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Further information & Actions to be taken can be obtained from British Society for Rheumatology (BSR) /British Health Professionals in Rheumatology (BHPR) Guideline for disease-modifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of Dermatologists (BAD) DYDLODEOHIURPWKH%65ZHVELWH

Abbreviations Used: FBC – Full Blood Count, U&Es – Urea & Electrolytes, LFTs – Liver Function Tests

'58* %$&.*5281' '26$*(5(48,5(0(176 021,725,1* This is an effective second- 125mg -250mg daily, increasing by FBC, U&Es, LFTs & urinary line drug used in the 125mg increments every 4 weeks to dipstick for protein prior to treatment of rheumatoid 500mg daily if tolerated. Some treatment. arthritis patients respond to a lower dose and occasionally up to 750mg a day FBC & u rinalysis every 2 weeks is required. If no re sponse in 1 until dose stable for 3 months and year, discontinue treatment. then month ly. FBC & urinalysis should be done in the week after Penicillamine should be taken at any dosage increment . least 30 minutes before a meal. If the patient is also taking iron tablets, The patient should be asked about antacids or digoxin then these the pr esence of rash or oral should be taken at least 2 hours ulceration at each visit. before or after penicillamine This is widely used for the 500mg daily increasing by 500mg FBC, U&Es & LFTs prior to long -term treatment of weekly increments up to 1g twice treatment. (RA), daily , if tolerated. ulcerative colitis & Crohns FBC & LFTs at 2 weeks, 4 weeks disease. Some patients may respond to a then monthly for the first 3 months

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 1 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   There are two preparations lower dose & some may require a then every 3 months thereafter. in use, Sulfasalazine EN higher dose up to 3g/day . FBC & LFTs should be repeated (ova l, film coated) and one month after any dose generic Sulf asalazine Treatment may be continued increase. (round, uncoated ) the indefinitely, the usual reason for former is considered to have stopp ing being loss of benefit. If following the first year, dose & fewer GI side effects. blood results have been stable, Sulf asalazine is sometimes co- frequency of blood tests can be Sulfasalazine EN is the only prescribed with other anti -rheumatic reduced to every 6 months for the preparation licensed for RA agents. second year of treatment. Thereafter, monitoring of blood for toxicity may be discarded.

The patient should be asked about the presence of rash o r oral ulceration at each vi sit.

Urgent FBC if patient complains of intercurrent illness during initiation of treatment. Sodium Aurothiomalate This is a slow-acting drug 10mg intramuscular (IM) test dose FBC, U&Es, LFTs & urinary (Myocrisin) effective in controlling (which should be given in the clinic dipstick prior to treatment disease activity in 60 -70% of followed by 30 minutes observation patients with rheumatoid to look for signs of allergic reaction) FBC & urinalysis prior to each arthritis. then 50mg one week later followed injection by 50mg weekly to a total dose of (ESR/CRP is useful to access Improv ement can be 500mg. response to therapy). Provided expected after 2 -3 months blood results are stable, the results (400 -600mg total dose), and If there is a clinical response, the of the FBC need not be available in the absence of toxicity frequency of injections can be before the injection is given but sodium aurothiomalate reduced to every 2 weeks up to a must be available before the next injections can be continued total dose of 1g . injection. indefinitely. In the absence of an improvement Urinalysis should be carried out

