CLS Statin Therapy & Pharmacology 2 — Questions and Answers
Question 1: Which statins are primarily metabolized by CYP3A4 and therefore have the most clinically significant interaction with strong CYP3A4 inhibitors like clarithromycin?
- Rosuvastatin and pravastatin
- Lovastatin and simvastatin (Correct answer)
- Fluvastatin and pitavastatin
- Pravastatin and rosuvastatin
Correct answer: Lovastatin and simvastatin
Lovastatin and simvastatin are extensively metabolized by CYP3A4, so potent CYP3A4 inhibitors markedly increase their plasma concentrations and myopathy risk.
Question 2: A patient on simvastatin 40 mg is started on amiodarone. Which action is most appropriate per prescribing guidelines?
- Discontinue simvastatin and switch to rosuvastatin 20 mg
- Reduce simvastatin dose to a maximum of 20 mg/day (Correct answer)
- No change is needed as this combination is safe
- Switch to atorvastatin 80 mg for equivalent efficacy
Correct 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.
Question 3: 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?
- Atorvastatin
- Rosuvastatin
- Fluvastatin
- Pravastatin (Correct answer)
Correct answer: Pravastatin
Pravastatin is not appreciably metabolized by CYP450 enzymes and is excreted largely unchanged, giving it a low drug-interaction profile.
Question 4: Rosuvastatin plasma concentrations are significantly increased by co-administration of which transporter-inhibiting drug?
- Gemfibrozil (Correct answer)
- Fenofibrate
- Ezetimibe
- Colestipol
Correct answer: Gemfibrozil
Gemfibrozil inhibits OATP1B1-mediated hepatic uptake and glucuronidation of rosuvastatin (and other statins), raising statin AUC and myopathy risk.
Question 5: Pitavastatin is unique among statins primarily because it is metabolized by which enzyme pathway, resulting in minimal drug interactions?
- CYP3A4 exclusively
- CYP2C9 exclusively
- CYP2C8 with minor glucuronidation
- Primarily glucuronidation with minimal CYP involvement (Correct answer)
Correct 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.
Question 6: A patient taking cyclosporine requires statin therapy. Which statin is most appropriate at the lowest approved dose due to cyclosporine markedly increasing statin exposure?
- Simvastatin 10 mg
- Atorvastatin 10 mg
- Pravastatin 20 mg
- Rosuvastatin 5 mg (Correct answer)
Correct 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.
Question 7: Which pharmacokinetic property of fluvastatin distinguishes it from most other statins in terms of CYP450 metabolism?
- It is primarily metabolized by CYP3A4
- It is primarily metabolized by CYP2C9 (Correct answer)
- It bypasses hepatic first-pass metabolism entirely
- It is an OATP1B1 substrate but not a CYP substrate
Correct 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.
CLS Statin Therapy & Pharmacology 2
Which statins are primarily metabolized by CYP3A4 and therefore have the most clinically significant interaction with strong CYP3A4 inhibitors like clarithromycin?