File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Page 1 of 9
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
10: Musculoskeletal and joint disease 10.1
Drugs used in rheumatic diseases and gout
10.1.1
Non-steroidal anti-inflammatory drugs (NSAIDs)
Please review recommendations from NICE before prescribing NSAID’s NSAIDs and renal impairment Patients at risk of renal impairment or renal failure (particularly elderly people) should avoid NSAIDs if possible. If NSAID treatment is necessary, then the lowest effective dose for the shortest possible duration should be used to control symptoms. The renal function of such patients should be carefully monitored during NSAID treatment. It is important to consider other concomitant disease states, conditions or medicines that may precipitate reduced renal function when prescribing NSAIDs. NSAID’S and Cardiovascular events Cyclo-oxygenase – 2 selective inhibitors are associated with an increased risk of thrombotic events e.g. myocardial infarction and stroke and should not be used in preference to non-selective NSAID’s except when specifically indicated i.e. for patient at a particularly high risk of developing gastrodoudenal ulceration or bleeding and after assessing their cardiovascular risk. Non selective NSAID’s may also be associated with a small increased risk of thrombotic events particularly when use at high doses and for long term treatment. Diclofenac (150mg daily and Ibuprofen 2.4g daily are associated with an increased risk of thrombotic events. The increased risk for diclofenac is similar to that of licensed doses of etoricoxib. Naproxen is associated with a low thrombotic risk, and low doses of ibuprofen (1.2g daily or less) have not been associated with an increased risk of myocardial infarction. The CHM has advised that the lowest effective dose of NSAID or COX 2 inhibitor should be prescribed for the shortest period to control symptoms and the need for long term treatment should be reviewed periodically. A Drug Safety Update October 2012 on the cardiovascular safety of NSAID’s has highlighted further evidence that diclofenac is associated with cardiovascular risks that are higher than the other two non-selective NSAIDs and similar to the COX-2 inhibitors. Naproxen and low dose ibuprofen are still considered to have the most favourable cardiovascular safety profiles of all non-selective NSAIDs.
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Page 2 of 9
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
CSM advice (gastro-intestinal side-effects) All NSAIDs are associated with serious gastro-intestinal toxicity; the risk is higher in the elderly. Evidence on the relative safety of 7 non-selective NSAIDs indicates differences in the risks of serious upper gastro-intestinal side-effects. Azapropazone [discontinued] is associated with the highest risk and ibuprofen with the lowest; piroxicam, ketoprofen, indometacin, naproxen and diclofenac are associated with intermediate risks (possibly higher in the case of piroxicam). Selective inhibitors of cyclo-oxygenase-2 are associated with a lower risk of serious upper gastro-intestinal side-effects than non-selective NSAIDs (but see caution below). Recommendations are that NSAIDs associated with low risk e.g. ibuprofen are generally preferred, to start at the lowest recommended dose, not to use more than one oral NSAID at a time, and to remember that all NSAIDs (including selective inhibitors of cyclo-oxygenase-2) are contra-indicated in patients with active peptic ulceration. The CSM also contra-indicates non-selective NSAIDs in patients with a history of peptic ulceration. The combination of a NSAID and low-dose aspirin may increase the risk of gastrointestinal side-effects; this combination should only be used if absolutely necessary and the patient monitored closely CSM warning (asthma) Any degree of worsening of asthma may be related to the ingestion of NSAIDs, either prescribed or (in the case of ibuprofen and others) purchased over the counter. Product Comments First line Ibuprofen Tablets (200mg, 400mg) Ibuprofen suspension 100mg/5ml Naproxen Tablets (250mg, 500mg) Naproxen Suppositories (500mg) Other Diclofenac is associated with an increased cardiac risk NSAID’s Diclofenac Sodium E/C Tablets Maximum total daily dose (25mg, 50mg) 150mg Diclofenac Sodium Maximum total daily dose Suppositories (12.5mg, 25mg, 150mg 50mg, 100mg) Only to be used for patients who are unable to take oral medicines or in whom oral medication is inappropriate. Diclofenac Sodium Injection Maximum total daily dose (75mg/3ml) 150mg 75mg one to two times a day for a maximum of 2 days by deep intramuscular injection R Diclofenac Sodium MR Tablets Maximum total daily dose
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
(75mg)
R
Diclofenac Sodium dispersible Tablets (50mg)
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150mg These are expensive compared the EC tablets and should be reserved for patients in whom compliance is a problem Maximum total daily dose 150mg These are expensive and should be reserved for use in nasogastric tubes
Indometacin Capsules (25mg) Mefenamic Acid Capsules (250mg) Mefenamic Acid Tablets (500mg)
Formulary Product status R Celecoxib Capsules (100mg) Etoricoxib Tablets (60mg, 90mg)
Restriction For patients at a particularly high risk of developing gastrodoudenal ulceration or bleeding and after assessing their cardiovascular risk (see CSM advice above).
