North Derbyshire Health Prescribing and New Technologies Strategy Group (Pants) And

SHARED CARE AGREEMENT LEFLUNOMIDE TABLETS

This document should be read in conjunction with the current SPC.

1. REFERRAL CRITERIA  Shared Care is only appropriate if it provides the optimum solution for the patient.  Prescribing responsibility will only be transferred when it is agreed by the consultant and the patient’s GP. This agreement is reached by the GP completing and returning the form provided.  When transfer agreed the patient will be issued with four weeks supply.

2. AREAS OF RESPONSIBILITY

GP responsibilities Consultant responsibilities a) Respond promptly to the shared care request. a) Discuss diagnosis, treatment options and b) Monitor the patient’s overall health and well- agree care package with patient. being and ensure compatibility with other b) Discuss potential benefits and adverse concomitant medication. effects of proposed treatment and ensure c) Arrange on-going monitoring as agreed with the compatibility with other concomitant specialist. medication. d) Raise any concerns or changes in the patients’ c) Undertake baseline tests FBC, U&E, physical health with the specialist. creatinine, LFTs, body weight and BP. e) Re-affirm the use of contraception. d) Provide baseline test results. f) Monitor U&E, FBC, LFTs and BP at e) Treat hypertension if required before recommended frequencies and refer to initiation. specialist if abnormal. f) Exclude pregnancy before commencement, g) Update ‘Patient Record Booklet’ issued by advise and document that adequate specialist. precautions are used. h) Provide prescription of Leflunomide after g) Prescribe Leflunomide until patient achievement of a stable dose regime by monitoring is stable, and then provide a four secondary care. week maintenance prescription. i) Stop treatment on the advice of the specialist or h) Request shared care via clinic letter immediately if any urgent need arises. supplying a copy of this shared care j) Report any adverse events to specialist and if agreement. relevant MHRA. i) Supply patient with a copy of this shared care k) Ensure the patient receives NO live vaccinations agreement. which includes the shingles vaccination. j) Monitor for response and adverse drug l) Ensure the patient is offered an annual flu reactions (ADRs). vaccination. k) Recommend dose of Leflunomide and m) Seek advice if patient travelling to a country frequency of monitoring. where live vaccinations are required. l) Review the patient periodically and promptly n) In the GP clinical system use the appropriate advise GP of any treatment changes. read code to denote the patient is receiving m) Evaluate any concerns raised by the patient treatment under a shared care agreement. In or GP. Emis 8BM5, System One XaB58. n) Provide and update Burton Hospitals Patient o) If patient fails to attend more than 2 monitoring Record Booklet. visits it is not safe to continue treatment – o) Report adverse events to MHRA Yellow card contact the Rheumatology Helpline for advice. scheme and GP. p) Ensure a nurse advice line is available for GP to contact department if necessary and respond promptly to messages left by GPs on the nurse advice line.

Leflunomide ESCA FINAL v2 March 17 Uncontrolled once printed Page 1 of 6 Patient responsibilities

a) To take the prescribed dose as recommended by the specialist. b) To attend all appointments with specialist and GP for all monitoring, always providing Patient Record Booklet. c) Inform specialists and GP of any other medication being taken including over the counter products. d) Agree methods of contraception for during treatment and for at least two years after for both men and women. e) Carry and present Patient Record Booklet to GP and community pharmacy at each prescribing and dispensing activity. f) Report any concerns of adverse effects to GP or consultant promptly. Do not wait for routine appointments.

3. CLINICAL INFORMATION

Licensed i. Prescribed indications Rheumatoid arthritis Psoriatic arthritis Leflunomide is an isoxazole derivative, indicated for the treatment of active rheumatoid arthritis. It has a novel mechanism of action that differs from other disease modifying anti-rheumatic drugs (DMARDs) used in the treatment of rheumatoid arthritis. Through inhibition of enzymes involved in pyrimidine ii. Therapeutic summary synthesis, Leflunomide arrests activated autoimmune lymphocytes and decreases the autoimmune response.

Therapeutic effect usually starts after 4 – 6 weeks and continued improvement is possible. Leflunomide is available in 10mg, 15mg, 20mg or 100mg tablets film coated tablets. Any dose adjustments should be done by the specialist consultant.

