Amlodipine besylate is a second generation calcium channel blocker that is used in the therapy of hypertension and angina pectoris. Amlodipine has been linked to a low rate of serum enzyme elevations during therapy and to rare instances of clinically apparent acute liver injury.


Amlodipine (am loe' di peen) belongs to the dihydropyridine class of calcium channel blockers and is used in the treatment of both hypertension and angina pectoris. Like other calcium channel blockers, amlodipine acts by blocking the influx of calcium ions into vascular smooth muscle and cardiac muscle cells during membrane depolarization. This action causes relaxation of vascular and arterial smooth muscle cells, resulting in arterial vasodilation and a decrease in cardiac work and oxygen consumption. Amlodipine was approved in the United States in 1992 and it remains in wide use, with several million prescriptions filled yearly. Current indications include hypertension and coronary artery disease (angina pectoris). Amlodipine is available generically and under the brand name of Norvasc. Tablet strengths include 2.5, 5, and 10 mg. The recommended dose in adults is 2.5 to 10 mg once daily, usually starting with the lowest dose. Chronic therapy is typical. Recently, multiple fixed dose combinations of amlodipine with other agents have become available including amlodipine (5 or 10 mg) with aliskiren (150 or 300 mg: Tekamlo), aliskiren with hydrochlorothiazide (12.5 and 25 mg: Amturnide), atorvastatin (10, 20, 40 or 80 mg: Caduet and generic), benzapril (10, 20 or 40 mg: Lotrel, Amlobenz, and generic), benzapril and hydrochlorothiazide (12.5 and 25 mg: Tribenzor), olmesaran (20 and 40 mg: Azor), and telmisartan (40 or 80 mg: Twynsta), valsartan (160 and 320 mg: Exforge) and valsartan with hydrochlorothiazide (25 mg: Exforge HCT). Like most calcium channel blockers, amlodipine is generally well tolerated. Side effects are largely due to the vasodilating activities and can include headache, flushing, dizziness, fatigue, nausea, diarrhea, palpitations, peripheral edema and rash.


Chronic therapy with amlodipine is associated with a low rate of serum enzyme elevations at rates that are similar to matched control populations. The enzyme elevations are usually mild, transient and asymptomatic and may resolve even during continued therapy. Clinically apparent liver injury from amlodipine is rare and described only in isolated case reports. In the few idiosyncratic cases reported, the latency period to onset of liver injury was usually 4 to 12 weeks, but examples with prolonged latency have also been published (10 months and several years). The latency period is shorter with recurrence on reexposure, including several instances of recurrence after liver injury due to other calcium channel blockers. The pattern of serum enzyme elevations is usually mixed or cholestatic. Rash, fever and eosinophilia have not been described and autoantibodies are not typical.

Likelihood score: C (probable but rare cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism of amlodipine hepatotoxicity is not known, but liver injury is probably due to production of a toxic intermediate in its metabolism.

Outcome and Management

The severity of liver injury from amlodipine ranges from mild and transient serum enzyme elevations to self-limited jaundice. Complete recovery is expected after stopping the drug and recovery is usually rapid (4 to 8 weeks). Cases with chronic or fulminant liver injury due to amlodipine have not been reported. Little information is available on recurrence with rechallenge but there may be some degree of cross-sensitivity to hepatotoxicity with other calcium channel blockers.

Drug Class: Cardiovascular Agents, Calcium Channel Blockers

Other Drugs in the Subclass, Calcium Channel Blockers: Diltiazem, Felodipine, Isradipine, Nicardipine, Nifedipine, Nimodipine, Nisoldipine, Verapamil


Case 1. Acute hepatitis-like syndrome attributed to amlopidine.

[Modified from: Basile C, Mascia E. Dihydropyridine calcium channel blockers: a rare and reversible cause of hepatotoxicity with cholestasis in a CAPD patient. Nephrol Dial Transplant 1999; 14: 2776-7. PubMed Citation]

A 76 year old man with diabetes and end-stage renal disease developed jaundice while on long term nifedipine therapy (60 mg daily for ~3 years) for hypertension. He was taking insulin, but no other medications. He had no risk factors for viral hepatitis and did not drink alcohol. Serum bilirubin was 2.5 mg/dL and rose over the next few months to 6.2 mg/dL. Tests for acute hepatitis A, B and C were negative and abdominal ultrasonography showed a normal liver and gallbladder. Nifedipine was stopped and he recovered rapidly. Several months later, amlodipine was started (10 mg daily) and within 6 weeks, he developed jaundice and a cholestatic pattern of serum enzyme elevations. Once amlodipine was stopped, liver tests improved and were normal three weeks later.

Key Points

Laboratory Values


One of the few reports of acute liver injury with jaundice attributed to calcium channel blockers. The patient initially developed a cholestatic hepatitis while on long term nifepidine therapy. Liver tests because steadily worse and nifepidine was ultimately withdrawn, whereupon liver tests fell to normal within 4 weeks. There was a recurrence of liver injury within 2 to 6 weeks of restarting another calcium channel blocker with a similar pattern of liver test abnormalities and a similar rapid improvement upon stopping. Both nifedipine and amlodipine are dihydropyridines, but there structures are dissimilar.



Amlodipine – Generic, Norvasc®


Cardiovascular Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 01 March 2016

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    (46 year old man was found to have abnormal liver tests one week after switching from ramipril to amlodipine [bilirubin 1.4 mg/dL, ALT 923 U/L, Alk P 102 U/L, INR 1.02], resolving within 3 weeks of stopping).
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