Group arrangements: Salford Royal NHS Foundation Trust (SRFT) Pennine Acute Hospitals NHS Trust (PAT)

Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients

with inflammatory dermatoses Lead Author: Dawn Lavery Dermatology Advanced Nurse Practitioner Additional author(s) N/A Division/ Department:: Dermatology, Clinical Support and Tertiary Medicine Applies to: (Please delete) Salford Royal Care Organisation Approving Committee Dermatology clinical governance committee Salford Royal Date approved: 13 February 2019 Expiry date: February 2022 Contents Contents

Section Page Document summary sheet 1 Overview 2 2 Scope & Associated Documents 2 3 Background 3 4 What is new in this version? 3 5 Policy 4 Drugs monitored by nurses 4 Acitretin 7 Alitretinoin Toctino 11 Apremilast 22 Azathioprine 26 Ciclosporin 29 Dapsone 34 Fumaric Acid Esters – Fumaderm and Skilarence 36 Hydroxycarbamide 39 Hydroxychloroquine 43 Methotrexate 50 Mycophenolate moefetil 57

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Standards 67 6 Roles and responsibilities 67 7 Monitoring document effectiveness 67 8 Abbreviations and definitions 68 9 References 68 10 Appendices N/A 11 Document Control Information 71 12 Equality Impact Assessment (EqIA) screening tool 73

Group arrangements: Salford Royal NHS Foundation Trust (SRFT) Pennine Acute Hospitals NHS Trust (PAT)

1. Overview (What is this policy about?)

The dermatology directorate specialist nurses are responsible for ensuring prescribing and monitoring for patients under their care, is in accordance with this protocol.

It is essential that practitioners remember to report (yellow card system) any serious adverse events (SAE) related to the use of systemic therapies.

2. Scope (Where will this document be used?)

Dermatology nurse specialists who are responsible for delivering systemic therapy monitoring clinics for patients who are being prescribed: acitretin, azathioprine, ciclosporin, dapsone, fumaric acid esters, hydroxycarbamide, hydroxychloroquine methotrexate, and mycophenolate mofetil, for the treatment of inflammatory dermatoses.

This protocol may also be of interest to dermatology medical staff.

Associated Documents

 Prescribing by Non-Medical Personnel  Trust Medicines Policy  Trust Medicines Formulary  Trust Health Records Policy  Policy for the Recording of Allergies, Hypersensitivities, Intolerances & ADRs. (“The Allergies Policy”)  Methotrexate - Use of Oral Methotrexate  Understanding Methotrexate  British Association of Dermatologists guidelines for systemic monitoring

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3. Background (Why is this document important?)

The use of systemic therapies in dermatology requires the use of guidelines for drug toxicity monitoring, as adverse effects can be significant in some patients. Most specialists recommend regular safety monitoring of these drugs based on clinical experience and the data from published literature, such as Product Specific Characteristics, the British National Formulary (BNF) and publications from various clinical trials in the specialty literature (refer to British Association of Dermatologists (BAD) web site. The adverse effects of systemic therapies as reported in research trials have limitations, as the patient characteristics are likely to be different from those in daily clinical practice.

Nurse-led drug monitoring clinics within the dermatology centre at Salford Royal NHS Foundation Trust are an innovative approach to improving care delivery and maintaining both a high standard of quality and efficient service. Nurse led clinics have freed up consultant appointments to enable patients to be seen earlier, thus reducing waiting lists. Areas of practice have been identified to enable dermatology nurses to utilise their skills, knowledge and clinical expertise in order to achieve both improvements in a range of outcomes and comparable clinical outcomes to medical colleagues.

The main objective of this protocol is to provide clear information that the responsible specialist nurse can use to ensure systemic therapies may be safely prescribed and monitored. It is expected that the protocol should be viewed with individual drug SPC’s (Summary of Product Characteristics) and together will provide sufficient up-to-date knowledge about the treatments.

This protocol provides an evidence-based approach with appropriate references to all recommendations in terms of predicting, assessing and counteracting any toxic effects related to the use of the systemic therapies in dermatology.

4. What is new in this version?

Updated protocol to include Skilarence.

Updated protocol to include Greater Manchester Medicine Group guidleines / shared care protocols for monitoring systemic therapies in primary care.

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5. Policy

5.1 Subsection

Define situation/condition Drug monitoring by a dermatology specialist nurse, for patients who are prescribed the following systemic agents to manage their skin condition:

 acitretin,  alitretinoin  apremilast  azathioprine  ciclosporin  dapsone  fumaderm and skilarence  hydroxycarbamide  hydroxychloroquine  methotrexate  mycophenolate moefetil

Criteria for inclusion The following are pre-requisites for patients to be referred to the nurse-led drug monitoring clinic:

The patient must:

 Be aged 18 years or older

 Have been referred from a dermatologist to the nurse-led drug monitoring clinic by entry in medical notes, electronic patient records or clinic letter

 Have been prescribed acitretin, alitretinoin, apremilast, azathioprine, ciclosporin, dapsone, fumaderm, hydroxychloroquine, methotrexate or mycophenolate moefetil by a dermatologist to manage their skin condition

 Have had full explanation from the medical staff of the purpose of treatment, the monitoring procedure required and potential adverse side effects. This should be documented in the medical notes or electronic patient records.

 Have had a detailed medical history taken and medical examination where necessary performed by the medical staff

 Have a full list of current medications documented in medical notes or electronic patient records

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 Have been informed by medical staff of all necessary precautions when taking the prescribed treatment.

 Have all preliminary investigations relevant to treatment carried out and documented in the medical notes or electronic patient records

 Have clear documentation of the planned drug dosage regimen and proposed follow up schedule in the medical notes or electronic patient records

 Have a clear plan for obtaining supplies of medications through the hospital pharmacy or their GP until their next medical review appointment

Criteria for exclusion  Unanticipated change in skin condition (e.g. severe flare up, infected, erythrodermic or pustular)  Significant out of range / abnormal changes to biochemical and haematological blood results  Unplanned pregnancy  Development of any new health problems which contraindicate treatment  Uncertainty on the part of the nurse about any side effects of treatment  Patient non-compliance with treatment or follow up arrangements  Overdose of medication

Action if excluded Refer back to dermatologist Action if patient declines Refer back to dermatologist

Characteristics of staff

Qualifications required First level nurse, minimum band 6, with at least 1 year dermatological experience

Additional requirements  Diploma or degree in nursing ( including a portfolio of evidence or working towards qualification)

 Knowledge of the anatomy and physiology of the skin.

 Knowledge of common skin conditions for which treatment is prescribed.

 Knowledge of topical and systemic treatments and side effects

 Knowledge of psychological effects of living with a Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 5 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

skin disease on the patient’s lifestyle

 The nurse must have undertaken a minimum of 3 months dermatology clinics where drug monitoring is undertaken under the supervision of a consultant dermatologist or an experienced highly specialist nurse. This will give the nurse the opportunity to gain knowledge about the management of dermatology patients receiving systemic therapies. The nurse will meet a set of competencies agreed by the supervising consultant dermatologist.

 Nurse led drug monitoring clinic to be run concurrently with the dermatologist clinic so that medical staff are available to provide advice when required Continued training requirements  The nurse will receive clinical supervision by a nominated dermatologist yearly  Maintain membership of the British Dermatological Nursing Group (BDNG)  Maintain a professional portfolio

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Description of treatment and drug monitoring – Refer to BNF or SPC for the most up to date information Description of treatment and drug monitoring – Refer to BNF or SPC for the most up to date information

Acitretin

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Acitretin . Administered orally . Hyperlipidaemia . Exclude pregnancy abdominal pain, diarrhoea, Neotigason . The usual starting before starting (test nausea, vomiting, dryness dose is between . Hepatic impairment for pregnancy within 2 and inflammation of mucous 25mg and 30mg a avoid in severe weeks before membranes, peripheral day for 2- 4 weeks, impairment—risk of treatment and oedema, reversible increase . Lower starting doses further impairment monthly thereafter; in serum-cholesterol and of 10mg daily may start treatment on day serum-triglyceride be appropriate for . Renal impairment 2 or 3 of menstrual concentrations (with high some patients, avoid in severe cycle)—women doses), headache, arthralgia, including those with impairment; increased (including those with myalgia, dryness of darrier’s disease. risk of toxicity history of infertility) conjunctiva (causing . The dose may be should avoid conjunctivitis and decreased altered after 2 to 4 . Pregnancy pregnancy and use tolerance to contact lenses), weeks, depending on avoid—teratogenic; effective alopecia (reversible on patient progress and effective contraception contraception (ideally withdrawal), abnormal hair tolerability. must be used—see 2 methods of texture, skin exfoliation, . The maximum daily Cautions contraception, one of pruritus, epidermal fragility, dose of acitretin is which is a combined sticky skin, dermatitis, 75mg per day. . Breast-feeding hormonal erythema, brittle nails, avoid contraceptive or an paronychia; less commonly intra-uterine device) hepatitis, dizziness, visual for at least 1 month disturbances, before, during, and for photosensitivity; rarely at least 3 years after peripheral neuropathy; very treatment (oral rarely benign intracranial progestogen-only hypertension (discontinue if contraceptives not severe headache, nausea,

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considered effective) vomiting, or visual . avoid concomitant disturbances occur), bone use of keratolytics; pain, exostosis (skeletal . do not donate blood hyperostosis and extra- during and for 2 years osseous calcification reported after stopping therapy following long-term treatment (teratogenic risk); with etretinate, and . check liver function at premature epiphyseal closure start, then every 2–4 in children, see Cautions weeks for first 2 above), night blindness, months and then ulcerative keratitis; also every 3 months; reported taste disturbance, . monitor serum- rectal haemorrhage, flushing, triglyceride and malaise, drowsiness, serum-cholesterol granulomatous lesions, concentrations before impaired hearing, tinnitus, treatment, 1 month initial worsening of psoriasis, after starting, then dry skin, sweating every 3 months; . diabetes (can alter glucose tolerance— initial frequent blood glucose checks); . investigate atypical musculoskeletal symptoms . in children use only in exceptional circumstances and monitor growth parameters and bone development (premature epiphyseal closure

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reported); . avoid excessive exposure to sunlight and unsupervised use of sunlamps;

Drug Interactions  Methotrexate. Increased risk of liver toxicity. Sporadic episodes of toxic hepatitis have been reported following Refer to BNF and SPC the concomitant use of etretinate and methotrexate.(Beck and Foged 1983; Zachariae 1984)  Tetracycline. In some cases with other retinoids, benign intracranial hypertension has been associated with concurrent tetracycline or minocycline administration (Katz HI, et al 1999). In the single reported case of pseudotumor cerebri occurring in a patient on acitretin, however, neither tetracycline nor minocycline was involved (Katz HI, et al 1999)..  Mini-pill. Acitretin decreases the anti-ovulatory effect of the progesterone pill (mini-pill) but has no effect on the combined preparations. (Mancano 2000; Berbis et al. 1988).  Phenytoin. Acitretin partially reduces the protein binding of phenytoin. The clinical significance of this is as yet unknown.  Antidiabetic agents. Increased risk of hypoglycaemia.  Corticosteroids. Increased risk of hyperlipidaemia.  Vitamin A. Intake should not exceed the recommended dietary allowance (2400–3000 IU daily).

Baseline tests  Fasting lipids  Liver Function tests  Glucose for patients with a history of diabetes or glucose intolerance  Creatinine, Urea and Electrolytes  Full blood count  Fasting Lipids  Exclude pregnancy before starting treatment for female patients (child bearing age) . Discuss the importance of pregnancy prevention and pregnancy prevention measures.

Monitoring  The medical staff referring to the clinic should indicate the planned follow-up appointment schedule in the medical notes or electronic patient records.  Patents should be followed up every 2–4 weeks for first 2 months and then every 2 to 3 months  Creatinine, Urea and Electrolytes

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 Blood tests should be performed every 2–4 weeks for first 2 months and then every 2 to 3 months  Liver Function Tests  Blood tests should be performed every 2–4 weeks for first 2 months and then every 2 to 3 months  Elevation of liver enzymes is common, occurring in 20-30% patients.  If abnormal results are obtained, weekly checks should be instituted and acitretin dose adjusted accordingly.  Acitretin should be discontinued if transaminases are elevated to three times their upper normal limit, and patients with bilirubin > 50 lmol L) 1 or alanine amino- transferase > 200 IU L should be referred to gastroenterology. In such cases it is advisable to continue monitoring hepatic function for at least 3 months. However, in those patients where the disease is particularly severe and all else has failed, therapy with acitretin could be continued in consultation with a gastroenterologist and would require a liver biopsy.  Fasting serum cholesterol and triglycerides  Blood test should be repeated every 3 months.  In the presence of a good therapeutic response to acitretin but persistently elevated lipid levels, dietary measures should be introduced before considering a lipid-lowering drug.  Patients with triglycerides > 5 mmol L should be referred to a lipidologist and investigated for other causes of hypertriglyceridaemia (e.g. alcohol, systemic lupus erythematosus, diabetes mellitus, hypo- thyroidism, renal and hepatic problems, hormonal dysfunction etc.).  Hypertriglyceridaemia approaching or over 10 mmol/L) warrants discontinuation of acitretin and urgent referral to a lipidologist, as it is a risk factor for acute pancreatitis.  Glucose  In diabetic patients who are insulin dependent and patients known to have glucose intolerance, Fasting Glucose should be checked prior to treatment and blood tests should be repeated after one month, and then every 3 months.  Patients should be advised to check their capillary glucose more frequently than usual during the first few weeks of treatment.  Radiological investigation  Investigation for skeletal changes need not be done routinely as there is a risk from exposure to radiation, the site of ossification is unpredictable and asymptomatic, and abnormal findings are common in normal individuals. However, targeted X-rays are indicated in patients becoming symptomatic. Pregnancy  Female patients of child bearing age and potential should be monitored every month and pregnancy should be excluded at each visit during treatment. Discuss the importance of pregnancy prevention and pregnancy prevention measures.

