with antacids, Avoid cholestyramine, intestinal absorbents and digestive enzymes. Adm tablets Adm at the beginning of meals. whole or chewed with the first bites of food. eGFR <50 ml/min: start with 2.5 mg daily and titrate according to response*. *Half-life prolonged therefore ↑ risk of hypoglycaemic episodes. Adm in a single dose the morning, ½ hour before breakfast. If doses >15 mg should be divided in 2 doses (before breakfast and dinner). Principal S ide E ffects Hypoglycaemia. Possible hives. GI disorders. Headaches, dizziness. Skin reactions. Hypoglycaemia. Hypoglycaemia. Skin reactions. GI disorders (mild).

166 R oute 167 Tabs 2 mg, 4 mg. Tabs 50 mg, Tabs 1-4 mg/24h. 50-100 mg/8h. Tab 5 mg. Tab 5-20 mg/24h. Administration and T herapeutic Dosage (Available Formulations) (Available 100 mg. P O : T D: P O : T D: P O : T D: (Brand Name) Active Ingredient

G limepiride (Amaryl and other generic brands) G lipizide (Glibenese, Minodiab) Acarbose (Glucobay)

alphaglucosidase

roup roup G Sulphonylureas Inhibitors of of Inhibitors Drug Sheets Do NOT use in type1 DM. Do NOT Not recommended for use in eGFR <30 ml/ min. (But in exceptional cases such as stage 5 or 5D, it may be used under supervision by endocrinology specialist). During Rx avoid alcoholic drinks. Adm ½ hour before meals. If a meal is skipped, do not adm. use in type1 DM. Do NOT In eGFR <30-60 ml/min, it can be used with an adequately adjusted dosage. May be used in stage 5 or 5D under supervision by endocrinologist. It is typically used with the combination of a glitazone (if no RF). associating with gemfibrozil Avoid (hypoglycaemia risk). Adm 15-30 min before meals. Adm 2, 3 or 4 times depending on the number of Adm meals. Do not adm when a meal is skipped. extra dose when meal. Hypoglycaemia. ↑ weight. Sickness. Abdominal pain. Hypoglycaemia GI disorders disorders Vision Cutaneous hypersensitivity reactions.

166 167 Tabs 60 mg, Tabs 0.5 mg, 1 Tabs 60-120 mg/8h. 0.1- 4 mg/lunch. 120 mg, 180 mg. P O : T D: P O : T D: 2 mg.

Nateglinide (Starlix) R epaglinide (Prandin)

ecretagogues S Drugs in Renal Replacement Therapy: A Guide to Clinical Practice for more information. Contraindications/ Precautions / O bservations Adm just before the start of meal. It is very important to eat foods rich in carbohydrates immediately after adm. Adm 30 min before meals. Inform the patient that after adm, take foods rich in carbohydrates within 30 min. S ee Page 177 Adm 10-15 min (max) before meals. It can be mixed only with NPH insulin. Adm just before the start of meal. It is very important to eat foods rich in carbohydrates immediately after adm. Principal S ide E ffects Hypoglycaemia. Erythema. Lipoatrophy, lipohypertrophy. Sodium retention and oedema.

168 R oute 169 Vial 1000 Vial Pen 100 ui/ml. Pen 100 ui/ml. 100 ui/ml. Vial Administration and T herapeutic Dosage (Available Formulations) (Available ui/10ml. Syringe 100 ui/ml. S C: S C: S C: Pen 100 ui/ml. S C/ IM/ IV: (Brand Name) Active Ingredient

Insulin Aspart (Novomix, Novorapid) Insulin G lulisine (Apidra) Insulin Lispro (Humalog) R egular/ S oluble Insulin (Actrapid, Humulin regular)

roup roup G Insulin apid R Insulin - used to treat type 1 DM and 2 type, when the latter cannot be controlled by diet alone. facilitating the transport of energy, It is a naturally occurring hormone. promotes the storage of body’s metabolites and ions (K+) through cell membranes stimulating the synthesis of glycogen from glucose, fats from lipids and proteins amino acids. Drug Sheets Adm ½ hour before breakfast/dinner. Adm 15 min or less before a meal. This insulin Adm 15 min or less before a meal. should have a cloudy/milky white appearance. Do not mix with any other insulin or diluent. adm by IV (risk of severe Do NOT hypoglycaemia). but Adm in a single dose at any time of day, always at the same time. For patients who require twice a day dosing, the dose can be adm in the evening or before bedtime. mix in the same syringe with other Do NOT insulin. Not recommended in pregnancy or breastfeeding. In HD patients, the average life of long-acting insulins is ↑. Insulin detemir or glargine are preferable in HD than human insulin NPH due to the ↑ risk of hypoglycaemia. Hypoglycaemia. Erythema. Lipoatrophy, lipohypertrophy. Sodium retention and oedema.

