Antiretroviral Agents in HIV-1 (trial)

13 Table 5B. Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Drug Formulation Dosing Recommendations Elimination Serum Half-life Adverse Events Delavirdine (DLV) Rescriptor ® 100, 200 mg tablets 400 mg tid; four 100 mg tablets can be dispersed in >3 oz of water to produce slurry; 200 mg tablets should be taken as intact tablets ▶ Take without regard to meals ▶ ≥1 h between dose and antacids CYP3A4 substrate and inhibitor; 51% excreted in urine (<5% unchanged) and 44% in feces 5.8 h ▶ Rash a ▶ Increased transaminase levels ▶ Headaches Efavirenz (EFV) Sustiva ® 50, 200 mg capsules or 600 mg tablets 600 mg once daily at or before bedtime ▶ Take on an empty stomach to reduce side effects Metabolized by CYPs 2B6 and 3A4 CYP3A4 mixed inducer/ inhibitor (more an inducer than an inhibitor) 40–55 h ▶ Rash a ▶ CNS symptoms b ▶ Increased transaminase levels ▶ False-positive results reported with some cannabinoid and benzodiazepine screening assays ▶ Teratogenic in nonhuman primate and potentially teratogenic in humans ▶ Hyperlipidemia Also available in: FTC/TDF/EFV Atripla ® FTC 200 mg + TDF 300 mg + EFV 600 mg 1 tablet once daily at or before bedtime Etravirine (ETR) Intelence ® 100 mg tablets 200 mg tablets 200 mg bid ▶ Take following a meal CYP3A4, 2C9, and 2C19 substrate 3A4 inducer; 2C9 and 2C19 inhibitor 41 ± 20 h ▶ Rash a ▶ Hypersensitivity reactions have been reported, characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure ▶ Nausea Nevirapine (NVP) Viramune ® Viramune XR ® 200 mg tablets or 50 mg/5 mL oral suspension 400 mg extended- release tablets 200 mg once daily for 14 days (lead-in period); thereaer, 200 mg bid OR 400 mg extended-release daily ▶ Take without regard to meals ▶ Repeat lead-in period if therapy is discontinued for >7 days ▶ In patients who develop mild to moderate rash without constitutional symptoms, continue lead-in period until rash resolves but no longer than 28 days total CYP450 substrate and 3A inducer; 80% excreted in urine (glucuronidated metabolites, <5% unchanged); 10% in feces 25–30 h ▶ Rash, including Stevens-Johnson syndrome a ▶ Symptomatic hepatitis, including fatal hepatic necrosis, has been reported c Rilpivirine (RPV) Edurant ® 25 mg tablets 25 mg once daily with a meal Undergoes oxidative metabolism via CYP3A4; parent drug and metabolite excreted in feces (85%) and urine (6.1%) 50 h ▶ Depression, insomnia, and headache (fewer CNS effects than with EFV) ▶ Rash (less than with EFV, NVP) ▶ AST elevation (comparable to EFV) ▶ No significant lipid effects Also available in: FTC/TDF/RPV Complera ® FTC 200 mg + TDF 300 mg + RPV 25 mg One tablet once daily with meal a During clinical trials, NNRTI was discontinued because of rash among 7% of NVP-treated, 4.3% of DLV-treated, 1.7% of EFV-treated, and 2% of ETR-treated patients. Rare cases of Stevens-Johnson syndrome have been reported with all NNRTIs; the highest incidence was seen with NVP. b Adverse events can include dizziness, somnolence, insomnia, abnormal dreams, confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. Overall frequency of any of these symptoms associated with use of efavirenz was 52% compared with 26% among controls subjects; 2.6% of those persons on EFV discontinued the drug because of these symptoms. Symptoms usually subside spontaneously aer 2–4 weeks. c Symptomatic, sometimes serious, and even fatal hepatic events (accompanied by rash in approximately 50% of cases) occur at significantly higher frequency in treatment-naive female patients with pre-NVP CD4 counts >250 cells/mm 3 or in treatment-naive male patients with pre-NVP CD4 counts >400 cells/mm 3 . NVP should NOT be initiated in these patients unless the benefit clearly outweighs the risk. is 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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