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Alitretinoin Toctino Name of medicine Route, dose and Contraindications Cautions Side effects frequency Alitretinoin Toctino . The recommended . Pregnancy is an . Patients should be . Psychiatric disorders start dose for absolute instructed never to Depression, Toctino is 30 mg contraindication to give this medicinal depression . Toctino is indicated once daily. treatment with product to another aggravated, anxiety, for use in adults . A dose reduction to Toctino person and to return aggressive tendencies, who have severe 10 mg once daily . Toctino is any unused capsules mood alterations, chronic hand may be considered contraindicated in to their pharmacist at psychotic symptoms, eczema that is in patients with woman of the end of treatment. and very rarely, unresponsive to unacceptable childbearing potential suicidal ideation, treatment with adverse reactions unless all of the . Patients should not suicide attempts and potent topical to the higher dose. conditions of the donate blood during suicide have been corticosteroids. . A treatment course Pregnancy therapy and for 1 reported in patients . Patients in whom of Toctino may be Prevention month following treated with systemic the eczema has given for 12 to 24 Program are met discontinuation of retinoids, including predominantly weeks depending . Toctino contains Toctino because of alitretinoin. Particular hyperkeratotic on response. soya oil and sorbitol. the potential risk to the care needs to be taken features are more Discontinuation of Patients who are foetus of a pregnant in patients with a likely to respond to therapy should be allergic to peanut, transfusion recipient. history of depression treatment than in considered for soya or with rare and patients on those in whom the patients who still hereditary fructose alitretinoin treatment eczema have severe intolerance should . High risk patients should therefore be predominantly disease after the not take this In patients with observed for signs of presents as initial 12 weeks of medicine. diabetes, obesity, depression and pompholyx treatment. . Toctino is cardiovascular risk referred for appropriate . Toctino should only . In the event of contraindicated in factors or a lipid treatment if necessary. be prescribed by relapse, patients nursing mothers. metabolism disorder However, dermatologists, or may benefit from . Toctino is also undergoing treatment discontinuation of physicians with further treatment contraindicated in with alitretinoin, more alitretinoin may be experience in the courses of Toctino. patients frequent checks of insufficient to alleviate use of systemic . Toctino for women With serum values for lipids symptoms and

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retinoids who have of childbearing hepatic insufficiency and/or blood glucose therefore further full understanding potential should be With severe renal may be necessary. It psychiatric or of the risks of limited to 30 days insufficiency is recommended that psychological systemic retinoid of treatment and With uncontrolled these patients are evaluation may be therapy and continuation of hypercholesterolemia started with 10 mg necessary. monitoring treatment requires With uncontrolled once daily and titrated requirements. a new prescription. hypertriglyceridemia up to the maximum . UV light Ideally, pregnancy With uncontrolled dose of 30 mg if The effects of UV light testing, issuing a hypothyroidism necessary. are enhanced by prescription and With retinoid therapy. dispensing of hypervitaminosis . Sorbitol Therefore patients Toctino should With hypersensitivity Toctino capsules should avoid excessive occur on the same either to alitretinoin, contain sorbitol. exposure to sunlight day. Dispensing of to other retinoids or Patients with rare and the unsupervised Toctino should to any of the hereditary problems of use of sun lamps. occur within a excipients listed in fructose intolerance Where necessary a maximum of 7 days particular in case of should not take this sun-protection product of the prescription. allergies to peanut or medicine. with a high protection . The capsules soya factor of at least SPF should be taken Receiving . Effects on ability to 15 should be used. with a meal once concomitant drive and use daily. treatment with machines . Patients who . Toctino should not tetracyclines (see Decreased night experience dryness of be prescribed if the section 4.5). vision has been the skin and lips patient's eczema reported in patients should be advised to can be adequately treated with alitretinoin use a skin moisturizing controlled by and other retinoids. ointment or cream and standard Patients should be a lip balm. measures, advised of this including skin potential problem and . Musculo-skeletal and protection, warned to be cautious connective tissue avoidance of when driving or disorders allergens and operating machines. Treatment with other irritants, and systemic retinoids has

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treatment with been associated with potent topical bone changes corticosteroids including premature epiphyseal closure, hyperostosis, and calcification of tendons and ligaments.

. Myalgia, arthralgia and increased serum creatinine phosphokinase values have been observed in patients treated with alitretinoin.

. Eye disorders Treatment with alitretinoin has been associated with dry eyes. The symptoms usually resolve after discontinuation of therapy. Dry eyes can be helped by the application of a lubricating eye ointment or by the application of tear replacement therapy. Intolerance to contact lenses may occur which may necessitate the patient to wear

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glasses during treatment.

. Treatment with systemic retinoids has been associated with corneal opacities and keratitis. Decreased night vision has been observed in patients treated with alitretinoin. These effects usually resolve after discontinuation of therapy.

. Patients experiencing visual difficulties should be referred to an ophthalmologist. Withdrawal of alitretinoin may be necessary.

. Benign intracranial hypertension Treatment with systemic retinoids, including alitretinoin, has been associated with the occurrence of benign intracranial hypertension, some of which involved

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concomitant use of tetracyclines Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances and papilloedema. Patients who develop signs of benign intracranial hypertension should discontinue alitretinoin immediately.

. Lipid Metabolism Alitretinoin has been associated with an increase in plasma cholesterol and triglyceride levels. Serum cholesterol and triglycerides (fasting values) should be monitored. Alitretinoin should be discontinued if hypertriglyceridaemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur (see section 4.8). Triglyceride levels in

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excess of 800 mg/dL (9 mmol/L) are sometimes associated with acute pancreatitis, which may be fatal.

. Thyroid function Changes in thyroid function tests have been observed in patients receiving alitretinoin, most often noted as a reversible reduction in thyroid stimulating hormone (TSH) levels and T4 [free thyroxine].

. Hepatobiliary disorders Treatment with other systemic retinoids has been associated with transient and reversible increases in liver transaminases. In the event of persistent clinically relevant elevation of transaminase levels, reduction of the dose or discontinuation of treatment should be considered.

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. Gastrointestinal disorders Systemic retinoids, including alitretinoin, have been associated with inflammatory bowel disease (including regional ileitis) in patients without a history of intestinal disorders. If severe diarrhoea is observed diagnosis of IBD should be considered and alitretinoin should be discontinued immediately.

. Allergic reactions Anaphylactic reactions have been rarely reported in systemic retinoids, in some cases after previous topical exposure to retinoids. Allergic cutaneous reactions are reported infrequently. Serious cases of allergic vasculitis, often with purpura (bruises and

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red patches) of the extremities and extracutaneous involvement have been reported. Severe allergic reactions necessitate interruption of therapy and careful monitoring.

Drug Interactions  Patients should not take vitamin A or other retinoids as concurrent medication due to the risk of Refer to BNF and hypervitaminosis A. SPC  Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of retinoids and tetracyclines. Therefore, concomitant treatment with tetracyclines must be avoided Baseline tests . Alitretinoin is recommended, within its licensed indication, as a treatment option for adults with severe chronic hand eczema that has not responded to potent topical corticosteroids if the person has: •severe disease, as defined by the physician's global assessment (PGA) and •a dermatology life quality index (DLQI) score of 15 or more. . PGA . DLQI . Creatinine, Urea and Electrolytes . Full blood count . Liver function tests . Fasting Lipids . Fasting glucose . Exclude pregnancy before starting treatment for female patients (child bearing age) . Discuss the importance of pregnancy prevention and pregnancy prevention measures.

Monitoring  All Patients should be assessed monthly in clinic whilst therapy is being stabilised.  Female patients of child bearing age should be seen monthly during treatment in line with the pregnancy prevention programme  Monitoring for male patients can then be reduced to 2 to 3 monthly.  Regular monitoring should be continued for the duration of treatment.

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 Creatinine, Urea and Electrolytes  The patient’s serum creatinine and urea and electrolytes should be checked at each monitoring visit  If there is significant deterioration in renal function, or if the creatinine rises above 1.5 times the baseline result, withhold treatment until discussed with dermatologist. The dose of Toctino may need to be reduced.  Full blood count  FBC should be checked at each monitoring visit.  If WBC <3.5 withhold Toctino and discuss with dermatologist  STOP treatment and seek advice if: Hb decreases by 3g/L  If Neutrophils <1.8 withhold and discuss with dermatologist  If platelets < 150 or anaemic, withhold and discuss with dermatologist  If MCV > 105fl inform dermatologist. Investigate by checking TFTs, Vit B12, and folate. Prescribe folate supplementation if deficiency is found.  Liver function tests  LFTS including GGT should be checked at each monitoring visit  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold and discuss with dermatologist  Fasting serum cholesterol and triglycerides  Patients should have fasting lipids checked prior to treatment and blood tests should be repeated after 4 weeks and then every 2 to 3 months.  In the presence of a good therapeutic response but persistently elevated lipid levels, dietary measures should be introduced before considering a lipid-lowering drug.  Patients with triglycerides > 5 mmol L should be referred to a lipidologist and investigated for other causes of hypertriglyceridaemia (e.g. alcohol, systemic lupus erythematosus, diabetes mellitus, hypo- thyroidism, renal and hepatic problems, hormonal dysfunction etc.).  Hypertriglyceridaemia approaching or over 10 mmol/L) warrants discontinuation of treatment and urgent referral to a lipidologist, as it is a risk factor for acute pancreatitis.

 Glucose  In diabetic patients who are insulin dependent and patients known to have glucose intolerance, Fasting Glucose should be checked prior to treatment and blood tests should be repeated after one month, and then every 3 months.  Patients should be advised to check their capillary glucose more frequently than usual during the first few weeks of treatment.

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In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance. Alitretinoin treatment should be stopped:

 as soon as an adequate response (hands clear or almost clear) has been achieved or  if the eczema remains severe (as defined by the PGA) at 12 weeks or  if an adequate response (hands clear or almost clear) has not been achieved by 24 weeks.

Pregnancy Prevention Program This medicinal product is TERATOGENIC. Toctino is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Program are met:  She understands the teratogenic risk.  She understands the need for rigorous follow-up, on a monthly basis.  She understands and accepts the need for effective contraception, without interruption, 1 month before starting treatment, throughout the duration of treatment and 1 month after the end of treatment. At least one and preferably two complementary forms of contraception including a barrier method should be used.  Even if she has amenorrhea she must follow all of the advice on effective contraception.  She should be capable of complying with effective contraceptive measures.  She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy.  She understands the need and accepts to undergo pregnancy testing before, during and 5 weeks after the end of treatment.  She has acknowledged that she has understood the hazards and necessary precautions associated with the use of Toctino.  These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.  The prescriber must ensure that:  The patient complies with the conditions for pregnancy prevention as listed above, including confirmation that she has an adequate level of understanding.  The patient has acknowledged the aforementioned conditions.  The patient has used at least one and preferably two methods of effective contraception including a Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 20 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

barrier method for at least 1 month prior to starting treatment and is continuing to use effective contraception throughout the treatment period and for at least 1 month after cessation of treatment.  Negative pregnancy test results have been obtained before, during and 5 weeks after the end of treatment. The dates and results of pregnancy tests should be documented. Contraception  Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception.  As a minimum requirement, female patients at potential risk of pregnancy must use at least one effective method of contraception. Preferably the patient should use two complementary forms of contraception including a barrier method. Contraception should be continued for at least 1 month after stopping treatment with Toctino, even in patients with amenorrhea. Pregnancy testing  According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL are recommended to be performed in the first 3 days of the menstrual cycle, as follows:  One Month prior to starting therapy  In order to exclude the possibility of pregnancy prior to starting contraception, it is recommended that an initial medically supervised pregnancy test should be performed and its date and result recorded. In patients without regular menses, the timing of this pregnancy test should reflect the sexual activity of the patient and should be undertaken approximately 3 weeks after the patient last had unprotected sexual intercourse. The prescriber should educate the patient about contraception. At the start of therapy  A medically supervised pregnancy test should also be performed during the consultation when Toctino is prescribed or in the 3 days prior to the visit to the prescriber, and should have been delayed until the patient had been using effective contraception for at least 1 month. This test should ensure the patient is not pregnant when she starts treatment with Toctino. Follow-up visits  Follow-up visits should be arranged at 28 day intervals. The need for repeated medically supervised pregnancy tests every month should be determined in consideration amongst other of the patient's sexual activity and recent menstrual history (abnormal menses, missed periods or amenorrhea). Where indicated, follow-up pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber. End of treatment  Five weeks after stopping treatment, women should undergo a final pregnancy test to exclude pregnancy

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Apremilast

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Apremilast Psoriasis Hypersensitivity to the Patients with rare hereditary Very common side effects active substance(s) or to problems of galactose (may affect more than 1 in Otezla is indicated for any of the excipients intolerance, lapp lactase 10 people) the treatment of listed (see BNF) deficiency or glucose- • diarrhoea moderate to severe galactose malabsorption • nausea chronic plaque psoriasis should not take this Common side effects (may in adult patients who Pregnancy medicinal product. affect up to 1 in 10 people) failed to respond to or • cough who have a Otezla should be dose • back pain contraindication to, or Breast-feeding reduced to 30 mg once daily • vomiting are intolerant to other in patients with severe renal • feeling tired systemic therapy impairment • stomach pain including cyclosporine, • loss of appetite methotrexate or Patients who are • frequent bowel movements psoralen and ultraviolet- underweight at the start of • difficulty sleeping (insomnia) A light (PUVA). treatment should have their • indigestion or heartburn body weight monitored • headaches, migraines or The drug is for Oral regularly. In the event of tension headaches administration. unexplained and clinically • upper respiratory tract The film-coated tablets significant weight loss, these infections such as cold, runny should be swallowed patients should be evaluated nose, sinus infection. whole, and can be taken by a medical practitioner and • inflammation and swelling of either with or without discontinuation of treatment the tubes in your lungs food. should be considered (bronchitis). • common cold Day 1 10mg daily (nasopharyngitis) Day 2 10mg BD Uncommon side effects Day 3 20mg am 10mg (may affect up to 1 in 100 pm people) Day 4 20mg Bd • rash Day 5 30mg am 20mg • weight loss Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 22 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

pm • allergic reaction Day 6 30mg Bd Continuing maintenance dose of 30mg Bd

No dose adjustment is needed in patients with mild and moderate renal impairment.

