• Severe, life-threatening (and in some cases fatal) hepatotoxicity reported, particularly during first 18 weeks of therapy. Patients have presented with nonspecific prodromal signs and symptoms of hepatitis and progressed to hepatic failure; these events often associated with rash. Patients with higher CD4⁺ T-cell counts and women are at increased risk of these hepatic events. Women with CD4⁺ T-cell counts >250 cells/mm³ (including pregnant women receiving long-term treatment for HIV infection) are at greatest risk, but hepatotoxicity can occur in both genders, all CD4⁺ T-cell counts, and at any time during treatment Patients with signs or symptoms of hepatitis or with increased serum transaminase concentrations in conjunction with rash or other systemic symptoms must discontinue nelfinavir and seek immediate medical evaluation.
• Severe, life-threatening skin reaction, including fatal cases, reported. Reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction. Patients with signs or symptoms of severe skin reactions or hypersensitivity must discontinue nelfinavir and seek immediate medical evaluation. Immediately measure serum transaminase concentrations if rash occurs during the first 18 weeks of nevirapine therapy.
• Essential that patients are monitored intensively during the first 18 weeks of nevirapine therapy to detect potential life-threatening hepatotoxicity or skin reactions. Extra vigilance needed during first 6 weeks since this is period of greatest risk.
• Hepatic injury has progressed despite discontinuation of nevirapine in some patients.
• Do not restart nevirapine following severe hepatic, skin, or hypersensitivity reactions.
• Strictly follow the recommendations regarding use of a low initial nevirapine dosage (Adults: 200 mg once daily for the first 14 days). Initiating therapy with this dosage reduces frequency of rash.

REMS:

FDA approved a REMS for nevirapine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).