Elimination
CYP3A4 substrate and inhibitor; 51% excreted in urine (< 5% unchanged) and 44% in feces
Metabolized by CYPs 2B6 and 3A4
CYP3A4 mixed inducer/ inhibitor (more an inducer than an inhibitor)
Serum/Half-life 5.8 hrs
Adverse Events
▶ Rasha ▶ Increased transaminase levels ▶ Headaches
40-55 hrs
▶ Rasha ▶ Central nervous system symptomsb ▶ Increased transaminase levels ▶ False-positive results reported with some cannabinoid and benzodiazepine screening assays
▶ Teratogenic in nonhuman primate and potentially teratogenic in humans
▶ Hyperlipidemia
CYP3A4, 2C9, and 2C19 substrate 3A4 inducer; 2C9 and 2C19 inhibitor
CYP450 substrate and 3A inducer; 80% excreted in urine (glucuronidated metabolites, < 5% unchanged); 10% in feces
41 ± 20 hrs
▶ Rasha ▶ Hypersensitivity reactions have been reported, characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure
▶ Nausea 25-30 hrs
▶ Rash, including Stevens-Johnson syndromea
▶ Symptomatic hepatitis, including fatal hepatic necrosis, has been reportedc
Undergoes oxidative metabolism via CYP3A4; parent drug and metabolite excreted in feces (85%) and urine (6.1%).
50 hours
▶ Depression , insomnia, and headache (fewer CNS effects than EFV)
▶ Rash (less than EFV, NVP) ▶ AST elevation (comparable to EFV) ▶ No significant lipid effects
c
Symptomatic, sometimes serious, and even fatal hepatic events (accompanied by rash in approximately 50% of cases) occur at significantly higher frequency in treatment-naïve female patients with pre-NVP CD4 counts > 250 cells/mm3
pre-NVP CD4 counts > 400 cells/mm3. NVP should NOT be initiated in these patients unless the or in treatment-naïve male patients with
benefit clearly outweighs the risk. This toxicity has not been observed when NVP is given as single doses to mothers or infants for prevention of mother-to-child transmission of HIV.
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