Chapter 10 page number 1 First line drugs Drugs recommended in both primary and secondary care Chapter 10 Musculoskeletal and Joint Diseases Second line drugs Alternatives (often in specific conditions) in both primary and secondary care Specialist initiated drugs Secondary care or GP with special interest initiation. Suitable for continuation by primary care. Shared care agreements may be applicable. Secondary care only drugs Drugs only suitable for secondary care use and initiated by appropriate team or specialist. Primary care prescribers should not be asked to prescribe. 10.1 Drugs used in rheumatic diseases and gout 10.1.1 Non-steroidal anti-inflammatory drugs (NSAIDs) In the management of inflammatory conditions and joint pain, drug therapy is just one option in overall management. Where medication is appropriate, evidence suggests simple analgesics e.g. Paracetamol should be tried before NSAIDs due to NSAIDs potential side effects. (1) NSAIDs and Cox 2 inhibitors compromise kidney function. Use with caution in patients susceptible to, or with impaired renal function. NSAIDs should not be used in patients with myeloma. (2) Non-selective NSAIDs may be associated with a small increased risk of thrombotic events (such as heart attack or stroke) when used at high doses and for long-term treatment (3). Lowest effective dose of NSAID or coxib should be prescribed for the shortest time necessary for control of symptoms. Review periodically (3). Concomitant aspirin (and possibly other antiplatelet drugs) greatly increase the gastrointestinal risks of NSAIDs. Aspirin should only be co-prescribed if absolutely necessary (3). For NSAID use in Migraine, Gynaecology and Dental pain, please see Central nervous sytem chapter 4, Obs & Gynae chapter 7 and ENT chapter 12. CSM warning (asthma): Any worsening of asthma may be related to ingestion of prescribed or purchased NSAIDs. See MHRA guidance on NSAIDs and gastro-intestinal events. See also Acute Trust Guideline for the use of NSAIDs in adults with acute pain and MHRA drug safety update (October 2012) on cardiovascular risk with diclofenac. Oral NSAIDs Ibuprofen 400mg tds (In higher doses safety advantage may be lost) (4) See MHRA Drug Safety Update June 2015 for further information and advice on cardiovascular risk if using 2400mg/day or more. Note: Recent evidence suggests Ibuprofen may antagonise antiplatelet effect of Aspirin. (5) Naproxen Diclofenac sodium Diclofenac Injection Piroxicam melt No evidence for GI benefit of E.C. prep (6). Short term use only. Use for gout. There is evidence that the cardiovascular risk with diclofenac is higher than other non-selective NSAIDs and similar to the selective COX- 2 inhibitors. See MHRA drug safety advice and Drug Safety Update (June 2013) regarding CV risk for further details. Paediatric use only. Third line in children unresponsive to or intolerant of Ibuprofen and Diclofenac. Diclofenac MR - not stocked routinely in hospital except for 100mg for peri-operative use and 75 mg for Rheumatology use. Diclofenac dispersible for perioperative pain relief.
Chapter 10 page number 2 Cox 2 inhibitors Following the latest guidance (7 ) on the use of COX 2 inhibitors in general and specifically in patients with established ischaemic heart disease or cerebrovascular disease: Patients with established ischaemic heart disease, cerebrovascular disease and peripheral artery disease should NOT be treated with Cox 2 specific/selective agents. If anti-inflammmatory therapy is indicated where possible use conventional NSAIDs with Omeprazole cover if indicated. ALL patients on COX 2 specific/selective agents should be reviewed at their next hospital or GP appointment and alternative therapies considered. Note: Do NOT prescribe routinely in those taking concomitant aspirin therapy as aspirin reduces the GI protective effect. There is currently no evidence to justify co-prescribing of Coxibs with a gastro-protective agent. Cox 2 selective/specific agents Meloxicam COX 2 selective agent. Etoricoxib Reserve for severe inflammatory arthritis unresponsive or intolerant to other NSAIDS. Contra indicated in patients with uncontrolled blood pressure, ischaemic heart disease or stroke. See MHRA Drug Safety Update Oct 16 for information on revised dosing for rheumatoid arthritis and ankylosing spondylitis. Within acute trust -for initiation by consultant prescribers only. 10.1.2 Corticosteroids 10.1.2.1 Systemic Corticosteroids Please see MHRA Drug Safety Update Aug 2017 for information and advice on the rare risk of central serous chorioretinopathy with local and systemic administration of corticosteroids. Prednisolone tablets 1mg, 5mg & 25mg Prednisolone oral solution 1mg/ml Non EC tablets should be prescribed. Please note plain prednisolone tablets 5mg may be crushed and dispersed in water and administered orally or via NG/PEG tube (off-label). For chronic use, prescribe minimum effective dose. Monitor for osteoporosis. ONLY for use in patients unable to tolerate plain prednisolone tablets 5mg. Please note oral solution 1mg/ml is more expensive than plain tablets 5mg. Methylprednisolone (Solu-Medrone intravenous injection) See MHRA Drug Safety Update Oct 17 for background information on the warning not to use Solu- Medrone 40mg Injection in patients with cows' milk allergy. Prednisolone soluble tablets 5mg ONLY for use in patients unable to tolerate prednisolone oral solution 1mg/ml. Please note soluble tablets 5mg are considerably more expensive than both plain tablets 5mg and oral solution 1mg/ml. 10.1.2.2 Local corticosteriod injections Administration should only be undertaken by health care professionals who have received appropriate training. Please see MHRA Drug Safety Update Aug 2017 for information and advice on the rare risk of central serous chorioretinopathy with local and systemic administration of corticosteroids.
