Nevirapine (Monograph)

Brand name: Viramune
Drug class: HIV Nonnucleoside Reverse Transcriptase Inhibitors
- Reverse Transcriptase Inhibitors
VA class: AM800
Chemical name: 11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b: 2′,3′-e)[1,4]diazepin-6-one
Molecular formula: C₁₅H₁₄N₄O
CAS number: 129618-40-2

Medically reviewed by Drugs.com on Aug 3, 2023. Written by ASHP.

Introduction

Antiretroviral; HIV nonnucleoside reverse transcriptase inhibitor (NNRTI).^{1 21 200 234}

Uses for Nevirapine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients;^{1 234} usually used in conjunction with 2 HIV nucleoside reverse transcriptase inhibitors (NRTIs).^{1 234}

Because of increased risk of potentially life-threatening hepatotoxicity, do not initiate in females (including postpubertal girls and adolescents) with pretreatment CD4⁺ T-cell counts >250/mm³ or in males (including adolescent boys) with CD4⁺ T-cell counts >400/mm³ unless potential benefits clearly outweigh risks.^{1 96 200 201 234} (See Hepatic Effects under Cautions.)

For initial treatment in antiretroviral-naive adults or adolescents, experts state nevirapine not recommended since it is associated with serious and potentially fatal toxicity (e.g., hepatic events and severe rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis) and did not meet noninferiority criteria when compared to efavirenz.²⁰⁰

For initial treatment in antiretroviral-naive pediatric patients, experts state that nevirapine and 2 NRTIs is an alternative (not preferred) regimen in those >14 days and <3 years of age.²⁰¹

Experts state that nevirapine and 2 NRTIs is the regimen of choice for initial treatment in neonates <14 days of age^{† [off-label]} when HIV infection confirmed.²⁰¹ Consultation with an expert in pediatric HIV infection recommended; unclear whether initiation of antiretroviral treatment within first 14 days of life improves outcome compared with initiation at >14 days of age.²⁰¹ If used, consider changing to fixed-combination lopinavir and ritonavir (lopinavir/ritonavir) and 2 NRTIs when infant is 14 days of age with postmenstrual age at least 42 weeks (i.e., time elapsed since first day of mother’s last menstrual period to birth plus time elapsed after birth).²⁰¹

Prevention of Perinatal HIV Transmission

Prophylaxis^{† [off-label]} in neonates born to HIV-infected women for prevention of perinatal HIV transmission^{† [off-label]};²⁰² used in conjunction with zidovudine.²⁰²

Empiric HIV therapy^{† [off-label]} in neonates born to HIV-infected women for prevention of perinatal HIV transmission^{† [off-label]};²⁰² used in 3-drug empiric regimen (zidovudine, lamivudine, and nevirapine) in neonates at highest risk of HIV acquisition.²⁰²

Pregnant HIV-infected women: Multiple-drug antiretroviral regimens are standard of care in the US for treatment of HIV infection in pregnant women and for prevention of perinatal HIV transmission.²⁰² In addition, to further decrease risk of perinatal HIV transmission, experts recommend that all pregnant HIV-infected women with plasma HIV-1 RNA levels >1000 copies/mL (or unknown HIV-1 RNA levels) near delivery receive an intrapartum IV zidovudine prophylaxis regimen initiated at the onset of labor (or 3 hours before scheduled cesarean delivery) and continued until delivery (unless contraindicated).

HIV-exposed neonates: Experts recommend that all neonates born to HIV-infected women (HIV-exposed neonates) receive an antiretroviral regimen (either prophylaxis or empiric HIV therapy) initiated as soon as possible after birth (preferably within 6–12 hours) and continued through 4–6 weeks of age.²⁰² Select antiretroviral prophylaxis regimen or empiric HIV therapy regimen based on likelihood of perinatal HIV transmission.²⁰² HIV-exposed neonates at low risk of perinatal HIV acquisition (i.e., infants born to women who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen) may receive a 4-week zidovudine prophylaxis regimen used alone.²⁰² HIV-exposed neonates at higher risk of HIV acquisition (e.g., those born to HIV-infected women who did not receive antepartum or intrapartum antiretrovirals, received only intrapartum antiretrovirals, or received antepartum and intrapartum antiretrovirals with suboptimal viral suppression near delivery) should receive a 2-drug prophylaxis regimen (6-week zidovudine prophylaxis and 3-dose nevirapine prophylaxis).²⁰² Alternatively, those at highest risk can receive a 3-drug empiric HIV therapy regimen (zidovudine, lamivudine, and nevirapine).²⁰²

