DOCSLIB.ORG

INTERACTIONS of WARFARIN Olga Řehulková

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
INTERACTIONS of WARFARIN Olga Řehulková Biomed. Papers 145(2), 27–38 (2001) 27 © O. Řehulková INTERACTIONS OF WARFARIN Olga Řehulková Clinical Department of R&D, IVAX-CR a. s., Ostravská 29, 747 70 Opava 9, Czech Republic Received November 9, 2001 Key words: Drug interactions / Warfarin / Oral anticoagulants / Anticoagulant treatment In this article, the author reviews and updates the basis of interactions with warfarin, illustrated with appropri- ate examples. The interactions with drugs, medicinal herbs and foods are summarised. INTRODUCTION have usually been shown to be due to other mecha- nisms5. Anticoagulated patients fed a vitamin K-free Optimum anticoagulant therapy should be aimed at diet developed further prolongation of prothrombin an adequate balance between effective prevention of time, while neomycin given to suppress vitamin K synt- intravascular thrombosis and the production of unwanted hesis by gut bacteria had a little effect on the degree of bleeding. Many factors may affect an individual pa- anticoagulation, suggesting the relative lack of impor- tient’s response to oral anticoagulants, including age, tance of gut bacterial synthesis of vitamin K. This is diet, environmental contaminants and disease status. especially because bacterial synthesis of vitamin K largely Interactions with warfarin are of particular importance takes place in the large bowel, from which absorption is not only because unexpected loss of anticoagulant con- poor6. trol may have serious consequences, but also because Chloramphenicol may alter the effects of warfarin by warfarin offer a useful mechanistic model to study the decreasing vitamin K production by bacteria in the gut, whole topic of interactions. The pharmacodynamics of but other mechanisms such as inhibiting hepatic me- warfarin can be easily and precisely measured, and with tabolism and/or altering the production of prothrombin modern analytical techniques, such as high-pressure li- may be involved7, 8, 9, 10, 11. quid chromatography (HPLC), liquid chromatography- Doxycycline and other tetracyclines, ampicillin, ben- mass spectroscopy (LC-MS), gas liquid chromatography zylpenicillin and aztreonam decrease vitamin K synthesis (GLC) and radioimmunoassay (RIA), the pharmacoki- secondary to alterations in intestinal flora and, there- netics of the drug can be monitored1. fore, may enhance the effect of warfarin4, 12. However, the significant potentiation is very rare if dietary intake of vitamin K is adequate4. DRUG-DRUG INTERACTIONS Cephamandole may enhance the hypoprothrombi- naemic response to warfarin due to interference with A very large number of drug interactions have been vitamin K synthesis in the gastrointestinal tract13, 14 and/ reported with warfarin. Interactions may occur through or with synthesis of vitamin K-dependent clotting fac- changes affecting either the pharmacodynamics or phar- tors4. Related cephalosporines with an N-methylthio- macokinetics of warfarin. Drugs may interact by more tetrazole side chain such as cefmetazole, cefmenoxime, than one mechanism. cefoperazone and latamoxef may be expected to behave similarly, although there appear to be no reports of an 1 Pharmacodynamic drug interactions interaction. Cephazolin, which has similar chain, may enhance the effect of warfarin to some extent14. Warfarin acts by inhibiting the vitamin K1-depen- The interactions caused by interference with the dent γ-carboxylation of clotting factors II (prothrombin), bacterial synthesis of vitamin K in the gastrointestinal VII, IX and X at a postribosomal stage in the liver, tract are generally considered unlikely to be of clinical leading to a build-up of biologically inactive precursor significance except, perhaps, in patients with an inad- clotting proteins2, 3, 4. Pharmacodynamic interactions may equate vitamin K intake12. be a result of a number of different mechanisms. Mineral oils (such as liquid paraffin) may reduce the absorption of vitamin K and enhance the effect of warfa- 1.1 Drugs affecting availability of vitamin K rin, but there is a little evidence that this is clinically Broad-spectrum antibiotics suppress production of important15. Mineral oils might also impair the absorp- vitamin K by the bowel flora and should theoretically tion of warfarin and lessen the effect of the anticoagu- increase the response to warfarin. While certain antibio- lant7, 16, 17. tics may potentiate warfarin action, these interactions 28 O. Řehulková Cholestyramine binds vitamin K in the gut, thus pre- euthyroid due to antithyroid agents may develop marked venting its absorption18. It also decreases the absorption hypoprothrombinemia if the antithyroid medications and may interrupt the enterohepatic recirculation of are ceased and they become thyrotoxic again46. warfarin, resulting