Which antihypertensive medication should be stopped in an elderly male with hypertension on amlodipine, beta blocker, and lisinopril, newly diagnosed with tuberculosis and starting first-line anti-TB regimen including rifampicin?

Which Antihypertensive Should Be Stopped?

Amlodipine (the calcium channel blocker) should be stopped or switched to an alternative antihypertensive agent when starting rifampicin-based anti-TB therapy. 1, 2, 3

Mechanism of Interaction

Rifampicin is a potent inducer of hepatic cytochrome P450 (CYP) enzymes, which dramatically accelerates the metabolism of amlodipine and other dihydropyridine calcium channel blockers. 1, 4 This interaction causes:

• Blood levels of amlodipine to decline by >50%, often becoming undetectable within days of starting rifampicin 1
• Significant worsening of blood pressure control, with 83.3% of patients requiring increased antihypertensive doses 1
• Hypertensive crises in 46% of patients, occurring at a mean of 9.1 days after rifampicin initiation, including hypertensive emergencies with acute pulmonary edema 1

Why Not the Other Medications?

Beta-blockers (particularly metoprolol, a class 1 BDDCS drug) also interact significantly with rifampicin through CYP2D6 induction, with blood levels declining >50% and becoming undetectable in many patients. 1, 4 However, the question asks which drug should be stopped, and amlodipine has the most clinically significant interaction.

Lisinopril (ACE inhibitor) is a class 3 BDDCS drug that undergoes minimal hepatic metabolism and is primarily renally eliminated. 4 ACE inhibitors exhibit minimal interactions with rifampicin and are actually recommended as preferred agents when rifampicin is started. 4

Recommended Antihypertensive Alternatives

When starting rifampicin-based anti-TB therapy, switch to or preferentially use:

• ACE inhibitors (like the patient's current lisinopril) - minimal interaction 4
• Angiotensin receptor blockers (specifically olmesartan) - minimal interaction 4
• Class 3 β-blockers (atenolol, nadolol) - minimal interaction as they are renally eliminated 4
• Spironolactone - minimal interaction 4
• Hydrochlorothiazide - minimal interaction 4

Critical Monitoring Requirements

If calcium channel blockers or class 1/2 beta-blockers must be continued temporarily:

• Monitor blood pressure very closely starting immediately after rifampicin initiation 1, 2
• Expect first dose increase requirement at mean 6.5 days after starting rifampicin 1
• Be prepared for hypertensive crisis around day 9, which may require emergency management 1
• Anticipate needing 4-8 additional units of antihypertensive medication to maintain BP <140/90 mmHg 1

Common Pitfalls to Avoid

• Never assume "close monitoring" is sufficient - the interaction is severe and predictable, requiring proactive medication changes 1, 2
• Do not simply increase calcium channel blocker doses - the induction effect is so profound that switching drug classes is more effective 1, 4
• Remember that blood pressure will normalize after rifampicin discontinuation (mean BP returns to 130/80 mmHg within 4 weeks), requiring dose reduction of any added agents 2
• In some cases, rifampicin may need to be discontinued if blood pressure cannot be controlled despite multiple medication adjustments 1

Special Consideration for This Elderly Patient

Given this patient is elderly and on triple antihypertensive therapy, he is at particularly high risk for:

• Hypertensive crisis with end-organ damage 1
• Medication non-adherence due to complex polypharmacy
• Adverse effects from rapidly escalating antihypertensive doses

The safest approach is to discontinue amlodipine before or immediately upon starting rifampicin, maintain the lisinopril (which has minimal interaction), and consider whether the beta-blocker should also be switched to a renally-eliminated alternative like atenolol. 1, 4