168 169 Vial 100 ui/ml. Vial Pen 100 ui/ml. Pen 100 ui/ml. 100 ui/ml. Vial S C: Syringe 100 ui/ml. S C: S C: S C: Pen 100 ui/ml.

Insulin Isophane (Humulin NPH, Insulatard) Insulin Lispro- protamine (Humalog basal) Insulin Detemir (Levemir) Insulin G largine (Lantus)

Intermediate insulin Intermediate insulin Prolonged Drugs in Renal Replacement Therapy: A Guide to Clinical Practice Contraindications/ Precautions / O bservations Do NOT mix with other insulin. Do NOT use insulin infusion pumps. Do NOT Not recommended in person <18 years. In elderly patients and with liver disease or kidney disease, glycaemic control should be intensified. Principal S ide E ffects Hypoglycaemia. Erythema. Lipoatrophy, lipohypertrophy. Sodium retention and oedema.

170 R oute MT Vial 100 ui/ml. Vial Pen 100 ui/ml. Pen 100 ui/ml. Pen 100 ui/ml. Pen 100 ui/ml. Pen 100 ui/ml. Administration and T herapeutic Dosage (Available Formulations) (Available S C: Insulin Pump Watch 100 ui/ml. S C: S C: S C: S C: S C: (Brand Name) Active Ingredient

Lispro 25% + lispro protamine 75% (Humalog mix 25 Kwikpen) Regular 30% + isophane 70% (Humulin 30:70, Novomix 30) Lispro 50% + lispro protamine 50% (Humalog mix 50 Kwikpen) Aspart 30% + aspart protamine 70% (Novomix 30) Aspart 50% + aspart protamine 50% (Novomix 50) Aspart 70% + aspart protamine 30% (Novomix 70)

roup roup G insulin Biphasic Recommendations in the Administration of Specific Drugs

171 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

1. Anti-infectious therapy in Peritoneal Dialysis (Drug sheet: Page 121)

This section summarizes the antibiotics used to treat peritoneal dialysis (PD)-related infections, according to the International Society of Peritoneal Dialysis (ISPD) Guidelines/ Recommendations1. Table 1 shows oral antibiotics used to treat exit-site and tunnel infection, Table 2 shows intraperitoneal antibiotic dosing recommendations for continuous ambulatory peritoneal dialysis (CAPD) patients and Table 3 shows intermittent dosing of antibiotics in automated peritoneal dialysis (APD).

Table 1: Oral Antibiotic Used in Exit-site and Tunnel Infection1

Therapeutic Dosage Antibiotic Daily (q.d); 2 times/day (b.i.d); 3 times/day (t.i.d); 4 times/day (q.i.d)

Amoxicillin 250–500 mg b.i.d.

Cephalexin 500 mg b.i.d to t.i.d.

Ciprofloxacin 250 mg b.i.d. 172 173 Clarithromycin 500 mg loading dose, then 250 mg b.i.d. or q.d.

Dicloxacillin 500 mg q.i.d.

Erythromycin 500 mg q.i.d.

Flucloxacillin (or 500 mg q.i.d. cloxacillin)

Fluconazole 200 mg q.d. for 2 days, then 100 mg q.d. Recommendations in the Administration of Specific Drugs

Therapeutic Dosage Antibiotic Daily (q.d); 2 times/day (b.i.d); 3 times/day (t.i.d); 4 times/day (q.i.d)

0.5–1 g/day titrated to response and serum Flucytosine trough levels (25–50 mg/mL)

Isoniazid 200–300 mg q.d.

Linezolid 400–600 mg b.i.d.

Metronidazole 400 mg t.i.d.

Moxifloxacin 400 mg q.d.

Ofloxacin 400 mg first day, then 200 mg q.d.