Maternal and neonatal regimens recommended for prevention of perinatal HIV transmission in the US may differ from those used in other countries.²⁰²

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding antiretroviral treatment of pregnant HIV-infected women and their infants and prevention of perinatal HIV transmission.²⁰²

Related/similar drugs

Biktarvy, Descovy, tenofovir, zidovudine, Atripla, Complera, Stribild

Nevirapine Dosage and Administration

Administration

Oral Administration

Administer orally with or without food.^{1 234}

Conventional (immediate-release) tablets and oral suspension: Use in adults, adolescents, and pediatric patients ≥15 days of age.¹

Extended-release tablets: Use in adults, adolescents, and pediatric patients ≥6 years of age.²³⁴

Extended-release Tablets

Extended-release tablets: Swallow whole;²³⁴ do not chew, crush, or divide.²³⁴

When considering use in a child ≥6 years of age, assess child for ability to swallow tablets.²³⁴

Oral Suspension

Shake suspension gently prior to each dose.¹

Administer using calibrated dosing syringe (especially for volumes <5 mL).¹ Alternatively, administer using dosing cup;¹ rinse cup with water and administer the rinse to the patient.¹

Dosage

Available as nevirapine (immediate-release tablets, extended-release tablets) and nevirapine hemihydrate (oral suspension);^{1 234} dosage expressed in terms of nevirapine.^{1 234}

Initiate therapy using a low dosage of immediate-release nevirapine for first 14 days since this appears to reduce frequency of rash.^{1 48 49 67 234} Do not use extended-release tablets during initial 14 days of nevirapine therapy.²³⁴

If mild to moderate rash without constitutional symptoms occurs during initial 14-day period of low dosage of immediate-release nevirapine, do not increase dosage until rash resolves.^{1 234} Do not continue initial low dosage beyond 28 days;^{1 234} if rash does not resolve by day 28, discontinue nevirapine and select alternative therapy.^{1 234}

If nevirapine therapy has been interrupted for >7 days for any reason and is not contraindicated, restart using the recommended low initial dosage of immediate-release nevirapine for first 14 days.^{1 234}

Pediatric Patients

Dosage usually based on body surface area (BSA) calculated using Mosteller formula.^{1 201 234} Investigational dosage based on weight has been recommended in certain neonates.^{201 202}

Treatment of HIV Infection

Oral

Neonates <14 days of age^†: If gestational age 34 to <37 weeks, experts recommend 4 mg/kg twice daily from birth to 1 week of age, then 6 mg/kg twice daily beginning at 1 week of age.²⁰² If gestational age ≥37 weeks, experts recommend 6 mg/kg twice daily.²⁰²

Neonates, infants, and children ≥15 days of age (oral suspension or immediate-release tablets): Manufacturer recommends 150 mg/m² once daily for first 14 days of therapy (lead-in period of low dosage), followed by 150 mg/m² twice daily.¹

Children 6 to <18 years of age (extended-release nevirapine): Manufacturer recommends 200 mg once daily if BSA 0.58–0.83 m², 300 mg once daily if BSA 0.84–1.16 m², or 400 mg once daily if BSA ≥1.17 m².²³⁴ If not already receiving nevirapine, use oral suspension or immediate-release tablets for lead-in period of low dosage (150 mg/m² once daily [up to 200 mg daily]) for first 14 days, then switch to extended-release tablets.²³⁴

Experts suggest that infants and children 1 month to <8 years of age require higher dosage than those ≥8 years of age.²⁰¹ When immediate-release nevirapine used, these experts recommend 200 mg/m² once daily for 14 days (lead-in period of low dosage) followed by 200 mg/m² twice daily (up to 200 mg twice daily) in those 1 month to <8 years of age and 120–150 mg/m² once daily for 14 days (lead-in period of low dosage) followed by 120–150 mg/m² twice daily (up to 200 mg twice daily) in those ≥8 years of age.²⁰¹ Some experts suggest lead-in period of low dosage not needed in pediatric patients ≤2 years of age.²⁰¹

Adolescents: Experts state usual adult dosage can be used.²⁰¹ (See Adults under Dosage and Administration.)