Rheumatoid arthritis iii. Dose & Route of 10mg ONCE DAILY increasing to 20mg if no contraindications. administration Psoriatic arthritis 10mg ONCE DAILY increasing to 20mg if no contraindications. Absorption of Leflunomide is unaffected by food but tablets should be swallowed whole. iv. Duration of treatment Dependent upon disease activity, benefits and any side effects. v. Adverse effects Gastro Intestinal (GI) - Diarrhoea is relatively common and may resolve in time See BNF / SPC for full list but may be treated symptomatically. Nausea and mild weight loss have also been reported. If severe, consider a wash out and consider stopping Leflunomide (please see below).

Liver Toxicity - Abnormal liver function may be a feature of active disease and therefore baseline LFTs, including gamma GT, will be measured when Leflunomide is prescribed. If liver enzymes rise to more than twice the normal upper limit, or twice an abnormal baseline, Leflunomide should be stopped and the Rheumatology Department informed. Alcohol intake should be limited and excessive alcohol consumption should be discussed with the specialist team. It is highly recommended that LFT are checked MONTHLY. Patients should also be asked to limit ALCOHOL intake. Excessive alcohol consumption should be discussed with the specialist team.

Skin reactions – May continue on full dose if rash / itch mild and consider treatment with antihistamines and / or topical skin lotion. If moderate, consider dose reduction and if severe or unmanageable, STOP treatment & consider wash out. Rare cases of ulcerative stomatitis and Stevens Johnson syndrome have been reported.

Hair loss - If mild / moderate consider dose reduction, if severe, STOP &

Leflunomide ESCA FINAL v2 March 17 Uncontrolled once printed Page 2 of 6 consider wash out.

Abnormal bruising or severe sore throat - Check FBC immediately and withhold until infection resolved.

Hypertension – A rise in blood pressure may occur but tends to be mild to moderate. This can be managed by the GP with conventional medical treatment. Assess any other cardiovascular risks. Consider dose reduction and / or co prescription with conventional antihypertensive therapy. If BP remains uncontrolled, STOP treatment and consider wash out.

Headache - Consider dose reduction If severe and in absence of any secondary cause. If still persists then STOP the treatment and consider wash out.

Pulmonary symptoms - Interstitial pneumonitis has been reported and if patients develop acute dyspnoea on treatment consider stopping the drug and discuss with the specialist team after doing a Chest X-ray. Acute pneumonitis or chronic pulmonary fibrosis may occur. This is not dose related. It presents with dry cough, dyspnoea and often fever.

Myelosuppression and decreased resistance to infection This is especially in relation to respiratory, urinary tract and shingles/Chickenpox. Temporarily withhold / advise stopping if patient is systemically unwell with significant infection requiring anti-infective treatment. Cholesyramine 8g is administered TDS for 11 days OR activated powdered charcoal QDS for 11 days. The duration of a complete washout is usually 11 days but may be modified depending on clinical or laboratory variables. vi. Wash out Procedure Concentration of active metabolite should be <20mcg / l (measured on 2 occasions 14 days part) in both men and women before conception. This is undertaken in secondary care. vii. Monitoring Pre-treatment assessment Requirements  FBC  U&E  LFT  Blood pressure  Body weight Monitoring continues as the responsibility of the specialist in accordance with local protocol until the patient is on a stable therapeutic dose.

Ongoing Monitoring FBC, LFT, U&E monthly. ESR / CRP maybe occasionally but no more than 3 monthly .

Blood pressure should be checked fortnightly for the first 3 months, then monthly.

Responding to abnormal results Please note that a rapid fall or consistent downward trend in any value should prompt caution and extra vigilance.

WBC < 3.5 x 109/l Withhold until discussed with specialist team Neutrophils < 2.0 x 109/l Withhold until discussed with specialist team Platelets < 150 x 109/l Withhold until discussed with specialist team AST/ALT > 2 times the Withhold until discussed with specialist upper limit of reference team range Abnormal bruising Withhold until discussed with specialist team

Leflunomide ESCA FINAL v2 March 17 Uncontrolled once printed Page 3 of 6 Oral ulceration, sore throat, Withhold until discussed with specialist nausea, vomiting, team diarrhoea New or increasing Withhold until discussed with specialist dyspnoea or dry cough team

Uncontrollable rash / itch Withhold until discussed with specialist team Hair or weight loss Withhold until discussed with specialist team Uncontrollable Withhold until discussed with specialist hypertension team Breathlessness Withhold until discussed with specialist team Leflunomide can interact with many other drugs but particularly ;  Phenytoin viii. Clinically relevant drug  Tolbutamide interactions  Warfarin For a full list of interactions  Rifampicin please refer to the BNF  Methotrexate- increased risk hepatotoxicity  LIVE vaccines should be avoided

The active metabolite of Leflunomide has a long half-life, usually 1 to 4 weeks. Serious undesirable effects might occur (e.g. hepatotoxicity, haematotoxicity or allergic reactions, see below), even if the treatment with Leflunomide has been stopped.

