New Medicine Report (Adopted by the CCG until review and further

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1 New Medicine Report (Adopted by the CCG until review and further DEXIBUPROFEN notice) Document Status Decision made at Suffolk D&TC 7 th September 2006 Traffic Light Decision Double Green Prescriber s Rating Nothing New Date of Last Revision 11 th September 2006 Approved Name Dexibuprofen Trade Name Seractil Manufacturer Genus Legal Status POM Indication Symptomatic treatment for the relief of pain and inflammation associated with osteoarthritis Acute symptomatic treatment of pain during menstrual bleeding (primary dysmenorrhoea) Symptomatic relief of other forms of mild to moderate pain such as muscularskeletal or dental pain Dosage 600mg to 900mg daily divided in up to three single doses For treatment of mild to moderate pain initially 200mg single dose and daily doses of 600mg are recommended (NB Half tablets are stated as not giving 200mg) Maximum single dose 400mg maximum daily dose 1200mg Not recommended <18 years of age Cost 300mg tablets mg tablets Possible Number of Suffolk All patients in Suffolk Patients Number Needed to Treat Not calculated Treatment Alternatives Ibuprofen Other analgesics within BNF Future Alternatives None known Possible Future Indications None known but other uses for similar products Not to be used for promotional purposes Page 1 of 9 May be freely copied by NHS agencies

2 Reviewer s Comments The release of dexibuprofen, S(+)-ibuprofen, in the UK adds another nonsteroidal anti-inflammatory product to the list of available NSAIDs It is the active isomer of ibuprofen and has been shown to be at least equivalent to double the dose of ibuprofen. It has been shown that the onset of action is shorter (15 minutes less) than that for racemic ibuprofen and it is perhaps conceivable that this may be seen as an advantage in certain circumstances. It has been suggested that some of the side effect profile, such as the interference with the triglyceride pathway, is specific to the R(-) isomer of ibuprofen and thus dexibuprofen is a cleaner drug. However the evidence suggests that the gastrointestinal effects, which are most common and cause the patients the majority of concern, at relative doses are similar. Evidence Reviewed Paper, Review, Abstract etc. Seractil Summary of Product Characteristics Phleps W Overview on clinical data of dexibuprofen Clin Rheumatol (2001) Suppl 1 S15 S21 Hawel R, Klein G, Singer F et al Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip Int J Clin Pharmacology & Therapeutics Vol41 No4/2003( ) Klein G, Neff H, Kullich W S(+) versus racemic ibuprofen Letter Lancet March p 681 Dionne RA, McCullagh L Enhanced analgesia and suppression of plasma β-endorphin by the S(+)-isomer of ibuprofen Clin Pharmacol Ther 1998;63: Tooley P Seractil Product Monograph Document Genus Level of evidence N/A IV Level of evidence 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 Review Dexibuprofen has been available for prescription in Europe and other parts of the world since it was first introduced in Austria in Ibuprofen is a racemic mixture of R(-)-ibuprofen and S(+)-ibuprofen in roughly equal parts. The S(+) isomer, also known as dexibuprofen, is twice as soluble in both water and acid than the racemic mixture and as such permits rapid absorption by the body and extensive distribution into target tissues. In the overview of the clinical data of dexibuprofen by Phleps several clinical trials and post-marketing surveillance studies were reviewed and a meta- I I I IV Not to be used for promotional purposes Page 2 of 9 May be freely copied by NHS agencies

3 analysis was performed. Six of the trials were double-blind studies and the others were a pharmacokinetic study and a long-term safety study both of which were open.it was found that in a dosage ratio of 0.5:1 dexibuprofen was equally efficacious as racemic ibuprofen. In addition 75% of the maximum daily dose of dexibuprofen (300mg three times a day) was equally efficacious as the maximum daily dose (50mg three times a day) of diclofenac sodium. In the paper by Dionne it is reported that the S(+) isomer of ibuprofen in an oral surgery model of acute pain provided faster onset and greater analgesic activity than the racemic mixture of ibuprofen. These results are shown in Table 1. Table 1 To show median time to onset of pain relief and duration of relief. S(+)-ibuprofen 200mg S(+)-ibuprofen 400mg Racemic ibuprofen 400mg n Median time to onset of pain relief (minutes) Median time to end of satisfactory pain relief (minutes) Median time to request for rescue medication (hours) Adverse Effects etc. For full information please refer to the Summary of Product Characteristics Phleps reports a meta-analysis of five randomised trials of up to 21 treatment days duration in the dose range of mg dexibuprofen and mg racemic ibuprofen. Adverse events classified as possible, probable and very probable were included as adverse reactions and analysed. The results are shown in Table 2. Table 2 To show the meta-analysis concerning % ADRs in five randomised doubleblind clinical studies % of patients reporting symptoms NB Multiple counts possible S(+)-ibuprofen Racemic ibuprofen n Gastrointestinal tract Central nervous system 2.54* 4.63 Skin Cardiovascular Others Changes in complete blood count Changes in laboratory values Total sum of ADRs 15.66* Withdrawals from treatment * p<0.05 Not to be used for promotional purposes Page 3 of 9 May be freely copied by NHS agencies

