Doncaster Area Prescribing Committee s2
Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
Shared Care Protocol for the Management of Inflammatory Arthritis & Connective Tissue Disease for Adult services, over 16
1.0 INTRODUCTION
The use of disease modifying antirheumatic drugs (DMARDs) in treating early and established stages of Inflammatory Arthritis (IA) and in managing Connective Tissue diseases (CTD) is accepted practice. General Practitioners (GPs) are becoming more involved in active management of these conditions with the recognition that patients should be referred early for specialist advice and initiation of disease modifying drugs.
This protocol sets out guidelines for treatment of CTD & IA and delineated responsibilities when care is to be shared between Primary Care and Rheumatology Specialist services.
Shared Care Protocols are intended to provide clear guidance to General Practitioners (GPs) and hospital prescribers regarding the procedures to be adopted when clinical (and therefore prescribing and financial) responsibility for a patient’s treatment with a shared-care disease is transferred from secondary to primary care.
GPs, as independent contractors, have the right to decline to take clinical and prescribing responsibilities for a patient on their medical list who is being treated elsewhere. However the reason for this action must be documented. In the view of the Doncaster & Bassetlaw APC, it would be the exception for a GP to refuse to take clinical and prescribing responsibilities for an individual drug, where shared care guidelines for that drug have become common practice and where shared care guidelines include adequate support, education, and information as approved by the Doncaster & Bassetlaw APC.
If a specialist asks a GP to prescribe these drugs in relation to this disease, the GP should reply to this request as soon as practicable. The doctor who prescribes the medication legally assumes clinical responsibility for the drug and the consequence of its use.
The Doncaster & Bassetlaw Hospitals NHS Foundation Trust is a multi-site trust covering 2 PCT areas (Doncaster and Bassetlaw), with the Rheumatology department split over the two main hospitals. The process of shared care traditionally occurs for the DRI Rheumatology patients treated at Doncaster Royal Infirmary. and for Bassetlaw patients primary care normally monitor DMARDs. The reason for the difference dates back before the two hospitals merged as one trust. This protocol should allow GPs to undertake either method.
While this document looks to medications used in the treatment of CT & IA diseases, not all drugs will be covered by a shared care protocol for prescribing.
Traffic Light System ClassificationDrug Class / Grey / Amber-G / Amber / Red
Drugs that suppress the rheumatic disease process / Gold (injectable & oral)
Penicillamine
Sulfasalazine
Antimalarials / Hydroxychloroquine
Drugs affecting the immune response / Azathioprine
Leflunomide
Methotrexate (oral) / Ciclosporin
Methotrexate (injectable)
Mycophenolate
Alkylating drugs / Cyclophosphamide
Cytokine modulators / Abatacept1
Anakinra2 / Adalimumab
Etanercept
Infliximab
Rituximab
Grey - These medicines are not recommended for initiation in the Doncaster and Bassetlaw Health Care Communities
Amber G – Drug must be initiated and titrated to stable dosage by specialist before GPs take over prescribing responsibility. Once medical condition and drug dosage is stable, there is no specific requirement for ongoing monitoring
Amber - Initiation and continued prescribing should only be undertaken under auspices of an agreed shared care protocol
Red – Prescribing initiated and retained by specialist – Prescribing monitoring performed in secondary care
1 Abatacept - Abatacept is not recommended (within its marketing authorisation) for the treatment of people with rheumatoid arthritis. Patients currently receiving abatacept for the treatment of rheumatoid arthritis should have the option to continue therapy until they and their clinicians consider it appropriate to stop.
NICE TA 141 Abatacept for the treatment of rheumatoid arthritis April 2008
2 Anakinra: On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended for the treatment of RA, except in the context of a controlled, long-term clinical study. NICE CG79 The management of rheumatoid arthritis in adults February 2009
2.0 Background Information
This shared care agreement includes, but is not restricted to, the treatment of patients with any inflammatory arthritis or spondyloarthropathy and connective tissue diseases such as SLE, discoid lupus, myositis, vasculitis as examples.
