Cardiovascular drugs: statin interactions: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Cardiovascular drugs: statin interactions

Sample item

A 64-year-old man on atorvastatin 40 mg is given clarithromycin for pneumonia. A week later he has severe muscle pain and dark urine, with a creatine kinase of 18,000 U/L. What is the mechanism of the interaction, and which statin would have been least affected?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. CYP3A4 inhibition raising statin levels; pravastatin or rosuvastatin would be less affected

Atorvastatin, simvastatin and lovastatin are metabolised by CYP3A4, and macrolides such as clarithromycin inhibit this enzyme, raising statin levels and the risk of myopathy and rhabdomyolysis. Pravastatin is not metabolised by CYP enzymes and rosuvastatin is minimally metabolised, so both are preferred when an interacting drug is needed. Treatment is to stop the statin and give intravenous fluids.

Option by option

  • A. Reduced renal tubular secretion; simvastatin would be less affected

    Tubular secretion is not the main pathway, and simvastatin is strongly affected by clarithromycin.

  • B. CYP3A4 inhibition raising statin levels; pravastatin or rosuvastatin would be less affected (correct)

    Correct. Higher exposure to a CYP3A4-dependent statin drives muscle toxicity.

  • C. Displacement from albumin; lovastatin would be less affected

    Statin toxicity here is not due to protein displacement, and lovastatin is CYP3A4-dependent.

  • D. CYP3A4 induction lowering statin levels; simvastatin would be less affected

    Clarithromycin inhibits rather than induces CYP3A4, and simvastatin is itself highly CYP3A4-dependent.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is B, CYP3A4 inhibition raising statin levels; pravastatin or rosuvastatin would be less affected. Atorvastatin, simvastatin and lovastatin are metabolised by CYP3A4, and macrolides such as clarithromycin inhibit this enzyme, raising statin levels and the risk of myopathy and rhabdomyolysis.

Why is "Reduced renal tubular secretion; simvastatin would be less affected" not the answer?

Tubular secretion is not the main pathway, and simvastatin is strongly affected by clarithromycin.

Why is "Displacement from albumin; lovastatin would be less affected" not the answer?

Statin toxicity here is not due to protein displacement, and lovastatin is CYP3A4-dependent.

Why is "CYP3A4 induction lowering statin levels; simvastatin would be less af…" not the answer?

Clarithromycin inhibits rather than induces CYP3A4, and simvastatin is itself highly CYP3A4-dependent.

What concept does this question test?

It tests Cardiovascular drugs: statin interactions in Pharmacology. Pravastatin is not metabolised by CYP enzymes and rosuvastatin is minimally metabolised, so both are preferred when an interacting drug is needed. Treatment is to stop the statin and give intravenous fluids.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Cardiovascular drugs: statin interactions?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.