The National Prescribing Centre has published MeReC Extra 43 (PDF) which contains an update on the current evidence regarding the clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) and details from two new studies in chronic obstructive pulmonary disease (COPD).
The antithrombotic effect of clopidogrel has been shown to be attenuated by PPIs at a pharmacokinetic level however the clinical significance of this interaction remains in debate. This MeReC reports results from a large observation study and an analysis of two randomised controlled trials (RCTs). These studies did not find a statistically significant increase in the rate of cardiovascular events in patients taking the combination. Clinicians are advised to continue to follow the current recommendations while this interaction is researched further.
This MeReC also discusses recent research in COPD. A systematic review of the risks and benefits of combination treatment with an inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) compared with a long-acting beta-agonist alone. The review found that there was no reduction of severe exacerbations, all-cause, respiratory or cardiovascular mortality associated with the combination treatment when compared to LABA alone. Combination therapy was associated with some adverse events including fungal, viral and bacterial infections of the respiratory tract, for example pneumonia.
Finally, a short term RCT compared the addition of a combination ICS/LABA (budesonide/formeterol) to tiotropium alone. The study design has several limitations and therefore the results need careful interpretation, clinicians are advised that practice should not change based upon this study alone.
Action: Clinicians who see patients with vascular disease or COPD will find this information useful and informative.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Eslicarbazepine acetate (Zebinix®) has been rejected for use as an adjunctive therapy in adults with partial-onset seizures with or without secondary generalisation. The review notes that efficacy has been demonstrated in three 12-week placebo controlled trials but that no active comparator studies have been completed. The economic analysis in the submission 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 British Medical Journal has published an analysis of the ACCORD Study. This analysis aimed to determine whether there is a link between hypoglycaemia and mortality among participants in the study.
ACCORD was stopped early when it became apparent that all-cause and cardiovascular mortality was higher in the intensively managed group (HbA1c < 6%) compared to the standard therapy group (HbA1c 7-7.9%). The analysis reviewed rates of self reported hypoglycaemia, hypoglycaemia requiring assistance from another individual and the more restrictive definition of hypoglycaemia requiring medical assistance and correlated these with mortality.
The analysis found that hypoglycaemia was associated with an increased risk of death in both arms of the study but that the increased risk of death in individuals in the intensive arm of the study could not be attributed to hypoglycaemia. A statistical difference in the rates of death was only apparent in individuals who had never previously experienced a hypoglycaemic episode requiring medical assistance. Overall, there was an increased relative risk of death in participants from both arms of the study who had already experienced at least one symptomatic, severe hypoglycaemic episode.
The authors conclude that, "susceptibility to severe hypoglycaemia may be a marker for an underlying disorder that increases the risk for death in patients with diabetes".
Action: This analysis indicates that patients with diabetes who experience a severe hypoglycaemia episode may benefit from a clinical review to ensure optimal management of risk factors for mortality. This study provides no justification for intensive glucose control while the reasons for the increased death rate found in the ACCORD trial remain unexplained.
The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for January 2010 (PDF).
This issue contains drug safety advice informing clinicians of an increased risk of Stevens-Johnson syndrome in genetically predisposed individuals of Thai or Han Chinese ethnic origin who take phenytoin. Clinicians should avoid using phenytoin in individuals who are known to be HLA-B*1502 positive but routine genetic screening is not currently recommended.
There is also a hot topic reviewing the use of methylphenidate in attention-deficit hyperactivity disorder (ADHD). Patient information leaflets are being updated to include the latest guidance on safe and effective use for patients and carers. Clinicians are reminded that:
- Treatment with methylphenidate should be supervised by a specialist
- Diagnosis should be made according to DSM-IV criteria or ICD-10 guideline
- Children and adolescents should have rigorous pre-treatment screening
- Patients should be monitored regularly during treatment including: blood pressure and pulse; height, weight, and appetite; onset or worsening of psychiatric symptoms and symptoms suggestive of heart disease
- Treatment should be interrupted at least yearly to determine whether continuation is needed
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.
The European Medicines Agency (EMEA) has issued a press release detailing a recent recommendation to add two new contraindications for ibrandonic acid 150mg tablets (Bonviva®).
The existing contraindications of hypersensitivity and hypocalcaemia will be added to as follows:
- Abnormalities of the oesophagus which delay oesophageal emptying such as stricture or achalasia
- Inability to stand or sit upright for at least 60 minutes
The current Summary of Product Characteristics (SPC) advises that individuals with a history of prolonged oesophageal transit time should pay particular attention to the dosing instructions.
It is unlikely that any bisphosphonate would be used or tolerated in patients with these contraindications as they would be likely to experience gastrointestinal side effects such as dysphagia, oesophagitis and oesophageal or gastric ulcers. These recommended changes will simply provide clarification and clearer information for clinicians and patients.
Action: Clinicians should be aware of these recommended changes and ensure that ibrandonic acid is not being used in patients with these contraindications.