The dose of apremilast should be reduced to 30 mg once daily in patients with severe renal impairment (creatinine clearance of less than 30 mL per minute estimated by the Cockcroft-Gault equation). For initial dose titration in this group, it is recommended that Otezla be titrated using only the AM schedule listed above and the PM doses be skipped Day 1 10mg daily Day 2 10mg daily Day 3 20mg daily Day 4 20mg daily Day 5 30mg daily Day 6 30mg daily Continuing maintenance dose of 30mg daily

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Drug Interactions  rifampicin – an antibiotic used for tuberculosis Refer to BNF and SPC  phenytoin, phenobarbital and carbamazepine - medicines used in the treatment of seizures or epilepsy  St John’s Wort – a herbal medicine for mild anxiety and depression.  Co-administration of strong cytochrome P450 3A4 (CYP3A4) enzyme inducer, rifampicin, resulted in a reduction of systemic exposure of apremilast, which may result in a loss of efficacy of apremilast. Therefore, the use of strong CYP3A4 enzyme inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin and St. John's Wort) with apremilast is not recommended. Co-administration of apremilast with multiple doses of rifampicin resulted in a decrease in apremilast area-under-the-concentration time curve (AUC) and maximum serum concentration (Cmax) by approximately 72% and 43%, respectively. Apremilast exposure is decreased when administered concomitantly with strong inducers of CYP3A4 (e.g. rifampicin) and may result in reduced clinical response.  In clinical studies, apremilast has been administered concomitantly with topical therapy (including corticosteroids, coal tar shampoo and saliycyilic acid scalp preparations) and UVB phototherapy.  There was no clinically meaningful drug-drug interaction between ketoconazole and apremilast. Apremilast can be co-administered with a potent CYP3A4 inhibitor such as ketoconazole.  There was no pharmacokinetic drug-drug interaction between apremilast and methotrexate in psoriatic arthritis patients. Apremilast can be co-administered with methotrexate.  There was no pharmacokinetic drug-drug interaction between apremilast and oral contraceptives containing ethinyl estradiol and norgestimate. Apremilast can be co-administered with oral contraceptives Baseline tests  PASI  DLQI  Weight. Patients who are underweight at the start of treatment should have their body weight monitored regularly. In the event of unexplained and clinically significant weight loss, these patients should be evaluated by a medical practitioner and discontinuation of treatment should be considered.  Urinalysis (check for proteinuria, albumin and blood - vigilance for renal impairment )  Liver Function tests  Creatinine, Urea and Electrolytes  Full blood count  Lipids  Pregnancy should be excluded before treatment can be initiated. Women of childbearing potential should use an effective method of contraception to prevent pregnancy during treatment .

Monitoring  The medical staff referring to the clinic should indicate the planned follow-up appointment schedule in the medical notes or electronic patient records. Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 24 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

 Patents should be followed up 1 month after starting treatment for first 2 months and then every 2-3 months  PASI and DLQI scores should be monitored during treatment to assess treatment efficacy. If there has not been an adequate improvement by week 16 as defined by either :  a 75% reduction in the PASI score from when treatment started (PASI 75) or  a 50% reduction in the PASI score (PASI 50) and a five-point reduction in DLQI from when treatment started. then the dermatologist may consider discontinuation.  Weight. Patients who are underweight at the start of treatment should have their body weight monitored regularly. In the event of unexplained and clinically significant weight loss, these patients should be evaluated by a medical practitioner and discontinuation of treatment should be considered  No routine blood monitoring is recommended by the manufacturer. However as the drug is newly licensed in dermatology routine monitoring is recommended at each visit for:  PASI  DLQI  PGA  Creatinine,  Urea and Electrolytes  Full blood count  Lipids should be checked 3 to 6 monthly  HbA1c should be checked 3 to 6 monthly  Weight (record 3 to 6 monthly )  Urinalysis (record 3 to 6 monthly to check for proteinuria, albumin and blood - vigilance for renal impairment )

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Azathioprine

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Azathioprine . Administered orally . Hypersensitivity to . Thiopurine . Haematological: Leucopenia, swallowed with mercaptopurine methyltransferase anaemia, neutropenia, Azathioprine is plenty of water, or status thrombocytopenia, converted to just after food to . Hepatic impairment . monitor for toxicity macrocytosis, erythroid mercaptopurine, an anti- minimise nausea reduce dose; monitor throughout hypoplasia. metabolite interfering liver function treatment; . Hepatic: Liver dysfunction with nucleic acid . Unlicensed indication . monitor full blood (tends to be dose-related). synthesis, and so acts for Severe refractory . Renal impairment count weekly (more . Gastrointestinal: Nausea, as an eczema reduce dose; frequently with loss of appetite and diarrhoea. immunosuppressant. higher doses or if . Mucocutaneous: Urticaria, . normal or high TPMT . Pregnancy severe hepatic or erythematous pruritus, oral Licensed indications: activity, 1–3 mg/kg treatment should not renal impairment) for ulceration and Systemic lupus daily; generally be initiated first 4 weeks . alopecia. erythematosus; during pregnancy; (manufacturer . Other: Myalgia, arthralgia, Pemphigus vulgaris; . Starting dose 1 advises weekly drug fevers, pancreatitis, Dermatomyositis- mg/kg/day increasing . Breast-feeding monitoring for 8 opportunistic infections and polymyositis. after 4-6 weeks to 2- Present in milk in low weeks but evidence idiosyncratic hypersensitivity 3 mg/kg/day. concentration; no of practical value reactions Time to therapeutic evidence of harm in unsatisfactory), response: . intermediate TPMT small studies—use if . thereafter reduce Approximately 2-3 activity, 0.5–1.5 potential benefit frequency of months mg/kg daily outweighs risk monitoring to at least every 3 months; . reduce dose in elderly; Bone marrow suppression . live vaccinations are contraindicated

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. Patients should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. high fever, infection, inexplicable bruising or bleeding, jaundice Drug Interactions . Allopurinol: Azathioprine dose should be reduced to 25% of the original dose [BNF 2013). Refer to BNF and SPC . Warfarin: Azathioprine inhibits the anticoagulant effects of warfarin [BNF 2013, Cronstein 2004, Rivier et al. 1993.]. Alternatively, consider increasing the dose of warfarin. . Phenytoin, sodium valproate, and carbamazepine: Azathioprine reduces the absorption of these drugs. . Angiotensin-converting enzyme (ACE) inhibitors: Co-prescription of azathioprine may cause anaemia [BNF 2013, Cronstein 2004] (if significant, consider alternative to ACE inhibitor or different systemic agent). . Aminosalicylates i.e. mesalazine, olsalazine, balsalazide or sulfasalazine, may contribute to bone marrow toxicity. . Co-trimoxazole and trimethoprim can cause life threatening haematoxicity [BNF 2013, Cronstein 2004]. . Live vaccines (e.g. oral polio, oral typhoid, MMR, BCG, yellow fever, varicella zoster) should be avoided in patients taking azathioprine. . Sunscreens should be encouraged to reduce sunlight exposure Baseline tests . Creatinine, Urea and Electrolytes . Full blood count . Liver function tests . TPMT Thiopurine S-methyltransferase . Check varicella zoster virus serology in patients with no history of varicella . Hepatitis B & C serology . HIV . Consider Chest x-ray. . Advise on the need for pneumococcal vaccine and a yearly influenza vaccination. . Any pre-malignant disease should be adequately treated before starting therapy . Patients should be up to date with relevant national cancer screening programmes. . Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers and

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remaining vigilant for presence of skin cancers. Monitoring  Patients should have weekly full blood count monitoring performed for the first month of azathioprine therapy every 2 weeks for 1 month and then monthly thereafter.  LFTs and U and E’s should be checked monthly until dose stable, then 3 monthly thereafter.  Once therapy has been stabilised, continuing assessments should be performed at a maximum interval of 3 months.  Full blood count  If WBC <3.5 withhold azathioprine and discuss with dermatologist  If Neutrophils <2.0 withhold azathioprine and discuss with dermatologist  If platelets < 150 or anaemic, withhold azathioprine and discuss with dermatologist  If MCV > 105fl inform dermatologist. Investigate by checking TFTs, Vit B12, folate Prescribe folate supplementation is deficiency is found.

 Creatinine, Urea and Electrolytes  If there is significant deterioration in renal function, or if the creatinine rises above 1.5 times the baseline result, withhold azathioprine until discussed with dermatologist. The dose of azathioprine may need to be reduced.  Liver function tests  LFTS including GGT should be checked monthly until dose stable, then 3 monthly thereafter  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold azathioprine and discuss with dermatologist  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.  Patients who develop rash or oral ulceration, should have their azathioprine withheld and their management should be discussed with a dermatologist  Patients who have abnormal bruising or a sore throat should have their azathioprine withheld until and FBC result is available. Their management should be discussed with a dermatologist  Patients should be up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers and remaining vigilant for presence of skin cancers.

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Ciclosporin Name of medicine Route, dose and Contraindications Cautions Side effects frequency Ciclosporin Administered orally . Contra-indicated in . Monitor kidney Renal: Renal impairment uncontrolled function—dose is a frequent and Ciclosporin: Is an Severe atopic hypertension, dependent increase in potentially serious dose- immunosuppressive dermatitis uncontrolled serum creatinine and dependent complication. agent, originally used . Short-term infections, and urea during first few Evident as reversible to prevent organ graft treatment (usually malignancy; in long- weeks may necessitate serum creatinine rejection, which for max. 8 weeks term management, dose reduction in increases, and exerts its but can be longer perform renal transplant patients necessitates reduction or immunosuppressant under specialist biopsies at yearly (exclude rejection if discontinuation of therapy action directly through supervision) of intervals kidney transplant) or (If serum creatinine effects on T- severe atopic . Use with tacrolimus discontinuation in non- consistently >30% above lymphocytes. dermatitis where specifically contra- transplant patients; patients baseline, conventional indicated; for patients in nephrotic syndrome decrease ciclosporin dose Licensed therapy ineffective other than transplant reduce dose by 25– by 25-50%). Irreversible indications: or inappropriate,. recipients 50% if serum creatinine renal damage may follow Severe atopic . initially 2.5 mg/kg . preferably avoid other more than 30% above long-term treatment at eczema; Severe to 4mg/kg daily in immunosuppressants baseline on more than toxic doses. psoriasis. 2 divided doses, if (increased risk of one measurement good initial infection and In patients with Cardiovascular: Prescribe by brand response not malignancies, nephrotic syndrome and Hypertension; which may Neoral achieved within 2 including lymphoma renal impairment initially require anti-hypertensive Or weeks, increase and skin cancer); 2.5 mg/kg daily therapy or dose reduction Capimune rapidly to max. 5 . Monitor liver function mg/kg daily; Hepatic impairment Mucocutaneous: Important . initial dose of 5 dosage adjustment Hypertrichosis, gingival mg/kg daily in 2 based on bilirubin and hypertrophy, rashes Patients should be divided doses if liver enzymes may be stabilised on a very severe. needed Haematological: particular brand of . Monitor blood Anaemia, leukopaenia,

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oral ciclosporin Severe psoriasis pressure—discontinue if thrombocytopenia because switching . where hypertension develops between formulations conventional that cannot be Gastrointestinal: without close therapy ineffective controlled by Nausea, vomiting, monitoring may lead or inappropriate, antihypertensives; abdominal pain, colitis. to clinically important . initially 2.5 mg/kg . Hyperuricaemia; changes in blood- to 4mg/kg daily in monitor serum Hepatic: ciclosporin 2 divided doses, potassium especially in Hepatic dysfunction, concentration. increased renal dysfunction (risk pancreatitis. Prescribing and gradually to max. of hyperkalaemia); dispensing of 5 mg/kg daily if no . Monitor serum Nervous system: ciclosporin should be improvement magnesium; measure Headaches, tremor, by brand name to within 1 month blood lipids before neuropathy, confusion, avoid inadvertent (discontinue if treatment and after the parasthesia, convulsions, switching response still first month of treatment; fatigue. If it is necessary to insufficient after 6 . avoid excessive switch a patient to a weeks); exposure to UV light, Other: Weight gain, different brand of . initial dose of 5 including sunlight; dysmenorrhea or ciclosporin, the mg/kg daily . Pregnancy amenorrhoea, patient should be justified if rapid crosses placenta; gynaecomastia monitored closely for control is required; . Breast-feeding (particularly when co- changes in blood- present in milk— administered with ciclosporin manufacturer advises avoid spironolactone), concentration, serum hyperkalaemia, creatinine, blood hyperuricaemia, pressure. hypomagnesaemia, hypercholesterolaemia. A rare syndrome of thrombocytopenia in combination with microangiopathic haemolytic anaemia and renal failure.

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Drug Interactions  Diclofenac: Reduce the dose of diclofenac by 50% Refer to BNF and  Colchicine: To be avoided SPC  Simvastatin: maximum dose 10 mg/day  Nifedipine: use with caution  Digoxin: May increase the serum levels of digoxin  St. John’s Wort: decreases ciclosporin activity  Potassium sparing diuretics.  Live vaccines (oral polio, oral typhoid, MMR, BCG, yellow fever, varicella zoster) should be avoided in patients taking ciclosporin.

