What statement best describes the interaction between atorvastatin and diltiazem?

• A. Both atorvastatin and diltiazem are metabolised by CYP3A4, and diltiazem can inhibit CYP3A4, leading to increased atorvastatin plasma concentrations and a higher risk of side effects
• B. Diltiazem increases atorvastatin excretion via renal pathways
• C. Atorvastatin inhibits diltiazem metabolism
• D. There is no interaction between the two drugs

Answer: (D)

The interaction hinges on how atorvastatin is cleared and how diltiazem affects that process. Atorvastatin is mainly metabolized by the liver enzyme CYP3A4. Diltiazem can inhibit CYP3A4 to a moderate degree. When these drugs are taken together, diltiazem can slow the metabolism of atorvastatin, leading to higher levels of the statin in the blood. This increased exposure raises the risk of muscle-related adverse effects, such as myopathy or rhabdomyolysis, especially at higher statin doses or with other risk factors.

Excretion isn’t the main mechanism here, so the idea that diltiazem would push atorvastatin out via renal pathways isn’t accurate. Atorvastatin doesn’t inhibit diltiazem’s metabolism, so that direction of interaction isn’t correct. And since there is a pharmacokinetic interaction to consider, saying there’s no interaction isn’t correct. In practice, if both must be used, clinicians may choose a non–CYP3A4-metabolized statin (like pravastatin or rosuvastatin), or reduce the atorvastatin dose and monitor for symptoms of toxicity.