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 2 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   continue at 50mg weekly to a total just before each injection. dose of 1g. The patient should be asked about If after 1g there is clinical the presence of rash o r oral improvement, reduce the frequency ulceration at each visit. of injections to every 3 -4 weeks. If no response after 1g total dose stop therapy. (MTX) This is widely used in the Initially 5mg to 7.5mg orally once FBC, U&Es, LFTs & CXR (unless treatment of rheumatoid weekl y. The initial dose is CXR done within the last 6 arthritis a nd psoriasis. increased by 2.5 -5mg every 2-6 months) prior to treatment. weeks until the disease is stabilised. Pulmonary function tests should be It has both The maximum licensed oral dose in considered in selected patients. immunosuppressant and RA is 20mg/week, but the BSR anti -inflammatory effects . suggests that doses of up to 25mg FBC, U&Es, LFTs should be done once weekly may be used every 2 weeks until the dose of It may be used off license MTX and monitoring stable for 6 for psoriatic arthritis, Crohns Folic acid is generally given a few weeks, then monthly thereafter, disease and some days after MTX therapy to reduce until the dose and disease are connective tissue diseases. the toxic effects and improve stable for 1 year. continuation of therapy and Best practice within NHS compliance. Folic acid can be given Thereafter the monitoring may be A&A involves dispensing any day as long as it is not on the reduced in frequency to once every only 2.5mg MTX tablets and same day as MTX. 2-3 months based on clinical QRW 10mg tablets . Patients judgement with due consideration should be reminded to If the maximum oral dose is for risk factors including age, check the dose and strength ineffective or causes intolerance the comorbidity, renal impairment etc – of the tablets with each subcutaneous (SC) route will be when monthly monitoring should prescription. considered before discontinuation of continue. the drug. The maximum licensed SC dose is 25mg weekly. The patient should be asked about the presence of rash o r oral Trimethoprim interacts with MTX so ulceration at each visit. this combination should not be used

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 3 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   concurrently (increased risk of Urgent FBC if patient complains of marrow aplasia) . intercurrent illness during initiation of treatment. If a patient has an active infection MTX therapy should be withheld until the infection resolves. Azathioprine is an effective In general the starting dose is from FBC, U&Es, creatinine and LFTs second -line drug used in the 1mg /kg body weight/day (can use to prior to treatment . treatment of rheumatoid to 3mg/kg body weight/day) And arthritis, other auto-immune should be adjusted within these FBC & LFTs should be done conditions and organ limits depending on the clinical weekly for 6 weeks, and then every transplantation . response and haematological 2 weeks until the dose is stable for It is an antiproliferative tolerance. 6 weeks and then monthly. immunosuppressant which When therapeutic response is is metabolised to evident consideration should be If maintenance dose is achieved mercaptopurine. given to reducing the maintenance and stable for 6 months consider dose to ensure the continuation of discussing with patient to reduce that response. monitor ing to 3 monthly.

If there is no response within three FBC & LFTs should be repeated 2 months consideration should be weeks after a dosage change then given to stopping Azathioprine . monthly.

In patients with renal and / or U&Es and creatinine should be hepatic insufficiency, dosages repeated 6 monthly. should be given at the lower end of the normal range. The patient should be asked about the presence of rash o r oral There are numerous drug ulceration at each visit. interactions involving azathioprine so the summary of product Urgent FBC if patient complains of characteristics should be consulted intercurrent illness during initiation when this is initially prescribed and if of treatment. any medicines are introduced.

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 4 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   Ciclosporin Ciclosporin is a potent For the treatment of severe active FBC, including differential WCC, immunosuppressant used in rheumatoid arthritis, initially U&Es , creatinine (check twice, 2 the treatment of severe 2.5mg/kg in two divided doses for 6 wee ks apart to obtain a mean rheumatoid arthritis, organ weeks and then the dose may be value for creatinine), LFTs, fasting and tissue transplantation, increased gradually at 2-4 week ly lipids, creatinine clearance prior to atopic dermatitis, nephrotic intervals by 25mg until clinically starting treatment with ciclosporin. syndrome and psoriasis. effective or the maximum dose of 4mg/kg/d ay is reached. Blood pressure should be ≤ 140/90 before treatment on two For the treatment of psoriasis and measurements 2 weeks apart. If atopic dermatitis the starting dose greater than this treat hypertension can be 2.5 -5mg/kg/day depending prior to starting ciclosporin therapy. on disease severity and then treated according to the response with a FBC & LFTs once a month until maximum recommended dose of dose and trend stable for 3 months 5mg/kg/day. and then 3 monthly.