10.1.2
Corticosteroids
10.1.2.1
Systemic corticosteroids – see Section 6.3
10.1.2.2
Local corticosteroid injections
Hydrocortisone Acetate Injection (25mg/1ml) Methylprednisolone Acetate Injection (40mg/1ml, 80mg/2ml) Methylprednisolone 80mg with Lidocaine 20mg Injection Triamcinolone injection 50mg/5ml (Adcortyl) Triamcinolone injection 40mg/ml (Kenalog)
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Page 4 of 9
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
10.1.3
Drugs which suppress the rheumatic disease process For information on monitoring and side effects see Sharepoint/ medicines/ medicine management/ shared care guidelines For patient information leaflets see Sharepoint/ medicines/ medicine management/patient information leaflets. Formulary Product status C Abatacept Infusion (250mg)
C
Adalimumab Pre filled pen (40mg)
C
Azathioprine Tablets (25mg, 50mg Certolizumab Injection 200mg
C
C
Cyclophosphamide Tablets 50mg
C
Ciclosporin Capsules (25mg,50mg) Ciclosporin liquid 100mg/ml Etanercept 25mg and 50mg injections
C
C
Golimumab 50mg/0.5ml prefilled syringe / pen
C
Hydroxychloroquine Tablets (200mg) Infliximab Infusion (100mg)
C
Restriction Consultant Rheumatologist use only for the treatment of RA.Supported for use in-line with NICE TA195 (Aug 2010) Consultant Rheumatologist and Consultant Gastroenterologist use only. Use supported for use in-line with NICE TA199 (PsA) August 2010, NICE TA143 (AS) May 2008 Consultant Rheumatologist use only Consultant Rheumatologist use only. Use supported for use in-line with NICE TA186 Feb 2010. Restricted for use within agreed protocols under the supervision of appropriate specialists Restricted for use within agreed protocols under the supervision of appropriate specialists Consultant Rheumatologist use only. Use supported for use in-line with NICE TA199 (PsA) August 2010, NICE TA143 (AS) May 2008 Consultant Rheumatologist use only. Supported for use in-line with NICE TA233 (AS) August 2011, NICE TA220 (PsA), April 2011, NICE TA225 (RA) June 2011 Consultant Rheumatologist use only Consultant Rheumatologist and consultant gastroenterologist use only. Use supported for use in-line with NICE TA199 August 2010, NICE TA143 (AS)
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
C C C C C
C
C
C
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May 2008 Consultant Rheumatologist use only
Leflunomide Tablets (10mg, 20mg, 100mg) Methotrexate syringes (various Consultant Rheumatologist use only strengths) Given as a once weekly injection Methotrexate Tablets 2.5mg Consultant Rheumatologist use only Given as a once weekly dose Penicillamine Tablets (50mg, Consultant Rheumatologist use only 250mg) Rituximab infusion 10mg/ml Consultant Rheumatologist use only for (10ml vial) patients who have had an inadequate response to or intolerance of other DMARDs (inc. one or more TNF inhibitor) Sodium Aurothiomalate Consultant Rheumatologist use only Injection (10mg/0.5ml, 50mg/0.5ml) GOLD Sulphasalazine tablets 500mg Consultant Rheumatologist use only when used for inflammatory arthritis. See section 1.5 for use in Ulcerative colitis Tocilizumab Infusion 20mg/ml Use supported for the treatment of (4ml vial, 10ml vial, 20ml vial) moderate to severe active rheumatoid arthritis (in combination with methotrexate) for patients in whom treatment with rituximab has failed or is contraindicated. For use in-line with NICE TA247 (Feb 2012).
