The British Medical Journal has published the results of a study that aimed to examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.
The study used observational data from the Nurses' Health Study which included data for 79,899 postmenopausal women. In 2000, a questionnaire was sent to 11,080 study participants with asthma or COPD and to 11,080 randomly selected controls. This questionnaire enquired about frequency, severity and duration of heartburn and acid regurgitation. The response rate was 86%.
The resulting data set contained 565,786 person years of follow up date and included 893 cases of hip fracture. The risk of a hip fracture for users of a PPI was 2.02/1,000 person year while in non-users it was 1.51/1,000 person years. This was a 35% increase in risk (95% confidence interval 1.13 - 1.62).
After correction for factors such as body mass index, physical activity and intake of calcium the risk was similar with a hazard ratio 1.36 (95% CI 1.13 to 1.63). The authors also report that the association was not altered after correction for reasons for PPI use.
The authors note that this study contains several strengths including prospective data collection and correction for several independent risk factors for hip fracture. Disease indication for the PPI has also been reduced in this analysis. There are however some limitations also, the data are still observational, hip fracture was self-reported and not confirmed in medical records and no data were available for bone mineral density.
The authors conclude that, "chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking". They also suggest careful evaluation of the need for long term, continuous use of PPIs, particularly among individuals with a history of smoking.
Action: This study adds to a growing body of evidence associating PPIs with fractures. Stepping down and stopping PPIs where possible would be a prudent risk management strategy.
The British Journal of Clinical Pharmacology has published the results of a study that aimed to assess the relationship between use of selective serotonin reuptake inhibitors (SSRIs) and injurious falls in nursing home residents with dementia. A press release has also been issued which has raised awareness in the general media (BBC).
This paper reviewed daily drug use and daily falls as recorded in 248 nursing home residents for a two year period starting January 2006. The average age of the study group was 82. This daily data collection results in a 85,074 person-day dataset. 152 residents sustained 683 falls, with 38 individuals falling on one occasion and 114 individuals falling more than once. The fall incidence was 2.9 falls per person per year.
SSRIs were used on a total of 11,105 person-days of the analysis period. A significant association was found between the risk of an injurious fall and increasing age, antidepressant use and antipsychotic use.
Dose-response relationships were also assessed by correcting drug dosage to a proportional "daily defined dose". Daily defined dose is a measure of drug consumption produced by the World Health Organization. Data models for a typical 85 year old female resident showed that, compared with non-use of an SSRI, a 0.25 proportional dose increased the risk of an injurious fall by 31%. A 0.5 proportional dose increased risk by 73% and 1.0 proportional use increased the risk by 198%. This risk increased even further with concomitant use of other sedatives or hypnotics.
The authors note that the study may be limited due to the data coming from a single nursing home establishment and that there were no users of fluoxetine or escitalopram during the study period.
The authors conclude that, "even at low doses, SSRIs are associated with increased risk of an injurious fall in nursing home residents with dementia".
Action: Clinicians should be aware of this new research linking SSRIs with falls. It may be prudent to consider the risk of falls and use the lowest effective dose of SSRIs when treating depression in elderly patients with dementia.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Exenatide once weekly (Bydureon®) has been accepted for restricted use in the treatment of type 2 diabetes mellitus in combination specified oral hypoglycaemic agents when adequate glycaemic control is not achieved despite being on maximally tolerated doses of these oral therapies. The restriction places this treatment as third line treatment option.
Fentanyl single dose nasal spray (Instanyl) has been accepted for restricted use for the management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain. The restriction allows use in patients who are unsuitable for other short-acting oral opioids (e.g. oral morphine) as an alternative to other buccal and sublingual fentanyl preparations.
Linagliptin (Trajenta®) has been accepted for restricted use in the treatment of adults with type 2 diabetes mellitus to improve glycaemic control. The restriction allows use in combination therapy with metformin when diet and exercise plus metformin alone does not provide adequate glycaemic control in patients for whom the addition of a sulphonylurea is inappropriate.
Ranolazine (Ranexa®) has been rejected for use as an add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line anti-anginal therapies. The clinical and economic case was insufficiently 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.
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