in a reduced anticoagulant effect19, 20. The antiepileptic agent valproic acid decreases he- Colestipol does not affect the absorption of warfarin. patic synthesis of procoagulant factors and, therefore, When colestipol is administered with warfarin, no de- may cause an increase in response to warfarin47. pressant effects on blood levels are seen21. The ingestion of large amount of tonic water neces- sitated a reduction in warfarin dosage. The enhanced 1.2 Drugs affecting receptor sensitivity effect was attributed to quinine content in tonic water48. Estrogens increase the synthesis of various clotting The interaction may be explained by decreasing hepatic factors and may thus reduce the effect of anticoagu- synthesis of procoagulant factors with quinine4. lants22, 23. Oral contraceptives increase clotting factor Cyclophosphamide has been associated with an in- concentrations and inhibit warfarin metabolism. The crease in warfarin activity when given with methotrexa- net effect depends on balance between these factors. te and fluorouracil49, but with a decrease when given Oral contraceptives are generally contraindicated in most with non-antineoplastic drugs50. The mechanism of in- patients taking warfarin since they are trombogenic1, 24. teraction lead to enhancement of warfarin effect consist Steroids with anabolic or androgenic properties, such in decreasing hepatic synthesis of procoagulant factors4. as oxymetholone25, 26, 27, stanozolol28, 29 and danazol30, 31, 32, Azathioprine or mercaptopurine (the metabolite may potentiate the action of warfarin allegedly by re- of azathioprine) may reduce the anticoagulant activity ducing clotting factor synthesis. The 17-alpha-alkylated of warfarin51, 52. Mercaptopurine showed to increase pro- steroids appear to be more likely to induce this reaction thrombin synthesis or activation in animal studies53. than the non-substituted steroids25, 26, 27, 33. However, there The antiarrhytmics disopyramide54 and quinidine55 may has been a report of topically applied testosterone, which enhance the effect of warfarin probably by alteration of does not have 17-alpha-alkyl substituent, enhancing war- procoagulant factor synthesis. However, this interaction farin34. does not seem to be consistent56, 57. Diuretics may antagonise the action of warfarin by Glucagon has been shown to increase the hypo- two pharmacodynamic mechanisms18: (a) patients in prothrombinemic effect of warfarin, resulting in bleeding cardiac failure have impaired clotting factor synthesis episodes59. The precise mechanism for this interaction due to hepatic congestion – correction of this state leads is not known, although it may be due to a depression of to increased clotting factor synthesis; (b) diuretics also the production of clotting factors in the liver, or an reduce the plasma volume producing an increased increase in warfarin sensitivity for its receptor site. concentration of clotting factors which may alter the anticoagulant effect of warfarin35. Chlorthalidone36 and 1.3 Drugs affecting haemostasis spironolactone35 have both been associated with a reduc- Any drug that alters platelet function may potentiate tion of warfarin activity probably as a consequence of warfarin action even though the prothrombin time re- diuresis concentrating the circulating clotting factors. mains unchanged1. Aspirin binds irreversibly to the ac- Bumetanide, furosemide and thiazides appear to have no tive site of cyclooxygenase in the prostacyclin synthethase effect on warfarin23. pathway, producing irreversible effects on platelet func- Certain cephalosporines, such as cefotetan, cefaman- tion which persist for the life of the aspirin-treated dole, cefoperazone, or moxalactam may cause marked platelet60, 61. Thus, even small doses of aspirin may affect hypoprothrombinemia and/or prolonged bleeding time haemostasis. Aspirin in high doses has a direct hypo- at concurrent use with warfarin38, 39, 40, 41. The main mecha- prothrombinemic effect62, 63. The dual impairment of nism of interaction consists in decreasing synthesis of haemostasis by the effect of aspirin on platelet activity vitamin K-dependent clotting factors. and by the effect of warfarin on fibrin formation causes Clofibrate may potentiate warfarin action, probably the increased susceptibility to hemorrhagic episodes64. by altering receptor sensitivity23, 37. Although clofibrate Of other salicylates, sodium salicylate, choline salicylate, displaces warfarin from albumin binding sites this does salsalate and magnesium salicylate have little effect on not appear to be a principal mechanism of the interac- platelet function and cause less gastrointestinal erosion tion42. and bleeding65, 66. Drugs altering thyroid function may affect anticoagu- Similar, but usually lesser effects on
Load more

Recommended publications
  • In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction
