Metoprolol is a cardioselective beta-blocker that is widely used in the treatment of hypertension and angina pectoris. Metoprolol has been linked to rare cases of drug-induced liver injury.
Metoprolol is considered a “selective” beta-adrenergic receptor blocker in that it has potent activity against beta-1 adrenergic receptors which are found in cardiac muscle, but has little or no activity against beta-2 adrenergic receptors found on bronchial and vascular smooth muscle. Metoprolol was approved for use in the United States in 1978 and is still widely used in the therapy of hypertension and angina pectoris with more than 27 million prescriptions filled yearly. Metoprolol is also used to reduce the risk of cardiovascular mortality after acute myocardial infarction. Metoprolol is available in standard 50 and 100 mg tablets as well as 25, 50, 100 and 200 mg extended-release tablets in generic forms as well as under the trade name of Lopressor and Toprol XL and as a fixed combination with a hydrochlorothiazide as Lopressor HCT and Dutoprolol. Parenteral formulations for intravenous use are also available. The usual initial oral dose of metoprolol in adults is 100 mg daily in one or two divided doses daily with subsequent adjustment based upon clinical response and tolerance; the usual maintenance dosage being 100 to 400 mg daily. The entended-release forms are given in doses of 25 to 100 mg once daily. Common side effects include bradycardia, hypotension, fatigue, dizziness, depression, insomnia, memory loss and impotence. Beta-blockers are contraindicated in patients with asthma, bradycardia and heart failure and should be used cautiously in the elderly and in patients with diabetes. As with all beta-blockers, sudden withdrawal can trigger rebound hypertension.
Metoprolol therapy has been associated with a low rate of mild to moderate elevations of serum aminotransferase levels which are usually asymptomatic and transient and resolve even with continuation of therapy. A few instances of clinically apparent, acute liver injury attributable to metoprolol have been reported. In view of its wide-scale use, metoprolol-induced liver injury is exceedingly rare. The typical liver injury associated with beta blockers has a latency to onset of 2 to 12 weeks and a hepatocellular pattern of liver enzyme. Symptoms of hypersensitivity (rash, fever, eosinophilia) and autoantibody formation have not been reported. Reported cases due to metoprolol have been self-limiting and resolved rapidly once drug was stopped.
Mechanism of Injury
The mechanism of drug-induced liver injury from metoprolol is not known. The agent is metabolized in the liver via the cytochrome P450 (largely CYP 2D6).
Outcome and Management
The severity of liver injury due to metoprolol ranges from mild serum aminotransferase elevations to mild acute hepatitis with jaundice. In large case series of acute liver failure due to medications, metoprolol has not been listed as a cause. Rechallenge has been reported to result in recurrence of injury and should be avoided. There is little information about cross-reactivity among the beta-blockers to hepatic injury. Switching to another beta-blocker after metoprolol-related acute liver injury should be done with caution and prospective monitoring.
|Medication:||Metoprolol (200 mg daily)|
|Severity:||1+ (Enzyme elevations and symptoms without jaundice)|
|Other medications:||Doxycycline, aspirin and cough suppressant 3 weeks previously|
|Time After Starting||Weeks After Stopping||ALT* (U/L)||Alk P* (U/L)||GGT* (mg/dL)||Other|
|Metoprolol (50 mg daily) given for 3 weeks|
|3 weeks||0||1140||168||244||Bilirubin 0.7 mg/dL|
|4 weeks||5 days||171||108||110|
|6 weeks||3 weeks||34||84||34|
|Metoprolol (50 mg daily) restarted for 5 days|
|5 days||0||66||144||Not done|
|7 weeks||6 weeks||24||126||26|
|DRUG||CAS REGISTRY NUMBER||MOLECULAR FORMULA||STRUCTURE|
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