AHA: Statin-CVD Drug Interactions Often Unavoidable, But Manageable

The risk for interactions between statins and other cardiovascular drugs may be unavoidable for heart patients, but it can be reduced with proper clinical management, according to the American Heart Association.

Healthcare providers should know dose limits, adverse effects and monitoring parameters associated with these drug-drug interactions (DDIs) to minimize toxicity risks, AHA writing committee chair Barbara Wiggins, PharmD, and colleagues wrote in a scientific statement on statin-cardiovascular disease drug interactions published Oct. 17 in the journal Circulation.

"A review of all medications that statin-treated patients are taking should be done at each clinical encounter and during transitions of care within a health system so that DDIs can be identified early, evaluated and managed appropriately by implementing dose adjustments, changing to a safer statin medication or discontinuing when needed," the statement noted.

Current guidelines recommend high-intensity statin treatment for patients with known atherosclerotic cardiovascular disease (ASCVD) who are age 75 and younger and moderate- to high-intensity statin therapy for heart patients who are older than age 75, have diabetes mellitus, have familial hypercholesterolemia, or have a 10-year ASCVD risk of 7.5% or greater.

The newly published statement highlighted potentially harmful interactions between the lipid lowering fibrate drug gemfibrozil and specific statin drugs.

"On the basis of pharmacokinetic evidence, the combination of gemfibrozil with lovastatin, pravastatin, and simvastatin is potentially harmful and should be avoided," the scientific statement noted. "Although gemfibrozil interacts with atorvastatin, pitavastatin and rosuvastatin, the result is only a minor increase in statin concentrations, and the combination may be considered if clinically indicated."

Recommendations for avoiding statin-fibrate DDIs include:

• Choosing fenofibrate or fenofibric acid over gemfibrozil, if possible, when used with a statin.
• When gemfibrozil is the only fibrate option, it should not be used with lovastatin, pravastatin or simvastatin.
• If gemfibrozil is used with other statins, "consideration should be given to the use of a lower statin dose to minimize risk."

Other specific recommendations included:

• Limiting doses of lovastatin or simvastatin to 20 mg/day or less when given with the calcium channel blocker amlodipine.
• Use of a non-CYP3A4-metabolized statin when used in combination with the calcium channel blockers verapamil or diltiazem.
• When used in combination with the antiarrhythmic drug amiodarone, lovastatin doses should not exceed 40 mg/d and simvastatin doses should not exceed 20 mg/d.
• Simvastatin doses should be limited to 10 mg/d when prescribed in combination with the antiarrhythmic drug dronedarone.
• Monitoring for digoxin toxicity is recommended in patients treated with a combination of digoxin and atorvastatin.
• Doses of both lovastatin and simvastatin should be limited to 20 mg/d in patients who are also taking the angina agent ranolazine.

The report noted that while statins are a cornerstone of immunosuppressant pharmacotherapy in heart transplant recipients, "considerable controversy exists on which statins and what doses to use because of potential DDIs with the calcineurin inhibitors (eg., cyclosporine and tacrolimus) that could lead to myopathy or rhabdomyolysis."

The writing committee noted that combining cyclosporine, everolimus, or sirolimus with lovastatin, simvastatin and pitavastatin is potentially harmful and should be avoided, as should the co-administration of tacrolimus and lovastatin, simvastatin or pitavastatin.

"While many of these drug combinations are safe, every patient is different and will tolerate medications differently," said Wiggins, who is a clinical pharmacy specialist in cardiology at the Medical University of South Carolina, Charleston. In a written press statement, Wiggins noted that patients should be told about potential interactions and encouraged to talk to their healthcare providers about unusual side effects or concerns.

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