Suffolk PCT Drug & Therapeutics Committee New Medicine Report (Adopted by the CCG until review and further notice)

Transcription

1 Suffolk PCT Drug & Therapeutics Committee New Medicine Report (Adopted by the CCG until review and further notice) This drug has been reviewed because it is a product that may be prescribed in primary care. Medicine Glucosamine Hydrochloride (Alateris, William Ransom & Son) Document status Agreed at July 2008 Suffolk DTC meeting Date of last revision 1 July 2008 Traffic light decision Double Green Prescribers rating 7.Not acceptable - Product without evident benefit over others but with potential or real disadvantages Mechanism of action Indication Usual dosage Treatment alternatives Place in therapy Future alternatives Evidence for use A constituent of glycosaminoglycans in cartilage and synovial fluid. Its mechanism of action in humans in unknown. Relief of symptoms in mild to moderate osteoarthritis (OA) of the knee. Two tablets (1250mg glucosamine) once daily. Paracetamol, NSAIDs As an alternative to unlicensed glucosamine preparations in patients currently prescribed glucosamine. None known at present Thirteen trials were submitted to the EMEA for the European licensing of glucosamine hydrochloride, all were in the Cochrane review discussed below. Cautions / side effects None of the trials submitted used this product. 5 of the trials in the licence application were found by the Cochrane reviewers to have inadequately concealed treatment allocation. A Cochrane review of glucosamine for treating osteoarthritis in 2005 concluded that eight randomised controlled trials that had adequate concealment of treatment, demonstrated a small non-significant benefit of glucosamine over placebo for pain relief in knee OA (standardised mean difference (SMD) -0.19, 95% confidence interval (CI) to 0.11). Results for joint function were conflicting Lequesne Index scores from 3 trials demonstrated a moderate difference, (SMD (95% CI to -0.01, n=599). Five other trials that used WOMAC scoring found a very small difference between glucosamine and placebo (WOMAC total score SMD (-0.30 to 0.00, n=672) and WOMAC function subscale SMD (-0.21 to 0.08, n=750). Glucosamine has not been studied systematically for adverse effects and interactions, unlike other newly licensed products. Adverse effects include nausea, abdominal pain, indigestion, constipation, diarrhoea. Headache, tiredness, rash, itching and flushing are less

2 common. Other possible effects include a worsening of glucose tolerance, raised lipid levels and possible exacerbation of asthma. Glucosamine and glucosamine-chondroitin supplements have been linked to interactions with coumarin anticoagulants. Patients treated with coumarin anticoagulants should therefore be monitored closely when initiating or ending glucosamine therapy. Contraindicated in patients allergic to shellfish (the source of the product). Cost for 28 days Costs of alternatives for 28 days (from Drug Tariff June 2007) Potential number of patients in Suffolk PCT for 60 tablets. Glucosamine sulphate (food supplement) 1500mg 5.66 Ibuprofen up to 800mg TDS 4.42 Paracetamol 4g OD 2.33 OA is a common condition and prevalence increases with advancing age. Around 10% of people over 55 are thought to have substantial disability due to OA of the knee. Hip and hand joints are also commonly affected. The mainstay of treatment is symptom management with analgesics such as paracetamol and non steroidal anti-inflammatory drugs. Interest in other therapies such as glucosamine has increased in recent years. Given the over 45 s population of Suffolk PCT is 253,642. It is possible that 10%, i.e 25,364 patients may be suffering with OA. Suffolk PCT currently spends 65,000 each year on glucosamine preparations. Given that the licensed preparation costs more than three times as much as the food supplement it is possible that Suffolk PCT could be spending 195,000 per year on glucoasamine if every patient currently prescribed it is switched to the licensed medicine. This cost would be reduced if it was prescribed strictly within license. Points for consideration The licensed dose of glucosamine hydrochloride delivers a similar amount of glucosamine as 1500mg glucosamine sulphate, the dose and salt most commonly used in trials. Existing published trial data involving both sulphate and hydrochloride salts of glucosamine has been used to support licensing of this product, no new trials have been carried out. Recent NICE guidance on OA (February 2008) does not recommend use of glucosamine. Recent SMC advice does not recommend the use of glucosamine (as hydrochloride) within NHS Scotland for relief of symptoms in mild to moderate OA of the knee. To conclude, glucosamine (either as the hydrochloride or sulphate

