Liver damage associated with minocycline use in acne - A systematic reviewof the published literature and pharmacovigilance data

Objective: Minocycline is an antibacterial drug used in the treatment of ac ne. Concern has been expressed over the possibility of severe adverse react ions to minocycline, including hepatitis. This study set out to identify an d characterise reported cases of hepatotoxicity associated with the use of minocycline. Methods: A systematic review of the literature including a search of comput erised databases and analysis of data from the Uppsala Monitoring Centre (W HO Collaborating Centre for international Drug Monitoring) was conducted. T he review involved a search for original case reports involving liver damag e in people using minocycline. Patients taking minocycline for reasons othe r than acne or those given intravenous minocycline were excluded. The searc h strategy involved an enquiry of computerised databases and a search for s econdary references. Cases were then classified appropriately. Results: 65 reported cases of hepatitis or liver damage in association with minocycline from either case reports or case series were identified from t he literature review. 58% of cases occurred in females and 94% were aged un der 40 years. For 20 case reports there was insufficient information to cla ssify the type of event, but for the remaining 45, 2 types of hepatic react ion were recognised: autoimmune hepatitis associated with lupus-like sympto ms occurring after a median duration of exposure to minocycline of 365 days in females (n = 20) and 730 days in males (n = 9), hypersensitivity reacti on associated with eosinophilia and exfoliative dermatitis occurring within 35 days of therapy (n = 16). Reports to the WHO of hepatic adverse drug reactions associated with minocy cline accounted for 6% (493) of all minocycline-related adverse drug reacti ons (8025). The pattern of distribution in relation to exposure demonstrate d 2 groups, similar to that described by the case reports. Conclusions: Severe cases of minocycline-associated hepatotoxicity appear t o be a hypersensitivity reaction and occur within a few weeks of commencing therapy. An autoimmune hepatitis usually presents after exposure to minocy cline of a year or more, is more common in women and is sometimes associate d with lupus-like symptoms.