Table 8. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Generic Name
Trade Name Nevirapine
Viramune Delavirdine
Rescriptor Efavirenz
Sustiva

Form 200 mg tabs 100 mg tabs 50, 100, 200 mg capsules

Dosing Recommendation 200 mg po qd x 14 days, then 200 mg po bid 400 mg po tid (four 100 mg tablets in > 3 oz. water to produce slurry) 600 mg po qHS

Oral bioavailability > 90% 85% 42% (increased with high fat content meal)

Serum half-life 25 - 30 hrs 5.8 hrs 40-55 hours

Elimination Metabolized by cytochrome p450; 80% excreted in urine (glucuronidated metabolites, < 5% unchanged), 10% in feces Metabolized by cytochrome p450 51% excreted in urine (< 5% unchanged) 44% in feces Metabolized by cytochrome p450; 14 – 34 % excreted in urine (glucuronidated metabolites, < 1% unchanged), 16 – 61 % in feces.

Drug interactions Induces cytochrome p450 enzymes

The following drugs have suspected interactions that require careful monitoring if co-administered with nevirapine: rifampin, rifabutin, oral contraceptives, protease inhibitors, triazolam and midazolam
Inhibits cytochrome p 450 enzymes

Not recommended for concurrent use: terfenadine, astemizole, alprazolam, midazolam, cisapride, rifabutin, rifampin, triazolam, ergot derivatives, amphetamines, nifedipine, anticonvulsants (phenytoin, carbamazepine, phenobarbitol)
Delavirdine increases levels of clarithromycin, dapsone, quinidine, warfarin, indinavir, saquinavir Buy Hoodia
Antacids or didanosine: separate delavirdine administration by > 1 hr
Mixed inducer/inhibitor of cytochrome p450 A4 enzymes; concentrations of concomitant drugs can be increased or decreased depending upon specific enzyme pathway involved.

Not recommended for concurrent use: astemizole, midazolam, triazolam, cisapride, ergot alkaloids. Efavirenz decreases levels of indinavir (31%), saquinavir (62%) and increases levels of nelfinavir (20%) and ritonavir (18%).
Other potentially significant drug interactions requiring careful monitoring when co-administered with efavirenz include: warfarin, clarithromycin, rifabutin, rifampin, and ethinyl estradiol. Enzyme inducers such as rifampin, rifabutin, phenobarbital, and phenytoin would be expected to decrease efavirenz concentrations.

Adverse Events Rash
Increased transaminase levels
Hepatitis
Rash
Headaches
Rash ¹
Central nervous systems symptoms ²
Increase transaminase levels
False positive cannabinoid test
Teratogenic in monkeys ³

¹ Severe rash may occur in up to 5% of patients; cases of Stevens-Johnson Syndrome have been reported.
²May include dizziness, somnolence, insomnia, abnormal dreams, confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria. The overall frequency of any of these symptoms associated with use of efavirenz was 52% compared with 26% in controls; 2.6% of those on efavirenz discontinued the drug due to these symptoms.
³No data are available regarding teratogenicity of other NNRTIs in non-human primates.

Generic Name Trade Name	Nevirapine Viramune	Delavirdine Rescriptor	Efavirenz Sustiva
Form	200 mg tabs	100 mg tabs	50, 100, 200 mg capsules
Dosing Recommendation	200 mg po qd x 14 days, then 200 mg po bid	400 mg po tid (four 100 mg tablets in > 3 oz. water to produce slurry)	600 mg po qHS
Oral bioavailability	> 90%	85%	42% (increased with high fat content meal)
Serum half-life	25 - 30 hrs	5.8 hrs	40-55 hours
Elimination	Metabolized by cytochrome p450; 80% excreted in urine (glucuronidated metabolites, < 5% unchanged), 10% in feces	Metabolized by cytochrome p450 51% excreted in urine (< 5% unchanged) 44% in feces	Metabolized by cytochrome p450; 14 – 34 % excreted in urine (glucuronidated metabolites, < 1% unchanged), 16 – 61 % in feces.
Drug interactions	Induces cytochrome p450 enzymes The following drugs have suspected interactions that require careful monitoring if co-administered with nevirapine: rifampin, rifabutin, oral contraceptives, protease inhibitors, triazolam and midazolam	Inhibits cytochrome p 450 enzymes Not recommended for concurrent use: terfenadine, astemizole, alprazolam, midazolam, cisapride, rifabutin, rifampin, triazolam, ergot derivatives, amphetamines, nifedipine, anticonvulsants (phenytoin, carbamazepine, phenobarbitol) Delavirdine increases levels of clarithromycin, dapsone, quinidine, warfarin, indinavir, saquinavir Buy Hoodia Antacids or didanosine: separate delavirdine administration by > 1 hr	Mixed inducer/inhibitor of cytochrome p450 A4 enzymes; concentrations of concomitant drugs can be increased or decreased depending upon specific enzyme pathway involved. Not recommended for concurrent use: astemizole, midazolam, triazolam, cisapride, ergot alkaloids. Efavirenz decreases levels of indinavir (31%), saquinavir (62%) and increases levels of nelfinavir (20%) and ritonavir (18%). Other potentially significant drug interactions requiring careful monitoring when co-administered with efavirenz include: warfarin, clarithromycin, rifabutin, rifampin, and ethinyl estradiol. Enzyme inducers such as rifampin, rifabutin, phenobarbital, and phenytoin would be expected to decrease efavirenz concentrations.
Adverse Events	Rash Increased transaminase levels Hepatitis	Rash Headaches	Rash ¹ Central nervous systems symptoms ² Increase transaminase levels False positive cannabinoid test Teratogenic in monkeys ³