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Statins and Antibiotics Can Be a Toxic Mix
Statins and antibiotics can be a toxic mix, according to highly publicized research published in the Annals of Internal Medicine. The study of more than 144,000 older statin users showed adding clarithromycin or erythromycin to the medication mix increased the risk of all-cause mortality and hospitalization for treatment of rhabdomyolysis or acute kidney injury. Those adverse events associated with the statin-antibiotic interaction may be rare, but clinicians cannot ignore the potential dangers. We recently asked Dr. Joseph Saseen, a professor and vice chair in the department of clinical pharmacy at the University of Colorado Anschutz Medical Campus, about what can be done to improve the care of statin users who need to take antibiotics. What was one of the biggest takeaways from the conversation? Pharmacists need to be more active in managing the medications patients are taking.
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PLN: Are physicians doing enough to minimize the mixing of antibiotics and statins?
Dr. Saseen: Prescribes are globally aware of the dangers associated with drug-drug interactions, but there’s a lack of knowledge about the risks associated with specific combinations, a lack of diligence in responding appropriately when the risks are known, or alert fatigue—prescribers may be aware of the risks, but dismiss them quickly. Even if prescribers are aware of the interaction between antibiotics and statins, they don’t always take appropriate actions to prevent it from occurring.
PLN: Which antibiotics and statins are associated with the highest risks?
Dr. Saseen: Azithromycin and clarithromycin are similar antibiotics that inhibit the metabolism of many statin drugs. That inhibition increases exposure to statins and puts patients at risk for myalgia and, the potentially more serious, myonecrosis and rhabdomyolysis. Risks associated with daptomycin are less known. Use of statins alone and daptomycin alone can increase risk of muscle toxicity, including rhabdomyolysis. So theoretically, that risk increases when the drugs are used together. There might not be pharmacokinetic data to back a known change in metabolism, but care recommendations suggest avoiding the use of statins and daptomycin in combination or, if the drugs are prescribed together, checking blood creatine kinase levels to assess patients for muscle toxicity. The potential for dangerous interactions with the use of daptomycin crosses all statins. Azithromycin and clarithromycin mainly interact with statins that require a significant amount of CYP3A4 metabolism. Not every statin carries the same magnitude of drug-drug interaction risk, which is localized to commonly used statins such as simvastatin and to some extent atorvastatin.
PLN: Are elderly patients at the greatest risk of harm?
Dr. Saseen: Actually, statins are now used in a broad range of patients to lower cardiovascular risks and cardiovascular events. That said, the very elderly, patients who are at least 75 years old, are more at risk for drug-drug interactions for a variety of reasons—they’re on more medications, they have different sensitivities to drugs, and they may have altered metabolism.
PLN: What preventative measures do you recommend?
Dr. Saseen: The first step is to avoid concomitant use of the therapies if at all possible. That can be done in many instances. But if using the drugs in combination is unavoidable, withholding statin therapy for the short period of time a patient is on an at-risk antibiotic is a reasonable course of action. There’s also the potential to use antibiotics or statins that aren’t associated with interaction risks. These are all reasonable approaches, but they’re not done nearly enough in practice.
PLN: How can pharmacists improve the safe use of antibiotics and statins?
Dr. Saseen: They must not only accept a more active role in medication management, but also embrace and own it. Some pharmacists are too passive, waiting for the providers to fix medication-related issues. Pharmacists need to be integrated and imbedded into health care systems as the ones responsible for making sure medication lists are appropriately documented and updated through transitions of care. Here at the University of Colorado, clinical pharmacists work within clinics and are actively involved in disease management by making sure medication recommendations are based on appropriate information such as the therapies patient are actually on. We have pharmacists involved in transitions of care, especially in our seniors clinic, and efforts are ongoing in primary care clinics to help patients as they transition from one institution to another or from the hospital to home—the riskiest points of care. There’s sometimes a passing of the buck to nurses and physicians, who make sure medication therapies are current and appropriate. But that approach is against the inter-professional culture that all health systems should incorporate to improve patient safety.
—Dan Cook
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