Pyrazinamide 25–35 mg/kg 3 times per week

Rifampicin 450 mg q.d. for <50 kg; 600 mg q.d. for >50 kg

Trimethoprim/ 80/400 mg q.d. sulfamethoxazole

Table 2: Intraperitoneal Antibiotic Dosing Recommendations in CAPD1

Intermittent Continuous Antibiotic (per exchange, once (all exchanges) daily) 172 173 Aminoglycosides Amikacin 2 mg/kg LD 25 mg/L, MD 12 mg/L Gentamicin, netilmicin or 0.6 mg/kg LD 8 mg/L, MD 4 mg/L tobramycin Cephalosporins Cefazolin, cephalothin 15 mg/kg LD 500 mg/L, MD 125 mg/L or cephradine

Cefepime 1000 mg LD 500 mg/L, MD 125 mg/L Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Intermittent Continuous Antibiotic (per exchange, once (all exchanges) daily)

Cephalosporins Ceftazidime 1000–1500 mg LD 250 mg/L, MD 125 mg/L Ceftizoxime 1000 mg LD 250 mg/L, MD 125 mg/L Penicillins LD 250–500 mg/L, Amoxicillin MD 50 mg/L

Ampicillin, oxacillin MD 125 mg/L or nafcillin No data Azlocillin LD 500 mg/L, MD 250 mg/L

LD 50000 units, Penicillin G MD 25000 units

Quinolones

Ciprofloxacin No data LD 50 mg/L, MD 25 mg/L

Others LD 1000 mg/L, Aztreonam MD 250 mg/L No data Daptomycin LD 100 mg/L, MD 20 mg/L

174 Linezolid Oral 200–300 mg q.d. 175

Teicoplanin 15 mg/kg LD 400 mg/L, MD 20 mg/L

15–30 mg/kg every Vancomycin LD 1000 mg/L, MD 25 mg/L 5–7 days

Antifungals Amphotericin Not applicable 1.5 mg/L

Fluconazole 200 mg intraperitoneal every 24–48 hours Recommendations in the Administration of Specific Drugs

Intermittent Continuous Antibiotic (per exchange, once (all exchanges) daily)

Combinations LD 1000 mg/L, MD 100 Ampicillin/sulbactam 2 g every 12 hours mg/L Imipenem/cilastin 1 g b.i.d. LD 250 mg/L, MD 50 mg/L

Quinupristin/ 25 mg/L in alternate bags (given in conjunction dalfopristin with 500 mg IV, b.i.d.)

Trimethoprim/ Oral 960 mg b.i.d. sulfamethoxazole

Daily (q.d); 2 times/day (b.i.d); Loading dose (LD); Maintenance dose (MD) Note: In patients with residual renal function (defined as >100 ml/day urine output), dosage should be empirically increased by 25%.

Table 3: Intermittent dosing of antibiotics in automated peritoneal dialysis (APD)1

Antibiotic Intraperitoneal (IP) Dose

Cefazolin 20 mg/kg IP daily, in long day dwell

Cefepime 1 g IP in 1 exchange per day

200 mg IP in 1 exchange per day, Fluconazole 174 every 24–48 hours 175

LD 1.5 mg/kg IP in long dwell, then 0.5 mg/kg IP Tobramycin daily in long dwell

LD 30 mg/kg IP in long dwell; repeat dosing 15 Vancomycin mg/kg IP in long dwell every 3–5 days (aim to keep serum trough levels >15 mg/mL)

Li P, Szeto CC, Piraino B et al. Peritoneal dialysis-related infections recommendations: 2010 Update. Perit Dial Int 2010; 30:393–423. http://www.pdiconnect.com/content/30/4/393.full.pdf (accessed 24 April 2012). Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

2. Erythropoiesis-Stimulating Agents (Drug sheet: Page 114)

Storage: In a refrigerator, between 2º C and 8º C. Do not administer as infusion. SC: remove from the refrigerator 15 minutes before administration, until it warms up to room temperature (no more than 1 hour). Do not accelerate the heating process (e.g. hand roll, microwave, steam boiler). Rotate injection sites: upper arms, abdomen (except 5 cm around the navel) and anterior thighs. If the amount to be administered exceeds 1 ml, choose more than one injection site. IV: administer in 1-5 minutes. It can be administered as bolus via the venous port of the extracorporeal circuit during HD, or alternatively at the end of dialysis, via the venous fistula needle followed by 10 ml of NS flush to ensure the drug is totally injected into the bloodstream. In HD, assess regularly the dosage of heparin to prevent clotting of the extracorporeal blood circuit. According to the National Institute for Health and Clinical Excellence (NICE) guidelines, in patients with anaemia of CKD, target haemoglobin (Hb) should be 10-12 g/dl. In order to keep the Hb level within the target range, action should be 176 taken when Hb levels are within 0.5 g/dl of the range’s limits. 177 For more information: • CG114 Anaemia management in people with chronic kidney disease: quick reference guide. Updated version (February 2011). Available at: http://www.nice.org.uk/nicemedia/ live/13329/52857/52857.pdf (accessed 24 Mar 2012). • KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease: 2007 Update of Hemoglobin Target. Recommendations in the Administration of Specific Drugs

Available at: http://www.kidney.org/professionals/ KDOQI/guidelines_anemiaUP/guide1.htm (accessed 30 Apr 2012).