Prevention of Perinatal HIV Transmission†

Prophylaxis in Neonates Born to HIV-infected Women†

Oral

Neonates at higher risk of HIV acquisition: 3 nevirapine doses (nevirapine oral suspension) during first week of life initiated as soon as possible after delivery in addition to usual 6-week neonatal zidovudine prophylaxis regimen.²⁰²

Give first nevirapine dose within 48 hours of birth, second dose 48 hours after first dose, and third dose 96 hours after second dose.²⁰²

Birth weight 1.5–2 kg: Experts recommend 8 mg of nevirapine for each of the 3 doses.²⁰²

Birth weight >2 kg: Experts recommend 12 mg of nevirapine for each of the 3 doses.²⁰²

Empiric HIV Therapy in Neonates Born to HIV-infected Women†

Oral

Recommended empiric HIV therapy regimen consists of zidovudine, lamivudine, and nevirapine initiated as soon as possible after birth (within 6–12 hours);²⁰² used in HIV-exposed neonates considered at highest risk of HIV acquisition.²⁰² (See Prevention of Perinatal HIV Transmission under Uses.)

Gestational age 34 to <37 weeks: Experts recommend 4 mg/kg of nevirapine twice daily from birth to 1 week of age, then 6 mg/kg twice daily beginning at 1 week of age.²⁰²

Gestational age ≥37 weeks: Experts recommend 6 mg/kg of nevirapine twice daily.²⁰²

Optimal duration of empiric HIV therapy in HIV-exposed neonates unknown.²⁰² Many experts recommend that 3-drug empiric regimen be continued for 6 weeks;²⁰² others discontinue nevirapine and/or lamivudine if results of neonate's HIV nucleic acid amplification test (NAAT) are negative, but recommend continuing zidovudine for 6 weeks.²⁰²

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.²⁰²

Adults

Treatment of HIV Infection

Oral

Immediate-release tablets: 200 mg once daily for first 14 days (lead-in period of low dosage), followed by 200 mg twice daily.^{1 200}

Extended-release tablets: 400 mg once daily, initiated after immediate-release nevirapine.²³⁴ In those not currently receiving nevirapine, use lead-in period of low dosage of immediate-release tablets (200 mg once daily for 14 days) then switch to extended-release tablets 400 mg once daily.²³⁴ In those already receiving twice-daily regimen of usual dosage of immediate-release nevirapine, switch to extended-release tablets 400 mg once daily (without 14-day lead-in period).²³⁴

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Children ≥15 days of age (oral suspension or immediate-release tablets): Dosage based on BSA (maximum 400 mg daily).¹

Children 6 to <18 years of age (extended-release nevirapine): Dosage based on BSA (maximum 400 mg daily).²³⁴

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Immediate-release nevirapine: Data insufficient to make dosage recommendation in patients with mild hepatic impairment (Child-Pugh class A);¹ some experts state dosage adjustments not necessary.²⁰⁰ Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).¹

Extended-release tablets: Not studied in patients with hepatic impairment.²³⁴ Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).²³⁴

Renal Impairment

Treatment of HIV Infection

Oral

Immediate-release nevirapine: Dosage adjustments not needed in patients with Cl_cr ≥20 mL/minute not undergoing dialysis.¹ Administer additional 200-mg dose of immediate-release nevirapine after each dialysis treatment.¹

Extended-release tablets: Not studied in patients with renal impairment.²³⁴

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 234}

Cautions for Nevirapine

Contraindications

• Moderate or severe hepatic impairment (Child-Pugh class B or C).^{1 234}

• Do not use for postexposure prophylaxis following occupational exposure to HIV (PEP) or for postexposure prophylaxis following nonoccupational exposure to HIV (nPEP).^{1 198 199 234} (See Hepatic Effects under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Dermatologic and Sensitivity Reactions

Severe, life-threatening skin reactions (including some fatalities) reported.^{1 234} Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous eruptions, ulcerative stomatitis, urticaria, drug reaction with eosinophilia and systemic symptoms (DRESS), and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction (including hepatic failure) reported.^{1 234}