Chapter 10 page number 3 Hydrocortisone acetate Methylprednisolone acetate (Depo- Medrone ) Triamcinolone acetonide 10.1.3 Drugs which suppress the rheumatic disease process (DMARDs) Consultant Rheumatologist or Consultant Paediatrician approval is required for all DMARDs. All DMARDS are supported by shared care agreements but GPs need to check service provision arrangements within their PCT. Hydroxychloroquine Sulfate Mepacrine - Unlicensed Sulfasalazine (EC) Sodium Aurothiomalate injection (Gold) Penicillamine Only EC is licensed for RA. Drugs affecting immune response initiation by Consultant Rheumatologist only Methotrexate Tablets 2.5mg only Azathioprine Leflunomide Ciclosporin Mycophenolate Given ONCE A WEEK only. Note Folic Acid 10mg is usually given ONCE A WEEK with Methotrexate to reduce side effects. It should NOT be taken on the same day as the Methotrexate See MHRA Drug Safety Update Jan 2015 for information on risk of bronchiectasis and risk of hypogammaglobulinaemia. For new pregnancy-prevention advice for women and men see MHRA Drug Safety Update Dec 15. Methotrexate injection Cyclophosphamide tablets Cyclophosphamide injection Cytokine modulators - initiation by Consultant Rheumatologist only
Chapter 10 page number 4 Abatacept see NICE TA195. see NICE TA375. Adalimumab See NICE TA 195. See NICE TA 199. See NICE TA 375. See NICE TA 383. Apremilast - See NICE TA433 Refer to MHRA Drug Safety Update Jan 17 for further information and advice on risk of suicidal thoughts and behaviour. Baricitinib See NICE TA466. Certolizumab See NICE TA375 See NICE TA383 See NICE TA415 See NICE TA445 Etanercept See NICE TA 195. See NICE TA 199. See NICE TA 375. See NICE TA 383. Golimumab See NICE TA220 and TA225. See NICE TA375. See NICE TA383. Infliximab See NICE TA 195. See NICE TA 199. See NICE TA 375. See NICE TA 383.