3. Iron Sucrose (Drug sheet: Page 113) (Venofer) Before the 1st administration: perform a test dose with 25 ml in 100 ml NS to administer in 15 minutes (to prevent possible adverse reactions). If it is well tolerated, administer the remainder in 15-60 minutes. Subsequent administrations: 100 mg in 15 min, 200 mg in 30 minutes. Dilute in 100 ml NS. To reduce the risk of extravasation after administration, extend and lift the patient’s arm, applying pressure at the injection site for one to 5 minutes. In bolus IV injection (undiluted), it may be administered at a rate of 1 ml per minute (5 min / vial), not exceeding 2 vials for each injection. It can be administered directly during the last 30 minutes of dialysis, followed by 10 ml of NS to flush the needle line so that the drug is completely administered into the bloodstream.

176 177 4. Insulin (Drug sheet: Page 168) I. Educate the patient in self-management of blood sugar control, with explanation on the symptoms of hypoglycaemia and hyperglycaemia: Symptoms of hypoglycaemia, for example: -- Anxiety, restlessness, irritability, palpitations, tachycardia, pallor, muscle weakness, tremors, sweating, intense hunger (due to adrenaline liberation). Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

-- Headache, sluggishness, slurred speech, abnormal behaviour with irritability, aggressiveness, confusion, drowsiness, double vision, and even seizures (due to lack of glucose in the CNS). Symptoms of hyperglycaemia, for example: -- Blurred vision, drowsiness, dry mouth and skin, loss of appetite, nausea, vomiting, thirst, tachypnoea.

II. Teach the proper technique in the administration of insulin to obtain an optimal uptake of the drug and to prevent insulin lipodystrophy. It is recommended to rotate the injection sites (see Figure 1). Also, emphasize in: • Hand washing before and after drug administration. • After each injection, you should remove and discard the needle properly.

Illustration 1: Rotating sites for SC administration of insulin

178 179

Areas to be rotated for SC administration of insulin:

• Abdomen (area of faster absorption of insulin) • Arms (areas of comparatively less faster absorption) • Thighs (areas of slow absorption) Recommendations in the Administration of Specific Drugs

Observations:

• If eGFR 10-50 ml/min decrease dosage by 25%. If GFR <10 ml/min reduce dosage by 50%. In elderly patients with deteriorating renal function this may lead to a steady decrease in insulin requirement and the accumulation of OAD permitted. In patients on HD it should be borne in mind that the lifetime of the intermediate insulin is increased. In patients with severe hepatic impairment this may reduce the need for insulin. • Medications that may reduce blood glucose lowering effect: corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic drugs and thyroid hormone. • Medications that may increase hypoglycaemic effect: beta-blockers, clonidine, lithium salts or alcohol. • Do not mix with other insulin in a continuous IV pump. • Vials or pens that are not in use should be kept in a refrigerator between 2° C and 8° C, avoiding freezing point. Once used it can be kept at room temperature for up to 6 weeks. It is not necessary to keep vials or 178 pens that are in use in the refrigerator, unless the heat 179 is excessive.

5. Hepatitis B vaccine (Drug sheet: Page 129) Be prepared for possible severe anaphylactic reaction. Store between 2° C and 8º C. Shake vial before administration and inject immediately after extraction of vaccine from the vial. Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Administration: • Do not administer intravenously. • Administer intramuscularly in the deltoid muscle. It should not be administered in the gluteal area, or intradermally (may lead to reduced immune response). • Exceptionally it may be administered SC, in subjects with thrombocytopenia or bleeding disorders. • It may be administered with hepatitis B immunoglobulin or with other vaccines but at different injection sites. Observations: • With HBvaxPRO ® if there is no concentration of anti- HBs >10 IU/L, it is recommended a second full series (3 doses). • With Engerix-B ®, the physician will determine if a booster dose is needed. • Vaccination is recommended for all healthcare workers at risk and HD patients, except those with positive HBsAg or HBsAb antibodies. • There are different regimes of immunity against hepatitis B vaccine (see local unit protocol). The doses depend on the vaccine used. Generally, the standard adult vaccination regime consists of 3 injections at 0, 1 and 6 months, with or without the fourth dose. 180 • The response to hepatitis B vaccine varies between 181 individuals. The desirable anti-HBs levels in serum are >100 MIU/ml, although levels of ≥10 MIU/ml are accepted as a protective immune response. • Patient’s antibody levels should be monitored annually. A booster dose of vaccine should be given if the levels decrease <10 MIU/ml. • Patients who plan to visit countries highly endemic for hepatitis B should be vaccinated with a booster dose. Recommendations in the Administration of Specific Drugs

