Clinically Relevant Drug-Drug Interactions in Primary Care

Mary Carpenter, PharmD; Holly Berry, PharmD; Allen L. Pelletier, MD


Am Fam Physician. 2019;99(9):558-564. 

In This Article

Statin Interactions


Amiodarone inhibits CYP3A4, which may decrease metabolism of certain statin drugs and increase the risk of statin-related muscle toxicity. Predisposing risk factors for muscle toxicity include age (older than 65 years), obesity, and renal/hepatic impairment.[30,31] Fluvastatin and pravastatin are metabolized through alternative pathways that do not affect amiodarone metabolism and are recommended over simvastatin and atorvastatin. When alternative statins are not appropriate, limit dosages of simvastatin to 20 mg per day or lovastatin to 40 mg per day when used concomitantly with amiodarone.[31]

Azole Antifungals

Azole antifungals inhibit CYP3A4, which is necessary in the metabolism of simvastatin, lovastatin, and, to a lesser degree, atorvastatin. Azole antifungals also inhibit CYP2C9, which is responsible for the metabolism of fluvastatin. These interactions can lead to an increase in statin concentration, thus increasing the risk of muscle toxicity.[32,33] Atorvastatin undergoes less metabolism by CYP3A4, but some cases of myopathy with CYP3A4 inhibitors have been reported.[34] Management options include use of rosuvastatin or pravastatin, which are not metabolized by CYP3A4, or use of an alternative antifungal such as terbinafine (Lamisil).[35]

Calcium Channel Blockers

The exact mechanism for the interaction between calcium channel blockers and statin drugs is unknown; however, inhibition of CYP3A4 metabolism may play a role.[36] These interactions and management strategies, including specific dosage recommendations with concomitant simvastatin, are found in Table 3.[36,37]