Contraindications  Severe immunodeficiency  Serious infections  Impaired liver function  Impaired renal function  Severe hypoproteinamia  Severe immunodeficiency states  Unexplained anaemia or cytopenia  Alcohol abuse ix. Contraindications and cautions Immunisations Patients must not receive LIVE vaccines. Annual flu vaccination is recommended. Consider treatment with Aciclovir for patients with no immunity to the varicella zoster virus when exposure has occurred or seek advice from the specialist.

Pregnancy & Lactation Pregnancy should be excluded before commencement of Leflunomide. Women planning to become pregnant should discontinue Leflunomide 2 years before conception or complete the washout procedure. Men should use effective contraception for 2 years after stopping Leflunomide. Blood concentrations should be checked prior to a planned pregnancy especially if within 2 years of discontinuation and if a washout has not been performed. The pharmaceutical company should be notified if a pregnancy occurs whilst taking Leflunomide. Breast feeding should be avoided. x. Supply, storage and reconstitution Not applicable. instructions

4. COMMUNICATION AND SUPPORT Leflunomide ESCA FINAL v2 March 17 Uncontrolled once printed Page 4 of 6 xi. Hospital contacts: xii. Out of hours contacts and procedures: Burton Hospitals 01283 511511 / 566333 Burton Hospitals 01283 511511 / 566333 ask for on-call pharmacist via switchboard Rheumatology Rheumatology Dr M Nisar ext 4111 Messages can be left on the nurse advice line out of hours. Dr R Laximinarayan ext 4068 01283 511511 ext 4112.

Clinical Rheumatology Nurse Specialist ext 4112 If the advice line is not staffed messages may be left 24 Bleep 274 available during office hours. hours a day. The team aim to respond at latest within two working days. The specialist nurses may also be bleeped via switchboard for urgent enquiries. xiii. Specialist support/resources available to GP including patient information

Leflunomide 10mg SPC updated 17/02/16 - https://www.medicines.org.uk/emc/medicine/26345

Leflunomide 10mg patient information leaflet updated 12/02/16 - https://www.medicines.org.uk/emc/medicine/2345

Leflunomide information issued by hospital to patient -

Leflunomide BHFT leaflet.pdf xiv. Prepared by Sam Hardy-Ainger – Interface Pharmacy Technician Jane Whitmore – Lead Clinical Nurse Specialist Rheumatology

In consultation with Dr M Nisar – Lead Consultant Rheumatologist

Reviewed by APG Dec 2016

Date Prepared Oct 2016

Review date Oct 2018

Acknowledgements Derbyshire Joint Area Prescribing Committee (JAPC)

References 1. JAPC shared care agreement Leflunomide reviewed January 2016 - http://www.derbyshiremedicinesmanagement.nhs.uk/assets/Clinical_Guidelines/Shared_Care_Guidelines/Leflun omide.pdf 2. SPC for Leflunomide 20mg updated 17/02/16 - https://www.medicines.org.uk/emc/medicine/26344 3. BSR – http://www.rheumatology.org.uk/Search/Default.aspx?SearchTerm=leflunomide 4. BSR pregnancy guidelines - https://www.guidelines.co.uk/bsr/ra-in-pregnancy-and-breastfeeding

Leflunomide ESCA FINAL v2 March 17 Uncontrolled once printed Page 5 of 6 GP RESPONSE TO SHARED CARE

Shared care is produced by GPs and specialists knowledgeable in the field of that drug usage. This allows a more convenient service to the patient and cost effective use of NHS resources.

Patient: NHS No:

Medicine requested for shared care: Leflunomide Consultant: tablets

Current Dose: Date last prescription was provided:

 I agree to participate in this shared care agreement for the treatment of the above named patient with Leflunomide.

 I will NOT be undertaking the GP responsibilities as described in the agreed shared care guideline. My clinical reasons for declining shared care for this patient are listed in the box below:

Yours sincerely

{GP name} {Surgery}

Please send a copy of this response to: 1. The specialist / consultant requesting shared care

2. It is the responsibility of the specialist / consultant requesting the shared care agreement to forward any declined responses to the Medicines Management Interface Technician, Pharmacy Department Burton Hospitals.

(Sending a copy of this form to the interface technician will help to identify the reasons shared care is not being undertaken allowing for changes to be made in future updates to improve patient care.)

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