14591_PT05_179_212.qxd
202
PART 5
2/14/11
1:23 PM
Page 202
Antiviral Drugs
bedtime or 2–3 hours prior. A history of mental illness or depression is a relative contraindication to the use of efavirenz. Dermatologic: Rashes can occur with all NNRTIs, although the nevirapine appears to be the biggest offender. Though some mild forms can be treated with antihistamines, any lesions involving the mucous membranes (suggesting Stevens-Johnson syndrome or similar eruptions) must be managed urgently and represent an absolute contraindication to rechallenge. Hepatotoxicity: All NNRTIs can cause a spectrum of hepatotoxicity, from asymptomatic transaminase elevations, to clinical hepatitis, to fulminant hepatic failure. Nevirapine-induced hepatotoxicity may occur in the context of a hypersensitivity reaction (see below). Monitoring of signs and symptoms of hepatitis and liver enzymes is important for all these agents. Hypersensitivity: Nevirapine can cause a hypersensitivity reaction characterized by flulike symptoms, fever, jaundice, and abdominal pain, with or without a rash. Fulminant hepatic failure and severe rash (e.g., toxic epidermal necrolysis) are the most feared manifestations of nevirapine hypersensitivity reactions. Interestingly, this syndrome appears to be more frequent in patients who are less immunocompromised (have higher CD4 counts) when starting nevirapine. The risk of nevirapine hypersensitivity syndrome may be reduced by using a “reverse taper� upon drug initiation: start with a lower dose and escalate to full dose over 2 weeks, when the risk is highest.