10: Musculoskeletal and joint diseases
Please select a topic:
10.1 Drugs used in rheumatic diseases and gout / 10.2 Drugs used in neuromuscular disorders10.3 Drugs for the relief of soft-tissue inflammation
Changes to the Formulary since previous version
(1.10..2013)
Section / Change / Reason for change10.1 / ADDED: Rituximab: screen for hepatitis B virus before treatment / MHRA Drug Safety Update
10.1 Drugs used in rheumatic disorders and gout
Non-steroidal anti-inflammatory drugs
· Celecoxib 100mg and 200mg capsules
· Diclofenac 12.5mg, 25mg, 50mg and 100mg suppositories
· Diclofenac 50mg dispersible tablets
· Diclofenac 75mg/2ml injection (Dyloject®) – Theatre use only
· Etodolac 600mg s/r tablets
· Ibuprofen 200mg and 400mg tablets
· Ibuprofen 100mg/5ml syrup
· Indometacin/Indomethacin 25mg capsule
· Indometacin/Indomethacin 75mg s/r capsule
· Mefenamic acid 500mg tablets
· Mefenamic acid 50mg/5ml suspension
· Nabumetone 500mg tablets
· Naproxen 250mg and 500mg e/c tablets
Aspirin and the salicylates
· Aspirin 300mg soluble tablets
· Aspirin 300mg e/c tablets
Dose
- Ibuprofen tablets 200mg, 400mg; syrup 100mg/5mL: 1.2-2.4g daily in 3-4 divided doses.
- Diclofenac sodium dispersible tablets 50mg, suppositories 12.5mg, 25mg, 50mg, 100mg: orally (or rectally), 75-150mg daily in 2-3 divided doses. Max total daily dose by any route, 150mg.
- Naproxen tablets e/c 250mg, 500mg: 0.5-1g daily in 1-2 divided doses; acute musculoskeletal disorder, 500mg initially then 250mg 6-8 hourly as required; max dose after first day 1.25g daily.
- Celecoxib capsules 100mg, 200mg; see BNF
- Etodolac tablets m/r 600mg: 600mg daily.
- Indometacin capsule 25mg; capsule m/r 75mg: dose varies with indication, see BNF.
- Mefenamic acid tablets 500mg; oral suspension 50mg/5ml: 500mg three times a day
- Nabumetone tablets 500mg: usually 1g at night.
- Aspirin tablets e/c 300mg, soluble tablets 300mg: see BNF
Prescribing notes
· Consider whether an NSAID is required; regular dosing of paracetamol is often adequate, e.g. for osteoarthritis.
· Naproxen or Ibuprofen should be used in preference to diclofenac.
· Patients that require NSAIDs should be prescribed them at the lowest effective dose and long-term use should be avoided if possible.
· Relative contra-indications to NSAIDs include heart failure, hypertension, renal impairment, peptic ulceration; absolute contra-indications include proven hypersensitivity to aspirin or any NSAID.
· NSAIDs may worsen asthma; they are contra-indicated if aspirin or any other NSAID has precipitated attacks of asthma.
· Long-term use of ibuprofen may interfere with the cardioprotective effects of low dose aspirin. Naproxen may be a suitable alternative.
· The CSM has advised that non-selective NSAIDs are contra-indicated in patients with previous or active peptic ulceration and that selective inhibitors of cyclo-oxygenase-2 are contra-indicated in active peptic ulceration (see also CSM advice below). While it is preferable to avoid NSAIDs in patients with active or previous gastro-intestinal ulceration or bleeding, and to withdraw them if gastro-intestinal lesions develop, nevertheless patients with serious rheumatic diseases (e.g. rheumatoid arthritis) are usually dependent on NSAIDs for effective relief of pain and stiffness.
CSM Advice: NSAIDs 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 NSAIDs except when specifically indicated (i.e. for patients at a particularly high risk of developing gastroduodenal ulceration or bleeding) and after assessing their cardiovascular risk.
Non-selective NSAIDs may also be associated with a small increased risk of thrombotic events particularly when used 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 lower thrombotic risk, and low doses of ibuprofen (1.2g daily or less) have not been associated with an increased risk of myocardial infarction. A small increased thrombotic risk cannot be excluded for other NSAIDs.
The CHM has advised (October 2006) that the lowest effective dose of NSAID or cyclo-oxygenase-2 selective inhibitor should be prescribed for the shortest period to control symptoms and that the need for long-term treatment should be reviewed periodically.
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 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.
Recommendations are that NSAIDs associated with a 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 can increase the risk of gastro-intestinal side-effects; this combination should be used only if absolutely necessary and the patient should be monitored closely.