For more information: • Immunisation against infectious disease 2006 p161-184- updated version available at: http://www.dh.gov.uk/prod_consum_dh/groups/dh_ digitalassets/documents/digitalasset/dh_131000.pdf

180 181

Appendix

183 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

REFERENCES Elaboration of drug sheets: Original edition (Spanish)

-- Agencia Española de Medicamentos y Productos Sanitarios). Disponible en: https://sinaem4.agemed.es/consaem/fichasTecnicas. do?metodo=detalleForm [acceso agosto 2010-febrero 2011] -- Agencia Europea del medicamento. Disponible en: http://www.emea. europa.eu [acceso agosto 2010-febrero 2011] -- Alvarez Pasquín MJ, Batalla Martínez C, Comín Bertrán E, Gómez Marco JJ, Mayer Pujadas MA et al. Grupo de trabajo de Enfermedades Infecciosas. Grupos de Expertos del PAPPS. Prevención de las enfermedades infecciosas. Aten Primaria 2007; 39 Supp 3:72-73 -- Carlos Morillas Ariño, E.Solà,JL Gorriz, F Coronel.”Manejo de la hiperglicemia en enfermedad renal crónica”. NefroPlus Vol.1 Nº2 Año 2008. -- Catálogo de Medicamentos 2010. Madrid: Consejo General de Colegios Oficiales de Farmacéuticos. -- Clinica Universitaria de Navarra[Internet]Navarra:AREADESALUD:28 octubre de 2009 [ actualización 25 de octubre; acceso 30 de octubre de 2010] Insuficiencia Renal Crónica. Disponible: http://www.cun. es/areadesalud/enfermedades/sistema-nefro-urinario/insuficiencia- renal-cronica/ -- fedialisis.com [Internet]:Fundación Española de Diálisis; 2003Guía para el Tratamiento de la Osteodistrofia Renal. Disponible: http:// fedialisis.com/informacion-medica/guias-consensuadas-sedyt/ osteodistrofia-renal/ [acceso 28 de octubre de 2010]. -- Fichas tecnicas de las especialidades farmacéuticas (acceso on-line) -- Guia Española de hipertensión 2005. Página 50-51. -- Guía de Práctica Clínica sobre Diabetes tipo 2. http://www.guiasalud. es/GPC/GPC_429_Diabetes_2_Osteba_rapid.pdf Ministerio de sanidad y consumo.Gobierno Vasco. 2010. 184 -- J.A. Chena y colaboradores. Diabetes Mellitus – Aspectos para 185 educadores. Novo Nordisk Pharma; 2001. -- J.V. Torregrosa, J. Cannata Andia, J. Bover, F, Carava, V, Lorenzo, A.L. Martin de Francisco, A. Martin Malo, I, Martinez, E. Gonzalez Perez, E. Fernandez Gonzalez, M. Rodríguez Portillo. Recomendaciones de la sociedad española de nefrología para el manejo de las alteraciones del metabolismo óseo-mineral en los pacientes con enfermedad renal Appendix

crónica. [Internet] Disponible en: http://www. .senefro.org. [acceso 17 de julio 2010] -- Mª. T. Gonzalez-Alvarez, J.Bover, E.Fernandez, A. Forraster, j.G. Hervás, A. Llopis. A.Palma, J.E. Ruiz, R. Sans, V. Torregrosa. Guia para el tratamiento de la osteodistrofia renal. Dyt [revista on-line] 2004 25(3):179-190. Disponible en: http://www.Sedyt.org/2004/ revista/numeros_enteros/253/2503_179_O_Gonzalez.pdf. [acceso 4 de noviembre 2010]. -- Medimecum – Guía de terapia farmacológica. ADIS; 2010. -- Papel de los análogos de insulina en el tratamiento de la diabetes,. http://www.gencat.cat/salut/depsalut/pdf/esbit603.pdf. -- Transplantomecum 2010. 2ª edición. F Oppenheimer (Ed.). Barcelona, Permanyer, 2010. -- Vademecum.es 2010. Disponible en: http://www.vademecum.es [acceso julio 2010- febrero 2011 ].

