NNRTIs
Non-Nucleoside Reverse Transcriptase Inhibitors

Delavirdine
Other names: DLV, Rescriptor
Form: 50, 100, 200 mg tables
Dosing:
     Normal: 400 mg TID: 600 mg BID
     Renal failure: Probably no change; Not dialyzed
    Liver failure: Use with caution
     Pediatric: NA
Food Effect: None
Oral bioavailability: 85%
Serum half-life: 5.8 hours
Intracellular half-life:
Elimination: Metabolized by cytochrome P450 (3a inhibitor) 51% excreted in urine (<5% unchanged), 44% in feces
Adverse Events: Rash, headache, increased transaminases, Steven-Johnson syndrome
FDA Pregnancy Category: C
Combination Regimens:
     DLV (400 mg TID) + IDV (800 mg TID)
     DLV (600 mg BID) + IDV (1200 mg BID)
     DLV (600 mg BID) + NFV (1250 mg BID)
     DLV (600 mg BID) + RTV (300 mg BID)
     DLV (600 mg BID) + FTV (1400 mg BID)
Comments: 200 mg tablets should be swallowed intact. Or, mix 4(four) 100 mg tab s in 3 oz of water thoroughly and drink promptly. Take antacids (eg. ddI) 1-hour apart from DLV. In achlorydia, take with orange or cranberry juice. If rash develops, discontinue and do not rechallenge. Easy to use with methadone or OCPs. No anti-HIV-2 activity. Less hepatotoxic than NVP or EFV in HBV or HCV patients.

Efavirenz
Other names: EFV, Sustiva
Form: 50, 100, 200 mg caps; 600 mg tabs
Dosing:
     Normal: 600 mg Q HS or QD
     Renal failure: Probably no change; not dialyzed
     Liver failure: NA (OK in mild to moderate liver disease)
     Pediatric: 10-15 kg: 200 mg QD
                      15-20 kg: 200 mg QD
                       20-25 kg: 300 mg QD
                       25-32 kg: 350 mg QD
                       32-40 kg: 400 mg QD
                       >40 kg: 600 mg QD
Food Effect: Avoid taking after high fat meals, levels increased by 50%;
Oral bioavailability: Data not available
Serum half-life: 40-55 hours
Intracellular half-life:
Elimination: Metabolized by cytochrome P450 (3a mixed inducer/inhibitor); 14-34% excreted in urine (glucuronidated metabolites, <1% unchanged); 16%-61% in feces
Adverse Events: Rash, CNS symptoms, dizziness, difficulty concentrating, nausea, vomiting, diarrhea, flu-like symptoms
FDA Pregnancy Category: C
Combination Regimens:
     EFV (600 mg QD) + IDV (1000 mg Q 8 H)
     EFV (600 mg QD) + NFV (1250 mg BID)
     EFV (600 mg QD) + RTV (500 mg BID)
     EFV (800 mg QD) + NVP (400 mg QD)
     EFV + AMP (600 mg BUD) + RTV (200 mg BID)
Comments: Expanded access available for oral suspension; potent at VL > 300K. CNS concentration low, but > IC95% for HIV. Birth defects reported in monkeys. Increases HDL cholesterol. No anti-HIV2 activity. EFV decreases FTV by 60%. RTV + FTV may be OK with EFV. EFV can reduce methadone and cause withdrawal, necessitating increase in methadone dose. Reduces TAZ levels significantly.

Emivirine
Other names: EMV, Coactinon
Form: 500 mg tabs
Dosing:
     Normal: 500 mg BID
     Renal failure: NA; probably no change; not dialized.
     Liver failure: NA
     Pediatric: NA
Food Effect: Take with food.
Oral bioavailability:
Serum half-life:
Intracellular half-life:
Elimination:
Adverse Events: Nausea, vomiting, diarrhea, rash, headache, dizziness.
FDA Pregnancy Category:
Combination Regimens:
Comments: Available in clinical trials only. Also known as MKCV-442. A nucleoside analogue that acts like a NNRTI. May have a role in prevention of vertical transmission because of high penetration of placental blood barrier. Causes significant reduction in IDV and NFV.

Nevirapine
Other names: NVP, Viramune
Form: 200 mg tabs; 10 mg/mL suspension in 240 cc bottle
Dosing:
     Normal: 200 QD x 14 days, then 200 BID; or, 400 mg QD.
     Renal failure: Probably no change. Dialized, take after dialysis.
     Liver failure: Use with caution.
     Pediatric: 120 mg/m2 QD x 14 days; then BID.
Food Effect: Take without regard to meals
Oral bioavailability: >90%
Serum half-life: 25-30 hours
Intracellular half-life:
Elimination: Metabolized by cytochrome P450 (3A inducer); 80% excreted in urine (Glucuronidated metabolites, <5% unchanged), 10% in feces.
Adverse Events: Rash, increased transaminase levels, hepatitis, flu-like symptoms; difficulty concentrating, nausea, vomiting, diarrhea, dizziness.
FDA Pregnancy Category: C
Combination Regimens:
     NVP (200 mg BID) + RTV (600 BID)
     NVP (200 mg BID) + IDV (800 mg Q 8H)
     NVP (200 mg BID) + NFV (1250 mg BID)
     NVP (400mg QD) + EVZ (800 mg QD)
Comments: Discontinue if severe rash and constitutional symptoms; do not rechallenge. Do not use with ketoconazole. May need to increase methadone dose. No anti-HIV-2 activity. Has potency at VL>100K. Use with caution with PEP. Check LFTs frequently, especially in first 4 weeks.

Cross-resistance:
K103N: Cross-resistance among the three currently available NNRTIs is extensive. The presence of the K103N mutation, seen frequently in patients failing delavirdine, nevirapine, or efavirenz, renders all three agents ineffective. However, some patients failing delavirdine or nevirapine have resistance due to other mutations, such as Y181C, thereby retaining some susceptibility to efavirenz. In such patients resistance assays can be used to determine the susceptibility to efavirenz, provided they are performed while the patient is stil taking the NNRTI.
      New NNRTIs are in development that may be effective against virus carrying the K103N mutation and double mutants. For that reason, it may be wise to discontinue therapy with failing NNRTIs, since the accumulation of additional mutaions may preclude the later use of these "second generation" drugs.
     After failure on a single PI, a dual PI combination may be a better salvage regimen when combined with an NNRTI.