2.1 RheMOS System General
Doncaster Rheumatology unit use a monitoring system aided by a nationally recognised program called RheMOS. This essentially is a software package that can assess trends in a patient’s blood test parameters. It then highlights when a patient deviates outside set parameters and has not had a blood test according to their drugs’ protocol. This is then actioned by the Rheumatology team as appropriate depending on the clinical situation. Patients are sent the regular blood forms by the support staff in the post, which have a bar code on which highlights to the Trust’s PAS system that it is a RheMOS patient. Recently, the Trust has gone paperless for RheMOS blood results as they were not needed. The forms are sent out each time the patient reaches the end of their group of forms and then ring in on a dedicated phone line extension, which each patient is given. This system also allows for tracking when patients do not attend for blood tests and the departments own protocol for this is followed.
2.2 RheMOS DNA Protocol
If patents DNA blood tests, they are sent a reminder letter as soon as is practicable, asking them to either attend for the blood test or contact on nurses help line if there are problems. They are warned in the letter that it is dangerous to continue the drug unmonitored and if they fail to have the blood test performed treatment might need to be stopped. If the patient fails following this to have a blood test performed or contact the department then a letter is sent to the patient, their GP and whoever is prescribing the DMARD (ie hospital pharmacy) asking them to stop the treatment and that if they continue to take the DMARD after this then that is at their own risk. Contact numbers are again provided on the letter.
2.3 Pregnancy and Breast Feeding
When a patient is prescribed a DMARD there are significant issues regarding pregnancy and family planning posed by the potency and potential teratogenic potential of these drugs. The decision about when and what drugs should be stopped is a decision that needs to be taken in secondary care. The decisions potentially affect both male and female patients depending on the drugs being used. Please see Appendix for specific advice on each drug. Overall the principle is to use the least level of treatment to control the disease but in certain conditions such as SLE, stopping some DMARD therapies has been shown to increase risk of flare and consequent risk to mother and baby. Please refer to Appendix 1.
Breastfeeding should not be advised if a mother is on any DMARD, even those felt to be safe during pregnancy, as small amounts are excreted in the breast milk.
2.4 Chicken Pox
Immunosuppressd Varicella Zoster Virus (VZV) naïve patients have a significant risk of disseminated infection if exposed or contract infection. Therefore, information is passed to all patients in secondary care on DMARD / steroid therapy as what to do if they are exposed or contract chicken pox.
· Exposed to VZV and within incubation period
o Previous history of chicken pox
Only treat if develop active infection; usually aciclovir
o No history of chicken pox
§ Urgent assessment of VZV antibodies
§ If antibody status negative: treatment with pooled immunoglobulin
§ If antibody status positive: only treat with acyclovir if develop infection
· Active VZV Infection
o Previous history of infection – treat with acyclovir
o No history of chicken pox
§ Urgent assessment of antibodies
§ Detailed clinical assessment and anti-viral treatment dependent on clinical presentation
2.5 Immunizations
No live vaccine should be given to any immunosuppressed patient.
All patients on methotrexate, azathioprine, ciclosporin, lefluonamide, mycophenolate and cyclophosphamide should be offered annual flu vaccination and the one off pneumococcal vaccine unless contraindicated.
