Dosing and uses of NVP, Viramune (nevirapine)
Adult dosage forms and strengths
oral suspension
- 50mg/5mL (240mL)
tablet, immediate-release
- 200mg
tablet, extended-release
- 400mg
HIV Infection
Indicated for treatment of HIV-1 infection in combination with other antiretrovirals; also used for prevention of maternal-fetal HIV transmission in women with no prior antiretroviral treatment
200 mg PO qDay x 14 days, THEn
If no rash, increase to 200 mg q12hr; if rash occurs wait until it is resolved before increasing
Prevention of maternal-fetal HIV transmission: 200 mg PO as a single dose at onset of labor, in combination with IV zidovudine
Extended-release tablets
- Initial therapy: When initiating therapy, give immediate-release tablet 200 mg PO qDay for 14 days, then extended-release tablet 400 mg PO qDay thereafter
- Switch from immediate-release: If already taking immediate-release regimen, may switch to extended-release 400 mg PO qDay without 14-day lead-in period of immediate-release nevirapine
Dosing Considerations
Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine should not be initiated in adult females with CD4+ cell counts >250 cells/mm³ or in adult males with CD4+ cell counts >400 cells/mm³ unless the benefit outweighs the risk
The 14-day lead-in period with immediate-release dosing must be strictly followed; it has been demonstrated to reduce the frequency of rash
If nevirapine extended-release interrupted >7 days, restart with lead-in dosing with immediate-release nevirapine
If mild-to-moderate rash (without constitutional symptoms) occurs during 14-day lead-in period, do not increase immediate-release dose or initiate extended-release regimen until the rash has resolved; duration of the lead-in dosing should not exceed 28 days, at which point an alternative regimen should be chosen; discontinue also if severe rash develops or rash with elevated hepatic transaminases or with constitutional symptoms occur
Administration
Extended-release tablets should be swallowed whole; do not chew, crush, or split
May take with or without food
Pediatric dosage forms and strengths
oral suspension
- 50mg/5mL (240mL)
tablet, immediate-release
- 200mg
tablet, extended-release
- 400mg
HIV Infection
Indicated for treatment of HIV-1 infection in combination with other antiretrovirals
Immediate-release
- <15 days: Safety and efficacy not established
- ≥15 days to 16 years: 150 mg/m² PO qDay for 2 wk; if no rash, then increase to 150 mg/m² q12hr; not to exceed 200 mg/dose
- >16 years: As adults; 200 mg PO qDay for 2 wk; if no rash or untoward effect occurs, then increase to 200 mg PO q12h
Extended-release
- <6 years: Safety and efficacy not established
- 6-18 years
- Switch from immediate-release tabs: If already taking immediate-release, may switch to extended- release without 14-day lead-in period of immediate-release nevirapine
- Initial therapy: Initiate with immediate-release 150 mg/m² PO qDay for 14 days (not to exceed 200 mg/day), THEN
- Extended-release dose based on BSA as follows:
- 0.58-0.83 m²: 200 mg PO qDay
- 0.84-1.16 m²: 300 mg PO qDay
- ≥1.17 m²: 400 mg PO qDay
Prevention of Maternal-Fetal HIV Transmission in Neonates
Additional prophylaxis with nevirapine is needed for HIV-exposed infants of women who did not receive antepartum ART (NIH perinatal guidelines July 2012)
Birth weight 1.5-2 kg: 8 mg/dose PO
Birth weight >2 kg: 12 mg/dose PO
Administer 3 doses in the first week of life; 1st dose 48 hr after birth, give 2nd dose 48 hr after 1st dose, and 3rd dose 96 hr after 2nd dose
Recommended in combination with 6 weeks of zidovudine
Dosing Considerations
The 14-day lead-in period with immediate-release dosing must be strictly followed; it has been demonstrated to reduce the frequency of rash
If nevirapine extended-release interrupted >7 days, restart with lead-in dosing with immediate-release nevirapine
If mild-to-moderate rash (without constitutional symptoms) occurs during 14-day lead-in period, do not increase immediate-release dose or initiate extended-release regimen until the rash has resolved; duration of the lead-in dosing should not exceed 28 days, at which point an alternative regimen should be chosen
