Which medication needs to be adjusted in a patient with hypertension and a history of aortic valve replacement, taking lisinopril (Angiotensin-Converting Enzyme Inhibitor), amlodipine (Calcium Channel Blocker), and warfarin (Anticoagulant), who has been started on first-line anti-tuberculosis (TB) medications, including rifampin (Rifampicin)?

Warfarin Dose Adjustment Required

Warfarin is the medication that must be adjusted when rifampin is initiated, as rifampin is a potent inducer of hepatic enzymes (particularly CYP2C9, CYP3A4, CYP1A2, and CYP2C19) that dramatically reduces warfarin's anticoagulant effect, often requiring 2-4 fold dose increases to maintain therapeutic INR in patients with mechanical valves. 1, 2, 3

Critical Drug Interaction Mechanism

• Rifampin induces hepatic microsomal enzymes and P-glycoprotein, causing reductions to ineffective levels of warfarin serum concentrations 1
• The FDA drug label explicitly warns that rifampin has "enzyme induction properties" and causes "important" drug interactions with warfarin, among other medications 2
• A documented case report showed a patient with mitral valve replacement required warfarin dose escalation from 52.5 mg/week to 210 mg/week (4-fold increase) during rifampin therapy, yet INR remained subtherapeutic throughout the entire 6-week treatment period 3

Immediate Management Strategy

Monitor INR every 2-3 days initially when rifampin is started, as the interaction begins within days and warfarin requirements will increase substantially 3, 4

• Expect to increase warfarin dose by 50-100% or more during rifampin therapy to maintain target INR of 2.5-3.5 (required for mechanical aortic valve replacement) 1, 3
• This patient has a mechanical aortic valve replacement and requires warfarin with target INR 2.5-3.5 plus low-dose aspirin, making adequate anticoagulation critical for preventing valve thrombosis 1
• Subtherapeutic anticoagulation in mechanical valve patients carries risk of catastrophic valve thrombosis and stroke 1

Post-Rifampin Management Challenge

Anticipate the need for rapid warfarin dose reduction when rifampin is discontinued, as the enzyme induction effect reverses over 2-5 weeks 3

• The case report demonstrated that after rifampin completion, the patient required multiple dose adjustments (initially increases, then reductions) over 5 weeks before stabilizing on 80 mg/week (versus 210 mg/week during rifampin) 3
• Check INR every 2-3 days for the first 2 weeks after rifampin discontinuation, then weekly until stable, to prevent supratherapeutic INR and bleeding 3, 4
• Reduce warfarin dose by approximately 30-50% when rifampin is stopped, then titrate based on INR response 3

Why Other Medications Do Not Require Adjustment

• Lisinopril (ACE inhibitor): No significant interaction with rifampin; antihypertensive efficacy is maintained 1
• Amlodipine (calcium channel blocker): While rifampin may modestly reduce amlodipine levels through CYP3A4 induction, blood pressure monitoring is sufficient and dose adjustment is rarely needed clinically 1
• Rifampin itself: Standard first-line TB dosing (600 mg daily for adults) does not require adjustment based on concurrent medications 1

Common Pitfalls to Avoid

• Underestimating the magnitude of interaction: Small warfarin dose increases (10-20%) are insufficient; expect to double or triple the dose 3
• Inadequate INR monitoring frequency: Weekly monitoring is too infrequent during this high-risk period; check every 2-3 days initially 3, 4
• Forgetting post-rifampin management: The interaction persists for weeks after rifampin discontinuation, requiring continued close monitoring and dose reductions to prevent bleeding 3
• Delaying warfarin dose increases: Mechanical valve patients cannot tolerate prolonged subtherapeutic anticoagulation; increase doses aggressively based on INR response 3