Atorvastatin × Verapamil

Verapamil inhibits CYP3A4, the enzyme that breaks down atorvastatin, and may raise atorvastatin levels (both SmPCs). No interaction study of this pair has been done, so the atorvastatin SmPC gives no figure. The interaction also works the other way: atorvastatin increases systemic exposure to verapamil by 43% (verapamil SmPC). The higher the atorvastatin level, the higher the risk of muscle damage (atorvastatin SmPC).

Muscle pain, cramps or weakness, sometimes with fever and malaise, and raised creatine kinase on blood tests. In rhabdomyolysis the urine turns dark and kidney function can suffer.

If the patient already takes verapamil, atorvastatin is started at the lowest possible dose and titrated up: the verapamil SmPC requires this and names atorvastatin. If verapamil is added to existing atorvastatin, a statin dose reduction is considered and cholesterol is rechecked (verapamil SmPC). For verapamil and other moderate CYP3A4 inhibitors, the atorvastatin SmPC advises considering a lower maximum atorvastatin dose and monitoring the patient; the documents set no specific dose limit for this pair. Ask the patient to report muscle pain, cramps or weakness promptly. Check creatine kinase if they occur, and stop atorvastatin if it is more than 5 times the upper limit of normal (atorvastatin SmPC). Fluvastatin, pravastatin and rosuvastatin are not metabolised by CYP3A4 and are less likely to interact with verapamil (verapamil SmPC).