Baseline tests  Dermatological and physical examination of lymph nodes  Weight to calculate dosage  Blood pressure required at least twice before starting  Renal function measurements, Creatinine and Urea and Electrolytes required at least twice before starting.  Creatinine results should be averaged to establish a baseline and 30% rise above baseline calculated  Full blood count  Fasting Cholesterol/Lipids  Liver function tests  Glucose for patients with a history of diabetes or glucose intolerance  In psoriasis, also exclude malignancies (including those of skin and cervix) before starting (biopsy any lesions not typical of psoriasis)  Treat patients with malignant or pre-malignant conditions of skin only after appropriate treatment (and if no other option)  Check varicella zoster virus serology in patients with no history of varicella  Hepatitis B & C serology  HIV.  Consider CXR.  Advise on the need for pneumococcal vaccine and a yearly influenza vaccination.  Patients should keep up to date with relevant national cancer screening programmes.

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 Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers.

Monitoring  Creatinine, Urea and Electrolytes  Monitor every 2 weeks until dose stable for 3 months then monthly thereafter.  Reduce dose by 25–50% if serum creatinine increases more than 30% above baseline (even if within normal range) and discontinue if reduction not successful within 1 month.  The patient’s serum creatinine must be measured at two weekly intervals during the first 3 months of treatment and every 4 weeks thereafter.  If creatinine rises above 30% baseline, withhold until discussed with dermatologist  If serum creatinine levels are raised by 30% or more from baseline at more than one measurement during therapy then the ciclosporin dose should be reduced.  Should creatinine levels rise more than 50% above baseline, ciclosporin dose should be reduced by 50%. Treatment should be discontinued if elevated serum creatinine levels do not decrease within one month.  If potassium >5.5mmon/l repeat bloods within 1 week. If still raised, withhold ciclosporin and discuss with dermatologist  Blood pressure  Measure at two weekly intervals during the first 3 months of treatment and monthly thereafter.  If a high reading is obtained, the nurse should wait 5 minutes, then repeat the blood pressure recording. Any diastolic reading > 90 mmHg should discussed with a dermatologist  Discontinue if hypertension develops that cannot be controlled by dose reduction or antihypertensive therapy. BP > 140/90 on 2 consecutive readings 2 weeks apart – treat hypertension before stopping ciclosporin (note possible drug interactions).  If BP cannot controlled, stop ciclosporin and obtain BP control before restarting ciclosporin.  Full blood count  FBC should monitored monthly until dose stable and then 3 monthly thereafter.  If platelets < 150 or anaemic, withhold ciclosporin and discuss with dermatologist  Liver function tests  LFTS including GGT should be checked monthly until the dose has been stable for 3 months and then 3 monthly  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold Ciclosporin and discuss with dermatologist  Fasting lipids  Fastining lipids should be checked 6 monthly

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 Those patients who have elevated lipids or who are at risk, e.g. those who have already had a myocardial infarct, or a cerebrovascular accident, should be given dietary advice and, if necessary drugs to reduce lipid levels.  Glucose  Fasting Glucose may be performed monthly in diabetic patients and patients known to have glucose intolerance.

 For patients who are prescribed ciclosporin long term, and who are stabilised on treatment, recommended monitoring intervals can be extended at the discretion of the dermatologist  Avoid excessive exposure to sunlight and avoid use of UVB or PUVA.  In atopic dermatitis, also allow herpes simplex infections to clear before starting (if they occur during treatment withdraw if severe);  Investigate lymphadenopathy that persists despite improvement in atopic dermatitis  Discontinue if lymphoproliferative disorder develops  Action to be taken if monitoring shows abnormalities Withhold Ciclosporin and contact specialist if: • Creatinine increase by > 30% of baseline value • Potassium > 5.5mmol/L • Platelets < 150 x 109/L • AST / ALT > 2 times the upper limit of normal • Blood Pressure > 160/95 (or > 50% of baseline) despite addition of standard antihypertensive therapy • Significant rise in lipids • Oral Ulceration / sore throat • Unexplained rash / abnormal bruising  Patients should keep up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers  Treatment is generally limited to a maximum of 6 months duration where possible.

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Dapsone

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Dapsone For most dermatological . Severe G6PD . cardiac or pulmonary - (dose-related and uncommon disease a typical starting deficiency disease; at doses used for leprosy), dose is 1-2 mg/kg daily . Known sulphone/ . anaemia (treat severe haemolysis, (100-150mg) sulphonamide allergy anaemia before methaemoglobinaemia, Dose should be . Severe anaemia starting); neuropathy, allergic dermatitis adjusted according to . avoid in acute . susceptibility to (rarely including toxic response porphyria haemolysis including epidermal necrolysis and Maintenance doses are . avoid during G6PD deficiency Stevens-Johnson syndrome), usually between 50- pregnancy and anorexia, nausea, vomiting, 200mg/day breast feeding. tachycardia, headache, In dermatitis insomnia, psychosis, hepatitis, herpetiformis, system agranulocytosis; dapsone control may be achieved syndrome (rash with fever and with low doses (eg eosinophilia)—discontinue 25mg/day) once the immediately (may progress to effects of a gluten free exfoliative dermatitis, hepatitis, diet start to work. hypoalbuminaemia, psychosis and death)

Drug Interactions  Probenecid: Excretion of dapsone is reduced and plasma concentrations are increased by concurrent Refer to BNF and SPC administration of probenecid. Rifampicin has been reported to increase the plasma clearance of dapsone.  Trimethoprim: Increased dapsone and trimethoprim concentrations have been reported following concurrent administration in AIDS patients. Baseline tests  Creatinine, Urea and Electrolytes  Full blood count  Liver function tests  Reticulocyte count  Glucose 6-phosphate dehydrogenase G6PD level in those at high risk of deficiency (Mediterranean, African Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 34 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

or Asian ancestry)

Monitoring  Full blood counts, reticulocyte count, renal and liver function tests, should be repeated regularly every week for this first month then monthly for 3 months  Monitoring may be reduced in frequency, based on clinical judgment with due consideration for risk factors including age, co morbidity, renal impairment, etc.  Once established and stabilized on treatment, It is essential that blood tests are repeated at 3 monthly intervals to clinically evaluate and monitor the patient, and prevent toxicity.  Creatinine, Urea and Electrolytes  If there is significant deterioration in renal function, or if the creatinine rises above 1.5 times the baseline result, withhold dapsone until discussed with dermatologist.  Full blood count  FBC should be checked at each monitoring visit.  If Hb drops by 20g/l withhold dapsone and discuss with dermatologist  If WBC <3.5 withhold dapsone and discuss with dermatologist  If Neutrophils <1.8 withhold dapsone and discuss with dermatologist  If platelets < 150 or anaemic, withhold dapsone and discuss with dermatologist  Reticulocyte count  Reticulocyte count should be repeated regularly every week for this first month then monthly for 3 months. Normal range is 50-100  Liver function tests  LFTS including GGT should be checked at each monitoring visit  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold dapsone and discuss with dermatologist  Serum methaemoglobin levels  Should be measured by arterial blood gas analysis, in patients complaining of light headedness, headaches, fatigue or shortness of breath, or bluish lips/fingers  Methaemoglobulinaemia occurs in patients taking more than 100mg per day. Results in bluish lips and fingers. Does not need treatment unless the patient is symptomatic from reduced tissue oxygenation  If the methaemoglobin level is >20% discontinue dapsone. If >30% consider treatment with methylene blue.  It is possible to reduce dapsone induced methaemoglobulinaemia by concurrent administration of cimetidine at a dose of 400mg three times daily (Coleman et al 1990)  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.

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Fumaric Acid Esters – Fumaderm

Name of medicine Route, dose and frequency Contraindications Cautions Side effects Fumaric Acid . Administered orally . Patients with . Patients who are Flushing of the face and a Esters . Fumaric Acid Esters abnormal white prescribed other feeling of warmth (Fumaderm and cell or platelet systemic (symptoms harmless and Fumaderm Skilarence) is normally counts medications for normally improve during Skilarence introduced slowly during psoriasis treatment) the first six weeks of . Patients with . Avoid concomitant treatment. significant renal use with drugs with Headache . There are two strengths of impairment. nephrotoxic potential tablet, Fumaric Acid Esters Indigestion (Fumaderm and . Women who are Skilarence) initial being pregnant/ Women Stomach cramps about one quarter the who are trying to strength of Fumaric Acid conceive Diarrhoea Esters (Fumaderm and Skilarence). . Women who are It is best to take fumaderm . Treatment is started with breastfeeding. at meal times with plenty Fumaric Acid Esters of liquid. If patients do get (Fumaderm and . Patients with Indigestion or diarrhoea, Skilarence) Initial and the active peptic milk products and yoghurt dose is gradually ulceration. can be helpful. Side increased. It is important to effects can be unpleasant follow the instructions . Patients with but tend to improve during carefully to keep the risk of significant current continued treatment. If side effects to a minimum. or previous liver they cause problems, disease, patients should reduce their does by one tablet. . Patients who are Week Tablet Breakfast Lunch Dinner unreliable at A reduction in circulating 1 (Initial - - 1 2 Initial 1 - 1 keeping hospital lymphocyte numbers is appointments. almost universal and Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 36 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

3 Initial 1 1 1 exceeds 50% of baseline 4 120mg - - 1 . Patients with a in about 10% of treated 5 120mg 1 - 1 6 120mg 1 1 1 history of patients (Ockenfels et al malignancy (1998) The normal final dose required is one Fumaric Acid Esters In the past there have tablet three times daily. been case reports of acute Occasionally higher doses renal failure but there has may be required. been no evidence for significant impairment of renal function in more 7 120mg 1 1 2 recent studies using 8 120mg 2 1 2 9 120mg 2 2 2 established treatment protocols. . Two tablets of Fumaric Acid Esters three times Elevation of liver enzymes daily is the maximum dose. . Higher doses not exceeding 360mg three times daily may occasionally be recommended by a dermatologist. Drug Interactions  There are no reported interactions between Fumaric acid esthers with other drugs (Mrowietz et al 1999) Baseline tests . Creatinine, Urea and Electrolytes . Full blood count . Liver function tests . Exclude pregnancy before starting treatment for female patients (child bearing age) . Discuss the importance of pregnancy prevention and pregnancy prevention measures. . Urinalysis to detect proteinuria albumin and blood. Send urine sample off for creatinine and protein and albumin ratio testing . Patients should be up to date with relevant national cancer screening programmes. . Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers

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Monitoring  Patients should be assessed 2-3 weeks after starting Fumaderm or Skilarence . They should be seen at 4 weekly intervals whilst Fumaderm therapy is being stabilised.  Once therapy has been stabilised, continuing assessments may gradually be extended, but should be performed at a minimum interval of 2 to 3 months  Urinalysis (to exclude proteinuria albumin and blood).  Send urine sample off for creatinine and protein and albumin ratio testing.  If urine tests are positive to send MSSU to exclude infection.  If sample is positive for proteinuria albumin or blood on 2 or more occasions, to refer to renal physicians for opinion  Creatinine, Urea and Electrolytes  The patient’s serum creatinine and urea and electrolytes should be checked at each monitoring visit  If there is significant deterioration in renal function, or if the creatinine rises above 1.5 times the baseline result, withhold Fumaderm/Skilarence until discussed with dermatologist. The dose of Fumaderm may need to be reduced.  Full blood count  FBC should be checked at each monitoring visit.  If WBC <3.5 withhold Fumaderm/Skilarence and discuss with dermatologist  If LYMPH count <0.7- STOP Fumaderm/Skilarence and discuss with dermatologist. Repeat blood tests within 1-2 weeks and request a lymphocyte sub section blood test. If the lymph count recovers to 0.7- or greater consider reintroduction of Fumaderm/Skilarence at a lower dose with close monitoring of FBC.  If Neutrophils <1.8 withhold Fumaderm/Skilarence and discuss with dermatologist  If platelets < 150 or anaemic, withhold Fumaderm/Skilarence and discuss with dermatologist  Liver function tests  LFTS including GGT should be checked at each monitoring visit  If there is a 2-fold rise in ALT or ALK. Phos (from upper limit of reference range), or if the patient is jaundiced, withhold Fumaderm/Skilarence and discuss with dermatologist  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.  Patients should keep up to date with relevant national cancer screening programmes.