MHRA Drug Safety Update
Diclofenac: new contraindications and warnings after a Europe-wide review of cardiovascular safety
Article date: June 2013
Summary
Available data indicate that the cardiovascular risk with diclofenac is similar to that of the selective COX-2 inhibitors. Consistent with COX-2 inhibitors, diclofenac is now contraindicated in those with: ischaemic heart disease; peripheral arterial disease; cerebrovascular disease; or established congestive heart failure (New York Heart Association [NYHA] classification II–IV). The new treatment advice applies to systemic formulations (ie, tablets, capsules, suppositories, and injection available both on prescription and via a pharmacy, P); it does not apply to topical (ie, gel or cream) formulations of diclofenac.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON286975
Systemic corticosteroids
· Prednisolone 1mg and 5mg tablets
· Prednisolone soluble 5mg tablets
· Prednisolone 2.5mg e/c tablets
Local coricosteroid injections
· Methylprednisolone 40mg/ml injection (Depo-Medrone®)
· Methylprednisolone 40mg/ml with lidocaine 10mg/ml injection
· Triamcinolone acetonide 40mg/ml injection (Kenalog®)
· Triamcinolone acetonide 10mg/ml injection (Adcortyl®)
Dose
- Prednisolone tablets 1mg, 5mg; tablets e/c 2.5mg; soluble tablets 5mg: see prescribing notes.
- Methylprednisolone acetate (Depo-Medrone®) vials 40mg/mL, 80mg/2mL, 120mg/3mL: deep intramuscular injection into gluteal muscle, 40-120mg, repeated after 2-3 weeks if required. Intra-articular injection, 4-80mg according to size.
- Adcortyl® Intra-articular (triamcinolone acetonide) injection 10mg/mL: by intra-articular injection, 2.5mg-15mg according to size (for larger doses use Kenalog®).
- Kenalog® Intra-articular (triamcinolone acetonide) injection 40mg/mL: by intra-articular injection, 5-40mg according to size; total max 80mg (for doses below 5mg, use Adcortyl® Intra-articular).
Prescribing notes
· Corticosteroids should ideally only be commenced after liaison with a rheumatologist, and a steroid card given when appropriate.
· Patients should be provided with written information (e.g. the Arthritis Research Campaign leaflet on steroids) and given the opportunity to discuss the benefits and risks of long-term corticosteroids before treatment is commenced.
· The recommended dose of prednisolone for polymyalgia rheumatica is 10-15mg daily for 3-4 weeks then tapered by e.g. 2mg per week until the dose is 10mg daily then more slowly reduced e.g. by 1mg per month to a maintenance dose of 5-7mg daily. Slow withdrawal may be tried after 18-24 months but approximately 50% of patients relapse and require long-term therapy.
· The recommended dose for giant cell arteritis is 60mg daily with the patient referred for an emergency temporal artery biopsy.
· Prophylactic bone protection should be offered to patients anticipated to receive any dose of prednisolone daily for longer than 3 months.
· Bone loss is related to the cumulative dose of glucocorticoids and preventative measures should therefore be considered in patients receiving intermittent courses of prednisolone resulting in a cumulative dose of 250mg or more in 3 months.
· Long-term steroids should be withdrawn gradually.
· Intra-articular steroids should be used judiciously and ideally any one joint should not be injected more than 3 times in 1 year.
Drugs which suppress the rheumatic disease process
· Abatacept injection (Restricted)
· Adalimumab 40mg injection (Restricted)
· Azathioprine 25mg and 50mg tablets
· Ciclosporin 25mg, 50mg and 100mg capsules (Neoral®)
· Ciclosporin 100mg/ml oral solution (Neoral®)
· Certolizumab injection (Restricted) – use as per NICE guidance only
· Etanercept 25mg and 50mg injection (Restricted)
· Golimumab injection (Restricted) – use as per NICE guidance only
· Hydroxychloroquine 200mg tablets
· Infliximab 100mg injection
· Leflunomide 10mg, 20mg and 100mg tablets
· Methotrexate 2.5mg tablets
· Methotrexate injection
· Penicillamine 125mg and 250mg tablets
· Rituximab 10mg/ml injection (Restricted)
· Sodium aurothiomalate 10mg and 50mg injection
· Sulfasalazine 500mg e/c tablets
· Sulfasalazine 250mg/5ml suspension
· Tocilizumab injection (Restricted)
Dose
- see BNF or consult product literature.
Prescribing notes
· Risks/benefits of disease-modifying antirheumatic drugs (DMARDs) should be discussed with patients before commencing using a written information sheet available from the Arthritis Research UK or the Rheumatology Day Unit Information Sheet.
· There is a shared care monitoring protocol in place for disease-modifying antirheumatic drugs (DMARDs).
