Nifedipine is a first generation calcium channel blocker used to treat hypertension and angina pectoris. Nifedipine therapy is associated with a low rate of serum enzyme elevations and has been linked to several instances of clinically apparent acute liver injury.


Nifedipine (nye fed' i peen) belongs to the dihydropyridine class of calcium channel blockers (first in its class and similar to amlodipine, felodipine and nicardipine) and is used for the treatment of hypertension and angina pectoris. Like other calcium channel blockers, nifedipine acts by inhibiting the transmembrane influx of calcium into cardiac and smooth muscle cells during depolarization. The inhibition of calcium influx causes arterial vasodilation and decreases cardiac work and oxygen consumption. Nifedipine was approved in the United States in 1982 and currently several million prescriptions are filled yearly. Current indications include hypertension and chronic stable and Prinzmetal's variant angina pectoris. It is also used off label to treat Raynaud phenomenon. Nifedipine is available in capsules of 10 and 20 mg and as extended release tablets of 30, 60 and 90 mg in several generic formulations as well as under brand names including Procardia, Adala, Afeditab, Nifediac, and Nifedical. The typical dose in adults is 30 to 60 mg daily, usually starting with lower doses. Nifedipine is generally well tolerated and side effects are largely due to its vasodilating activities and can include dizziness, flushing, headache, fatigue, nausea, diarrhea, palpitations, bradycardia, peripheral edema and skin rash.


Mild and transient elevations in serum aminotransferase levels may occur during nifedipine therapy, but often resolve even with continuation of therapy. Clinically apparent acute liver injury with jaundice due to nifedipine is rare and described only in isolated case reports. The time to onset of injury is typically 1 to 2 months and the pattern of serum enzyme elevations is usually hepatocellular or mixed. Rash, arthralgias, fever and eosinophilia can occur, but are not prominent. Chronic aminotransferase elevations during continued therapy with nifedipine have been described sometimes with histological features of alcoholic liver disease (steatosis and Mallory bodies), but chronic liver injury after withdrawal has not. Nifedipine has not been implicated in cases of vanishing bile duct syndrome or acute liver failure in the published literature.

Likelihood score: B (likely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism of nifedipine hepatotoxicity is not known, but is likely to be due to production of a toxic or immunogenic intermediate during its metabolism by the liver.

Outcome and Management

The severity of liver injury from nifedipine ranges from mild and transient serum enzyme elevations to self-limited jaundice to an alcoholic hepatitis-like syndrome. Complete recovery is expected after stopping the drug and recovery is usually rapid (3 to 8 weeks). There is little information on cross sensitivity to liver injury among the various calcium channel blockers, but related medications should be started with caution in patients with clinically apparent liver injury from nifedipine.

Drug Class: Cardiovascular Agents, Calcium Channel Blockers

Other Drugs in the Subclass, Calcium Channel Blockers: Amlodipine, Diltiazem, Felodipine, Isradipine, Nicardipine, 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.



Nifedipine – Generic, Adalat®, Procardia®


Cardiovascular Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 11 January 2017

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