English edition -- Ashley C, Currie A. The renal drug handbook 3rd ed. Oxford: Radcliffe Publishing; 2009. -- The electronic Medicines Compendium (eMC) http://www.medicines.org.uk/EMC/about.aspx

-- British National Formulary http://bnf.org

Useful websites: Pharmacology: Spanish edition

-- Agencia Española de medicamentos y productos sanitarios (AEMPS): https://sinaem4.agemed.es/consaem/fichasTecnicas. do?metodo=detalleForm 184 -- www.cedimcat.info/html/ca/dir2451/doc10713.html 185 -- www.farmaceuticonline.com/spd.htm -- Guía de administración de Medicamentos Vía Parenteral: Servicio de Farmacia. Hospital Universitario Son Espases. Palma de Mallorca. http://www.elcomprimido.com/FARHSD/GAP_HUSD_ EDICION6_2010_INTERNET/A_INICIO_GAP.htm Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

-- Principios de farmacología: http://www.iqb.es/cbasicas/farma/toc06.htm -- Vademecum: http://www.vademecum.es/

Journals in nephrology: -- Advances in Chronic Kidney Diseases: http://www.journals. elsevierhealth.com/periodicals/yjarr/issues -- American Journal Kidney Diseases: http://www.ajkd.org/ -- American Journal of Nephrology: http://content.karger.com/ ProdukteDB/produkte.asp?Aktion=JournalHome&ProduktNr=2 23979&ContentOnly=false -- Kidney & Blood Pressure Research: http://content.karger.com/ ProdukteDB/produkte.asp?Aktion=JournalHome&ProduktNr=22425 8&ContentOnly=false -- Journal of the American Society of Nephrology: http://jasn.asnjournals. org/ -- Journal of Renal Care: http://www.edtnaerca.org/pages/education/jrc. php -- Nephrology Dialysis Transplantation: http://ndt.oxfordjournals.org/ -- Nephrology Nursing Journal: http://www.nephrologynursing.net/ -- Nephron: http://content.karger.com/ProdukteDB/produkte.asp?Aktion =JournalHome&ProduktNr=223854&ContentOnly=false -- Revista de Nefrología: http://www.revistanefrologia.com/modules. php?name=home -- Seminars in Dialysis: http://onlinelibrary.wiley.com/journal/10.1111/ (ISSN)1525-139X/issues -- Seminars in Nephrology: http://www.seminarsinnephrology.org/ -- Transplantation: http://journals.lww.com/transplantjournal/pages/ default.aspx -- American Journal of Transplantation: www.amjtrans.com/

186 Nephrology and Transplant Associations/Societies: 187 Spanish edition

-- Associació Catalana d’Infermeria Nefrològica: http://www.acin.cat/ -- Sociedad Andaluza de Trasplante de Órganos y Tejidos (SATOT): http://www.satot.org/index.cfm?n=3409 Appendix

-- Societat Catalana de Trasplantament: http://www.sctransplant.org/ indexcas.html -- Sociedad Española de Diálisis y Trasplante (SEDYT): http://www. sedyt.org/2004/ -- Sociedad Española de Enfermería Nefrológica (SEDEN): http://www. seden.org/ -- Sociedad Española de Nefrología (SEN): http://www.senefro.org/ index.php -- Sociedad Española de Trasplante (SET): http://www.setrasplante.org/ -- Sociedad Latinoamericana de Nefrología e Hipertensión: http://www. slanh.org/ -- Sociedad Madrileña de Trasplantes: http://www.smtrasplantes.org/

English edition

-- Anaemia Nurse Specialist Association: www.anaemianurse.org/ -- British Renal Society: http://www.britishrenal.org/ -- ERA-EDTA European Dialysis and Transplant Registry: http://www.era-edta-reg.org/index.jsp?p=1 -- European Dialysis and Transplant Nurse Association/European Renal Care Association: http://www.edtnaerca.org/ -- European Society for Organ Transplantation: www.esot.org/ -- National Institute for Health and Clinical Excellence: http://www.nice. org.uk -- Renal Association: http://www.renal.org/home.aspx -- Royal College of Nursing Nephrology Nursing Forum: http://www. rcn.org.uk/development/communities/rcn_forum_communities/ nephrology -- UK Renal Pharmacy Group: www.renalpharmacy.org.uk/

Others: 186 187 -- Calculador MDRD FGe: http://nephron.org/mdrd_gfr_si -- http://www.foodvalues.us/ -- http://www.nephron.com/ -- http://www.transplant360.com/

Index

189 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Index (Drugs in alphabetical order)