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Hydroxycarbamide

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Hydroxycarbamide . given orally . Live vaccines . Hepatic impairment Bone marrow suppression should be avoided by . Renal impairment Diarrhoea . Hydroxycarbamide patients receiving Vomiting (Hydroxyurea) is hydroxycarbamide Constipation given as a twice daily . Pregnancy Nausea dose. . Hydroxycarbamide Anorexia may be a potent Alopecia (dose related) . To initiate therapy, mutagenic agent. Generalised Hydroxycarbamide Hydroxycarbamide hyperpigmentation and (Hydroxyurea) is should not be hyperpigmentated nail bands normally prescribed administered to Oral ulceration at a dose of 500mg patients who are Stomatitis twice daily for the pregnant unless the Photosensitivity first four weeks. The benefits outweigh the Onycholisis, onychodystrophy dose may be possible hazards. Palma and planatar increased by 500mg Women of child- keratoderma increments per bearing potential have Hyperuricaemia and gout month up to a to take contraceptive Dysuria and Renal impairment maximum of 2g/day. precautions before the Abnormal liver function tests The daily dose start of and during (elevated bilrubin and should be titrated to treatment with transaminases clinical response, hydroxycarbamide. Flu like Symptoms and bone marrow . If pregnancy still characterised by fever, chills toxicity. occurs during and malaise associated with a treatment the negative infection screen possibility of genetic Xerosis . Elderly patients and consultation should be Non blistering erythema those with renal used. muliforme impairment may be Hydroxycarbamide Drug related Lupus at increased risk of crosses the placenta. Leg ulceration

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toxicity and should . Lactation be started on a lower . As hydroxycarbamide dose of 500mg daily. passes into breast- milk, breast-feeding has to be interrupted . The clinical response before the start of is slow and takes treatment. several weeks, a . Fertility therapeutic trail . Hydroxycarbamide should therefore last may be genotoxic, at least 2 months therefore, if a patient intends to become pregnant after a therapy with hydroxycarbamide a genetic consultation is recommended. . Men under therapy are advised to use safe contraceptive measures during and for at least 3 months after therapy. They should be informed about the possibility of sperm conservation before the start of therapy. Drug Interactions  Didanosine: increased risk of toxicity when hydroxycarbamide given with didanosine—avoid concomitant Refer to BNF and SPC use  Stavudine: Increased risk of toxicity when hydroxycarbamide given with stavudine—avoid concomitant use  Hydroxycarbamide belongs to Cytotoxics and will have the following interaction information:  Clozapine: Avoid concomitant use of cytotoxics with clozapine (increased risk of agranulocytosis)

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Baseline tests  Full blood count  Creatinine, Urea and Electrolytes  Liver function tests  Haematinics (ie ferritin, vit b12, folate) are optional but recommended as their deficiency will be masked by the development of drug induced macrocytosis.  Exclude pregnancy before starting. Discuss the importance of pregnancy prevention and pregnancy prevention measures  Patients should be up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers and remaining vigilant for presence of skin cancers.

Monitoring  It is recommended that patients should have their full blood count, including platelet count and differential white cell count, checked prior to commencing the drug and, at least, weekly intervals for at least the first six weeks. Subsequently, the intervals between haematological assessments may be gradually extended, provided there is no cause for concern.  The maximal interval for blood monitoring should not exceed three months.  Creatinine, Urea and Electrolytes  The patient’s serum creatinine and urea and electrolytes should be checked at each monitoring visit  If there is significant deterioration in renal function, or if the creatinine rises above 1.5 times the baseline result, withhold hydroxycarbamide until discussed with dermatologist. The dose of hydroxycarbamide may need to be reduced.  Full blood count  FBC should be checked at each monitoring visit.  If WBC <3.5 withhold hydroxycarbamide and discuss with dermatologist  If Neutrophils <1.8 withhold hydroxycarbamide and discuss with dermatologist  If platelets < 150 or anaemic, withhold hydroxycarbamide and discuss with dermatologist  If MCV > 105fl inform dermatologist. Investigate by checking TFTs, Vit B12, folate .  If >3g/L drop in HB STOP therapy and discuss with dermatologist  Liver function tests  LFTS including GGT should be checked at each monitoring visit  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold methotrexate and discuss with dermatologist  If there is an unexplained fall in albumin, withhold hydroxycarbamide and discuss with dermatologist  Patients who develop rash or oral ulceration, should have their hydroxycarbamide withheld and their Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 41 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

management should be discussed with a dermatologist  Patients who develop infection, inexplicable bleeding or bruising should have their hydroxycarbamide withheld until a FBC is available and their management should be discussed with a dermatologist.  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.  Patients should keep up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers.

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Hydroxychloroquine

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Hydroxychloroquine 200mg to 400mg per . known hypersensitivity • The occurrence of Mucocutaneous: (Plaquenil) day. to 4-aminoquinoline retinopathy is very Pruritic erythematous macular The minimum compounds uncommon if the rash occurring soon after Hydroxychloroquine: effective dose should recommended daily dose treatment commenced, blue- An anti-malarial drug, be employed. This . pre-existing is not exceeded. The black pigmentation of skin. which is also effective in dose should not maculopathy of the administration of doses in rheumatoid arthritis and exceed eye excess of the Gastrointestinal: systemic lupus 6.5mg/kg/day recommended maximum Nausea, diarrhoea, abdominal erythematosus. Mode of (calculated from . pregnancy is likely to increase the cramps. action may be related to ideal body weight Hydroxychloroquine risk of retinopathy, and inhibition of cellular and not actual body has been used accelerate its onset. Renal: Haematuria, proteinuria enzyme release and weight). relatively safely in which may rarely progress to interference with pregnancy but need to • All patients should have nephrotic syndrome. intracellular function. Initially 400mg daily discuss with an ophthalmological Licensed indications: in divided doses. dermatologist. examination before Ocular: Cycloplegia, i.e active rheumatoid initiating treatment with paralysis of the ciliary muscles arthritis (including The dose can be . lactation Women Plaquenil. Thereafter, (would manifest with focusing juvenile idiopathic reduced to 200mg should not breastfeed ophthalmological difficulty and pupillary arthritis), systemic and when no further whilst on examinations must be dilatation, usually of minimal discoid lupus improvement is hydroxychloroquine. repeated at least every severity), erythematous; evident. 12 months. The keratopathy (reversible even dermatological examination should on continuation of treatment), conditions caused or The maintenance . hepatic or renal include testing visual photophobia (patients should aggravated by sunlight. dose should be impairment acuity, careful be advised to wear sunglasses increased to 400mg ophthalmoscopy, in bright light), irreversible Time to response: daily if the response fundoscopy, central retinopathy (maculopathy), but Approximately 3-6 lessens Relative visual field testing with a no cases of retinopathy found months. contraindications: red target, and colour when treatment for < 10 years In patients with Psoriasis vision. or when dose < 6.5/kg/day porphyria cutanea Pre-existing (Rheum Dis Clin N America.

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tarda, twice weekly maculopathy of the eye This examination should 1994, 20: 243-263). dose may be used Epilepsy be more frequent and G6PD deficiency adapted to the patient in Other: Other rare side-effects Porphyria the following situations: include headache, bleaching of Myesthenia gravis - daily dosage exceeds skin and hair, proximal Elderly 6.5mg/kg lean body myopathy, peripheral weight. Absolute body neuropathy, thrombocytopenia weight used as a guide to and agranulocytosis (very dosage could result in an rare). overdosage in the obese. - renal insufficiency - visual acuity below 6/8 - age above 65 years - cumulative dose more than 200 g.

Plaquenil should be discontinued immediately in any patient who develops a pigmentary abnormality, visual field defect, or any other abnormality not explainable by difficulty in accommodation or presence of corneal opacities. Patients should continue to be observed for possible progression of the changes.

Patients should be advised to stop taking the drug immediately and

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seek the advice of their prescribing doctor if any disturbances of vision are noted, including abnormal colour vision.

Plaquenil should be used with caution in patients taking medicines which may cause adverse ocular or skin reactions. Caution should also be applied when it is used in the following:

• patients with hepatic or renal disease, and in those taking drugs known to affect those organs. Estimation of plasma hydroxychloroquine levels should be undertaken in patients with severely compromised renal or hepatic function and dosage adjusted accordingly.

• patients with severe gastrointestinal, neurological or blood disorders.

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Although the risk of bone marrow depression is low, periodic blood counts are advisable as anaemia, aplastic anaemia, agranulocytosis, a decrease in white blood cells, and thrombocytopenia have been reported. Plaquenil should be discontinued if abnormalities develop.

Caution is also advised in patients with a sensitivity to quinine, those with glucose-6-phosphate dehydrogenase deficiency, those with porphyria cutanea tarda which can be exacerbated by hydroxychloroquine and in patients with psoriasis since it appears to increase the risk of skin reactions.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose

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malabsorption should not take this medicine.

Small children are particularly sensitive to the toxic effects of 4- aminoquinolines; therefore patients should be warned to keep Plaquenil out of the reach of children.

All patients on long-term therapy should undergo periodic examination of skeletal muscle function and tendon reflexes. If weakness occurs, the drug should be withdrawn.

Hydroxychloroquine has been shown to cause severe hypoglycaemia including loss of consciousness that could be life threatening in patients treated with and without antidiabetic medications. Patients treated with hydroxychloroquine should be warned about the risk of hypoglycaemia

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and the associated clinical signs and symptoms. Patients presenting with clinical symptoms suggestive of hypoglycaemia during treatment with hydroxychloroquine should have their blood glucose level checked and treatment reviewed as necessary Drug Interactions  Antacids: reduce absorption of hydroxychloroquine. Avoid administration within 4 hours of dose. Refer to BNF and SPC  Amiodarone, droperidol and moxifloxacin: increased risk of ventricular arrhythmias: avoid concomitant use.  Ciclosporin: possible increase in plasma concentration of ciclosporin.  Digoxin: possible increase in plasma concentration of digoxin.  Mefloquine: increased risk of convulsions.  May enhance the effect of hypoglycaemic agents.

Baseline tests  Visual acuity assessment using the Royal College of Optometrist reading chart  Assessment by optometrist  Full blood count  Creatinine, Urea and Electrolytes  Liver function tests  G6PD (high risk groups).  Exclude pregnancy before starting. Discuss the importance of pregnancy prevention and pregnancy prevention measures. Monitoring  Occular assessment  Annual review by an optometrist  Annual symptom enquiry about visual symptoms  Annual rechecking of visual acuity and assessing for blurred vision using the reading chart provided by The Royal College of Ophthalmologists.  Discuss with ophthalmologist if on treatment for >5 years.

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 Liver function tests  LFTS including GGT should be checked 6 monthly  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold methotrexate and discuss with dermatologist  If there is an unexplained fall in albumin, withhold treatment and discuss with dermatologist  Creatinine, Urea and Electrolytes  The patient’s serum creatinine and urea and electrolytes should be checked 6 monthly  Full blood count  FBC should be checked 6 monthly  If WBC <3.5 withhold hydroxycarbamide and discuss with dermatologist  If Neutrophils <1.8 withhold hydroxycarbamide and discuss with dermatologist  If platelets < 150 or anaemic, withhold hydroxycarbamide and discuss with dermatologist  If MCV > 105fl inform dermatologist. Investigate by checking TFTs, Vit B12, folate .  If >3g/L drop in HB STOP therapy and discuss with dermatologist  Patients who develop rash or oral ulceration, should have their treatment withheld and their management should be discussed with a dermatologist  Patients who develop infection, inexplicable bleeding or bruising should have their treatment withheld until a FBC is available and their management should be discussed with a dermatologist.  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.

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Methotrexate

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Methotrexate . Usually given orally . active infection and . Lower doses should be . Haematological: but may be immunodeficiency used in the frail elderly Neutropenia, A folic acid antagonist administered by the syndromes or if there is significant thrombocytopenia, and its major site of intramuscular or . Hepatic impairment renal impairment. macrocytosis and rarely action is the enzyme subcutaneous route avoid—dose-related . Regular folic acid aplastic anaemia. dihydrofolate reductase. . Methotrexate is toxicity; supplements are Its main therapeutic given as a single . Renal impairment thought to reduce . Hepatic: effect is inhibition of weekly dose. reduce dose; risk of toxicity and a dose of Cirrhosis and fibrosis, risk DNA synthesis but it . A small test dose nephrotoxicity at high 5mg once a day should factors are alcohol abuse, also impairs RNA and (2.5mg – 5mg) is doses; avoid in be prescribed (except obesity and previous liver protein synthesis. It is given to detect severe impairment on day of MTX). disease. Alcoholism is an thus an antimetabolite patients who may be . Pregnancy . Pneumococcal absolute contraindication, cytotoxic agent. unduly sensitive to avoid (teratogenic; vaccination (single but one or two glasses of the drug fertility may be dose) and annual wine or two pints of beer a Important . If the full blood count reduced during influenza vaccine week are permitted. is stable after 7 days, therapy but this may should be given. . Note that the dose is methotrexate is be reversible); Passive immunisation . Gastro-intestinal: Nausea, a weekly dose. continued. 2.5–10 effective should be carried out vomiting, abdominal pain, . To avoid error with mg once weekly, contraception using Varicella zoster constipation and diarrhoea, low dose . Increase dose required during and immunoglobulin (VZIG) flatulence, taste methotrexate, it is according to for at least 3 months in non-immune patients disturbance, gingival recommended that: response in steps of after treatment in if exposed to hyperplasia the patient is 2.5–5 mg at intervals men or chickenpox or shingles. carefully advised of of at least 1 week; women;(Donnenfeld . As there is a potential . Pulmonary: the dose and Subsequent doses et al 1994, increased risk of Pneumonitis is a rare early frequency and the may be gradually Chakravarty et al malignancy, any pre- complication, manifesting reason for taking increased by, usually 2003) malignant disease as a troublesome dry methotrexate and 2.5mg – 5mg steps . Breast-feeding should be adequately cough. If drug not any other prescribed according to clinical discontinue breast- treated before starting discontinued, pneumonitis Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 50 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

medicine (e.g. folic response and any feeding; present in therapy and patients may be followed by acid); accompanying milk should be up to date interstitial fibrosis. The . only one strength of toxicity. with relevant national latter may occur without methotrexate tablet - . usual dose 7.5–15 cancer screening preceding pneumonitis, and 2.5 mg should be mg once weekly; programmes. can be progressive and prescribed and . Max. weekly dose 30 . extreme caution in thus lethal. dispensed; mg; blood disorders (avoid if . the prescription and . Lower doses should severe); . Mucocutaneous: Rashes, the dispensing label be considered for . peptic ulceration, urticaria, erythematous clearly show the frail elderly patients . ulcerative colitis, pruritus, oral ulceration, dose and frequency who often have poor diarrhoea and ulcerative skin pain and alopecia of methotrexate renal function. stomatitis (withdraw if administration; . stop treatment if stomatitis develops— . Renal: Acute tubular . The patient is inadequate response may be first sign of necrosis is a rare warned to report after 3 months at the gastro-intestinal toxicity) complication. Renal immediately the optimum dose; . risk of accumulation in impairment is a relative onset of any feature . If maximum oral pleural effusion or contraindication, but of blood disorders dose is not effective ascites—drain before therapy may still be used if (e.g. sore throat, or causes treatment; serum creatinine is bruising, and mouth intolerance, consider . acute porphyria monitored and dosage ulcers), liver toxicity i.m. or subcutaneous . Blood count adjusted accordingly. (e.g. nausea, route of Bone marrow vomiting, abdominal administration suppression can occur . Other: Headaches, discomfort and dark . before abruptly; factors likely to depression, irritability and urine), and discontinuation of the increase toxicity include enteritis. Opportunistic respiratory effects drug. advanced age, renal infections may occur. (e.g. shortness of . If nausea is a side impairment, and Suppression of ovarian and breath). effect Ondansetron 8 concomitant use with testicular function may mg 2 hours pre another anti-folate drug occur. methotrexate dose (e.g. trimethoprim). and 12 hours post A clinically significant . Temporarily withhold MTX dose is helpful drop in white cell count if patient is systemically or platelet count calls unwell. for immediate