· The MHRA has received reports of prescription and dispensing errors for methotrexate that have resulted in serious and fatal adverse reactions. Methotrexate tablets should be prescribed in 2.5mg strength only. The 10mg strength should not be used since they may be confused with the 2.5mg tablets.
· Providing monitoring procedure is followed, NSAIDs may be prescribed with methotrexate.
· Folic acid 5mg should be prescribed weekly, 24 hours after methotrexate to reduce toxicity.
· The brand of ciclosporin to be dispensed should be specified since there are differences in bioavailability.
· The tumour necrosis factor (TNF) antagonists adalimumab, infliximab, etanercept, abatacept, certolizuamb, golimumab, tocilizumab and rituximab are reserved for specialist use on the treatment of patients with severe rheumatoid arthritis, ankolysing spondylitis and psoriatic arthritis. They should only be used in accordance with the respective guidance from NICE.
MHRA Drug Safety Update
Rituixmab: screen for hepatitis B virus before treatment
Article date: December 2013
Summary
Screening for hepatitis B virus is now recommended in all patients (not only those at risk of this infection) before starting treatment for all indications. A patient with positive serology for hepatitis B virus should be referred to a specialist in liver disease before starting treatment with rituximab. During treatment, these patients should be monitored and managed to prevent reactivation of the virus.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON350669
Drugs for treatment of gout
· Colchicine 500 microgram tablets
· Allopurinol 100mg and 300mg tablets
· Allopurinol 100mg/5ml suspension
· Febuxostat 80mg & 120mg tablets
· Rasburicase 7.5mg injection
Dose
- Colchicine tablets 500micrograms: 500micrograms-1mg initially, then usually 500micrograms 3 times daily until pain relief or vomiting or diarrhoea occur, or a total dose of 6mg has been reached; the course should not be repeated within 3 days.
- Allopurinol tablets 100mg, 300mg: initially 100-300mg daily; maintenance dose according to severity, 100-900mg daily (doses above 300mg should be divided).
- Febuxostat tablets 80mg, 120mg: -80mg once daily, if after 2–4 weeks serum uric acid greater than 6mg/100mL, increase to 120mg once daily
Prescribing notes
· NSAIDS should be used to treat acute attacks of gout.
· Aspirin is not indicated for gout.
· Colchicine may be preferable to indometacin in the elderly, patients receiving anticoagulants or in heart failure, or when NSAIDs are contra-indicated.
· The dose of colchicine should be reduced if diarrhoea occurs.
· Allopurinol should be used to prevent recurrent attacks of gout.
· Allopurinol must not be started during an acute attack of gout since it may exacerbate and prolong it.
· To prevent an acute attack of gout on introduction of allopurinol, low dose colchicine (500micrograms 1-2 times daily) or NSAID should be prescribed concomitantly for 6-8 weeks.
· Allopurinol must be started at low dose.
· If acute gout occurs while the patient is receiving allopurinol, continue the prophylactic agent and add in NSAID or colchicine.
· Allopurinol can be started 2-3 weeks after recovery from the acute attack.
· The dose of allopurinol should be reduced in renal impairment and older patients.
· Patients can be given a supply of colchicine and advised to start treatment if they feel an attack coming on. Early treatment with colchicine can prevent a full blown attack of acute gout developing.
· Febuxostat is contra-indicated in ischaemic heart disease and congestive heart failure.
· Rasburicase is only to be used for cytotoxic hyperuricaemia.
10.2 Drugs used in neuromuscular disorders
Drugs which enhance neuromuscular transmission
· Neostigmine 2.5mg/ml injection
· Edrophonium chloride 10mg/ml injection
· Pyridostigmine 60mg tablets
Dose
- Pyridostigmine bromide tablets 60mg: 30-120mg 3 times daily or according to individual circumstances. Doses above 450mg daily should only be given after consultation with the supervising neurologist.
- Neostigmine metilsulfate injection 2.5mg/mL: by subcutaneous or intramuscular injection, 1-2.5mg at suitable intervals during the day; usual total daily dose 5-20mg.
Prescribing notes
· Treatment for myasthenia gravis should only be initiated on specialist advice.
· Edrophonium is used in hospital as a diagnostic test for myasthenia gravis.
· Pyridostigmine bromide 60mg orally is approximately equivalent to neostigmine 15mg orally, or 1-1.5mg by intramuscular or subcutaneous injection.
· Pyridostigmine bromide has a longer duration of action than neostigmine and is first choice for oral use. Neostigmine is useful in patients requiring parenteral treatment.
· An antimuscarinic (e.g. propantheline 15mg orally as required up to 3 times daily or adjusted to individual circumstances) may be required to treat side-effects such as sweating, colic, excessive salivation and diarrhoea.
· In more severe cases, prednisolone ± a corticosteroid-sparing agent (azathioprine) may be prescribed under specialist supervision for myasthenia gravis.