Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the therapy of hypertension and heart failure. Lisinopril is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury that can be severe and even fatal.
Lisinopril (lye sin' oh pril) was the third ACE inhibitor to be approved for use in the United States and is still widely used for therapy of hypertension and heart failure. Like other ACE inhibitors, lisinopril inhibits the conversion of angiotensin I, a relatively inactive molecule, to angiotensin II which is the major mediator of vasoconstriction and volume expansion induced by the renin-angiotensin system. Other enzymes besides that which converts angiotensin I to II may also be inhibited, which may account for some of the side effects of the ACE inhibitors. Lisinopril was approved for use in the United States in 1987 and is currently one of the most widely prescribed medications in clinical practice, with more than 60 million prescriptions filled yearly. Current indications include hypertension, heart failure and to improve survival after acute myocardial infarction. Lisinopril is available in 2.5, 5, 10, 20, 30 and 40 mg tablets in many generic forms and under the trade names Prinivil and Zestril. The recommended initial dose in adults is 5 to 10 mg daily with subsequent adjustments based upon blood pressure response and tolerance. The average maintenance dose for hypertension is 20 to 40 mg once daily; the maximum recommended dose is 80 mg daily. Lower doses are recommended for heart failure and for chronic therapy after an acute myocardial infarction. Lisinopril is also available in fixed combinations with hydrochlorothiazide (generically and as Prinzide and Zestoretic). Common side effects include dizziness, fatigue, headache, cough, gastrointestinal upset and skin rash.
Lisinopril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (<2%) that, in controlled trials, was no higher than with placebo therapy. These elevations were transient and rarely required dose modification. Rare instances of clinically apparent acute liver injury have been reported in association with lisinopril therapy. Despite its widescale use, fewer than a dozen cases of clinically apparent acute liver injury attributed to lisinopril therapy have been published. The latency to onset has ranged from 2 to 48 weeks and the pattern of serum enzyme elevations has been hepatocellular, in contrast to the typical cholestatic pattern that occurs wtih other ACE inhibitors. Immunoallergic manifestations (rash, fever, eosinophilia) are infrequent and most patients do not develop autoantibodies. Several reported cases were associated with signs of acute liver failure and deaths from complications have been reported.
Likelihood score: B (likely but rare cause of clinically apparent liver injury).
Mechanism of Injury
The cause of the minor serum aminotransferase elevations associated with lisinopril therapy is not known. The cases of clinically apparent liver injury due to lisinopril are idiosyncratic and likely due to a reaction to a minor metabolite. Lisinopril has minimal hepatic metabolism.
Outcome and Management
Most instances of acute liver injury reported with lisinopril use have been self limited, but there have been reports of acute liver failure and death. Patients with severe lisinopril induced acute liver injury should avoid use of other ACE inhibitors, although cross sensitivity to liver injury among the members of this class of agents has rarely been shown and, in some cases of lisinopril associated liver injury, patients had previously tolerated other ACE inhibitors.
|Medication:||Lisinopril (20 mg daily)|
|Severity:||5+ (hepatic failure, death)|
|Latency:||One week to symptoms, 2 weeks to jaundice|
|Other medications:||Furosemide, bisoprolol, enalapril previously|
|2 weeks||0||2510||90%||18.5||Furosemide stopped|
|5 weeks||3 weeks||2561||20%||40.3||Lisinopril stopped|
|6 weeks||4 weeks||520||30%||37.4|
|8 weeks||6 weeks||97||42%||70.1|
|11 weeks||9 weeks||52||60%||13.9||Emergency surgery|
|DRUG||CAS REGISTRY NUMBER||MOLECULAR FORMULA||STRUCTURE|
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