Amlodipine Regret, Stopping, and Restarting: What Real Patients Experience
At a glance
- Drug class / dihydropyridine calcium channel blocker, a peripheral arterial vasodilator [1]
- Discontinuation in trials / about 1.5% on amlodipine vs about 1% on placebo, for adverse reactions [1]
- Most common reaction / edema, dose related: 1.8% at 2.5 mg, 3.0% at 5 mg, 10.8% at 10 mg vs 0.6% on placebo [1]
- Half-life / mean 34 hours intravenous, 36 hours single oral dose, 45 hours with repeated daily dosing [2]
- Simvastatin cap / the label says to limit simvastatin to 20 mg daily with amlodipine [1]
What the trials recorded about stopping
In placebo-controlled trials, 1,730 patients took amlodipine and 1,250 took placebo. About 1.5% of the amlodipine group discontinued for adverse reactions, against about 1% of the placebo group [1].
Edema is the label's most common adverse reaction and is dose related: 1.8% at 2.5 mg (N=275), 3.0% at 5 mg (N=296), 10.8% at 10 mg (N=268), against 0.6% on placebo (N=520) [1].
How long amlodipine stays in the body
In 12 healthy volunteers, a single 10 mg intravenous dose gave a mean plasma half-life of 34 hours and a single 10 mg oral dose 36 hours; in 28 volunteers taking 15 mg once daily for 14 days the mean half-life was 45 hours, with steady state after seven doses [2]. Those measurements do not show when blood pressure changes after stopping.
Restarting: what the label specifies
The labeled usual initial adult dose is 5 mg once daily, maximum 10 mg once daily. The label says 2.5 mg may be used to start in small, fragile or elderly patients, patients with hepatic impairment, or when adding amlodipine to other antihypertensive therapy, with 7 to 14 days between titration steps unless faster titration is clinically warranted [1]. The label does not specify whether someone restarting should use a previous dose.
The label warns that worsening angina and acute myocardial infarction can develop after starting or increasing the dose, particularly in severe obstructive coronary artery disease [1]. It also says to limit simvastatin to 20 mg daily in patients on amlodipine, and that moderate and strong CYP3A inhibitors raise amlodipine exposure, with monitoring for hypotension and edema [1].
What treatment was doing
CAMELOT randomized 1,991 patients with coronary artery disease and diastolic blood pressure below 100 mm Hg to amlodipine 10 mg, enalapril 20 mg, or placebo for 24 months. Cardiovascular events occurred in 110 (16.6%) on amlodipine and 151 (23.1%) on placebo, hazard ratio 0.69 (95% CI 0.54-0.88); the enalapril group had 136 events (20.2%), not significantly different from placebo [3]. The trial did not test stopping the drug.
Frequently asked questions
Can I stop amlodipine suddenly?
Will ankle swelling come back if I restart amlodipine?
Can I restart amlodipine at the dose I took before?
References
- U.S. National Library of Medicine, DailyMed. Amlodipine Besylate prescribing information. Amlodipine Besylate label
- Faulkner JK, McGibney D, Chasseaud LF, Perry JL, Taylor IW. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol. 1986;22(1):21-5. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily
- Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292(18):2217-25. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial