Ciclosporin for Rheumatology and Dermatology use (Adults)

Transcription

1 Shared Care Guideline Ciclosporin for Rheumatology and Dermatology use (Adults) Introduction This shared care agreement outlines the responsibilities between the specialist and the generalist for managing the prescribing of ciclosporin for indications listed below. Indication Rheumatic and connective tissue disease Severe psoriasis in patients in whom conventional therapy is inappropriate or ineffective. Other cutaneous disease Dosage and administration Indications not covered by this shared care guideline: Prevention of graft rejection (see separate shared care guideline from tertiary centre). Endogenous uveitis Nephrotic syndrome For ALL indications patients should remain on the brand initiated and prescribing should be brand specific. Rheumatic and connective tissue disease Initiated at 1-2mg/kg day orally in two divided doses for six weeks (as per the Yorkshire DMARD guidelines).then increase every two weeks by incremental doses of 25mg until clinically effective. Maximum dose should not exceed 4mg/kg/day. If after 3 months of treatment at the maximum permitted or tolerable dose the response is considered inadequate treatment should be discontinued. For maintenance treatment the dose has to be titrated individually according to tolerability. Cutaneous disease The usual dose is 2.5-5mg/kg in 2 divided doses. The daily dose is usually gradually increased but should not exceed 5mg/kg/day. Initial doses of 5mg/kg per day are justified in patients whose condition requires rapid improvement. Administration Ciclosporin should be taken twice daily, every twelve hours. The 100mg capsule is large and patients may prefer to take the 50mg strength. The oral solution (Neoral brand) can be mixed with orange juice (or squash) or apple juice to improve taste, or mixed with water immediately before taking. Rinse the container with juice or water to ensure the total dose is taken. Do not mix with grapefruit juice. The measuring syringe should not be rinsed with water, alcohol or any other liquid. If it is necessary to clean the measuring device, the outside should be wiped with a dry tissue.

2 Due to the oily component of ciclosporin (Neoral) solution adherence to enteral feeding tubes may occur resulting in subtherapeutic doses. Contraindications and cautions Adverse drug reactions Contraindications : Hypersensitivity to ciclosporin or to any of the other excipients Concomitant use of tacrolimus Concomitant use of rosuvastatin (SPC recommendation) or simvastatin (MHRA recommendation Aug 2012) Concomitant use of aliskiren, dabigatran, lercanidipine (BNF advises to avoid) Abnormal renal function Uncontrolled hypertension Infections not under control Malignancy (other than of skin when being used in dermatology) Pregnancy ciclosporin is compatible with pregnancy at the lowest effective dose and mothers should not be discouraged from breast feeding. (from new BSR guidance) Live vaccines (see interactions) For full list see SPC at Many side effects associated with ciclosporin therapy are dosedependent and responsive to dose reduction. Common Nausea, vomiting, abdominal pain, diarrhoea, gingival hyperplasia, tremor, headache, paraesthesia. Hypertension Hypertension (BP >130/>80mmHg) is a commonly encountered adverse effect which the GP will be best placed to monitor and treat. Standard antihypertensives can be used but avoid diltiazem, nicardipine, felodipine and verapamil as they may increase plasma ciclosporin levels. Benign gingival hyperplasia This is relatively common with ciclosporin especially when nifedipine is co-prescribed. Patients should be advised to brush their teeth twice daily. Hirsutism Hirsutism may be a problem, particularly to dark skinned females. Facial hair bleaches and depilatory creams are safe and often effective but electrolysis should be avoided because of infection risk. Headache, tremor, and paraesthesiae These adverse effects are frequently seen. If persistent or severe, they may reflect toxic levels of ciclosporin. In this case, the patient should be referred back to the specialist. Hepatic dysfunction and hyperlipidaemia Hepatic dysfunction and hyperlipidaemia should be routinely monitored for. In the event of increased lipids being found, restriction of dietary fat and, if appropriate, a dose reduction, should be considered. Some statins are contra-indicated with ciclosporin or must be used at a lower dose (see under interactions).ciclosporin may enhance statin myopathy. Nephrotoxicity

3 An acute nephrotoxicity may occur with ciclosporin which is usually identified by serum creatinine monitoring and is reversible by dose reduction. If serum creatinine consistently >30% above patients baseline, decrease ciclosporin dose by 25-50%. A chronic nephrotoxicity may also occur requiring withdrawal of this drug. Cancer risk Like all immunosuppressant s, ciclosporin increases the risk of developing lymphomas and other malignancies, particularly those of the skin. Patients should be advised to avoid excessive exposure to the sun and use high factor sunscreens. For full list see BNF or SPC at Drug Interactions Ciclosporin is metabolised by cytochrome P450 and therefore interacts with many drugs that are also metabolised by this group of liver enzymes. The following drugs /foods increase or reduce ciclosporin levels Interacting drugs Antibiotics - Erythromycin, clarithromycin, azithromycin Calcium channel blockers - Diltiazem, nicardipine verapamil. Lercanidipine(BNF advises to avoid) Antifungals - Fluconazole, itraconazole, ketoconazole Grapefruit juice or fruit Others - metoclopramide, oral contraceptives, danazol, allopurinol, amiodarone, colchicine Rifampicin Antiepileptics Carbamazepine, phenobarbital, phenytoin Anti-obesity - Orlistat St John s Wort Other interacting agents: Effects on ciclosporin blood levels Tacrolimus contraindicated Statins Simvastatin and rosuvastatin are contra-indicated with ciclosporin Atorvastatin should be used at a maximum dose of 10mg daily in combination with ciclosporin Pravastatin can be used to a maximum dose of 40mg daily in combination with ciclosporin NSAIDs and other nephrotoxic drugs (e.g. aminoglycosides,amphotericin B, ciprofloxacin, trimethoprim, methotrexate (unless initiated by consultant team) Diclofenac see above under NSAIDS. In addition always half the dose of diclofenac when ciclosporin is co-prescribed. Potassium-sparing medicines may exacerbate ciclosporin-

