In a man in his 60s with hypertension and a prosthetic aortic valve who is taking lisinopril, amlodipine, hydralazine, and heparin, which medication should be adjusted before initiating standard four‑drug anti‑tuberculosis therapy (rifampin, isoniazid, pyrazinamide, ethambutol)?

Hydralazine Requires Adjustment Before Starting Anti-TB Therapy

Hydralazine (Option C) is the medication that needs adjustment before initiating standard four-drug anti-tuberculosis therapy, primarily due to the significant drug interaction between rifampin and hydralazine that can lead to treatment failure and the compounded hepatotoxicity risk.

Primary Drug Interaction Concern

Rifampin's Effect on Hydralazine

• Rifampin is a potent inducer of the CYP 3A P450 enzyme system, which significantly increases the metabolism of many drugs 1
• Hydralazine undergoes hepatic metabolism and its levels can be substantially reduced by rifampin's enzyme-inducing effects, potentially leading to inadequate blood pressure control 1
• This interaction may necessitate either dose adjustment or switching to an alternative antihypertensive agent before starting TB treatment 1

Hepatotoxicity Risk

• The standard four-drug TB regimen (rifampin, isoniazid, pyrazinamide, ethambutol) carries significant hepatotoxicity risk, particularly with rifampin, isoniazid, and pyrazinamide 1
• Hydralazine can also cause hepatotoxicity, creating an additive risk when combined with hepatotoxic anti-TB medications 1
• Liver function monitoring is essential, with treatment stopped if AST/ALT rises to five times normal or if bilirubin rises 1

Why Other Medications Are Safer

Amlodipine (Option A) - No Adjustment Needed

• Calcium channel blockers like amlodipine do not have clinically significant interactions with standard anti-TB drugs 1
• Amlodipine can be safely continued without dose adjustment during TB treatment 2

Lisinopril (Option B) - No Adjustment Needed

• ACE inhibitors including lisinopril do not require dose adjustment with anti-TB therapy 1
• Lisinopril is safe to continue and provides effective blood pressure control without interaction concerns 3

Heparin (Option D) - Critical for Prosthetic Valve

• Heparin must be continued without interruption in this patient with a prosthetic aortic valve to prevent catastrophic thromboembolic complications 4
• Patients with mechanical or bioprosthetic valves require continuous anticoagulation; interruption risks valve thrombosis with high morbidity and mortality 4
• Anti-TB drugs do not significantly affect heparin pharmacokinetics 1

Clinical Management Algorithm

Before Starting TB Treatment:

1. Discontinue hydralazine and replace with a rifampin-compatible antihypertensive 1
2. Preferred alternatives: Continue lisinopril and amlodipine, which provide adequate blood pressure control without TB drug interactions 1
3. Maintain heparin at therapeutic levels for prosthetic valve protection 4
4. Obtain baseline liver function tests before initiating TB therapy 1

During TB Treatment:

• Monitor liver function weekly for 2 weeks, then every 2 weeks for the first 2 months 1
• Continue anticoagulation monitoring for prosthetic valve management 4
• Assess blood pressure control regularly, as the combination of lisinopril and amlodipine should provide adequate control 5

Critical Pitfalls to Avoid

• Never discontinue anticoagulation in a patient with a prosthetic valve, even temporarily, without bridging therapy 4
• Do not continue hydralazine with rifampin-based TB therapy due to unpredictable blood pressure control from drug interactions 1
• Stop all hepatotoxic drugs (rifampin, isoniazid, pyrazinamide) if AST/ALT exceeds 5 times normal 1
• Avoid adding multiple new antihypertensives when adequate control can be achieved with the existing lisinopril-amlodipine combination 1