The National Prescribing Centre has published MeReC Extra 47 (PDF) which discusses the latest information regarding ezetimibe (Ezetrol®), antipsychotic drugs and the management of infections in primary care.
The section covering ezetimibe reviews a recent editorial in the Drugs and Therapeutics Bulletin that questioned whether this drug provides good value for money. This discussion reviews the recommendations from NICE and notes that the "acquisition cost considerably over simvastatin 40mg". It is also noted that the current evidence base for ezetimibe has not shown improvements in patient orientated outcomes.
The section covering antipsychotic drugs discusses the results of a meta-analysis that compared first and second generation antipsychotic drugs (also termed typical or conventional and atypical respectively) in early psychosis. This analysis found no significant differences in efficacy or rates of discontinuation between the two classes. There was more weight gain with the second generation drugs and more extrapyramidal symptoms with the first generation drugs. The current NICE guidance does not favour a particular class of antipsychotic so drug selection should be tailored to the individual patient after consideration of the side effect profile and acquisition cost.
This issue also directs readers to updated advice from the Health Protection Agency in the management of common infections in primary care. This update takes into account the advice of other organisations, such as NICE, SIGN and CKS.
Action: Clinicians who prescribe lipid modifying drugs, antipsychotic drugs or who treat infections in primary care will find this information useful and informative.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Eslicarbazepine (Zebinix®) has been accepted for restricted use after a resubmission for patients with highly refractory epilepsy who remain uncontrolled with existing anti-epileptic drugs as adjunctive therapy in adults with partial-onset seizures with or without secondary generalisation.
Oxycodone hydrochloride injection (OxyNorm®) has been accepted for restricted use for the treatment of moderate to severe pain in patients with cancer who have difficulty in tolerating parenteral morphine or diamorphine therapy.
Glucosamine sulphate (Glusartel®) has been rejected for use in patients for the relief of symptoms in mild to moderate osteoarthritis (OA) of the knee. The economic analysis was not sufficiently robust to gain acceptance.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The manufacturer of Epanutin®, a brand of phenytoin, has written to healthcare professionals advising of a short term supply problem. Phenytoin is used in the treatment of epilepsy. A copy of the letter (PDF) has been made available by the Pharmaceutical Services Negotiating Committee.
The supply problem is affecting the 25mg, 50mg and 100mg strengths. The 25mg and 50mg strengths are expected to be back in stock by week ending 19th November 2010 with the 100mg strength expected week ending 26th November 2010 although stock imported from Greece is expected at the same time as the lower strengths.
It should be noted that phenytoin is also available in a 100mg tablet but a permanent change to this product would be expensive. The Drug Tariff currently lists 28 tablets at £30.00 compared to £2.83 for 84 capsules.
Action: Clinicians should be aware of this supply shortage. Interim prescriptions for alternative strengths or formulations may be necessary while the supply chain is restocked.
The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for November 2010 (PDF).
This issue contains drug safety advice warning clinicians of drug interactions that may affect the clinical efficacy of tamoxifen and advising that inadvertent overdose have been reported with the new memantine (Ebixa®) pump device for Alzheimer’s disease.
Additionally, the hot topic section reviews that available data for bisphosphonate use and oesophageal cancer and concludes that there is insufficient evidence of a link.
Finally, in the hot topic section there is a review of some recent safety data for tiotropium (Spiriva®) in the Respimat® device. A recent study using this device found a non-significant increase in all-cause mortality compared with placebo. This finding is at odds with data for the dry powder device (HandiHaler®) where use was associated with a decrease in all-cause mortality. These new results may be a chance finding and further research is required. In the meantime it is recommended that suspected adverse events for either presentation should be reported, the recommended maximum dose should not be exceeded and that the Respimat device should be used with caution in patients with known cardiac rhythm disorders.
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.
The Lancet has published two studies this week that have the potential to reopen the debate about standard versus intensive lipid lowering. The first of these studies is a meta-analysis of statin trials and the second is a randomised controlled trial of simvastatin 80mg versus simvastatin 20mg. Both studies have been reported in the general media (BBC, Telegraph).
The meta-analysis included 26 trials involving 169,138 participants. All of these studies recruited at least 1,000 participants and ran for at least 2 years. 5 of the studies compared a standard statin dose with an intensive dose with the remaining 21 studies comparing statin therapy with a placebo control. This study also compared rates of some adverse events between the study groups. The analysis of the 5 studies with active comparators identified a 15% relative risk reduction (95% CI 11%-18%, p<0.0001) in cardiovascular events. The comparison of adverse effects focussed on haemorrhagic strokes and cancers and found no difference in event rates between the groups.
The authors conclude that, "further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke". They also indicate that for each 1mmol/L reduction in LDL there is a reduction in cardiovascular risk of approximately 20%.
This study does have some limitations. While it did assess adverse events there was no assessment of mild reactions or of liver dysfunction, myopathy and rhabdomyolysis. The conclusions are also based on clinical data alone without any consideration of the relative benefit in terms of additional acquisition costs that would be involved in using more intensive statin therapies.
The second study is the results of the SEARCH study, a randomised controlled trial involving 12,064 participants aged 18 to 80 years with a history of myocardial infarction. Participants were randomly assigned to treatment with either simvastatin 20mg daily or simvastatin 80mg daily. The study ran for a mean of 6.7 years with a composite primary endpoint of coronary death, myocardial infarction, stroke or arterial revascularisation..
At the end of follow up there was a non-significant reduction in major vascular events of 6% (relative risk ratio 0.94, 95% CI 0.88-1.01, p=0.10). There was no apparent difference in the rates of haemorrhagic stroke, vascular death or non-vascular death. There was a higher rate of myopathy (0.9%) in patients taking simvastatin 80mg compared to those taking simvastatin 20mg (0.03%).
The authors conclude that, "the 6% reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials". They also suggest that the higher rate of myopathy could be avoided by using other regimens to intensively lower LDL.
The conclusions of this study are restricted as it did not reach statistical significance in the primary outcomes. The authors also note that over the duration of the study, the introduction of more aggressive targets had the effect of reducing the net difference in LDL cholesterol between the two groups as more non-study treatments were started. The suggestion that alternative intensive lipid regimens could be used to reach lower targets and avoid the risk of myopathy seen with simvastatin 80mg does not consider the relative benefits in terms of higher acquisition costs.
Action: These two studies both appear to champion treating LDL to lower levels to prevent cardiovascular events. Neither study has assessed the impact of milder adverse drug reactions nor has any assessment be made of the relative benefits of more intensive lipid lowering treatments versus the acquisition costs to the NHS.