enalapril and Cholestasis--Intrahepatic

A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

Topics: Acetaminophen; Betamethasone; Bronchitis; Chlorpheniramine; Cholestasis, Intrahepatic; Clindamycin; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enalapril; Female; Foot Dermatoses; Hand Dermatoses; Humans; Insulin; Methylprednisolone; Middle Aged; Mucositis; Stevens-Johnson Syndrome

Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported.. To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril.. Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature.. The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously.. Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Chemical and Drug Induced Liver Injury, Chronic; Cholangiopancreatography, Endoscopic Retrograde; Cholestasis, Intrahepatic; Enalapril; Fosinopril; Humans; Jaundice; Liver; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Ramipril

Topics: Angiotensin-Converting Enzyme Inhibitors; Bile Canaliculi; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Enalapril; Humans; Male; Middle Aged

Topics: Aged; Cholestasis, Intrahepatic; Drug Therapy, Combination; Enalapril; Female; Flecainide; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Tachycardia