Patients with signs or symptoms of severe skin or hypersensitivity reactions (severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, and/or hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and renal dysfunction) must permanently discontinue nevirapine and seek immediate medical evaluation.^{1 234}

Must be initiated using low dosage of immediate-release nevirapine for first 14 days (200 mg once daily in adults or 150 mg/m² once daily in pediatric patients); this lead-in period of low dosage reduces frequency of rash.^{1 234} If mild to moderate rash without constitutional symptoms occurs during initial 14 days, dosage should not be increased until rash resolves.^{1 234} Do not continue initial low dosage beyond 28 days; discontinue nevirapine and select alternative therapy.^{1 234}

Monitor closely if isolated rash of any severity occurs.^{1 234}

Risk factors for severe cutaneous reactions include failure to follow recommended initial low dosage during first 14 days and delay in discontinuing nevirapine after onset of initial symptoms.^{1 234}

Women appear to be at higher risk of developing rash than men.^{1 234}

Prednisone not recommended for prevention of nevirapine-associated rash.^{1 234} (See Specific Drugs under Interactions.)

Do not restart nevirapine following hypersensitivity reaction, severe rash, or rash in conjunction with increased serum transaminase concentrations or other systemic symptoms.^{1 234}

Patient Monitoring

Serious adverse effects include hepatitis, hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions reported.¹

Intensive monitoring required during first 18 weeks of therapy to detect potentially life-threatening hepatic events and skin reactions; extra vigilance warranted during first 6 weeks (period of greatest risk).^{1 234} Optimum frequency of monitoring during this period not established;^{1 234} some experts recommend clinical and laboratory monitoring more often than once monthly and liver function tests at baseline, prior to dosage escalation, and 2 weeks after dosage escalation.^{1 234}

Continue frequent clinical and laboratory monitoring after initial 18-week period and throughout nevirapine therapy.^{1 234}

Hepatic Effects

Severe, life-threatening (and in some cases fatal) hepatotoxicity, including fulminant and cholestatic hepatitis (e.g., transaminase elevations with or without hyperbilirubinemia, prolonged partial thromboplastin time, or eosinophilia), hepatic necrosis, and hepatic failure, reported.^{1 234} Hepatic events can occur at any time during therapy.^{1 234} Risk of hepatic events (regardless of severity) greatest during the first 6 weeks of therapy; substantial risk continues through 18 weeks of therapy.^{1 234}

Some patients present with nonspecific prodromal signs and symptoms of fatigue, malaise, anorexia, nausea, jaundice, liver tenderness, and/or hepatomegaly, with or without initially abnormal serum transaminase concentrations.¹ Rash observed in 50% of those with symptomatic hepatic adverse events.^{1 234} Fever and flu-like symptoms accompany some of these hepatic events.^{1 234} Some events, particularly those with rash or other symptoms, have progressed to hepatic failure with serum transaminase elevation, with or without hyperbilirubinemia, hepatic encephalopathy, prolonged partial thromboplastin time, and/or eosinophilia.^{1 86 234}

Patients with higher CD4 counts and women are at increased risk of hepatic events.^{1 234} Women with CD4 counts >250 cells/mm³, including pregnant women receiving long-term treatment for HIV infection, are at considerably higher risk of these events.^{1 234} Increased liver enzymes and/or HBV or HCV infection associated with increased risk.^{1 234}

Serious hepatotoxicity reported in individuals not infected with HIV who received nevirapine as part of a multiple-drug regimen for postexposure prophylaxis following occupational or nonoccupational exposure to HIV.^{1 86 87} Do not use in HIV postexposure prophylaxis regimens following occupational or nonoccupational exposure to the virus.^{1 199 234}

Intensive clinical and laboratory monitoring essential.^{1 234} (See Patient Monitoring under Cautions.)

Consider possibility of hepatotoxicity if there are signs or symptoms of hepatitis (e.g., fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly), even if liver function tests are initially normal or alternative diagnosis is possible.^{1 234}

Hepatic injury has progressed despite discontinuation of nevirapine in some patients.^{1 234}

Patients with signs and symptoms of hepatitis must seek immediate medical attention, have liver function tests performed (serum transaminase concentrations), and be advised to discontinue nevirapine as soon as possible.^{1 86 234} If nevirapine is discontinued because of hepatitis or increased serum transaminase concentrations associated with rash or other systemic symptoms, it should be permanently discontinued and not reinitiated.^{1 86 234}

Interactions

Concomitant use with certain drugs not recommended (e.g., St. John’s wort).^{1 234} (See Specific Drugs under Interactions.)

