Antibacterials: macrolide and statin interaction: 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 · Antibacterials: macrolide and statin interaction

Sample item

A 66-year-old man on simvastatin 40 mg is given clarithromycin for pneumonia. Four days later he has severe muscle pain, dark urine and a markedly raised creatine kinase. Which mechanism is most likely?

AClarithromycin displaces simvastatin from albumin onlyBClarithromycin reduces renal tubular secretion of simvastatinCClarithromycin inhibits CYP3A4, raising simvastatin levelsDClarithromycin induces CYP3A4, producing a toxic metabolite

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

The answer and the reasoning

C. Clarithromycin inhibits CYP3A4, raising simvastatin levels

Simvastatin and lovastatin are extensively metabolised by CYP3A4, and clarithromycin and erythromycin are potent inhibitors, so statin exposure rises and rhabdomyolysis may follow. Azithromycin interacts much less, and the statin should be paused during the macrolide course. Pravastatin and rosuvastatin are less dependent on CYP3A4.

Option by option

A. Clarithromycin displaces simvastatin from albumin only
Displacement from albumin is a minor effect and cannot produce a several-fold rise in exposure.
B. Clarithromycin reduces renal tubular secretion of simvastatin
Simvastatin is cleared mainly by hepatic metabolism rather than renal tubular secretion.
C. Clarithromycin inhibits CYP3A4, raising simvastatin levels (correct)
Correct. CYP3A4 inhibition markedly raises simvastatin exposure.
D. Clarithromycin induces CYP3A4, producing a toxic metabolite
Induction would lower statin exposure and is not the effect of macrolides.

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.

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is C, Clarithromycin inhibits CYP3A4, raising simvastatin levels. Simvastatin and lovastatin are extensively metabolised by CYP3A4, and clarithromycin and erythromycin are potent inhibitors, so statin exposure rises and rhabdomyolysis may follow.

Why is "Clarithromycin displaces simvastatin from albumin only" not the answer?

Displacement from albumin is a minor effect and cannot produce a several-fold rise in exposure.

Why is "Clarithromycin reduces renal tubular secretion of simvastatin" not the answer?

Simvastatin is cleared mainly by hepatic metabolism rather than renal tubular secretion.

Why is "Clarithromycin induces CYP3A4, producing a toxic metabolite" not the answer?

Induction would lower statin exposure and is not the effect of macrolides.

What concept does this question test?

It tests Antibacterials: macrolide and statin interaction in Pharmacology. Azithromycin interacts much less, and the statin should be paused during the macrolide course. Pravastatin and rosuvastatin are less dependent on CYP3A4.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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 Antibacterials: macrolide and statin interaction?

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.