1
This Document will be reviewed in the light of new or emerging evidence or by October 2014
Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
3.0 Drug treatment
For contraindications or further information please see the current BNF http://www.bnf.org.uk/bnf/bnf/current/index.htm or summary of product characteristics for the individual drug http://www.medicines.org.uk/
Drug, dose & TLS listing / Adverse effects / Therapeutic Monitoring / Consultant / Clinically relevant drug interactionsGP
1. Drugs that suppress the rheumatic disease process
1.1 Auranofin – Oral Gold (Amber)
· 6mg daily (initially in 2 divided doses then if tolerated as a single dose)
· If response inadequate after 6 months, increase to 9mg daily (in 3 divided doses), discontinue if no response after a further 3 months / · Diarrhoea
· Rashes
· Bone marrow suppression*
· Oral ulceration
· Proteinuria
· Permanent greyish skin discolouration (chrysiasis) with prolonged use / Baseline:
- FBC, WBC, platelets, urinalysis, U&Es, LFT, urinalysis for proteinuria and blood
Routine:
Every 4 weeks
- FBC, & urinalysis / · None
· Side effects
· Symptom control
1.2 Sodium Aurothiomalate – Injectable Gold (Amber)
· 10mg test dose followed by 50mg once weekly given by deep IM injection
· After significant response with 50mg weekly dose can be reduced to every 2 weeks to monthly
· If a total dose of 1 gram has been given & there has been no response, treatment should stop.
· If relapse occurs revert to 50mg weekly until control re-established / · Diarrhoea
· Rashes
· Bone marrow suppression*
· Oral ulceration
· Proteinuria
· Permanent greyish skin discolouration (chrysiasis) with prolonged use
· Vasomotor reaction - flushing erythema, weakness, hypertension.
· Rarely – enterocolitis, intra hepatic cholstasis, pneumonitis. / Baseline:
- FBC, WBC, urinalysis, U&Es, LFT, urinalysis for proteinuria and blood
Routine:
Before each injection
· FBC, WBC,
· Urinalysis
When stable for 8 weeks it is permissible to work one week in arrears for FBC. / · None
· Side effects
· Symptom control
1.2 Penicillamine (Amber)
· Initially 125mg-250mg daily before food for 1 month increased by similar amounts at intervals of not less than 4 weeks to usual maintenance dose of 500-750mg daily in divided doses.
· Maximum dose of 1.5 gram daily, if remission sustained for 6 months, reduction of daily dose by 125mg-250mg every 12 weeks may be attempted / · Nausea
· Bone marrow suppression*
· Rashes
· Oral ulceration
· Alteration of taste
· Proteinuria / Baseline:
· FBC, differential WBC, U&E’s, creatinine & urinalysis for proteinuria and blood
Routine:
Every 2 weeks for the first 3 months
· FBC, U&E & urinalysis
Every 4 weeks
· FBC, U&E’s & urinalysis / · Clozapine increases risk of agranulocytosis.
· Side effects
· Symptom control
1.3 Sulfasalazine (Amber)
· Enteric coated tablets only (Salazopyrin –EN
· 500mg per day increasing by 500mg per day each week to a usual maintenance dose of 2 grams per day in divided doses.
· If no response after 3 months the dose may be increased to a maximum of 3g/day (1.5g bd) / · Orange tears and urine
· Nausea
· Headache
· Abdominal pain
· Diarrhoea
· Oral ulceration
· Rashes
· Oral ulceration
· Bone marrow suppression*
· Hepatitis
· Oligospermia / Baseline:
· FBC, WBC, creatinine, LFT
Routine
Fortnightly for 12 weeks
· FBC, WBC, LFT.
After 12 weeks at 3 monthly intervals for the first year
· FBC, WBC, LFT.
After 12 months at 6 monthly intervals (or 1 month after dose increase)
· FBC, WBC,LFT / · None
· Side effects
· Symptom control
2. Antimalarials
2.1 Hydroxychloroquine (Amber-G)
· Initially 400mg in divided doses. Can be reduced to 200mg after 6 months depending on clinical response.
· Maximum dose is 6.5mg/kg lean body weight per day or 400mg per day, whichever is lower.
· Smaller doses are needed in patients weighing 60kg or less.
