Toxic epidermal necrolysis nevirapine

Nevirapine is a non-nucleoside reverse transcriptase inhibitor used to treat HIV-infected patients that causes mild to severe skin rash and even Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) in a substantial proportion (16%) of patients. Nevirapine also induces hepatotoxicity. These adverse clinical symptoms may also occur in non-HIV subjects taking the drug as postoperative prophylaxis [15]. 

Fagot, J.-P. et al., Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis, AIDS, 15, 1843, 2001. 

Nevirapine has been associated with severe, life-threatening rash (Stevens-Johnson syndrome, toxic epidermal necrolysis), which in some cases, has been fatal. When severe rash occurs, discontinue nevirapine. 

Nevirapine (Viramune) is approved for the treatment of HIV infection in adults and children as part of a combination therapy. During the first 12 weeks of treatment, patients must be closely monitored for the development of potentially fatal hepatic toxicity (i.e., hepatitis, hepatic necrosis, and hepatic failure) and skin reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions). Although these toxici-ties are rare, common side effects include mild to moderate rash, fever, nausea, fatigue, headache, and elevated liver enzymes. 

Wetterwald E, Le Cleach L, Michel C, David F, Revuz J. Nevirapine-induced overlap Stevens-Johnson syndrome/ toxic epidermal necrolysis. Br J Dermatol 1999 140(5) 980-2. 

B. Nevirapine Nevirapine is currently used in alternative combination regimens and is effective in preventing HIV vertical transmission when given as single doses to mothers at the onset of labor and to the neonate. Hypersensitivity reactions with nevirapine include Stevens-Johnson syndrome and a life-threatening toxic epidermal necrolysis. Nevirapine is metabolized by CYP3A4, and its blood levels are increased by cimetidine and macrolide antibiotics and decreased by enzyme inducers such as rifampin. 

Chat J, Maimaigudi BM, Xu L, Uetiecht J (2008) Demonstration of the metabolic pathway responsible for nevirapine-induced skin rash. Chem Res Toxicol 21 1862-1870 Claes P, Winizen M, Allard S et al (2004) Nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcysteine. Eur J Intern Med 15 255-258... 

Skin Nevirapine has again been associated with fatal toxic epidermal necrolysis [161 ] and Stevens-Johnson syndrome extensive enough to have been called toxic epidermal necrolysis [162", 163" ]. Based on studies in rats, it has been suggested that the molecule that is responsible for such reactions is formed from nevirapine by hydroxylation to a reactive quinone methide, and cotreatment with a CYP enzyme inhibitor, 1-aminobenzotriazole, resulted in a lower incidence of reactions [164 ]. The authors proposed that the hepatotoxicity of nevirapine is due to the quinone methide after its formation in the liver, and that rashes may be due to the quinone methide formed in the skin by sulfation of the 12-hydroxy metabolite followed by loss of the sulfate species. 

Leng K, Lonsdorf A, Hartmann M. Fatal outcome of nevirapine-associated toxic epidermal necrolysis. Int J STD AIDS... 

---