A 58-year-old Indian male with atrial fibrillation is on warfarin (INR target 2–3) for stroke prevention. He develops a urinary tract infection and is prescribed ciprofloxacin 500 mg twice daily. One week later, his INR is found to be 5.2 with spontaneous bruising on his arms. The mechanism of this adverse interaction involves the structure marked **B** in the diagram. Which of the following best explains the clinical consequence?

Question

Accepted Answer

A. Ciprofloxacin inhibits CYP2C9, reducing warfarin metabolism and increasing its plasma levels, leading to supratherapeutic INR and bleeding risk. ## Why Option 1 is correct

Ciprofloxacin is a CYP2C9 inhibitor (part of the SICKFACES.COM mnemonic under structure **B** — CYP450 Inhibitors). When CYP2C9 is inhibited, metabolism of warfarin (a CYP2C9 substrate) is reduced, causing warfarin plasma levels to rise. This results in supratherapeutic INR and increased bleeding risk — exactly what this patient experienced (INR 5.2, spontaneous bruising). This is one of the most clinically important drug interactions taught in Indian medical curricula and is explicitly cited in KD Tripathi as a critical warfarin–CYP2C9 inhibitor interaction.

## Why each distractor is wrong

- **Option 2**: Ciprofloxacin is an inhibitor, not an inducer, of CYP2C9. Induction would decrease warfarin levels and INR, causing loss of anticoagulation — the opposite of what occurred here.
- **Option 3**: While protein displacement can occur with some drugs, it is not the primary mechanism of ciprofloxacin–warfarin interaction. The dominant mechanism is CYP2C9 inhibition. Protein displacement alone would cause only a transient, mild increase in INR.
- **Option 4**: Ciprofloxacin does not inhibit vitamin K-dependent clotting factor synthesis; this is not a recognized mechanism of fluoroquinolone action. The interaction is purely pharmacokinetic (CYP inhibition), not pharmacodynamic.

**High-Yield:** Fluoroquinolones (especially ciprofloxacin) are CYP2C9 inhibitors — always check INR when adding them to warfarin; other CYP2C9 inhibitors include metronidazole, fluconazole, sulfonamides, and amiodarone.

[cite: KD Tripathi 9e Ch 3, Ch 4 — Drug Interactions & CYP450 Metabolism]

Answer

B. Ciprofloxacin induces CYP2C9, accelerating warfarin metabolism and reducing its anticoagulant effect, leading to thromboembolism

Answer

C. Ciprofloxacin competitively displaces warfarin from plasma protein binding, increasing free warfarin concentration and INR

Answer

D. Ciprofloxacin inhibits hepatic vitamin K-dependent clotting factor synthesis, potentiating warfarin's anticoagulant effect independently

Explanation

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