In an elderly man taking amlodipine, a β‑blocker, and lisinopril who is started on rifampicin‑containing first‑line anti‑tuberculosis therapy, which antihypertensive should be stopped?

Amlodipine Should Be Stopped

In an elderly man on amlodipine, a β-blocker, and lisinopril who is started on rifampicin-containing first-line anti-tuberculosis therapy, amlodipine (the calcium channel blocker) should be stopped or significantly increased in dose, as rifampicin is a potent inducer of hepatic cytochrome P450 enzymes that dramatically reduces the efficacy of dihydropyridine calcium channel blockers.

Mechanism of Drug Interaction

• Rifampicin is one of the most potent inducers of hepatic drug-oxidation enzymes, accelerating systemic elimination and increasing hepatic first-pass metabolism of many drugs 1

• Dihydropyridine calcium channel blockers (like amlodipine) are primarily metabolized by the liver, making them highly susceptible to rifampicin's enzyme-inducing effects 1

• This interaction results in significantly diminished antihypertensive effects of calcium channel blockers, requiring either much greater doses or additional antihypertensive agents to maintain blood pressure control 1

Clinical Evidence

• A prospective study of 160 hypertensive patients on anti-tuberculosis therapy demonstrated that rifampicin significantly diminishes the hypotensive effects of calcium channel blockers, beta-blockers, and diuretics 2

• In this study, mean blood pressure rose from 130/80 mmHg to 154/96 mmHg during rifampicin-based therapy despite adding additional antihypertensive drugs, and returned to 130/80 mmHg within four weeks after discontinuing anti-tuberculosis treatment 2

• Case reports of four elderly hypertensive patients showed that shortly after starting rifampicin, blood pressure rose in all patients on dihydropyridine calcium channel blockers (nisoldipine, nifedipine, barnidipine, or manidipine), requiring either much greater doses or additional agents 1

• After rifampicin withdrawal, blood pressure fell in all patients and antihypertensive doses had to be reduced 1

Why Not the Other Medications?

ACE Inhibitors (Lisinopril)

• Lisinopril is not significantly metabolized by hepatic cytochrome P450 enzymes and is primarily excreted unchanged by the kidneys, making it resistant to rifampicin's enzyme-inducing effects

• The clinical study showed rifampicin affects multiple drug classes, but the interaction is most clinically significant with calcium channel blockers due to their extensive hepatic metabolism 2

Beta-Blockers

• While rifampicin can affect beta-blockers, the magnitude of interaction is less pronounced than with calcium channel blockers 2

• Many beta-blockers have alternative elimination pathways or are less dependent on the specific cytochrome P450 isoforms most strongly induced by rifampicin

Practical Management Algorithm

1. Immediately upon starting rifampicin-based anti-TB therapy:

   • Discontinue amlodipine or anticipate need for dose escalation
   • Continue lisinopril and beta-blocker as these are less affected

2. Monitor blood pressure closely:

   • Daily for the first week
   • Weekly for the first month of anti-TB therapy 2

3. If blood pressure rises despite continuing lisinopril and beta-blocker:

   • Increase doses of these medications first
   • Consider adding a thiazide diuretic, which is also less affected by rifampicin 3

4. After completing anti-TB therapy:

   • Reassess antihypertensive regimen within 4 weeks
   • Expect blood pressure to decrease as rifampicin's enzyme-inducing effects resolve 1, 2
   • May be able to restart amlodipine at lower doses or reduce other antihypertensives

Critical Pitfall to Avoid

• Do not simply increase amlodipine dose dramatically while on rifampicin, as this creates risk of severe hypotension once anti-TB therapy is completed and enzyme induction resolves 1

• Never discontinue rifampicin for blood pressure control, as rifampicin is critical for short-course TB therapy and should not be stopped for minor side effects 4, 5