Administration
Shake suspension gently and administer entire measured dose
5 mL or less: Use oral syringe
Extended-release tablets should be swallowed whole; do not chew, crush, or split
May take with or without food
NVP, Viramune (nevirapine) adverse (side) effects
>10%
Diarrhea (15-20%)
Rash (15-20%)
Headache (11%)
Neutropenia (10-11%)
Fever (8-11%)
1-10%
Ulcerative stomatitis (4%)
Increased LFTs (2-4%)
Abdominal pain (2%)
Paresthesia (2%)
Nausea
Anemia
Peripheral neuropathy
Myalgia
Frequency not defined
Potentially fatal hepatotoxicity (fulminant hepatitis, cholestatic hepatitis, hepatic failure, hepatic necrosis)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Rhabdomyolysis
Postmarketing Reports
Body as a whole: Fever, somnolence, drug withdrawal, redistribution/accumulation of body fat
Gastrointestinal: Vomiting
Liver and biliary: Jaundice, fulminant and cholestatic hepatitis, hepatic necrosis, hepatic failure
Hematology: Anemia, eosinophilia, neutropenia Investigations: decreased serum phosphorus
Investigations: Decreased serum phosphorus
Musculoskeletal: Arthralgia, rhabdomyolysis associated with skin and/or liver reactions
Neurologic: Paraesthesia
Skin and appendages: Allergic reactions including anaphylaxis, angioedema, bullous eruptions, ulcerative stomatitis and urticaria have all been reported; hypersensitivity syndrome and hypersensitivity reactions with rash associated with constitutional findings (eg, fever, blistering, oral lesions, conjunctivitis, facial edema, muscle or joint aches, general malaise, fatigue, or significant hepatic abnormalities, drug reaction with eosinophilia and systemic symptoms [DRESS])
Warnings
Black box warnings
Monitoring during the first 18 wk of therapy essential; extra vigilance warranted during first 6 wk of therapy (period of greatest risk)
Fatal and nonfatal hepatotoxicity
- Discontinue immediately with signs or symptoms of hepatitis or increased transaminase levels combined with rash or other systemic symptoms
Fatal and nonfatal skin reactions
- Discontinue immediately if severe skin or hypersensitivity reactions occur or if any rash with systemic symptoms occurs
Contraindications
Hypersensitivity
Moderate or severe hepatic impairment (Child-Pugh class B or C)
Coadministration with drugs (eg, CYP inducers) where significant decreases in nevirapine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance to other NNRTIs
Use as part of postexposure prophylaxis (PEP) regimens
Cautions
Risk of hepatotoxicity
- Discontinue in patients with signs/symptoms of hepatitis, or with increased LFTs combined with rash
- Hepatic injury may progress despite treatment discontinuation
- Female gender and higher CD4 are higher risk factors
Do not increase dose if patient experiences rash during 14 day initial dosing period of 200 mg/day
Risk of severe, life threatening skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity
Discontinue if severe rash or any rash accompanied by constitutional findings occurs
Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs
Redistribution/accumulation of body fat may occur (cushingoid appearance)
Pregnancy and lactation
Pregnancy category: C
Lactation: HIV+ women are advised not to breastfeed
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of NVP, Viramune (nevirapine)
Mechanism of action
Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI); activity against HIV-1 by binding to reverse transcriptase, and thereby blocking RNA- and DNA-dependent DNA polymerase actions including HIV-1 replication
Does not require intracellular phosphorylation for activity
Absorption
Bioavailability: >90%
Peak Plasma: 2-4 hr
Distribution
Distributed widely; crosses placenta; enters breast milk; CSF penetration approximates 50% of plasma
Protein Bound: 50-60%
Vd: 1.2-1.4 L/kg
Metabolism
Extensively hepatic via CYP3A4 (hydroxylation to inactive compounds)
May undergo enterohepatic recycling
Elimination
Half-life: Decreases over 2-4 wk with chronic dosing due to autoinduction (ie, half-life initially 45 hr and decreases to 23 hr)
Excretion: Urine (~81% as metabolites, <3% as unchanged drug); feces (10%)