4 induced hyperkalaemia and should only be initiated with regular monitoring of U&E s. Live vaccines avoid Digoxin, colchicine ciclosporin may increases levels of these drugs For full list see BNF or SPC at Duration of Treatment Responsibilities of the specialist initiating treatment Long term Dermatology patients: 6 moths to 1 year in majority of patients General: To assess the suitability of the patient for treatment. To ensure that the patient/carer has received counselling and understands the therapy, its benefits, limitations, continued monitoring (where applicable), adverse effects. Inform the GP of the information provided to the patient. To review the patient as agreed intervals and copy all relevant results to the GP Carry out disease and drug monitoring as listed below Formally hand over to GP by letter and patient informed Responsibilities of the General Prescribing: Initiate treatment with ciclosporin. The GPs will be typically asked to take up the monitoring and prescribing of ciclosporin approximately 2 months after it. has been initiated. Disease & drug monitoring: Monitor bloods according to schedule: Blood Baseline pressure Urinalysis FBC U+Es LFTS Urate and lipids 24 hour urine creatinine clearance Blood pressure U+Es FBC LFTS Lipids In Rheumatic and connective tissue disease Serum creatinine needs to be measured at least twice before commencing treatment. In cutaneous disease A dermatological and physical examination including blood pressure and renal function required before starting. Then every 2 weeks until stable dose reached for more than 6 weeks and no change in NSAID therapy (RA patients). After the first month of treatment. Discuss shared care arrangement with patient. Support and advise GPs as required. Assess response to treatment and initiate any dose changes as clinically appropriate including discontinuation of treatment. General and Prescribing: Monitor and prescribe as recommended by the specialist. The

5 Practitioner GPs will be typically asked to take up the monitoring and prescribing of ciclosporin approximately 2 months after it has been initiated or when the patient is on a stable dose. Vaccinations note annual influenza vaccine and single dose pneumococcal vaccine should be offered unless otherwise advised by the specialist. If patients are exposed to chickenpox or shingles, passive immunisation should be carried out using varicella zoster immunoglobulin. Please contact consultant microbiologist for further advice or refer to the green book (chapter 34). Notify specialist if treatment with ciclosporin is discontinued or if unable to take on shared care.. Ensure there are no drug interactions with any other medications initiated in primary care. Prescribe by brand Disease & drug monitoring: Carry out drug monitoring as listed and communicate abnormal results to the specialist. Ensure the correct brand of ciclosporin is prescribed as stated by the prescriber. Urgent drug discontinuation/ referral to specialist as clinically appropriate To stop treatment on the advice of the specialist. To refer back to the specialist if the patient s condition deteriorates. To identify adverse effects if the patient presents with any signs and liaise with the hospital specialist where necessary. To report adverse effects to the specialist and where appropriate to the Commission on Human Medicines/MHRA (Yellow Card scheme). Unless otherwise stated by the secondary care specialist, apply the following monitoring frequencies following handover from secondary care: Blood Monthly for 4 months then every 3 months. pressure U+Es FBC LFTs Lipids At consultations On dose increase at week 2,4, 8 and then every 3 months as above. Every 3 months. If no change at 6 months stop monitoring routinely Ask about oral ulceration, unexplained bruising/ bleeding, rash, sore throat. Discontinue ciclosporin and seek advice from initiating team if: WCC <3.5x10 9 /L Neutrophils <2 x 10 9 /L AST or ALT >3 times upper limit of normal Platelets <140 x10 9 /L

6 Responsibilities of the Patient / Carer: Communication Blood pressure Potassium Creatinine Lipids General : >160/95 or risen >20mmHg (despite the addition of standard antihypertensive therapy. >5.5mmol/l Rises by >30% of baseline on 2 consecutive occasions one week apart. Significant rise Report any possible side effects to their GP, in particular potential signs and symptoms of bone marrow suppression (e.g. unexplained bruising, bleeding, sore throat, infection etc.) Practice safe exposure to the sun Ensure they have adequate supply of medication. Attend appointments including those for drug monitoring. Discuss options if considering pregnancy with GP/specialist To notify the Dr issuing prescriptions (hospital or GP) if wishing to start any new medication purchased over the counter (including herbal remedies) Specialist to GP: The specialist will inform the GP when they have initiated ciclosporin and when there are any subsequent changes in treatment. Inform the GP of the information provided to the patient Ensure that brand of ciclosporin has been communicated with GP GP to Specialist: To inform specialist if not able to take on the monitoring and prescribing Irrespective of whether prescribing responsibility has been accepted or not, inform the consultant of relevant medical information regarding the patient and changes to the patient s medication regime irrespective of indication. Notify specialist if treatment with ciclosporin discontinued. Specialist Contacts Prescribing specialist to be contacted via Hospital switchboard on Medicines Information

7 References British National Formulary on line 30/09/15 Summary of Product Characteristics Accessed 30/09/15 BSR/BHPR guideline for disease-modifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of Dermatologists. Chakravarty K et al. Rheumatology Click here to access Yorkshire Regional Rheumatology DMARD Guidelines, 6 th Edition, revised May Click here to access the DMARD Guidelines