FDA Drug Safety Communications: A Narrative Review and Clinical Considerations for Older Adults

Abstract

Background The United States Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the post-marketing period. This has resulted in an increase in communication from the FDA in recent years about the safety of certain drugs. It is important to stay abreast of the current literature on drug risks in order to effectively communicate these risks to patients, other health care providers, and the general public. Objective To summarize four new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. Methods The FDA website was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature supporting the drug safety concern. Results FDA drug safety communications for four drugs were chosen based on the potential clinical importance in older adults. A warning for citalopram was made due to potential problems with QT prolongation in patients taking >40 mg/day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20 mg/day maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship has been shown for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in those with decreased renal function. This medication should be used with caution in older adults. Finally, several warnings were made regarding statins. Routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury from statin use, and thus liver enzymes are no longer recommended to be routinely monitored. Statin-induced cognitive changes are rare and insufficient evidence is currently available to establish causality. Statins appear to moderately increase the risk of developing diabetes (versus placebo), and regular screening for diabetes should be considered, especially for those taking high-dose statins and those with multiple risk factors for diabetes. Conclusion FDA drug safety communications incorporate complex methodologies which investigate the risks (and relative benefits) of medication therapy. Clinicians caring for older adults need to be aware of the most current evidence behind these drug risks in order to effectively communicate with and care for their patients.

Simvastatin Attenuates TGF-�1-Induced Epithelial-Mesenchymal Transition in Human Alveolar Epithelial Cells

“…More importantly, statins are commonly accepted to be safe and show tolerance in elderly patients [20,41,44,45]. Thus, statins are a potential therapeutic choice for IPF treatment.…”

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

“…Statin-induced jaundice is calculated at a risk of 1 in 17,434 users per year, based on a population in Iceland [29]. Periodic monitoring of liver enzyme activity seems not to be useful in either detecting or preventing serious liver injury, thus justifying the discontinuation of the previous recommendation for routine, serial liver enzyme monitoring during chronic statin therapy [30]. According to statement from 28 th February 2012 the Food and Drug Administration (FDA) recommends checking liver function tests at baseline and later as clinically warranted [31].…”

ESC/EAS Guidelines for the management of dyslipidaemias

“…212,214 Recent reviews are encouraging about the safety of long-term statin therapy. 221,222 ALT is recommended 8 -12 weeks after the start of lipid-lowering therapy or dose change, but routine control of ALT during treatment is not recommended and should be performed, if indicated, based on clinical observations. In patients whose liver function tests rise above three times the ULN, explanations such as alcohol ingestion or non-alcoholic fatty liver disease should be sought and the levels monitored.…”

“…Progression to liver failure is exceedingly rare, therefore routine monitoring of ALT during statin treatment is no longer recommended. 221 Patients with mild ALT elevation due to steatosis have been studied during statin treatment and there is no indication that statins cause any worsening of liver disease.…”