Acarbose ...... page 166 Candesartan ...... page 152 Acetylsalicylic acid ...... page 130 Captopril ...... page 150 Aciclovir ...... page 128 Cefazolin ...... page 126 Alfacalcidol ...... page 137 Cefotaxime ...... page 126 Allopurinol ...... page 119 Ceftazidime ...... page 126 Aluminium hydroxide ...... page 132 Cefuroxime ...... page 126 Amikacin ...... page 121 Chlortalidone ...... page 141 Amlodipine ...... page 147 Cholestyramine ...... page 163 Amoxicillin ...... page 126 Ciclosporin ...... page 155 Ampicillin ...... page 126 Cinacalcet ...... page 138 Antithymocyte Ciprofloxacin ...... page 123 immunoglobulin (rabbit) ...... page 159 Clarithromycin ...... page 122 Atenolol ...... page 145 Clonidine ...... page 153 Atorvastatin ...... page 164 Clopidogrel ...... page 130 Azithromycin ...... page 122 Co-amoxiclav ...... page 126 Aztreonam ...... page 126 Codeine ...... page 104 Basiliximab ...... page 159 Co-trimoxazole (trimethoprim Bemiparin ...... page 117 and sulfamethoxazole) ...... page 125 Bezafibrate ...... page 162 Dalteparin ...... page 117 Biphasic insulin ...... page 170 Daptomycin ...... page 124 Bisoprolol ...... page 145 Darbepoetin alfa ...... page 114 Bumetanide ...... page 142 Dexketoprofen ...... page 102 Calcitriol ...... page 137 Diclofenac ...... page 102 Calcium acetate ...... page 132 Digoxin ...... page 131 Calcium acetate with Diltiazem ...... page 149 magnesium carbonate ...... page 135 Dipyridamole ...... page 130 Calcium carbonate ...... page 133 Doripenem ...... page 126 Disodium pamidronate ...... page 138 190 Calcium polystyrene 191 sulphonate ...... page 136 Doxazosin ...... page 146 Index

Enalapril ...... page 150 Glyceryl trinitrate ...... page 131 Enoxaparin ...... page 117 Heparin sodium ...... page 116 Eplerenone ...... page 143 Hepatitis B vaccine ...... page 129 Eprosartan ...... page 152 Hydralazine ...... page 154 Ertapenem ...... page 126 Ibuprofen ...... page 103 Erythropoietin alpha ...... page 114 Imipenem ...... page 126 Erythropoietin beta ...... page 115 Indapamide ...... page 141 Esomeprazole ...... page 110 Insulin aspart ...... page 168 Everolimus ...... page 158 Insulin detemir ...... page 169 Famotidine ...... page 109 Insulin glargine ...... page 169 Febuxostat ...... page 120 Insulin glulisine ...... page 168 Felodipine ...... page 147 Insulin isophane ...... page 169 Fenofibrate ...... page 162 Insulin lispro ...... page 168 Fentanyl ...... page 105 Insulin lispro-protamine ...... page 169 Ferric carboxymaltose ...... page 113 Irbesartan ...... page 152 Ferrous fumarate...... page 112 Iron sucrose ...... page 113 Ferrous gluconate ...... page 112 Ispaghula ...... page 160 Ferrous sulphate ...... page 112 Lacidipine ...... page 147 Filgrastim ...... page 139 Lactulose ...... page 160 Fluvastatin ...... page 164 Lansoprazole ...... page 110 Folic acid ...... page 116 Lanthanum carbonate ...... page 133 Fosinopril ...... page 150 Lenograstim ...... page 139 Furosemide ...... page 142 Lercanidipine ...... page 147 Ganciclovir ...... page 129 Levofloxacin ...... page 123 Gemfibrozil ...... page 163 Linezolid ...... page 125 Gentamicin ...... page 121 Lisinopril ...... page 150 Glibenclamide ...... page 165 LMWH (low molecular Gliclazide ...... page 165 weight heparin) ...... page 117 Glimepiride ...... page 166 Losartan ...... page 152 Glipizide ...... page 166 190 Magnesium hydroxide 191 Glycerol ...... page 162 and liquid paraffin ...... page 161 Drugs in Renal Replacement Therapy: A Guide to Clinical Practice

