Ciclosporin 25mg, 50mg, 100mg capsules Ciclosporin oral solution 100mg/ml

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1 Shared Care Protocol Ciclosporin for the treatment of rheumatoid arthritis Name of drug, form and strength Background Ciclosporin 25mg, 50mg, 100mg capsules Ciclosporin oral solution 100mg/ml Ciclosporin is a cyclic polypeptide with immunosuppressive properties. Studies suggest that ciclosporin inhibits the development of cell-mediated reactions. It appears to block the resting lymphocytes in the G0 to G1 phase of the cell cycle, and also inhibits lymphokine production and release, including interleukin 2 (Tcell growth factor). The available evidence suggests that ciclosporin acts specifically and reversibly on lymphocytes. It does not depress haemopoeisis and has no effect on the function of phagocytic cells. Response to treatment may take up to 3 months. Patients should be stabilised on a particular brand of oral ciclosporin because switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration. Therapeutic indication Local enhanced services for shared care Dose Rout of administration Duration of The guidance in this document should be read in conjunction with the Summary of product characteristics (SmPC) and current British National Formulary (BNF) Treatment of severe active rheumatoid arthritis. Rheumatoid arthritis Criteria for shared care 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 consultant. The patient s clinical condition is considered to be stable or predictable; have received at least 2 months of treatment and their blood results remain within acceptable limits. The patient s GP has not declined shared care The patient understands shared care and is in agreement that this should proceed For the first 6 weeks of treatment the recommended dose is 3 mg/kg/day orally given in 2 divided doses. If the effect is insufficient, the daily dose may then be increased gradually as tolerability permits, but should not exceed 5 mg/kg/day. To achieve full effectiveness, up to 12 weeks of Ciclosporin therapy may be required. For maintenance treatment the dose has to be titrated individually to the lowest effective level according to tolerability Oral If responding then treatment is usually long term, maybe withdrawn after a

2 treatment prolonged period of disease remission in selected cases at Consultant s discretion (typically at 5 years). Adverse effects Renal dysfunction Hypertension Blood and lymphatic system disorder Hepatobiliary disorders Cautions and contraindications Monitoring requirements Cautions Pregnancy manufacturer advises avoid unless potential benefit outweighs risk. Lactation manufacturer advises avoid present in milk. Elderly increased risk of systolic hypertension or creatinine increases (monitor renal function with particular care). Hyperuricaemia Increased risk of malignancies related to duration and degree of immunosuppression. Can increase risk of hypomagnaesmia and hyperkalaemia. Patients who have no history of exposure to varicella zoster virus (VZV) i.e. chickenpox or herpes zoster (shingles), should avoid contact with individuals with chickenpox or herpes zoster. Varicella zoster immunoglobulin (VZIG) is recommended for individuals who are at increased risk of severe varicella (including patients taking immunosuppressant medicines e.g. azathioprine, ciclosporin, methotrexate, leflunomide) and who have no antibodies to varicella zoster virus and who have significant exposure to chickenpox or herpes zoster. If the patient is infected with VZV, appropriate measures should be taken, which may include antiviral therapy and supportive care. Infections may be more severe, consider early and vigorous treatment. Avoid excessive exposure to UV light, including sunlight (BNF) Contra-indications Uncontrolled hypertension. Uncontrolled infections. Malignancy Abnormal baseline renal function Pre-treatment screening A full blood count, U&Es, creatinine, lipids and LFTs should be carried out at the start of treatment (as a baseline). Blood pressure should be within normal range on two separate occasions prior to treatment Check varicella zoster serology in patients where there is an unclear history of chicken pox or shingles. Ongoing monitoring Full blood count, U&Es, LFTs every 2 weeks for 6 weeks, then monthly for 3 months and every 3 months thereafter. Blood pressure and glucose at each monitoring visit. If subsequent dose increase required or concomitant NSAIDs introduced or increased monitor FBCs, U&Es and LFTs every 2 weeks for six weeks thereafter revert to the previous schedule.