For other conditions precise regimes U&E s including potassium and will be issued by the consultant creatinine every 2 weeks until the responsible. dose and trend stable for 3 months and then monthl y. There are numerous drug interactions involving ciclosporin Check fasting lipids six monthly. and is it recommended that the Summary of Product Characteristics Blood pressure should be checked be consulted at the time of first each time the patient attends for prescription and if any other drugs monitoring (every 2 weeks until the are introduced. dose has been stable for 3 months) and maintained ≤ 140/90. In particular, the dose of diclofenac should be halved if ciclosporin is co- prescribed . U&Es should be checked if a NSAID is added to therapy or the dose increased.

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 5 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   Leflunomide is used as a The recommended maintenance FBC, U&Es, creatinine & LFTs “disease modifying dose is 10 -20mg once daily when should all be checked prior to antirheumatic drug”. It is monotherapy is used. In cases of initiation of therapy. used in adults for the combination therapy with another If a patients blood pressure is treatment of active potentially hepatotoxic DMARD >140/90 on two consecutive rheumatoid arthritis & such as MTX, 10mg once a day is reading 2 weeks apart, their psoriatic arthritis . recommended. hypertension should be treated before commencing therapy. The A loading dose of 100mg daily for 3 patients weight should be checked days may be used to speed up the prior to therapy commencing – this onset of effect . Unacceptable GI is to allow assessment of weight side effects may occ ur when a loss which may be attributable to loading dose is given and ofte n this leflunomide. is omitted in routine clinical practice. A loading dose is not recommended FBC, LFTs should be checked when used as part of combination every two weeks for 6 months and therapy. It should only be if stable then 2 monthly thereafter. prescribed by specialists The dose may have to be reduced experienced in the treatment of or consideration given to stopping rheumatoid di seases. leflumonide if ALT > 2 -3 times upper limit of normal.

Blood checks should be continued long -term, at least once a month, if co -prescribed with another immunosuppressant or potentially hepatotoxic agent.

Bloo d pressure & weight should be checked at each monitoring visit (as above) .

Opportunistic infections can occur when taking immuno-suppressant

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 6 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   drugs. Vigilance is necessary as the drug may need to be withdrawn and a washout procedure may be required. Details of this can be found in the summary of product characteristics This is licensed for use in The typical regimen is 200mg- FBC, U&Es & LFTs prior to RA, connective tissue 400mg once daily. Dosage may be treatment. diseases (systemic and reduced to 200mg daily depending discoid lupus) and some on clinical response. Patients should be asked about photosensitive visual impairment which is not dermatological conditions. corrected by glasses. The near visual acuity of each eye should be recorded prior to therapy (optometrist visit).

Patient should have an annual review either by an optometrist or by enquiring about visual symptoms, rechecking visual acuity and assessing for blurred vision.

Patients should be advised to report any visual disturbance.

Always refer to the manufacturer’s Summary of Product Characteristics (available from http://medicines.org.uk ) if further information is required for the above medicines.

Bibliography 1. BSR/BHPR Guideline for disease-modifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of Dermatologists. Available from http://rheumatology.oxfordjournals.org/cgi/data/kel216a/DC1/1 (accessed 15th April 2011) 2. Leflunomide (Arava ®). Electronic Medicines Compendium. Available from www.medicines.org (accessed 18 th April 2011)

5HIHUHQFH ADTC 4 (3) 6XSHUVHGHV ADTC 4 (2) Page 7 of 7 :ULWWHQE\ Kathryn Wilson, Senior Pharmacist, Clinical Services, Dr M Duncan & Dr S Shetty, Consultant Rheumatologists th 'DWH:ULWWHQ April 2011 'DWHDSSURYHG 15 November 2013    5HYLHZGDWH November 2016   Appendix 2. A recommended monitoring schedule when starting DMARDs (Adapted from the BSR and BHPR guideline for the prescription and monitoring of non-biologic disease- modifying anti-rheumatic drugs, 2017) 

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Appendix 3. Precautions when prescribing biologics 6

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