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Prescribe concomitant withdrawal of Folic acid methotrexate and supplementation at a introduction of dose of 5mg daily. supportive therapy Omit dose on . Liver toxicity Liver Methotrexate day if cirrhosis reported. advised by Treatment should not dermatologist. be started or should be discontinued if any abnormality of liver function tests or liver biopsy is present or develops during therapy. Abnormalities can return to normal within 2 weeks after which treatment may be recommenced if judged appropriate . Caution required with patients who drink excessive alcohol. Advise to stay within 4– 6 units / week (Chalmers et al 2005) . Pulmonary toxicity may be a special problem in rheumatoid arthritis. Lung injury in psoriasis or following treatment with methotrexate is rare. If suspected the BSR regimen may be

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followed. (patient to seek medical attention if dyspnoea, cough or fever); monitor for symptoms at each visit—discontinue if pneumonitis suspected. . Aspirin and other NSAIDs. If aspirin or other NSAIDs are given concurrently the dose of methotrexate should be carefully monitored. Patients should be advised to avoid self- medication with over- the-counter aspirin or ibuprofen . Patients receiving methotrexate must not receive immunization with live vaccines. Inactivated polio is available although suboptimal response may be seen. . Annual flu vaccination is recommended. (Saporito and Metenter 2004) . In patients receiving methotrexate exposed to chickenpox or shingles, passive

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immunization should be carried out using VZIG. Drug Interactions  Phenytoin: Antifolate effect of methotrexate is increased. Refer to BNF and SPC  Probenecid, penicillin, NSAIDs: Methotrexate excretion is reduced. (Clinically significant interaction between NSAID and methotrexate is rare).  Tolbutamide: Serum concentration of methotrexate may be increased.  Co-trimoxazole, trimethoprim: Antifolate effect of methotrexate is increased and greatly increases the risk of marrow aplasia.  Live vaccines  Excess alcohol should be avoided (or limit to max. 6 units per week) Baseline tests  Creatinine, Urea and Electrolytes  Full blood count  Liver function tests  Serological markers of fibrosis e.g. Aminoterminal peptide of type 111 procollagen ( P111NP ) (Chalmers et al 2005)  BAD does not recommend routine liver biopsy on all patients receiving methotrexate. However, if there is history of pre-existing liver disease, a baseline ultrasound guided liver biopsy should be performed. This should be undertaken soon after the methotrexate is started, usually within 3–4 months [ Roenigk et al 1998, Kuijpers and Kerkhof 2000)  Chest x-ray or pulmonary function tests may be considered if pre-existing lung disease e.g.asthma  Hepatitis B and C  HIV in high risk patients  Consider VZV serology (if no Hx of varicella).  Provide NPSA shared-care monitoring record booklet.  Patients should be up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers.

Monitoring  Full blood counts, renal and liver function tests, should be repeated regularly every week for the first 4 weeks, every 2 weeks for 1 month, then monthly thereafter for 3 months until stable to clinically evaluate and monitor the patient, and prevent methotrexate toxicity.  Consider increased frequency of monitoring after dose increase.  Monitoring may be reduced in frequency to 3 monthly , based on clinical judgment with due consideration for risk factors including age, comorbidity, renal impairment, etc

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 Creatinine, Urea and Electrolytes  The patient’s serum creatinine and urea and electrolytes should be checked at each monitoring visit  If there is significant deterioration in renal function, or if the creatinine rises above 2 times the baseline result, withhold methotrexate until discussed with dermatologist. The dose of methotrexate may need to be reduced.  Full blood count  FBC should be checked at each monitoring visit.  Withhold oral methotrexate and contact dermatologist if: • WCC < 4 x 109/L • Neutrophils < 2 x 109/L • Platelets < 150 x 109/L or anaemic • If MCV > 105fl inform dermatologist. Investigate by checking TFTs, Vit B12, folate . Increase dose of folic acid to 10mg daily.  Liver function tests  LFTS including GGT should be checked at each monitoring visit  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold methotrexate and discuss with dermatologist. (minor elevations of AST/ALT are common)  If there is an unexplained fall in albumin, withhold methotrexate and discuss with dermatologist  Serological markers of fibrosis e.g. Aminoterminal peptide of type 111 procollagen  Recommended for detection of early liver disease and should be checked every 3 months (Chalmers et al 2005, Boffa et al 1996)  Normal range is: 1.7 to 4.2 ng/ml  (NB. PIIINP may be falsely raised in psoriatic arthritis / other fibrotic disorders)  Consider liver biopsy in adult psoriatic patients on methotrexate if:  Pre treatment >8.0 or  Three samples > 4.2 in a twelve month period or  Two samples > 8 consecutively  Consider withdrawing methotrexate if three samples > 10 in a twelve month period.  If abnormal, discuss with dermatologist. The decision whether to perform liver biopsy, withdraw or continue treatment despite raised PIIINP levels must also take into account other factors, such as disease severity, patient age and the ease with which alternative therapies may be used in place of methotrexate.  Patients who develop rash or oral ulceration, new or increasing dyspnoea or cough should have their methotrexate withheld and their management should be discussed with a dermatologist

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 Patients who develop infection, inexplicable bleeding or bruising should have their Methotrexate withheld until a FBC is available and their management should be discussed with a dermatologist.  Oral methotrexate is a safe and effective medication if taken at the right dose and with appropriate monitoring. However, over the last ten years there have been over a hundred patient safety incidents in England alone including 25 deaths as a result of prescribing, dispensing, administration or monitoring incidents. The National Patient Safety Agency (NPSA) has issued a safety alert concerning the use of oral methotrexate  All patients should be issued with a NPSA monitoring booklet and this should be updated at every visit.  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.  Patients should be up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers.  Methotrexate is teratogenic, so effective contraception is required in women of child-bearing age, or men whose partner is of child-bearing age, and for 6 months afterwards. MTX may result in a reversible decrease in fertility.  Women must not breastfeed while they are taking methotrexate.

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Mycophenolate Mofetil

Name of medicine Route, dose and Contraindications Cautions Side effects frequency Mycophenolate . Administered orally . Hypersensitivity too . full blood counts Common: Mouth ulcers, Mofetil MMF every week for 4 nausea, pruritus and . Mycophenolate . Renal impairment weeks then twice a metallic taste, diarrhoea, Mycophenolate mofetil is given as a no data available in month for 2 months nausea, vomiting, mofetil (MMF) is a twice daily dose. cardiac or hepatic then every month in abdominal cramps and pro-drug of the active transplant patients the first year dyspepsia metabolite of . In dermatological with renal (consider interrupting mycophenolic acid. It diseases, MMF is impairment treatment if Less Common: is a suppressor of T usually added to a . Pregnancy neutropenia Uro-genital: Sterile and B cell proliferation coexisting regimen avoid—congenital develops); haematuria, urinary tract and adhesion and of oral malformations . exclude pregnancy infection, renal tubular inhibits inosine corticosteroids or reported; effective before starting necrosis. monophosphate another contraception treatment; dehydrogenase that immunosuppressive required before . elderly (increased Haematological: eventually blocks the agent, and it is treatment, during risk of infection, Abnormal bruising with or progression to DNA advisable to start at treatment, and for 6 gastro-intestinal without sore throat may synthesis and a relatively low dose weeks after haemorrhage and indicate bone marrow proliferation of 250-500mg bd. discontinuation of pulmonary oedema); failure, Severe rash, treatment; . children (higher leucopaenia (WBC <3.5 Time to response: 6 . If the full blood . manufacturer of incidence of side- and neutrophils <2.0), weeks to 3 months count is stable Myfortic® also effects may call for thrombocytopaenia Mycophenolate advise that men temporary reduction (platelets <120), proteinuria mofetil can be should use of dose or (>300 mg/L) gradually increased condoms during interruption); over the next 1 to 2 treatment and for . active serious gastro- Gastrointestinal: months to 1g bd. 13 weeks after last intestinal disease GI ulceration, bleeding and dose (risk of haemorrhage, perforation; cholestasis; . Once disease . Breast-feeding ulceration and pancreatitis. control is avoid—present in perforation); Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 57 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

established the milk in animal . increased Other: Opportunistic maintenance dose studies susceptibility to skin infections; neurological should be reduced cancer (avoid symptoms; malignancy risk. to the minimum exposure to strong required. sunlight); . Bone marrow suppression Patients should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. infection or inexplicable bruising or bleeding . Patients receiving MMF must not receive immunization with live vaccines. Inactivated polio is available although suboptimal response may be seen. . Annual flu vaccination is recommended. . In patients receiving MMF exposed to chickenpox or shingles, passive immunization should be carried out using VZIG.

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Drug Interactions  Antacids: Containing aluminium and magnesium hydroxide cause a decrease in the absorption of Refer to BNF and MMF by 33% and bioavailability by 17% (Bullingham et al 1996) SPC  Cholestyramine: May decrease the absorption of MMF and bio-availability by 40% (CellCept (mycophenolate mofetil capsules) Product information package insert (June 1995).  Probenecid: Prevents renal tubular secretion and causes an increase in plasma concentration of MMF.  Aciclovir: Causes increase in the concentration of both MMF and aciclovir. However, the increase is significant only in renal impairment.  Rifampicin  Live vaccines (e.g. oral polio, oral typhoid, MMR, BCG, yellow fever, varicella zoster) should be avoided in patients taking MMF Baseline tests . Creatinine, Urea and Electrolytes . Full blood count . Liver function tests . Chest xray . CXR. . Hepatitis B and C, HIV in high risk patients . Consider VZV serology (if no Hx of varicella). . Exclude pregnancy before starting treatment for female patients (child bearing age). Discuss the importance of pregnancy prevention and pregnancy prevention measures. . Advise on the need for pneumococcal vaccine and a yearly influenza vaccination. . Patients should be up to date with relevant national cancer screening programmes. . Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers. Monitoring  Patients should be assessed weekly for the first month in clinic whilst Mycophenolate mofetil therapy is being stabilised. Monitoring should then continue every 2 weeks for 2 months and then monthly thereafter.  Regular monitoring should be continued for the duration of treatment.  Creatinine, Urea and Electrolytes  The patient’s serum creatinine and urea and electrolytes should be checked at each monitoring visit  If there is significant deterioration in renal function, or if the creatinine rises above 1.5 times the baseline result, withhold MMF until discussed with dermatologist. The dose of MMFmay need to be reduced.  Full blood count  FBC should be checked at each monitoring visit. Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 59 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

 If WBC <3.5 withhold MMF and discuss with dermatologist  STOP MMF and seek advice if: Hb decreases by 3g/L  If Neutrophils <2.0 withhold MMF and discuss with dermatologist  If platelets < 150 or anaemic, withhold MMF and discuss with dermatologist  If MCV > 105fl inform dermatologist. Investigate by checking TFTs, Vit B12, folate. Prescribe folate supplementation if deficiency is found.  Liver function tests  LFTS including GGT should be checked at each monitoring visit  If there is a 2-fold rise in ALT or ALK. Phos (from upperlimit of reference range), or if the patient is jaundiced, withhold MMFand discuss with dermatologist  In addition to the above, any rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance.  Patients who have abnormal bruising or a sore throat should have their MMF withheld until a FBC result is available. Their management should be discussed with a dermatologist  Patients should be up to date with relevant national cancer screening programmes.  Give advice on sunscreen and sun avoidance and remaining vigilant for presence of skin cancers.

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Funding arrangements

 The nurse will confirm that funding has been requested for any high cost drugs that are controlled by NICE and agreed by their local Clinical Commissioning Group (written/email confirmation from Performance and Commissioning SRFT required).

Prescribing arrangements

 There should be a clear plan for prescription management and obtaining supplies of medications through SRFT pharmacy or the GP until their next medical review appointment

Nurse led clinic set up

 Following consultation in the dermatology clinic, patients who are being referred to nurse-led drug monitoring clinic will be given a clinical outcome sheet to take to reception so that an appointment can be made for them before they leave the department. Where there is no available appointment for follow up monitoring in the desired timescale, the patient will be booked into a dermatology doctor led clinic of the supervising consultant.

 Patients will be given appointments to attend the nurse-led drug monitoring clinic for 20 to 30 minutes.

 Patients can be seen in the nurse-led clinic for a maximum of 3 consecutive visits without medical review. They should see their supervising consultant at least once per annum.

 Where problems necessitate earlier review, or where patients are experiencing problems request earlier review, this can be arranged either in the nurse-led clinic or dermatologist clinic at the nurse’s discretion.

 The nurse will discuss the problem with the medical staff, before the appointment is arranged or where this is not possible, arrange the appointment and alert them by letter, Actions will be documented in the electronic patient records.

 Any telephone conversation which takes place between the patient and the nurse will be documented in the electronic patient records.