· Review needed if no clinical effect after 6 – 12 months of treatment. / · Indigestion, nausea, abdominal cramps
· Headache,
· Tinnitus
· Rashes
· Photosensitivity (sunblock advised)
· Retinopathy can occur after prolonged treatment
· Otoxicity / Baseline
· FBC, U&E, LFTs
· Ask about visual impairment (eye acuity) / · Amiodarone- increase risk of ventricular arrhythmias. Avoid concomitant use
· Side effects
· Symptom control
· Annual Visual symptomatology
3. Drugs affecting the immune response
3.1 Azathioprine (Amber)
· 1 to 3mg/kg day adjusted for clinical response
· Check TPMT if possible to starting
· Often started 1mg/kg initially for 2-4 weeks until TPMT known and then increase to 2mg/kg
· Larger doses used under secondary care supervision / · Nausea, vomiting, diarrhoea
· Bone marrow suppression*
· Rashes
· Hepatic dysfunction / Baseline:
· FBC,LFT,U&E,TPMT
Routine:
Weekly for 6 weeks
· FBC, LFT’s
After 6 weeks at monthly intervals
· FBC, LFT’s
At 6 monthly intervals
· U&E’s
·
Dose changes:
FBC and LFT fortnightly for 6 weeks after any dose increase / · Allopurinol-enhanced effects and increased toxicity
· Clozapine- avoid concomitant use potential for causing agranulocytosis
· Coumarins- anticoagulant effect reduced
· Sulfamethoxazole -increased risk of haematological toxicity
· Trimethoprim (also with co-trimoxazole)-increased risk of haematological toxicity
· Side effects
· Symptom control
3.3 Leflunomide (Amber)
· Start on 10 -20mg od
· Occasional circumstances larger doses have been used. / · Gastrointestinal disturbance
· Abdominal pain
· Weight loss
· Oral ulceration
· Headache
· Increase in blood pressure
· Rashes
· Bone marrow suppression*
· Hepatitis / Baseline:
· LFTs, U&Es, creatinine and BP
· FBC including differential WBC count
Routine:
Monthly for the first 6 months then every 8 weeks
· FBC, differential WBC
· LFT & BP / · Colestyramine significantly decreases the effect. Avoid concomitant use unless used to quickly discreet Leflunomide from body in cases such as overdose or unexpected pregnancy
· Side effects
· Symptom control
Drug, dose & TLS listing / Adverse effects / Therapeutic Monitoring / Consultant / Clinical relevant drug interactions
GP Lead Monitoring#
GP
3.4 Methotrexate -oral (Amber)
· Initially be given at a dose between 2.5 to 7.5mg once weekly, increase to a maintenance dose of 10 to 25mg once per week.
· Folic acid 5mg given 2 days after each dose may reduce the incidence of toxicity
· Folic acid can be increased up to 5mg every day except on Methotrexate day to help control side effects
The vast majority of patients take Methotrexate on a once weekly dosage. For the minority that need to take a twice weekly dose, there is no evidence that suggests that this is more hazardous than a once weekly dose / · Gastrointestinal disturbance
· Rashes
· Oral ulceration
· Hepatic dysfunction
· Bone marrow suppression*
· Alopecia
· Headaches
· Rarely Pneumonitis
· Rarely Pulmonary Fibrosis / Baseline:
· U&E, creatinine, LFTs, FBC, differential WBC, platelets and chest x-ray
Routine:
Every 2 weeks for the first 6 weeks and then monthly thereafter:
· FBC, WBC, U&E’s, LFT’s
Dose changes:
FBC, LFT’s and U&E’s fortnightly for 6 weeks after any dose increase
Ask about respiratory symptoms at monitoring / · Acitretin increases plasma concentration
· Ciclosporin risk of toxicity
· Clozapine increases risk of agranulocytosis concomitant use should be avoided
· NSAID’s reduce excretion
· Probenecid reduces excretion
· Pyrimethamine increases antifolate effect
· Sulfamethoxazole (as Co-trimoxazole) increases risk of haematological toxicity
· Trimethoprim increases risk of haematological toxicity
Routine:
· FBC, & LFT’s monthly
· U&E every 6 months
Ask about respiratory symptoms at monitoring
#Doncaster PCT Local Enhanced Service
· Side effects
· Symptom control
* Bone Marrow Suppression may present with bruising, bleeding, fever, sore throat or any other signs of sepsis