Which antihypertensive should be stopped in an elderly male on amlodipine, a beta‑blocker, and lisinopril who is started on first‑line anti‑tuberculosis therapy?

Which Antihypertensive to Discontinue in a Patient Starting First-Line Anti-TB Therapy

Beta-blocker should be stopped in this patient starting rifampin-based anti-tuberculosis therapy. 1

Rationale for Beta-Blocker Discontinuation

Drug-Drug Interaction with Rifampin

• Rifampin is a potent CYP3A4 inducer that significantly reduces plasma concentrations of beta-blockers metabolized through this pathway, including metoprolol, carvedilol, and bisoprolol. 2
• The magnitude of this interaction can reduce beta-blocker efficacy by 50-80%, potentially leading to inadequate heart rate and blood pressure control during the critical TB treatment period. 2
• Unlike amlodipine (which has a 35-50 hour half-life providing sustained effect even with reduced levels), beta-blockers have shorter half-lives making them more vulnerable to clinically significant interactions. 3, 4

Why Amlodipine Should Be Continued

• Amlodipine's unique pharmacokinetic profile makes it the safest choice to continue despite rifampin co-administration. 3, 4
• Its extremely long half-life (40-60 hours) and low clearance (7 mL/min/mg) mean that even if rifampin reduces plasma levels by 50%, therapeutic blood pressure control is maintained throughout the 24-hour dosing interval. 3, 4
• The gradual onset and offset of amlodipine's effect (taking 7-10 days to return to baseline after discontinuation) provides a buffer against the fluctuating CYP3A4 induction effects of rifampin. 3
• Amlodipine can be dose-adjusted upward (from 5mg to 10mg) if needed during TB therapy, with continuous blood pressure monitoring to guide titration. 2, 4

Why Lisinopril Should Be Continued

• ACE inhibitors like lisinopril are not metabolized by CYP3A4 and have no significant drug-drug interactions with rifampin-based TB regimens. 1
• Lisinopril provides renal protection and cardiovascular risk reduction that is particularly important in elderly patients, making it a priority to maintain. 1
• The combination of an ACE inhibitor plus a calcium channel blocker (lisinopril + amlodipine) is explicitly recommended by guidelines as an effective dual-therapy regimen for hypertension control. 1

Practical Implementation Algorithm

Immediate Actions (Day 1 of TB Treatment)

• Discontinue the beta-blocker immediately when starting the rifampin-containing first-line TB regimen (isoniazid, rifampin, pyrazinamide, ethambutol). 5
• Continue lisinopril at current dose. 1
• Continue amlodipine at current dose initially. 4

Monitoring Schedule

• Check blood pressure and heart rate at 1 week, 2 weeks, and 4 weeks after beta-blocker discontinuation to assess adequacy of dual-therapy (lisinopril + amlodipine). 4
• Monitor for rebound hypertension or tachycardia in the first 3-5 days after beta-blocker withdrawal, though this is uncommon with gradual beta-blocker elimination. 1

Dose Adjustment Strategy

• If blood pressure rises above 140/90 mmHg after beta-blocker discontinuation, increase amlodipine from 5mg to 10mg daily. 4
• If blood pressure remains uncontrolled on lisinopril + amlodipine 10mg, add a thiazide diuretic (hydrochlorothiazide 12.5-25mg daily) rather than reintroducing the beta-blocker. 1
• Do not attempt to restart the beta-blocker until TB treatment is completed (minimum 6 months), as rifampin's CYP3A4 induction persists throughout therapy. 2, 5

Critical Pitfalls to Avoid

Common Errors

• Never continue beta-blockers with rifampin assuming "monitoring will suffice" – the interaction is too significant and unpredictable to manage safely. 2
• Do not abruptly stop beta-blockers in patients with coronary artery disease or recent MI – in such cases, taper over 1-2 weeks while closely monitoring for ischemic symptoms, though this scenario is not indicated in the question. 1
• Avoid adding nondihydropyridine calcium channel blockers (diltiazem, verapamil) as beta-blocker substitutes – these have negative inotropic effects and are contraindicated in heart failure. 1

Monitoring Considerations

• Check serum creatinine and potassium 2-4 weeks after any ACE inhibitor dose adjustment to detect hyperkalemia or acute kidney injury, particularly important in elderly patients. 1
• Assess for peripheral edema with amlodipine dose increases – this is the most common side effect, occurring in 10-30% of patients on 10mg daily, and is more frequent in elderly patients and women. 1, 4

Special Consideration for This Elderly Patient

• Elderly patients have reduced drug clearance and increased sensitivity to antihypertensive effects, making the lisinopril + amlodipine combination particularly appropriate as both drugs can be carefully titrated. 1
• The absence of a beta-blocker may actually improve this patient's exercise tolerance and reduce risk of falls, as beta-blockers can cause bradycardia and orthostatic hypotension in the elderly. 1