What medication needs adjustment in a 60-year-old male with hypertension (HTN) and a history of aortic valve replacement, currently on lisinopril, amlodipine, heparin, and hydralazine, before starting anti-tuberculosis (TB) treatment?

Hydralazine Requires Dose Adjustment Before Starting Anti-TB Treatment

Hydralazine must be dose-adjusted or temporarily discontinued before initiating anti-tuberculosis therapy because rifampin (a core component of standard TB regimens) significantly induces hepatic metabolism and accelerates hydralazine clearance, potentially reducing its antihypertensive efficacy. 1

Why Hydralazine is the Correct Answer

Drug Interaction Mechanism

• Rifampin is a potent inducer of the cytochrome P450 enzyme system, which increases the metabolism of numerous medications including hydralazine 1
• This enzyme induction can reduce serum concentrations of hydralazine to subtherapeutic levels, compromising blood pressure control 1
• The interaction is clinically significant enough that dose adjustments are necessary before starting TB treatment 1

Standard TB Regimen Components

• The preferred 6-month TB regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months 1, 2
• Rifampin is one of the two most critical anti-TB drugs (along with isoniazid) and cannot be omitted from standard regimens 1
• All first-line TB medications should be administered together to prevent acquired drug resistance 1

Why Other Medications Do NOT Require Adjustment

Amlodipine (Calcium Channel Blocker)

• While rifampin can induce metabolism of some calcium channel blockers, amlodipine has a long half-life and the clinical impact is generally manageable without preemptive dose adjustment 3
• No specific guideline recommendations exist for mandatory amlodipine adjustment before TB treatment initiation 1

Lisinopril (ACE Inhibitor)

• Lisinopril is not metabolized by the liver and is eliminated unchanged by the kidneys 3
• There are no significant drug interactions between lisinopril and rifampin or other first-line TB medications 1
• ACE inhibitors can be safely continued during TB treatment without dose modification 1

Heparin (Anticoagulant)

• Heparin is not metabolized by cytochrome P450 enzymes and has no significant interaction with rifampin 1
• The patient's indication for heparin (post-aortic valve replacement) requires continued anticoagulation, and heparin can be safely administered during TB treatment 1
• No dose adjustment of heparin is needed when initiating anti-TB therapy 1

Clinical Management Approach

Before Starting TB Treatment

• Review the patient's current hydralazine dose and blood pressure control 1
• Consider temporarily increasing hydralazine dose in anticipation of rifampin-induced metabolism, or switch to an alternative antihypertensive agent less affected by enzyme induction 1
• Ensure close blood pressure monitoring during the first 2-4 weeks of TB treatment 1

Monitoring During TB Treatment

• Measure blood pressure at 2,4, and 8 weeks after initiating TB therapy to assess adequacy of blood pressure control 4, 5
• If blood pressure becomes uncontrolled, increase hydralazine dose or add/substitute alternative antihypertensive agents 1
• Continue monitoring liver function tests given the hepatotoxic potential of isoniazid, rifampin, and pyrazinamide 4, 5

Important Clinical Pitfalls

Common Mistake: Ignoring Drug Interactions

• Providers often fail to anticipate rifampin's broad enzyme-inducing effects on concurrent medications 1
• This oversight can lead to loss of blood pressure control and cardiovascular complications in high-risk patients like this one with aortic valve replacement 1

Critical Consideration: Hepatotoxicity Monitoring

• While not the primary concern for this question, baseline liver function testing (AST, ALT, bilirubin) is mandatory before starting TB treatment 4, 5
• The combination of multiple antihypertensive medications and anti-TB drugs requires vigilant monitoring for drug-induced hepatitis 1, 5

Answer: C. Hydralazine