Screening and follow up

 All patients should be screened and followed up and have any necessary screening investigations performed in line with BAD guidelines:

 It is the responsibility of the dermatology medical staff to complete work up for systemic treatment and perform any necessary clinical examinations for patients in line with BAD guidelines. This would include: relevant disease severity assessment scores, DLQI measurements, blood tests, chest x-rays, urinalysis, and physical examinations including hest auscultation for breath and heart sounds Lymph node examination of cervical, supraclavicular, axillary and inguinal nodes, abdominal examination for any masses or hepatosplenomegaly. Full skin examination for malignancies.

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 The nurse should ensure that a detailed medical history is documented to exclude any contraindications. A full list of current medications should be documented. Allergies should be recorded.

 The nurse should ensure that patients have been informed of all necessary precautions when taking biologics

 There should be a clear documentation from the referring dermatologist of the planned drug dosage regimen and proposed follow up schedule in the electronic patient record (EPR).

Patient information

 The nurse must ensure that patients have received a full explanation of the purpose of treatment with systemic therapies, the assessment and monitoring procedures required and potential adverse side effects. This should be documented in the electronic patient record (EPR).

 Written information should be provided (available on the BAD website) and patients given adequate time to consider their decision.

 In clinical circumstances where these therapies are being used outside their licensed indications, it is good clinical practice to obtain informed written consent from the patient

Written/verbal advice for patients who are being prescribed immunosuppressive systemic agents

 Patients should receive influenza vaccine unless there is known hypersensitivity to egg products. They should also receive pneumococcal vaccine on one occasion

 The importance of immediately reporting to us any serious adverse events including  signs or symptoms of: severe infection, warranting a course of treatment with antibiotics or hospitalisation  tuberculosis (e.g. a cough that doesn’t go away, un explained or unintentional weight loss, reduced appetite, fever, extreme tiredness, night sweats),

 The importance of complying with any national cancer screening programmes (e.g. bowel cancer screening, cervical smears and mammograms for females, prostate cancer screening for men). Importance of breast and testicular self-examination.

 The importance of regular skin surveillance to detect skin cancer and reporting any new skin lesions or existing lesions including moles if there is a change in appearance including: Asymmetry, Border, Colour, Diameter, or Elevation or if they start to itch, bleed, scab or are non healing.

 Sun beds and sunbathing should be avoided to reduce the risk of skin cancer. Skin cancer prevention advice should be reinforced including: use of a sunscreen with at least SPF 30 (the higher the better), with good 5 star UVA protection, spending time in the shade between 11am and 3pm, and wearing a T shirt, hat and sunglasses.

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 Avoid live vaccinations such as those for polio, rubella (german measles), BCG, varicella zoster and yellow fever. Live vaccines should be avoided 2 weeks before, during and 6 months after treatment with biologic therapies. ‘Inactivated’ vaccines and flu and pneumococcal vaccinations are safe and recommended.

 Some systemic agents are not licensed in pregnant women or nursing mothers. Patients with child bearing potential need to avoid conception during treatment and for up to 6 months after discontinuation (refer to the Summary of Product Characteristics for exact guidance). Use of appropriate contraception is therefore strongly advised. Some systemic agents may be tetragenic or affect fertility. Male patients should avoid fathering children unless approved by their dermatologist.

 Immunosupressive systemic agents may increase the risk of getting an infection. The importance of having any symptoms of suspected infection assessed promptly to determine if antibiotic treatment is indicated should be discussed. If an infection is diagnosed then patients should temporarily omit their treatment until they have completed any prescribed treatment and then resume treatment once they have recovered from their symptoms. Patients should also advise their dentist that they are being prescribed this treatment.

 The risk of infection may also be increased following a surgical procedure. In the likelihood of any future planned major surgery, a treatment break during the pre and post-operative period is normally advised. As a general rule it takes five half-lives for a product to be completely eliminated from the body. Some studies have used four half-lives to determine the interval prior to surgery for interrupting therapy. The washout periods for interrupting therapy should be based on four to five half-lives:

 The importance of attending for regular follow up should be explained and prescriptions will be withheld for safety reasons, in the event of patients failing to attend monitoring appointments as requested, without prior notification.

 Provide the contact details for the dermatology nurse specialists and advise the patient to contact us in the event of them having any future concerns via the helpline number 0161 206 4080 or by email [email protected].

 The specialist nurse must give the patient information on the risks and benefits of treatment and explain the screening, monitoring and follow up schedule

 The specialist nurse should confirm the patient has understood all information given to them

Follow up procedure

At each follow up visit the nurse will make the following patient assessment and record the following information in the patient’s electronic patient records:

 Date.

 Diagnosis

 Past medical history

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 Allergies

 List of medications including all concomitant medications and any topical therapies. Identify any changes to regimes or new drugs prescribed.

 Present systemic treatment prescribed – dose, frequency, duration.

 Assess patient’s response to treatment and any current problems relating to skin disorder. Use validated assessment tools where appropriate e.g. PASI, DLQI, PGA. If the patient reports any joint problems record a PEST.

 Weigh patients as required and for any BADBIR registered patients

 Waist measurements for any BADBIR registered patients

 Assess patient for any adverse reactions or side effects relating to the medication.

 General health symptom enquiry should be undertaken to detect presence of infection, and malignancy (including skin).

 Any physical clinical examination should be performed by the medical staff in line with BAD guidelines.

 Where significant adverse events are noted, the nurse may instruct the patient at their clinic visit or over the telephone to reduce dosage of medication or to temporarily discontinue medication. In these circumstances the nurse will discuss the patient with the medical staff at the earliest opportunity.

 Assessment of compliance with topical and systemic medication. Provide patient education.

 Remind patients of any necessary precautions relevant to treatment.

 Monitoring and follow up plans should be discussed with the patient. The medical staff referring to the clinic should indicate the planned follow-up appointment schedule in the electronic patient records.

 Regular review of the clinical status of the patient is essential to ensure early detection of adverse effects, particularly infection.

Screening investigations

 Screening investigations should be undertaken for each drug line with BAD guidelines Refer to protocol section “description of treatment and drug monitoring” Screening should include:  Disease specific severity score eg PASI, EASI, UAS7, HS PGA  DLQI  PGA  Height, Weight and Waist measurements

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 Current smoking status Health benefits of smoking cessation/avoidance advised due to increased risk of malignancy when prescribed immunosuppressant treatments.  Current alcohol status Health benefits of restricting alcohol intake advised due to association with skin disease flare ups and increased risk of liver function abnormalities.

Follow up Investigations Follow up investigations should be undertaken for each drug line with BAD guidelines Refer to protocol section “description of treatment and drug monitoring” Monitoring should include:  Disease specific severity score eg PASI EASI UAS7 HS PGA score  DLQI  PGA  Weight and Waist measurements  Current smoking status Health benefits of smoking cessation/avoidance advised due to increased risk of malignancy when prescribed immunosuppressant treatments.  Current alcohol status Health benefits of restricting alcohol intake advised due to association with skin disease flare ups and increased risk of liver function abnormalities.

 Patients will be given blood request forms, and asked to have their bloods checked in the dermatology department, immediately following their consultation. The nurse in clinic will access results of the blood tests via Allscripts Sunrise Enterprise within 48 hours after their appointment

 Any abnormalities will be highlighted and documented in the patient’s electronic patient records. The nurse will take appropriate action dependant on the results. This may involve adjusting dosage of medication, arranging extra blood tests or further investigation, reporting abnormalities immediately to the dermatologist where continuation of treatment may compromise patient safety, or making the patient an urgent appointment to be reviewed in the dermatologist clinic.

 The nurse will contact the patient to discuss any abnormal findings and inform him/her of any subsequent changes to planned treatment or follow up review, in light of blood test results.

 All other monitoring investigations not detailed in this policy are the responsibility of medical staff to arrange where necessary following medical review. Any further tests/investigations requested by the dermatologist, should be documented in the notes by the referring doctor.

Follow up documentation  Document any advice and information sought from dermatologist.

 Document if the patient is referred back earlier than planned to dermatologist for future drug monitoring and the reason why.

 Document if a repeat prescription for systemic therapy is requested from dermatologist or prescribed by the practitioner if he/she is a qualified non medical prescriber. Note the prescription duration.

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 Qualified non-medical prescribers must adhere to the Trust policy and guidelines for prescribing by non-medical personnel if they use their prescribing powers. Clinical management plans must be agreed between the dermatologist, nurse and patient for any medications which are unlicensed.

 Document any changes to biologic or systemic treatment, prescribed medication, dosage and frequency

 Document any suggested changes made to topical treatments by the dermatologist or nurse. If prescriptions are made on a GP management plan, one copy should be given to the patient, and another sent for scanning onto EPR.

 Document number of weeks until the next planned reviewed either by the specialist nurse or dermatologist.

 Offer the patient opportunity to enter relevant research studies such as BADBIR and/or pharmacogenetics.

 Document Signature, designation and contact number.

 Dictate communication letter after each visit for the referring dermatologist and GP.

Handling medication incidents

 Any medication incidents must be reported via the AIR system in accordance with the trust policy for Incident reporting.

 If an non-medical Prescriber suspects that a patient is experiencing/has experienced an adverse drug reaction (ADR) to a medicine or combination of medicines the non-medical prescriber will inform the consultant clinician responsible for the patient’s continuing care.

 The non medical prescriber will evaluate the suspected adverse drug reaction(s) in accordance with the guidance issued by the Committee on Safety of Medicines and decide if he/she needs complete a “Yellow Card” to notify the CSM of a suspected adverse drug reaction. If the decision is made to report via the Yellow Card Scheme it is advisable for the non medical prescribers to inform the Medicines Information Department of the suspected adverse drug reaction (Ext 65223).

 The Non medical prescriber will complete the Trust’s “Adverse Incident” reporting form if the patient has had a significant adverse reaction.

 The incident will be recorded in the patient’s written medical records and Electronic Patient Record using Allscripts Sunrise Enterprise.

 Where appropriate the patient specific CMP should be updated to list the suspected/observed allergy/adverse drug reaction and details documented in accordance with the Trust Policy for the Recording of Allergies, Hypersensitivities, Intolerances & ADRs. (“The Allergies Policy”)

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Did Not Attend Policy

 Where the patient does not attend for monitoring appointments without prior notification, the nurse will contact the patient by letter. If there is a repeated failure to attend (2 visits) the dermatologist should be informed and the General Practitioner should be informed. No further medication should be prescribed until monitoring is resumed

 DNA screening appointment Rebook appointment and send out appointment letter and DNA letter to the patient, GP and dermatologist. If DNA for a second time, alert the referring doctor and make further appointment for the dermatologist clinic.

 DNA follow-up appointment Send standard DNA letter to GP, referring dermatologist and patient . Ask GP to follow-up patient & monitor bloods or ask patient to attend the dermatology department at SRFT. Rebook follow up into the next available follow-up appointment slot If patient repeatedly DNA’s, discuss with referring doctor. The dermatologist and the General Practitioner should be informed.

 No further medication should be prescribed until monitoring is resumed.

GMMMG Approved Shared Care Guidelines for systemic therapy monitoring GMMMG Approved Shared Care Guidelines for systemic therapy monitoring for the following drugs can be found on http://gmmmg.nhs.uk/html/gmmmg_app_scgs.php  Azathioprine  Ciclosporin  Hydroxychloroquine  Methotrexate Prescribing responsibility will only be transferred when: • Treatment is for a specified indication and duration. • Treatment has been initiated and established by the secondary care specialist. They are deemed to be stable when: o Patients on Azathioprine and Methotrexate must have received at least 3 months of therapy AND o Are stabilised on a suitable dose AND o The patient’s blood results have been within acceptable limits AND o Concordance has been established • The patient’s initial reaction to and progress on the drug is satisfactory. • The GP has agreed in writing in each individual case that shared care is appropriate. • The patient’s general physical, mental and social circumstances are such that he/she would benefit from shared care arrangements.

On this page you will find all the shared care protocols that have been approved by the GMMMG. All SCPs have been approved by the Trust Drug and Therapeutics Committee’s and their local CCG.

Shared care protocols that are past their review date or have been superceeded by a new version/change in RAG status can be found on the Shared Care Guideline Archive pages.

Shared Care Protocols with a NEW flag or UPDATED flag may be subject to a lag period to allow for

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commissioning approval and implementation by Trusts/CCGs. Please check with your individual Trust or CCG.

The GMMMG process for Consultants requesting and GPs accepting Individual Patients for Shared Care can be found here

Standard Form of Words for Requesting Shared Care Across Greater Manchester to be inserted in standard clinic/discharge letter from consultant to GP following outpatient or inpatient consultation. Dear Dr [insert Doctors name here]

Patient name: [insert Patients name here] Date of birth: [insert date of birth] NHS Number: [insert NHS Number] Diagnosis: [insert diagnosis here]

As per the agreed Greater Manchester shared care protocol for [insert drug name] for the treatment of [insert indication]this patient is now suitable for prescribing to move to primary care.

This drug has been deemed as appropriate for shared care by the Greater Manchester Medicines Management Group. A copy of the approved shared care protocol for this drug can be found on the GMMMG website at http://gmmmg.nhs.uk/html/gmmmg_app_scgs.php

The patient fulfils criteria for shared care and I am therefore requesting your agreement to participate in shared care. Where baseline investigations are set out in the shared care protocol I have carried these out.

I confirm I have explained to the patient: the risks and benefits of treatment, the baseline tests conducted, the need for monitoring, how monitoring will be arranged, and the roles of the consultant / nurse specialist, GP and the patient in shared care. I confirm the patient has understood and is satisfied with this shared care arrangement at this time.

Treatment was started on [insert date started] [insert dose].

If you are in agreement, please undertake monitoring and treatment from [insert date] NB: date must be at least 1 month from initiation of treatment.

Please could you reply to this request for shared care and initiation of the suggested medication to either accept or decline within 14 days. A form is available on the GMMMG website to facilitate this, if you so wish.