    In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Sodium Channel Na Channels;Na+ Channels
    Sodium Channel Na channels;Na+ channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na +) through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (Voltage-gated, voltage-sensitive, or voltage-dependent sodium channel also called VGSCs or Nav channel) or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. Voltage-gated Na+ channels can exist in any of three distinct states: deactivated (closed), activated (open), or inactivated (closed). Ligand-gated sodium channels are activated by binding of a ligand instead of a change in membrane potential. www.MedChemExpress.com 1 Sodium Channel Inhibitors & Modulators (+)-Kavain (-)-Sparteine sulfate pentahydrate Cat. No.: HY-B1671 ((-)-Lupinidine (sulfate pentahydrate)) Cat. No.: HY-B1304 Bioactivity: (+)-Kavain, a main kavalactone extracted from Piper Bioactivity: (-)-Sparteine sulfate pentahydrate ((-)-Lupinidine sulfate methysticum, has anticonvulsive properties, attenuating pentahydrate) is a class 1a antiarrhythmic agent and a sodium vascular smooth muscle contraction through interactions with channel blocker. It is an alkaloid, can chelate the bivalents voltage-dependent Na + and Ca 2+ channels [1]. (+)-Kav… calcium and magnesium. Purity: 99.98% Purity: 98.0% Clinical Data: No Development Reported Clinical Data: Launched Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg 50 mg A-803467 Ajmaline Cat. No.: HY-11079 (Cardiorythmine; (+)-Ajmaline) Cat. No.: HY-B1167 Bioactivity: A 803467 is a selective Nav1.8 sodium channel blocker with an Bioactivity: Ajmaline is an alkaloid that is class Ia antiarrhythmic agent.
    [Show full text]
  • 1. Diuretics: Definition, Classification According to the Localization of Action in Nephron, Strength and Speed of Onset and Duration of Effect
    DRUGS AFFECTING THE FUNCTIONS OF EFFECTOR ORGANS AND SYSTEMS LESSON 13. DIURETIC DRUGS Key questions: 1. Diuretics: definition, classification according to the localization of action in nephron, strength and speed of onset and duration of effect. 1.1. Carbonic anhydrase inhibitors (acting on the proximal renal tubules) – acetazolamide. 1.2. Loop diuretics (acting on the ascending part of loop of Henle): furosemide, bumetanide, torasemide. 1.3. Thiazide (hydrochlorothiazide, bendroflumethiazide) and thiazide-like (chlorthalidone, indapamide, xipamid, metolazone) diuretics acting on the initial part of the distal renal tubules. 1.4. Potassium-sparing diuretics (acting on the distal renal tubules and collector renal tubules): sodium channels inhibitors (triamterene, amiloride), aldosterone antagonists (spironolactone, eplerenone). 1.5. Osmotic diuretics (acting on the proximal renal tubules, the descending part of the loop of Henle and collector renal tubules) – mannitol. 1.6. Side effects of diuretics, including water-electrolyte and metabolic disorders. 1.7. Use of diuretics: arterial hypertension, chronic heart failue, edemas, oliguric renal failure, acute intoxications, hyperaldosteronism, glaucoma, etc 1.8. Criteria for diuretics selection: speed of onset and time to maximum diuretic effect; the duration and intensity of the effect; the level of electrolytes and blood coagulation potential; glomerular filtration rate; methods and mechanisms of excretion. 1.9. Combined use of diuretics. Rational combination of different diuretics and diuretics with drugs of other pharmacological groups. 1.10. Absolute contraindications to the use of diuretics 2. Drugs that increase the glomerular filtration: xanthines, cardiac glycosides, dopamine; mechanism of action, clinical use. 3. Uricosuric drugs: indacrinone, ticrynafen (rarely use). 4. Antagonists of the antidiuretic hormone (aquaretics), acting on the collector renal tubules: demeclocycline, conivaptan, tolvaptan 5.
    [Show full text]
  • WO 2013/043925 Al FIG. 14
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/043925 Al 28 March 2013 (28.03.2013) WIPOIPCT (51) International Patent Classification: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, A61K 31/4196 (2006.01) A61K 45/06 (2006.01) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, A61K 31/495 (2006.01) A61P 3/10 (2006.01) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (21) International Application Number: RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, PCT/US2012/056419 TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (22) International Filing Date: ZM, ZW. 20 September 2012 (20.09.2012) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available)·. ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 61/537,411 21 September 2011 (21.09.2011) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (71) Applicant: GIUEAD SCIENCES, INC. [US/US]; 333 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Lakeside Drive, Foster City, California 94404 (US).