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
10.1.4
Gout and cytotoxic-induced hyperuricaemia
Product Colchicine Tablets (500micrograms)
Allopurinol Tablets (100mg, 300mg)
Comments Acute attacks of gout are usually treated with high doses of NSAIDs such as diclofenac, etoricoxib, indometacin, ketoprofen, naproxen, piroxicam, or sulindac. Colchicine is an alternative. Aspirin is not indicated in gout. Allopurinol and uricosurics are not effective in treating an acute attack and may prolong it indefinitely if started during the acute episode. Colchicine is probably as effective as NSAIDs. Its use is limited by the development of toxicity at higher doses, but it is of value in patients with heart failure since, unlike NSAIDs, it does not induce fluid retention; moreover, it can be given to patients receiving anticoagulants. Intra-articular injection of a corticosteroid may be used in acute monoarticular gout [unlicensed indication]. A corticosteroid by intramuscular injection can be effective in podagra. Treatment of gout, 500micrograms 2 - 4 times daily until symptoms releived, max 6mg per course. Not to be used for acute attacks of gout Allopurinol is a well tolerated drug which is widely used. It is especially useful in patients with renal impairment or urate stones where uricosuric drugs cannot be used; it is not indicated for the treatment of asymptomatic hyperuricaemia. It is usually given once daily, since the active metabolite of allopurinol has a long half-life, but doses over 300 mg daily should be divided. It may occasionally cause rashes.
Formulary Product status R Febuxostat Tablets (80mg, 120mg)
C
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Rasburicase Infusion (1.5mg, 7.5mg vials)
Restriction Restricted to use in patients with chronic hyperuricaemia who are unable to tolerate allopurinol or in whom allopurinol is contra-indicated. Supported for use in-line with NICE TA164 Dec 2008. Consultant Haematologist use only. For use during first cycle of chemotherapy in patients with a high tumour load and/or allopurinol
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
intolerance
Page 7 of 9
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Page 8 of 9
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
Drugs used in neuromuscular disorders 10.1.5
Drugs which enhance neuromuscular transmission
Neostigmine Injection (2.5mg/1ml) Pyridostigmine Tablets (60mg) Formulary Product status S Edrophonium Injection (10mg/ml)
10.1.6
Restriction Anaesthetists and Neurologists use only
Skeletal muscle relaxants
Baclofen SF Liquid (5mg/5ml) Baclofen Tablets (10mg) Dantrolene Capsules (25mg) Formulary Product status R Tizanidine Tablets (2mg, 4mg)
C
Baclofen Intrathecal Injection (10mg/20ml)
Restriction Consultant Neurologist use only for patients who have failed on oral baclofen Consultant Neurologist use only
Nocturnal leg cramps Formulary Product status R Quinine Bisulphate Tablets (300mg)
Restriction Quinine is not a routine treatment for nocturnal leg cramps and should only be considered when cramps cause regular disruption of sleep. Quinine should only be considered when cramps are very painful or frewquent: when other causes of cramp have been ruled out: and when nonpharmacological measures have not worked. After initial trial of 4 weeks treatment, treatment should be stopped if there is no benefit.
File name: Musculoskeletal & Joint disease Formulary BNF Section 10.
Original Date of issue: 30/03/2006
Last Reviewed: 08/03/2013
Version: 4
Department: Pharmacy
Review Date:08/03/2015
Authorised: Drug and Therapeutics Committee
10.2
Drugs for the relief of soft-tissue inflammation
10.2.1
Enzymes
Page 9 of 9
Hyaluronidase Injection 1500 units (Hyalase)
10.2.2
Rubefacients and other topical antirheumatics
Benzydamine 3% Cream (100g) (Difflam) Diclofenac Sodium 1% Gel (20g) Transvasin Cream (40g) Formulary Product status R Capsaicin cream 0.075% (Axsain) C Capsaicin cream 0.025% (Axsain)
Restriction For neuropathic pain and phantom limb pain For use by Consultant Rheumatologist for symptomatic relief in osteoarthritis