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.^{1 234} Mechanisms and long-term consequences of fat redistribution unknown; causal relationship not established.^{1 234}

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.^{1 101 234}

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; however, time to onset is variable and can occur many months after initiation of antiretroviral therapy.^{1 234}

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry (APR) at 800-258-4263 or [Web].^{1 202 234}

Available data from the APR do not indicate an increased risk for overall major birth defects among infants born to women who received nevirapine during pregnancy compared with US background rate for major birth defects.^{1 234}

Experts states that nevirapine in conjunction with 2 NRTIs not recommended for initial treatment in antiretroviral-naive pregnant women because of greater potential for adverse events, complex lead-in dosage regimen, and low barrier for HIV resistance.²⁰²

Severe hepatic events, including fatalities, reported in HIV-infected pregnant women receiving long-term nevirapine therapy as part of multiple-drug antiretroviral treatment.^{1 234} Because of risk of potentially life-threatening hepatotoxicity, do not initiate nevirapine in pregnant women with pretreatment CD4⁺ T-cell counts >250/mm³ unless potential benefits clearly outweigh risks.^{1 96 200} If initiated in such women, caution recommended.²⁰² (See Hepatic Effects under Cautions.)

May be continued if tolerated in women who become pregnant, regardless of CD4⁺ T-cell count.²⁰²

Fertility

Evidence of impaired fertility in female rats at exposure level approximately equivalent to that provided by usually recommended human dosage.^{1 234} Human data insufficient to determine risk of infertility in patients receiving nevirapine.^{1 234}

Advise females with reproductive potential that, based on results from fertility studies in rats, nevirapine may impair fertility and it is not known whether effects on fertility are reversible.^{1 234}

Lactation

Distributed into milk.^{1 58 65 234}

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.^{1 202 234}

Pediatric Use

Immediate-release tablets and oral suspension: Safety and pharmacokinetics evaluated in children 15 days to <3 months of age.¹ Safety, pharmacokinetics, and efficacy evaluated in children 3 months to 18 years of age.¹

Extended-release nevirapine: Can be used in children ≥6 years of age based on pharmacokinetic, safety, and antiretroviral activity data in pediatric patients 3 to <18 years of age and efficacy data from adults.²³⁴ Not recommend in those 3 to <6 years of age because of insufficient pharmacokinetic data in this age group;²³⁴ not recommended in those <3 years of age because of inability to swallow tablets.²³⁴

Immediate-release nevirapine recommended by some experts for initial treatment of confirmed HIV infection in certain neonates <14 days of age^† (see Treatment of HIV Infection under Uses).²⁰¹ Also recommended for prophylaxis^† or empiric HIV therapy^† for perinatal HIV transmission in certain neonates <14 days of age (see Prevention of Perinatal HIV Transmission under Uses).²⁰²

Adverse effects reported in children generally similar to those reported in adults; granulocytopenia reported more frequently in children than adults.¹ Stevens-Johnson syndrome or Stevens-Johnson/toxic epidermal necrolysis transition syndrome reported rarely.¹ Allergic reactions, including anaphylaxis, also reported.¹

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.^{1 234}

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 234}

Hepatic Impairment

Carefully monitor those with hepatic impairment (e.g., those with hepatic fibrosis or cirrhosis) for toxicity.¹

Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).^{1 234}

Renal Impairment

Modification of usual dosage of immediate-release nevirapine dosage forms not necessary in patients with Cl_cr ≥20 mL/minute not requiring dialysis;¹ additional dose of immediate-release nevirapine necessary following dialysis.¹ Pharmacokinetics not evaluated in those with Cl_cr <20 mL/minute.^{1 234} (See Renal Impairment under Dosage and Administration.)