3 salt) is not considered suitable for prescribing. Current clinical evidence for its efficacy is inconsistent and not convincing in spite of many randomised clinical trials. The trials showed a clear dichotomy between sponsored trials and independent trials, suggesting bias or unequal quality of preparation used. Where benefits for glucosamine were found the effect was small. Decisions from other bodies Comments sought from - Decision review date Ipswich Hospital not assessed KP West Suffolk Hospital not assessed SW Norfolk Therapeutic Advisory Group not assessed FM Cambridgeshire Joint Prescribing Group not assesses DM Scottish Medicines Consortium Rejected TBC References Glucosamine (as hydrochloride), 625mg tablets (Alateris ). Scottish Medicines Consortium: June Available via ay%202008%20for%20website.pdf Glucosamine Hydrochloride (Alateris ). UKMI New Medicines Profile: May Available via Glucosamine in osteoarthritis: MTRAC review. Available via Glucosamine therapy for treating osteoarthritis. Cochrane Systematic Review: Towheed TE, et al Available via Charts to be used in the decision making process in Suffolk PCT Quality of Evidence categories I Strong evidence from at least 1 RCT II-1 Evidence from a well designed CT without randomisation II-2 Evidence from well designed cohort or case controlled study II-3 Evidence from multiple time series or dramatic results III Opinions of respected clinicians or expert committees IV Evidence inadequate Cost utility categories

4 Per life year gained A Less than 3,000 B 3,000 to 20,000 C > 20,000 D Negative life years Recommendations informed by cost utility and quality of evidence Quality of evidence A B C D I ++ (high) ++ - X II X III X IV (low) Key to table above ++ Strongly recommended + Recommended - Beneficial but high cost X Not recommended 0 Not proven Adapted from: Quick and Clean : authorative health technology assessment for local health care contracting Andrew Stevens, Duncan Collin-Jones & John Gabbay. Health Trends Vol 27 No Prescriber s Rating Definitions [With acknowledgement to Prescrire] Bravo! -The drug is a major therapeutic advance in an area where previously no treatment was available. A real advance - The product is an important therapeutic innovation but has certain limitations. Offers an advantage - The product has some value but does not fundamentally change present therapeutic practice. Possibly Helpful - The product has minimal additional value, and should not change prescribing habits except in rare circumstances. Judgement reserved - The Committee postpones its judgement until better data and a more thorough evaluation of the drug are available. Nothing New - The product may be a new substance but is superfluous because it does not add to the clinical possibilities offered by previous products available. In most cases these are me-too products. Not acceptable - Product without evident benefit over others but with potential or real disadvantages To decide if a medication is to be used in Suffolk PCT

5 Criterion Tends to poor 2 Medium 4 Tends to good Quality of evidence in the IV III II-2 II-1 I papers reviewed Magnitude of effect Low xxxx Medium xxxx High inferred from the trials reviewed Known side effect profile High xxxx Medium xxxx Low Known interactions High xxxx Medium xxxx Low Concern re: possible side High xxxx Medium xxxx Low effects not yet uncovered Balance of benefit to harm Poor xxxx Medium xxxx Good (side effects, toxicity, interactions etc) NNT High xxxx Medium xxxx Low Comparison of Poor xxxx Medium xxxx Good effectiveness with other medicines in use for the same condition Severity of condition to be Trivial xxxx Medium xxxx Severe treated Cost utility score D C B?A A Recommendations informed by cost utility and quality of evidence 0 X To Decide Where A Medication Is To Be Used In Suffolk Skills of the prescriber Criterion Red Amber Green Double Green Experience of the Specific Specific Specific General condition Diagnosis Specific Specific Specific General Monitoring progress of Difficult Specific General General treatment Therapy Patient selection Difficult Specific Specific Easy Initiation of treatment Difficult Difficult Easy Easy Dose titration Difficult Specific Easy Easy Monitoring of side Complex Easy Easy Easy effects Method of administration Complex Normal Normal Normal

6 Discontinuation of treatment Complex Complex Easy Easy