Antiarrhythmics: amiodarone and warfarin 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 · Antiarrhythmics: amiodarone and warfarin interaction

Sample item

A 68-year-old man with atrial fibrillation has a stable INR of 2.5 on warfarin. Amiodarone is started and two weeks later the INR is 5.8 with no bleeding. What is the explanation?

AAmiodarone reduces gut flora vitamin K productionBAmiodarone inhibits CYP2C9, reducing clearance of S-warfarinCAmiodarone induces warfarin metabolism and causes a paradoxical riseDAmiodarone displaces warfarin from its vitamin K epoxide reductase target

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

The answer and the reasoning

B. Amiodarone inhibits CYP2C9, reducing clearance of S-warfarin

Amiodarone inhibits CYP2C9 and CYP3A4, reducing clearance of S-warfarin, the more potent isomer, so the INR can double. The warfarin dose often needs to be reduced by a third to a half, with close INR monitoring, and the effect builds up and persists because of amiodarone's long half-life. It also raises digoxin levels by inhibiting P-glycoprotein.

Option by option

A. Amiodarone reduces gut flora vitamin K production
Reduced gut flora vitamin K is the mechanism of broad-spectrum antibiotic interaction, not amiodarone.
B. Amiodarone inhibits CYP2C9, reducing clearance of S-warfarin (correct)
Correct. Inhibition of CYP2C9-mediated clearance raises effective warfarin exposure.
C. Amiodarone induces warfarin metabolism and causes a paradoxical rise
Induction would lower the INR, which is the opposite of what is seen.
D. Amiodarone displaces warfarin from its vitamin K epoxide reductase target
Amiodarone does not act at the VKOR enzyme; the interaction is pharmacokinetic.

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 B, Amiodarone inhibits CYP2C9, reducing clearance of S-warfarin. Amiodarone inhibits CYP2C9 and CYP3A4, reducing clearance of S-warfarin, the more potent isomer, so the INR can double.

Why is "Amiodarone reduces gut flora vitamin K production" not the answer?

Reduced gut flora vitamin K is the mechanism of broad-spectrum antibiotic interaction, not amiodarone.

Why is "Amiodarone induces warfarin metabolism and causes a paradoxical rise" not the answer?

Induction would lower the INR, which is the opposite of what is seen.

Why is "Amiodarone displaces warfarin from its vitamin K epoxide reductase ta…" not the answer?

Amiodarone does not act at the VKOR enzyme; the interaction is pharmacokinetic.

What concept does this question test?

It tests Antiarrhythmics: amiodarone and warfarin interaction in Pharmacology. The warfarin dose often needs to be reduced by a third to a half, with close INR monitoring, and the effect builds up and persists because of amiodarone's long half-life. It also raises digoxin levels by inhibiting P-glycoprotein.

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 Antiarrhythmics: amiodarone and warfarin 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.