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Sodium Channel Na Channels; Na+ Channels
    Sodium Channel Na channels; Na+ channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (Voltage-gated, voltage-sensitive, or voltage-dependent sodium channel also called VGSCs or Nav channel) or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. Voltage-gated Na+ channels can exist in any of three distinct states: deactivated (closed), activated (open), or inactivated (closed). Ligand-gated sodium channels are activated by binding of a ligand instead of a change in membrane potential. www.MedChemExpress.com 1 Sodium Channel Inhibitors, Agonists, Antagonists, Activators & Modulators (+)-Kavain (-)-Sparteine sulfate pentahydrate Cat. No.: HY-B1671 ((-)-Lupinidine sulfate pentahydrate) Cat. No.: HY-B1304 (+)-Kavain, a main kavalactone extracted from Piper (-)-Sparteine sulfate pentahydrate ((-)-Lupinidine methysticum, has anticonvulsive properties, sulfate pentahydrate) is a class 1a antiarrhythmic attenuating vascular smooth muscle contraction agent and a sodium channel blocker. It is an through interactions with voltage-dependent Na+ alkaloid, can chelate the bivalents calcium and and Ca2+ channels. magnesium. Purity: 99.98% Purity: ≥98.0% Clinical Data: Launched Clinical Data: Launched Size: 10 mM × 1 mL, 5 mg, 10 mg Size: 10 mM × 1 mL, 50 mg (Rac)-AMG8379 20(S)-Ginsenoside Rg3 ((Rac)-AMG8380) Cat. No.: HY-108425B (20(S)-Propanaxadiol; S-ginsenoside Rg3) Cat.
    [Show full text]
  • List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify
    List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify, abnormal basal ganglia function, abuse of medicines, Aceperone, Acepromazine, Aceprometazine, Acetildenafil, Aceto phenazine, Acetoxy Dipt, Acetyl morphone, Acetyl propionyl morphine, Acetyl psilocin, Activation syndrome, acute anxiety, acute hypertension, acute panic attacks, Adderall, Addictions to drugs, Addictions to medicines, Addictions to substances, Adrenorphin, Adverse effects of psychoactive drugs, adverse reactions to medicines, aggression, aggressive, aggressiveness, agitated depression, Agitation and restlessness, Aildenafil, Akuammine, alcohol abuse, alcohol addiction, alcohol withdrawl, alcohol-related brain damage, alcohol- related liver damage, alcohol mix with medicines for adverse reaction, Alcoholism, Alfetamine, Alimemazine, Alizapride, Alkyl nitrites, allergic breathing reactions to meds, choking to anaphallectic shock, & death; allergic skin reactions to meds, rash, itchyness, hives, welts, etc, Alletorphine, Almorexant, Alnespirone, Alpha Ethyltryptamine, Alpha Neoendorphin, alterations in brain hormones, alterations in mental status, altered consciousness, altered mind, Altoqualine, Alvimopan, Ambien, Amidephrine, Amidorphin, Amiflamine, Amisulpride, Amphetamines, Amyl nitrite, Anafranil, Analeptic, Anastrozole, Anazocine, Anilopam, Antabuse, anti anxiety meds, anti dopaminergic activity, anti seizure meds, Anti convulsants, Anti depressants, Anti emetics, Anti histamines, anti manic meds, anti parkinsonics, Anti psychotics, Anxiety disorders,
    [Show full text]
  • Summary of Product Characteristics
    Irish Medicines Board Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Phyllocontin Continus 225mg Prolonged -release Tablets 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains Aminophylline Hydrate 225 mg For a full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Film -coated, prolonged -release tablet Product imported from the UK: Pale yellow tablets with the Napp logo marked on one side and SA on the other. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications For the treatment and prophylaxis of bronchospasm and inflammation associated with asthma, emphysema and chronic bronchitis. Also indicated in adults for the treatment of cardiac asthma and left ventricular or congestive cardiac failure. 4.2 Posology and method of administration Route of Administration Oral. The tablets should be swallowed whole and not chewed or crushed. Chewing or crushing may lead to a rapid release of aminophylline with the potential for toxicity. Adults The usual daily dose is two PHYLLOCONTIN CONTINUS tablets 225 mg twice daily following an initial week of therapy on 1 tablet 12 -hourly. Children: The maintenance dose is 12 mg/kg 12 -hourly adjusted to the nearest 225 mg. It is recommended that half the maintenance dose be given for the first week of therapy if the patient has not previously been receiving xanthine preparations. Some children with chronic asthma require and tolerate much higher doses (13 -20 mg/kg twice daily). Lower doses (based on the usual adult dose) may be required by adolescents. Phyllocontin Continus tablets 225 mg are not suitable as a starting dose for children weighing under 40 kg.