3 Actions to take in the event of abnormal test results or symptoms Lipids every six months Abnormal Full Blood Count result Result White cell count < 3.5 x 10 9 / L Neutrophils > 1.6 but < 2.0 x 10 9 /L Action immediately. nurse specialist. Check trend. Neutrophils < 1.6 x 10 9 /L Platelets >100 but < 150 x 10 9 /L Platelets <100 x 10 9 /L MCV > 105fl Lymphocytes < 0.5 x 10 9 /L Abnormal Liver Function Test >2 fold rise in aspartate transaminase (AST), alanine transaminase (ALT) (from upper limit of reference range) > 3 fold rise in AST, ALT(from upper limit of reference range) Renal function test Creatinine >30% above baseline and/or calculated GFR <60ml/min/1.73m 2 Potassium > 5.5mmol/ L Other Significant rise in fasting lipids High blood pressure >140/90 on two consecutive readings two weeks apart immediately nurse specialist immediately Check B12, folic acid and thyroid stimulating hormone (TSH). Supplement as appropriate or discuss with hospital consultant or specialist nurse. nurse specialist nurse specialist. immediately Repeat in 1 week and if still >30% above baseline withhold and discuss with hospital Withhold ciclosporin until discussed with rheumatology team Withhold ciclosporin until discussed with rheumatology team Treat raised blood pressure before stopping ciclosporin (note interactions with several antihypertensives). If blood pressure cannot be controlled, stop ciclosporin and achieve blood pressure control before restarting ciclosporin. Discuss with rheumatology team.

4 Responsibilities of the hospital Responsibilities of the GP Request shared care with the patient s GP using the mid Essex approved template letter and shared care protocol. Agreement to shared care will be assumed unless GP advises otherwise. Inform the GP after each clinic attendance if there is any change to treatment or monitoring. Inform GP of patients who do not attend clinic appointments. To provide any advice to the patient/carer / GP when requested. Initiate treatment, prescribe and monitor until patient is stable or clinical condition is predictable. Routine clinic follow-up on a regular basis. Send a letter to the GP after each clinic attendance ensuring current dose, most recent blood results and frequency of monitoring are stated. Evaluation of any reported adverse effects by GP or patient. Advise GP on review, duration or discontinuation of treatment where necessary. Ensure that backup advice is available at all times. Agreement to shared care protocol Report any adverse events to the hospital specialist, where appropriate. Request advice from the hospital specialist when necessary. Monitor patient s overall health and well-being. Prescribe the drug treatment as described. To carry out blood test and monitor patients as detailed in the shared care protocol FBC Every 3 months LFTs ESR and CRP Every 6 months U&Es and creatinine Every 3 months Blood lipids Every 6 months Clinically important drug interactions Other information Contact information Help in monitoring the progression of disease. Prompt referral to specialist if there is any change in patient s status. NSAIDs; particular caution with concomitant NSAIDs, especially diclofenac, closely monitor renal function if NSAID is introduced or dose increased. Statins; avoid simvastatin and rosuvastatin. Adjust dose of atorvastatin to maximum dose of 10mg daily if concomitant use is unavoidable. Avoid grapefruit and grapefruit juice. Live vaccines; avoid due to increased risk of infection when given with ciclosporin Colchicine; avoid or adjust colchicine dose. Concurrent infection During a serious infection i.e. hospitalisation or requiring antibiotics, ciclosporin should be temporarily discontinued until the patient has recovered from the infection. Consider restarting ciclosporin one week after stopping antibiotic treatment. Consultant (direct line for urgent queries): (to be included on clinic letter) Secretaries: Clinical Nurse specialists:

5 Title Document reference Author Ciclosporin in Rheumatoid Arthritis Shared Care Protocol CiclosporinRheumSC PRO201810V3.0 final Stella Muorah, Senior Interface Pharmacist, MECCG Clare Drain, Medicines Information Manager, MEHT Consulted with Approved by Dr Emese Balogh, Consultant Rheumatologist, MEHT Mid Essex Area Prescribing Committee Date approved January 2019 Next review date January 2021 Previous version CiclosporinRheumatologyGUI v2.0FINAL Key changes New template. Additional information regarding adverse effect, contraindication and drug interaction added. Reference abnormal biochemistry results updated.

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