4 Economic Information A comparison of prices for a 28 day treatment course using ibuprofen, Brufen and Seractil is shown in Table 3. Table 3 To show comparative prices for ibuprofen, Brufen and Seractil Medicine Dose No tablets Cost Ibuprofen 400mg tds 84 (OP) 3.80 Ibuprofen 600mg tds 84 (OP) 5.94 Ibuprofen 600mg tds 84 (ex 100) 3.77 Brufen 400mg tds 84 (ex 100) 6.85 Brufen 600mg tds 84 (ex 100) Seractil 300mg bd 84 (ex 60) 8.84 Seractil 300mg tds 84 (ex 60) Seractil 400mg bd 84 (ex 60) 9.31 Seractil 400mg tds 84 (ex 60) DT price August 2006, Brufen & MIMS price August 2006 SUFFOLK DRUG AND THERAPEUTICS COMMITTEE New Drug Bulletin Dexibuprofen (Seractil ) SUFFOLK DRUG AND THERAPEUTICS COMMITTEE RECOMMENDATION: Dexibuprofen for pain relief Suffolk Drug and Therapeutics Committee decision on dexibuprofen: Prescriber s Rating 6: 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. Traffic Light decision Double Green GP initiated and prescribed. Indication: Symptomatic treatment for the relief of pain and inflammation associated with osteoarthritis Acute symptomatic treatment of pain during menstrual bleeding (primary dysmenorrhoea) Symptomatic relief of other forms of mild to moderate pain such as muscularskeletal or dental pain Not to be used for promotional purposes Page 4 of 9 May be freely copied by NHS agencies

5 Dosage: 600mg to 900mg daily divided in up to three single doses For treatment of mild to moderate pain initially 200mg single dose and daily doses of 600mg are recommended (NB 400mg tablets are scored although halving the tablet will not give an exact half dose) Maximum single dose 400mg maximum daily dose 1200mg Not recommended <18 years of age Cost: 300mg tablets mg tablets Further Comments: Dexibuprofen is an isomer of ibuprofen which has been available in Europe since 1994 It has a slightly quicker onset of action than ibuprofen, and is comparable in efficacy to diclofenac 50mg at the licensed doses. Local consultants have been consulted according to the usual procedure there was little real enthusiasm for using the drug. Suffolk D&T Committee felt that dexibuprofen offers little or no advantage over other NSAIDs. Dexibuprofen carries a black triangle in common with all new drugs. All suspected adverse reactions should be reported to the CSM on a yellow card. *Suffolk D&T s Prescriber s Rating ranges from Grade 1: Bravo! The drug is a major therapeutic advance in an area where previously no treatment was available to Grade 7 Not acceptable - product without evident benefit over others but with potential or real disadvantages. Paul Berry Prescribing Medical Advisor September 2006 These notes are only intended to provide brief guidance. Please refer to the latest Summary of Product Characteristics (Data Sheet) for full prescribing details. Not to be used for promotional purposes Page 5 of 9 May be freely copied by NHS agencies

6 Charts to be used in the decision making process in Suffolk Quality of Evidence categories Cost utility categories Per life year gained I Strong evidence from at least 1 RCT A Less than 3,000 II-1 Evidence from a well designed CT without randomisation B 3,000 to 20,000 II-2 Evidence from well designed cohort or case controlled study C > 20,000 II-3 Evidence from multiple time series or dramatic results D Negative life years III Opinions of respected clinicians or expert committees IV Evidence inadequate Recommendations informed by cost utility and quality of evidence Key to Table at Right Quality of evidence A B C D ++ Strongly recommended I ++ (high) ++ - X + Recommended II X - Beneficial but high cost III X X Not recommended IV (low) 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 Not to be used for promotional purposes Page 6 of 9 May be freely copied by NHS agencies

7 To Decide If A Medication Is To Be Used In Suffolk Criterion Tends to poor 2 Medium 4 Tends to good Quality of evidence in the papers reviewed IV III II-2 II-1 I Magnitude of effect inferred from the trials reviewed Low xxxx Medium xxxx High Known Side Effect Profile High xxxx Medium xxxx Low Known Interactions High xxxx Medium xxxx Low Concern re Possible Side Effects Not Yet Uncovered High xxxx Medium xxxx Low Balance of Benefit To Harm (side effects toxicity interactions etc) Poor xxxx Medium xxxx Good NNT High xxxx Medium xxxx Low Comparison Of Effectiveness With Other Medicines In Use For Poor xxxx Medium xxxx Good The Same Condition Severity of Condition to be Treated Trivial xxxx Medium xxxx Severe Cost Utility Score D C B?A A Recommendations informed by cost utility and quality of evidence 0 X Prescriber s Rating Definitions 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. Not to be used for promotional purposes Page 7 of 9 May be freely copied by NHS agencies

8 With acknowledgement to Prescrire Not to be used for promotional purposes Page 8 of 9 May be freely copied by NHS agencies

9 To Decide Where A Medication Is To Be Used In Suffolk Skills of the prescriber Criterion Red Amber Green D Green Experience Of The Condition Specific Specific Specific General Diagnosis Specific Specific Specific General Monitoring Progress Of Treatment Difficult Specific General General Therapy Patient Selection Difficult Specific Specific Easy Initiation Of Treatment Difficult Difficult Easy Easy Dose Titration Difficult Specific Easy Easy Monitoring Of Side Effects Complex Easy Easy Easy Method Of Administration Complex Normal Normal Normal Discontinuation Of Treatment Complex Complex Easy Easy Not to be used for promotional purposes Page 9 of 9 May be freely copied by NHS agencies