What medication needs to be adjusted in a patient with tuberculosis (TB), presenting with shortness of breath and productive cough, who is on lisinopril, hydrochlorothiazide, amlodipine, and warfarin, and has been initiated on anti-tuberculosis (anti-TB) medications, including rifampicin?

Warfarin Requires Dose Adjustment

Warfarin (Answer A) must be adjusted when rifampicin-containing anti-TB therapy is initiated, as rifampicin is a potent inducer of hepatic cytochrome P450 enzymes that significantly increases warfarin metabolism and clearance. 1, 2

Mechanism of Rifampicin-Warfarin Interaction

• Rifampicin induces the hepatic cytochrome P450 oxidative enzyme system, which dramatically increases warfarin metabolism and reduces its anticoagulant effect 1, 2
• This enzyme induction typically requires doubling the warfarin dose during concurrent rifampicin therapy to maintain therapeutic INR (2.0-3.0) 2
• The interaction begins within days of rifampicin initiation and persists throughout the entire course of TB treatment 2

Critical Management During TB Treatment

• Increase warfarin monitoring frequency to weekly after initiating rifampicin-containing anti-TB regimen (isoniazid, rifampicin, pyrazinamide, ethambutol) 3, 2
• Expect subtherapeutic INR values requiring sequential warfarin dose increases over 2-3 months to achieve therapeutic anticoagulation 2
• The warfarin dose will likely need to be doubled from baseline to maintain therapeutic INR during rifampicin therapy 2
• Continue frequent INR monitoring (every 1-2 weeks minimum) throughout the entire 6-month TB treatment course 2

Dangerous Post-TB Treatment Period

The highest bleeding risk occurs after rifampicin discontinuation, when enzyme induction resolves and warfarin clearance returns to baseline 2, 4

• After stopping rifampicin, warfarin fractional clearance can decrease from 15.2 to 4.2 ml/min, causing plasma warfarin concentrations to double 4
• This creates a critical 4-week window where supratherapeutic INR and bleeding complications (including macroscopic hematuria) commonly occur 2
• Reduce warfarin dose by approximately 50% within 1-2 weeks of rifampicin discontinuation, returning to the pre-TB treatment dose 2
• Monitor INR weekly after rifampicin cessation until stable therapeutic INR is achieved at the maintenance warfarin dose 2

Why Other Medications Don't Require Adjustment

• Lisinopril (ACE inhibitor): No significant interaction with rifampicin or other first-line anti-TB medications 3
• Hydrochlorothiazide (thiazide diuretic): No dose adjustment needed with anti-TB therapy 3
• Amlodipine (calcium channel blocker): While rifampicin may induce its metabolism, this does not typically require dose adjustment for blood pressure control 3

Common Pitfalls to Avoid

• Never assume warfarin dose stability during TB treatment - the interaction is profound and requires proactive management 2
• Never discontinue frequent INR monitoring after achieving therapeutic range during rifampicin therapy, as the dose requirement remains elevated throughout treatment 2
• Never forget to reduce warfarin dose after completing TB therapy - failure to do so results in dangerous supratherapeutic INR and bleeding within 2-4 weeks 2, 4
• Do not confuse this with corticosteroid interactions, which require doubling the corticosteroid dose (not warfarin) when rifampicin is added 3