Chapter 10 page number 5 10.1.4 Drugs used for the treatment of gout ACUTE For additional guidance on the treatment of acute TREATMENT attacks of gout please see BNF Rituximab See NICE TA195. See health care professional letter (November 2013) Sarilumab- See NICE TA 485. Please note CCG Bluteq approval is required. Secukinumab See NICE TA407. See NICE TA445. Tocilizumab See NICE TA247. See NICE TA375 Tofacitinib See NICE TA480. Please note CCG Bluteq approval is required. Ustekinumab - For treatment of active psoriatic arthritis in accordance with NICE TA340. information on risk of exfoliative dermatitis. Colchicine LONG-TERM CONTROL Allopurinol Febuxostat Sulfinpyrazone Acute gout. Causes acute vomiting & diarrhoea which is therapy limiting see BNF. Maximum dose per course 6mg, do not repeat within 3 days. See MHRA Alert Do not start during an acute attack; usually started 1-2 weeks after the attack has settled Long-term control of gout. To be prescribed only when patients have failed on Allopurinol. See NICE TA164. See MHRA Alert Consider for allopurinol allergic patients. Benzbromarone unlicensed use. For Consultant Rheumatologist prescribing only. Hyperuricaemia associated with cytotoxic drugs Rasburicase For Haematology/Oncology use only. Used in leukemic patients with large tumours where rapid cell death is expected on commencement of treatment. 10.2 Drugs used in neuromuscular disorders See also Central nervous system Chapter 4 and Anaesthesia Chapter 15 10.2.1 Drugs that enhance neuromuscular transmission Pyridostigmine bromide
Chapter 10 page number 6 10.2.2 Skeletal muscle relaxants see CNS chapter 4 for other muscle relaxants and Botulinum toxin (specific funding required for individual uses) Diazepam Use short term, with care. Can cause sedation and addictive. Quinine Sulfate 200mg Quinine is no longer recommended as a routine treatment for nocturnal leg cramps, and should only be considered when cramps cause regular disruption of sleep. See MHRA Drug Safety Alert for details. See MHRA Drug Safety Update Nov 17 for further information and advice on dose-dependent QTprolonging effects and updated medicine interactions. Trust recommended dose is 200mg at night. 10.3 Drugs for treatment of soft tissue disorders and topical pain relief 10.3.1 Enzymes 10.3.2 Rubefacients and other topical antirheumatics Rubefacients The use of rubefacients is not recommended Collagenase clostridium histolyticum- For treatment of Dupuytren s contracture in line with NICE TA459. NSAIDs Ibuprofen 5% gel Use of topical NSAIDs discouraged due to; - Conflicting evidence as to effectiveness. - Concerns about cost-effectiveness. - Some reports of side effects See NICE CG59 Causes photosensitivity reactions. Patients should avoid direct sunlight, ultraviolet rays, sunbeds and sunlamps (10). Capsacicin Capsaicin strength 0. 025% Capsaicin strength 0. 075% Miscellaneous Pilocarpine tablets For diabetes mellitus neuropathy as advised by consultant endocrinologist. For post herpetic neuralgia. Used for relief of dry mouth and eyes in patients with Sjogren s Syndrome. Iloprost Consultant Rheumatologist or Consultant Vascular Surgeon approval required. NHS Swindon, NHS Wiltshire and Great Western Hospitals NHS Foundation Trust in collaboration with Avon & Wiltshire Mental Health Partnership. References: 1) Anon. Choosing a non-steroidal anti-inflammatory drug. MeReC Bulletin 1994; 5:45-48. 2) Acute renal failure precipitated by NSAID s in multiple myeloma American Journal of Hematology 58:142-144 (1998). 3) Safety of Selective and non-selective NSAIDS Prof. G. Duff (Chairman, Commission of Human Medicines) Oct06..http://www.info.doh.gov.uk/doh/embroadcast.nsf/vwDiscussionAll/A99C5CE8C60EEB5380257211002E4A40 4) Henry.D et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 1996, 312,1563-1566. 5) N.Eng. J.Med, 2001 Vol 345,No 25 1809-1817 6) Lehn OF, Jensen ON, et al. Enteric-coated and plain naproxen tablets in osteoarthritis; tolerability and efficacy. Eur J Rheumatol Inflamm. 1992;12(2):31-6 http://www.hubmed.org/display.cgi?issn=01401610&uids=1364936.
Chapter 10 page number 7 Huskinsson EC, Bernstein RM, et al. Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated and standard formulations. Eur J Rheumatol Inflamm. 1992;12(2):27-30. http://www.hubmed.org/display.cgi?issn=01401610&uids=1364935. Khong TK, Downing ME, et al. The efficacy and tolerability of enteric and non-enteric coated naproxen tablets: a double-blind study in patients with osteoarthritis. Curr Med Res Opin. 1991;12(8):540-546. http://www.hubmed.org/display.cgi?issn=03007995&uids=1764957. 7) MHRA/CSM advice to healthcare professionals on the safety of selective COX-2 inhibitors 17 th February 2005. 8) Anon. Bisphosphonates for osteoporosis. DTB 2001; 39:68-72. 9) GWH local consultant recommendation. 10) MHRA Drug Safety Update - Volume 2, Issue 11, June 2009. 11) BNF 63, March 2012