    [Show full text]
  • DIGOXIN TABLETS BP 0.25 Mg)
    PACKAGE LEAFLET: INFORMATION FOR THE USER CARDEXIN 0.25 (DIGOXIN TABLETS BP 0.25 mg) Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again. If you have any further questions, please ask your doctor or pharmacist or nurse. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4. In this leaflet: 1. What Digoxin tablets are and what they are used for 2. Before you take Digoxin tablets 3. How to take Digoxin tablets 4. Possible side effects 5. How to store Digoxin tablets 6. Further information 1. What Digoxin tablets are and what they are used for Digoxin belongs to a group of medicines called cardiac glycosides, these slow down the rate of the heart but increase the force with which the heart muscle contracts, making the heart work more efficiently. Digoxin tablets are used to treat: • Heart failure. • Irregular heartbeats or heart rhythm. 2. Before you take Digoxin tablets Do not take Digoxin tablets if you: • are allergic (hypersensitive) to Digoxin tablets, other related medicines such as digitoxin, or any of the ingredients in the tablet (see section 6). An allergic reaction may include a rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue. If this is the first time your doctor has prescribed this medicine for you, tell them if you have taken any cardiac glycoside (such as digoxin, digitoxin) within the last two weeks.
    [Show full text]
  • ‏Summary of Product Characteristics Name Of
    ‏ SUMMARY OF PRODUCT CHARACTERISTICS NAME OF THE MEDICINAL PRODUCT Digoxin KERN PHARMA 0.25 mg tablets QUALITATIVE AND QUANTITATIVE COMPOSITION Digoxin KERN PHARMA 0.25 mg tablets Each tablet contains: Digoxin. 0.25 mg Lactose monohydrate 95.52 mg, maize starch, hydrolysed maize starch, rice starch and other excipients. For a full list of excipients, see section 6.1 PHARMACEUTICAL FORM Digoxin KERN PHARMA 0.25 mg tablets: Round, biconvex, white tablets scored on both sides. The purpose of the score line is to facilitate breaking of the tablet for ease of swallowing or, if necessary, for dividing into equal doses . CLINICAL PARTICULARS: Therapeutic indications Cardiac failure: Digoxin KERN PHARMA is indicated for the treatment of chronic cardiac failure where the principal cause is systolic dysfunction. The greatest therapeutic benefit is achieved in patients with ventricular dilatation. Digoxin KERN PHARMA is specifically indicated where cardiac failure is accompanied by atrial fibrillation. Supraventricular arrhythmias: Digoxin KERN PHARMA is indicated for the treatment of certain supraventricular arrhythmias, particularly atrial fibrillation and flutter, where its principal beneficial effect is to reduce the ventricular rate. Posology and method of administration The dose of Digoxin KERN PHARMA for each patient must be tailored individually according to age, lean body weight, and renal function. The suggested doses are intended only as an initial guide. Adults and children over 10 years: Rapid oral administration: 0.75 to 1.5 mg as a single dose. ‏ In less urgent cases, or when there is a major risk of toxicity, for example in the elderly, the oral loading dose should be administered in divided doses at intervals of 6 hours, with approximately half of the total dose given as the first dose.
    [Show full text]
  • Large-Scale Transcriptional Profiling of Molecular Perturbations Reveals
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.26.268458; this version posted August 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Large-Scale Transcriptional Profiling of Molecular Perturbations Reveals Cell Type 2 Specific Responses and Implications for Environmental Screening 3 4 Kun Zhang,a,b Yanbin Zhaoa,b,1 5 6 a School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 7 Dongchuan Road, Shanghai 200240, China; 8 b Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, China; 9 10 1Corresponding author: 11 Yanbin Zhao 12 Tel.: +86 188 1820 7732; E-mail: [email protected] 13 14 Abstract 15 Cell-based assays represent nearly half of all high-throughput screens currently conducted for 16 risk assessment of environmental chemicals. However, the sensitivity and heterogeneity 17 among cell lines has long been concerned but explored only in a limited manner. Here, we 18 address this question by conducting a large scale transcriptomic analysis of the responses of 19 discrete cell lines to specific small molecules. Our results illustrate heterogeneity of the 20 extent and timing of responses among cell lines. Interestingly, high sensitivity and/or 21 heterogeneity was found to be cell type-specific or universal depending on the different 22 mechanism of actions of the compounds. Our data provide a novel insight into the 23 understanding of cell-small molecule interactions and have substantial implications for the 24 design, execution and interpretation of high-throughput screening assays.
    [Show full text]