Statin Therapy & Pharmacology Flashcards

Which statins are primarily metabolized by CYP3A4 and therefore have the most clinically significant interaction with strong CYP3A4 inhibitors like clarithromycin?

Answer: Lovastatin and simvastatin

Lovastatin and simvastatin are extensively metabolized by CYP3A4, so potent CYP3A4 inhibitors markedly increase their plasma concentrations and myopathy risk.

A patient on simvastatin 40 mg is started on amiodarone. Which action is most appropriate per prescribing guidelines?

Answer: Reduce simvastatin dose to a maximum of 20 mg/day

Amiodarone inhibits CYP3A4 and increases simvastatin exposure; the FDA recommends capping simvastatin at 20 mg/day when co-administered with amiodarone.

Which statin undergoes minimal hepatic CYP metabolism and is excreted primarily unchanged in bile and urine, making it least susceptible to CYP-mediated drug interactions?

Answer: Pravastatin

Pravastatin is not appreciably metabolized by CYP450 enzymes and is excreted largely unchanged, giving it a low drug-interaction profile.

Rosuvastatin plasma concentrations are significantly increased by co-administration of which transporter-inhibiting drug?

Answer: Gemfibrozil

Gemfibrozil inhibits OATP1B1-mediated hepatic uptake and glucuronidation of rosuvastatin (and other statins), raising statin AUC and myopathy risk.

Pitavastatin is unique among statins primarily because it is metabolized by which enzyme pathway, resulting in minimal drug interactions?

Answer: Primarily glucuronidation with minimal CYP involvement

Pitavastatin undergoes minimal CYP2C9 metabolism and is primarily cleared via glucuronidation, resulting in a very low drug-interaction profile.

A patient taking cyclosporine requires statin therapy. Which statin is most appropriate at the lowest approved dose due to cyclosporine markedly increasing statin exposure?

Answer: Rosuvastatin 5 mg

Cyclosporine is a potent OATP1B1 inhibitor; the FDA recommends a maximum rosuvastatin dose of 5 mg/day in patients receiving cyclosporine.

Which pharmacokinetic property of fluvastatin distinguishes it from most other statins in terms of CYP450 metabolism?

Answer: It is primarily metabolized by CYP2C9

Fluvastatin is predominantly metabolized by CYP2C9, making it susceptible to interactions with CYP2C9 inhibitors such as fluconazole rather than with CYP3A4 inhibitors.