Standard Wording for Requesting Shared Care Across Greater Manchester to be inserted in standard clinic/discharge letter from consultant to GP following outpatient or inpatient consultation can be found here or a form is available here as an editable word document to facilitate this, if you so wish.

Shared Care Agreement Form

Specialist request

*IMPORTANT: ACTION NEEDED

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Dear Dr [insert Doctors name here]

Patient name: [insert Patients name here] Date of birth: [insert date of birth] NHS Number: [insert NHS Number] Diagnosis: [insert diagnosis here]

This patient is suitable for treatment with [insert drug name] for the treatment of [insert indication]

This drug has been accepted for Shared Care according to the enclosed protocol (as agreed by Trust / CCG / GMMMG). I am therefore requesting your agreement to share the care of this patient.

The patient has been fully counselled on the medication.

Treatment was started on [insert date started] [insert dose].

If you are in agreement, please undertake monitoring and treatment from [insert date] NB: date must be at least 1 month from initiation of treatment.

Baseline tests: [insert information]

Next review with this department: [insert date]

You will be sent a written summary within 14 days. The medical staff of the department are available at all times to give you advice. The patient will not be discharged from out-patient follow-up while taking [insert text here].

Please use the reply slip overleaf and return it as soon as possible. Thank you.

Yours

GPs should reply to request for shared care to either accept or decline within 14 days. A form is available online as an editable word document to facilitate this.

Standards

Standards are explicitly stated throughout the policy.

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6. Roles & responsibilities

The dermatology directorate specialist nurses are responsible for ensuring prescribing and monitoring for patients under their care, is in accordance with this protocol.

Patients will be seen in the dermatology nurse led clinic for the purpose of assessing and evaluating their response to various systemic therapies prescribed for specified diagnosed dermatological conditions.

The dermatology directorate specialist nurses have overall responsibility for developing, implementing and monitoring the effectiveness of this policy.

The dermatologists have overall responsibility for monitoring the effectiveness of this policy and recommending any changes to current practice in light of any national developments.

7. Monitoring document effectiveness

This protocol will be reviewed on bi annual basis or in the intervening period if new evidence is published that means an update or revision is necessary.

8. Abbreviations and definitions

AIR = Adverse incident report BADBIR = British Association of Dermatologists Biologics Interventions Registry study BAD = British Association of Dermatologists BNF = British National Formulary CXR = Chest X-ray DLQI = Dermatology life quality index DNA = DID NOT ATTEND EASI = Eczema Area Severity Index score EPR = Electronic patient record FBC = Full blood count LFTs = Liver Function Tests MTX = Methotrexate MMF = Mycophenolate mofetil NPSA = National patient safety agency PASI = Psoriasis area and severity index PIIP = Aminoterminal peptide of type 111 procollagen SAE = serious adverse events SPC’s (Summary of Product Characteristics) TPMT = Thiopurine methyltransferase U and E = Urea and Electrolytes Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 70 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

9. References

British Association of Dermatologists www.bad.org.uk

Beck HI, Foged EK. (1983) Toxic hepatitis due to combination therapy with methotrexate and etretinate in psoriasis. Dermatologica 1983; 167:94–6.

Berbis P, Bun H, Geiger JM et al. (1988) Acitretin (RO10-1670) and oral contraceptives: interaction study. Arch Dermatol Res 1988; 280:388–9.

BNF (2013) British National Formulary. Published jointly by BMJ Group and Pharmaceutical Press, the publishing division of the Royal Pharmaceutical Society. July 2013.

Boffa MJ, Smith A, Chalmers RJ et al. (1996) Serum type III procollagen aminopeptide for assessing liver damage in methotrexate-treated psoriatic patients. Br J Dermatol 1996;135:538– 44.

Bullingham R, Shah J, Goldblum R, Schiff M. Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients Br J Clin Pharmacol 1996;41:513–6.

CellCept (mycophenolate mofetil capsules) Product information package insert (June 1995). New Jersey, USA: Roche Laboratories Inc., 1995.

Chakravarty T, McDonald, H, Pullar,T, Taggart H, Chalmers, RJC, Oliver, RS Mooney, Somerville, M, Bosworth A, Kennedy, T. (2008) on behalf of the British Society for Rheumatology, British Health Professionals in Rheumatology Standards, Guidelines and Audit Working Group in consultation with the British Association of dermatologists BSR/BHPR guideline for disease- modifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of Dermatologists Published by Oxford University Press on behalf of the British Society for Rheumatology.

Chalmers RJG, Kirby B, Smith A et al.(2005) ement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicentre audit and health economic analysis. Br J Dermatol 2005;152:444–50.

Chakravarty EF, Sanchez-Yamamoto D, Bush TM. (2003) The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practice patterns and pregnancy outcomes. J Rheumatol 2003;30:241–6.

Cronstein BN. Pharmacogenetics in the rheumatic diseases. Ann Rheum Dis 2004;63(Supp. 2):ii25–7.

Coleman MD, Scott Ak, breckenidge Am et al (1990) the use of cimetidine as a selective inhibitor of Dapsone hydroxylation in man. Br J Clin Pharacol 1990; 30: 761-767

Department of Health (1999) Making a difference document Strengthening the nursing, midwifery and health visiting contribution to health and health care. Department of Health. London.

Nurse-led drug monitoring clinic protocol for the use of systemic therapies in dermatology for patients with inflammatory dermatoses Reference Number GSCDerm01(13) Version 3 Issue Date: 11/06/2019 Page 71 of 77 It is your responsibility to check on the intranet that this printed copy is the latest version

Department of Health (2000) The NHS Plan : A plan for investment. A plan for reform. Department of Health: London.

Department of Health (2002) Implementing the NHS Plan - ten key roles for nurses. Chief Nursing Officer, Department of Health: London.

Donnenfeld AE, Pastuszak A, Noah JS, Schick B, Rose NC, Koren G. (1994) Methotrexate exposure prior to and during pregnancy. Teratology 1994;49:79–81.

Imuran Summary of product characteristics 25 & 50mg: 23 July and 5 August, Glaxo smith Cline http://emc.medicines.org.uk

Katz HI, Waalen J, Leach EE.(1999) Acitretin in psoriasis: an overview of adverse effects. J Am Acad Dermatol 1999; 41:S7–12.

Kuijpers AL,van de Kerkhof (2000) Risk-benefit assessment of methotrexate in the treatment of severe psoriasis. Am J Clin Dermatol 2000;1:27–39.

Saporito FC, Menter MA. (2004) Methotrexate and psoriasis in the era of new biologic agents. J Am Acad Dermatol 2004;50:301–9.

Meggitt, SJ, AV Anstey, MF Mohd Mustapa, NJ Reynolds and S Wakelin (2011) British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011 BJD Vol. 165, No. 4, October 2011 (p711-734)

Mancano MA.(2000) Drug interactions with oral contraceptives. Pharm Times 2000; 66:26.

Mrowietz U, Chrsitophers E, Atmeyer P (1999) Treatment of sever psoriasis with fumaric acid esthers: scientific background and guidelines for therapeutic use. Br J Dermatol 1998: 141: 424-42

Ockenfels HM, Scultewolter T, Ockenfels G et al (1998) the antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokines network. Br J Dermatol 1998: 139: 390-395

NMC (2002) Code of Professional Conduct t, NMC London

Ormerod,AD, E Campalani and MJD Goodfield, (2010) British Association of Dermatologists' guidelines on the efficacy and use of acitretin in dermatology BJD, Vol. 162, No.5, May 2010 (p952-963)

Rivier G, Khamashta MA, Hughes GR. Warfarin and azathioprine: a drug interaction does exist. Am J Med 1993;95:342.

Roenigk HH Jr, Auerbach R, Maibach H, Weinstein G, Lebwohl M. (1998) Methotrexate in psoriasis: Consensus Conference. J Am Acad Dermatol 1998;38:478–85.

Zachariae H. (1984) Methotrexate and etretinate as concurrent therapies in the treatment of psoriasis. Arch Dermatol 1984; 120:155.

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10. Appendices

 N/A

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11. Document Control Information

All sections must be completed by the author prior to submission for approval

Lead Author: Dawn Lavery Dermatology Advanced Nurse Practitioner Lead author contact 64080 [email protected] details: Consultation Name of person or group Role / Department / Committee (Care Org) Date List the persons or Professor Griffiths Dermatology Consultant groups who have Head of psoriasis clinic team February contributed to this Salford Royal 2019 policy. (please state which Care Organisation)

Endorsement Name of person or group Role / Department / Committee (Care Org) Date List the persons or Dr Emma McMullen Consultant Dermatologist, Dermatology 13 February groups who have clinical director 2019 seen given their Salford Royal support to this policy. Michael Kirk Chair of dermatology clinical governance 13 February (please state which committee 2019 Care Organisation) Salford Royal

Keywords / phrases: Dermatology, Nurse led, Drug monitoring, Systemic therapies, Inflammatory, dermatoses, Acitretin, Apremilast, Allitretinoin, Azathioprine, Ciclosporin, Daposne Fumaderm, Skilarence Hydroxycarbamide, Hydroxychloroquine, Methotrexate, Mycophenolate moefetil Communication The dermatology advanced nurse practitioner will have overall responsibility for plan: writing and updating this policy. The contents of the policy will be disseminated and discussed with the dermatology directorate specialist nurses who undertake drug monitoring clinics.

This policy will be approved by a nominated consultant dermatologist, dermatology clinical director, and the local clinical governance lead.

The dermatology directorate specialist nurses have overall responsibility for implementing and adhering to this policy.

The nurse must have undertaken a minimum of three months dermatology clinics where drug monitoring is undertaken under the supervision of a nominated consultant dermatologist and highly specialist dermatology specialist nurse. This will give the nurse the opportunity to gain knowledge about the management of dermatology patients receiving systemic therapies.

Nurse led Drug Monitoring Clinics are to be run concurrently with the Dermatologist clinic so that medical staff are available to provide advice when required

The use and adherence to this protocol by the dermatology directorate specialist nurses may be subject to an internal audit.

Document review This document will be reviewed by the author, or a nominated person, at least once arrangements: every three years or earlier should a change in legislation, best practice or other change in circumstance dictate.

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This section will be completed following committee approval

Policy Approval: Name of Approving Committee: Dermatology clinical governance committee Salford Royal Chairperson: Michael Kirk Chair of dermatology clinical governance committee Approval date: 13 February 2019

Chairperson’s approval (tick) Formal Committee decision X

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12. Equality Impact Assessment (EqIA) screening tool

Legislation requires that our documents consider the potential to affect groups differently, and eliminate or minimise this where possible. This process helps to reduce health inequalities by identifying where steps can be taken to ensure the same access, experience and outcomes are achieved across all groups of people. This may require you to do things differently for some groups to reduce any potential differences.

1a) Have you undertaken any consultation/ Yes involvement with service users, staff or other Please state: groups in relation to this document? Protocol sent to Dermatology and clinical governance committee for consultation

1b) Have any amendments been made as a No result? Please Comment: 2) Does this policy have the potential to affect any of the groups below differently or negatively? This may be linked to access, how the process/procedure is experienced, and/or intended outcomes. Prompts for consideration are provided, but are not an exhaustive list. Protected Group Yes No Unsure Reasons for decision Age (e.g. are specific age groups excluded? Would the same √ process affect age groups in different ways?) Sex (e.g. is gender neutral language used in the way the policy or √ information leaflet is written?) Race (e.g. any specific needs identified for certain groups such √ as dress, diet, individual care needs? Are interpretation and translation services required and do staff know how to book these?) Religion & Belief (e.g. Jehovah Witness stance on blood √ transfusions; dietary needs that may conflict with medication offered.) Sexual orientation (e.g. is inclusive language used? Are there √ different access/prevalence rates?) Pregnancy & Maternity (e.g. are procedures suitable for √ pregnant and/or breastfeeding women?) Marital status/civil partnership (e.g. would there be any √ difference because the individual is/is not married/in a civil partnership?) Gender Reassignment (e.g. are there particular tests related √ to gender? Is confidentiality of the patient or staff member maintained?) Human Rights (e.g. does it uphold the principles of Fairness, √ Respect, Equality, Dignity and Autonomy?) Carers (e.g. is sufficient notice built in so can take time off work √ to attend appointment?) Socio/economic (e.g. would there be any requirement or √ expectation that may not be able to be met by those on low or limited income, such as costs incurred?) Disability (e.g. are information/questionnaires/consent forms √ available in different formats upon request? Are waiting areas

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suitable?) Includes hearing and/or visual impairments, physical disability, neurodevelopmental impairments e.g. autism, mental health conditions, and long term conditions e.g. cancer. Are there any adjustments that need to be made to √ ensure that people with disabilities have the same access to and outcomes from the service or employment activities as those without disabilities? (e.g. allow extra time for appointments, allow advocates to be present in the room, having access to visual aids, removing requirement to wait in unsuitable environments, etc.) 3) Where you have identified that there are potential differences, what steps have you taken to mitigate these?

4) Where you have identified adjustments would need to be made for those with disabilities, what action has been taken?

5) Where the policy, procedure, guidelines, patient information leaflet or project impacts on patients how have you ensured that you have met the Accessible Information Standard – please state below:

……………………………………………………………………………………………………………… EDI Team/Champion only: does the above ensure compliance with Accessible Information Standard o Yes o No If no what additional mitigation is required:

Will this policy require a full impact assessment? No

Please state your rationale for the decision:

(a full impact assessment will be required if you are unsure of the potential to affect a group differently, or if you believe there is a potential for it to affect a group differently and do not know how to mitigate against this - Please contact the Inclusion and Equality team for advice on [email protected])

Author: Dawn Lavery Date: 13 February 2019

Sign off from Equality Champion: Date:

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