A patient on warfarin for atrial fibrillation starts ciprofloxacin for a urinary tract infection. Five days later, INR is 6.2. The most important mechanism for this drug interaction is:

• A Ciprofloxacin inhibits CYP1A2 and CYP2C9, reducing warfarin metabolism
• B Ciprofloxacin displaces warfarin from albumin binding sites, increasing free warfarin
• C Ciprofloxacin eliminates gut flora that produce vitamin K2 (menaquinone), reducing warfarin's competitive substrate ✓
• D Ciprofloxacin chelates warfarin in the gut reducing absorption of both drugs

Explanation

The dominant mechanism for fluoroquinolone-warfarin interaction is eradication of intestinal flora (particularly Bacteroides and Prevotella species) that synthesize vitamin K2 (menaquinone), an important contributor to clotting factor carboxylation. Reducing available vitamin K2 substrate potentiates warfarin's anticoagulant effect, raising the INR. CYP inhibition by ciprofloxacin (particularly of CYP1A2) contributes to a lesser extent for the (S)-warfarin enantiomer. Both mechanisms together can produce clinically dangerous INR elevation.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.