Meropenem ...... page 126 Propranolol ...... page 146 Metformin ...... page 165 Quinapril ...... page 151 Methoxy polyethylene Rabeprazole ...... page 111 glycol-epoetin beta ...... page 115 Ramipril ...... page 151 Methyldopa ...... page 153 Ranitidine ...... page 109 Methylprednisolone ...... page 140 Regular insulin Metoclopramide ...... page 118 (Soluble insulin) ...... page 168 Metolazone ...... page 141 Repaglinide ...... page 167 Metronidazole ...... page 127 Rituximab ...... page 159 Morphine ...... page 106 Sevelamer ...... page 136 Moxonidine ...... page 153 Sirolimus ...... page 158 Mycophenolate Mofetil (MMF) ... page 157 Sodium acid phosphate Mycophenolic acid ...... page 157 with Sodium phosphate...... page 161 Nateglinide ...... page 167 Sodium Lauryl Sulphate, Nebivolol ...... page 145 Sodium acetate, Sodium citrate . page 161 Nicardipine ...... page 148 Sodium polystyrene sulphonate . page 136 Nifedipine ...... page 148 Soluble insulin Norfloxacin ...... page 123 (Regular insulin) ...... page 168 Nystatin ...... page 127 Spironolactone ...... page 144 Olmesartan ...... page 152 Sulfamethoxazole/Trimethoprim Omeprazole ...... page 111 (see co-timoxazole) ...... page 125 Ondansetron ...... page 118 Tacrolimus ...... page 156 Oxycodone ...... page 107 Teicoplanin ...... page 124 Pantoprazole ...... page 111 Telmisartan ...... page 152 Paracetamol ...... page 103 Tigecycline ...... page 125 Paricalcitol ...... page 137 Tinzaparin ...... page 117 Pegfilgrastim ...... page 139 Torasemide ...... page 143 Perindopril ...... page 151 Tramadol ...... page 108 Pethidine ...... page 108 Trandolapril ...... page 151 Piperacillin + Tazobactam ... page 126 Valganciclovir ...... page 129 192 Prednisolone ...... page 140 Valsartan ...... page 152 193 Index

Vancomycin ...... page 124 Verapamil ...... page 149

192 193

Combined for effective phosphorus control

Start with OsvaRen®. Stay with OsvaRen®. OsvaRen® combines calcium and magnesium to: • achieve excellent long-term phosphorus control1 • keep calcium levels in the target range2 • reach a protective serum magnesium level3

Literature References 1. Deuber HJ, Long-term ef cacy and safety of an oral phosphate binder containing both calcium acetate and magnesium carbonate in hemodialysis patients. Nieren- und Hochdruck- krankheiten 8: 403–408, 2004 2. De Francisco ALM et al., A controlled randomized comparison of calcium acetate/magnesium carbonate (OsvaRen®) to Sevelamer Hydrochloride (Renagel®) in Haemodialysis Patients: The CALMAG Study. NDT 25: 3707–17, 2010 3. Marzell B et al., Association of serum magnesium with mortality – results from a large European database. Free Communication SuO 008, ERA-EDTA Prague 2011 OsvaRen® abbreviated prescribing information OsvaRen® 435 mg / 235 mg lm-coated tablets. Composition: Each lm-coated tablet contains: Calcium acetate, 435.00 mg equivalent to 110 mg calcium and magnesium carbonate, heavy 235.00 mg equivalent to 60 mg magnesium. Excipients: Tablet core: Starch, pregelatinised, from maize, maize starch, sucrose, gelatine, croscarmellose sodium, magnesium stearate. Film coating: Castor oil, re ned, hypromellose. Indications: Treatment of hyperphosphataemia associated with chronic renal insuf ciency in patients undergoing dialysis (haemodialysis, peritoneal dialysis). Contraindications: OsvaRen® is contraindicated in patients with: Hypophosphataemia, Hypercalcaemia with or without clinical symptoms, e.g. as a result of an overdose of vitamin D, a paraneoplastic syndrome (bronchial carcinoma, breast cancer, renal cell carcinoma, plasmacytoma), bone metastases, sarcoidosis or immobilisation osteoporosis; Elevated serum magnesium levels of more than 2 mmol/l, and/or symptoms of hypermagnesaemia; AV-block III°; Myasthenia gravis; Hypersensitivity to the active substances or to any of the excipients. Side effects: Very common (≥ 1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Gastrointestinal disorders: Common: Soft stools, gastrointestinal irritation like nausea, anorexia, sensation of fullness, belching and constipation, diarrhoea. Metabolism and nutrition disorders: Common: Hypercalcaemia either asymptomatic or symptomatic, asymptomatic hypermagnesaemia. Uncommon: Moderate to severe symptomatic hypercalcaemia, symptomatic hypermagnesaemia. Very rare: Hyperkalaemia, magnesium-induced osteal mineralisation disturbances. Special warning: Contains sodium (not more than 5.6 mg per each lm coated tablet) and sucrose. Read the package lea et before use. Supply classi cation: Prescription only medicine. Fresenius Medical Care Nephrologica Deutschland GmbH. 61346 Bad Homburg v.d.H., Germany. Date: February 2010. The names of this medicinal product in the Member States of the EEA are as follows: B: Renepho, Other countries: OsvaRen®. OsvaRen® has received marketing authorisations in: A, B, CY, CZ, D, DK, E, EST, F, FIN, GB, GR, H, I, IRL, IS, L, LT, LV, M, N, NL, P, PL, S, SK, SLO, SRB (status: February 2010). The registration procedure for other countries is currently in progress.