Extended-release tablets not studied in patients with renal impairment.²³⁴

Common Adverse Effects

Rash, nausea, headache, fatigue, abnormal liver function test results.^{1 234} Adverse effects reported with extended-release tablets similar to those reported with immediate-release tablets.²³⁴

Drug Interactions

Metabolized by CYP3A and CYP2B6.^{1 234}

Inhibits CYP3A and CYP2B6.^{1 234}

Induces CYP3A and CYP2B6.^{1 234}

The following drug interactions are based on studies using nevirapine immediate-release tablets and are expected to also apply to extended-release tablets.^{1 234}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A or 2B6 with possible alteration in metabolism of nevirapine and/or other drug.^{1 47 234}

Nevirapine does not appear to affect plasma concentrations of drugs that are substrates of other CYP isoenzymes (e.g., 1A2, 2D6, 2A6, 2E1, 2C9, 2C19).^{1 234}

Specific Drugs

Nevirapine Pharmacokinetics

Absorption

Bioavailability

Immediate-release nevirapine: Well absorbed from GI tract; absolute bioavailability is 91–93%.^{1 75} Peak plasma concentrations attained within 4 hours.¹

Extended-release tablets: Peak plasma concentrations attained at a median of approximately 24 hours after dose.²³⁴

Commercially available immediate-release tablets and oral suspension are bioequivalent at dose ≤200 mg.¹

Bioavailability of 400 mg of nevirapine as extended-release tablets relative to 400 mg as immediate-release tablets is approximately 75%.²³⁴

Food

Food does not appear to affect absorption of immediate-release tablets.¹

Difference in bioavailability of nevirapine extended-release tablets under fasted or fed conditions not considered clinically important.²³⁴

Special Populations

Immediate-release nevirapine in children: Steady-state trough concentrations similar to concentrations in adults receiving recommended dosage.¹

Extended-release tablets in children 6 to <18 years: Overall mean systemic nevirapine exposure after switch from immediate-release to extended-release nevirapine similar to that reported with immediate-release.²³⁴

Immediate-release nevirapine in pregnant women: Pharmacokinetics generally similar to that reported in nonpregnant adults;²⁰² dosage adjustments not recommended during pregnancy.²⁰²

Immediate-release tablets in patients with mild, moderate, or severe renal impairment: Pharmacokinetics not altered.¹ AUC decreased in individuals requiring dialysis.¹ Accumulation of nevirapine metabolites noted in individuals requiring dialysis.¹

Immediate-release tablets in patients with mild to moderate hepatic impairment: Pharmacokinetics not altered in most patients; trough concentrations twofold higher in 15% of patients with hepatic fibrosis.¹ Increased nevirapine AUC noted in 1 patient with moderate hepatic impairment (Child-Pugh class B) and ascites.¹

Extended-release tablets: Not studied in pregnant women²⁰² or in patients with hepatic or renal impairment.²³⁴

Distribution

Extent

Distributed into CSF; concentrations in CSF are 45% of concurrent plasma concentrations.¹

Crosses placenta;^{1 65} distributed into human milk^{58 65 1} and semen.⁸⁸

Plasma Protein Binding

60%.¹

Elimination

Metabolism

Metabolized by CYP3A and CYP2B6.¹

Elimination Route

Excreted in urine (81%) mainly as glucuronide conjugates of hydroxylase metabolites and in feces (10%).¹

Half-life

45 hours after a single dose and 25–30 hours after multiple doses.¹

Special Populations

Clearance greater in children than adults.¹

Stability

Storage

Oral

Tablets

Conventional (immediate-release): 25°C (may be exposed to 15–30°C).¹

Extended-release: 25°C (may be exposed to 15–30°C).²³⁴

Suspension

25°C (may be exposed to 15–30°C).¹

Actions and Spectrum

• Pharmacologically related to other NNRTIs (e.g., delavirdine, efavirenz, etravirine, rilpivirine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretrovirals.^{1 21}

• Active against HIV-1; inactive against HIV-2.^{1 3 22 71}

• Nevirapine inhibits replication of HIV-1 by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase.^{1 3}

• HIV-1 with reduced susceptibility to nevirapine have been selected in vitro and have emerged during therapy with the drug.^{1 3 5 21 22}

• Strains of HIV-1 resistant to nevirapine may be cross-resistant to some other NNRTIs.^{1 28 42}

• Cross-resistance between nevirapine and NRTIs unlikely since the drugs bind at difference sites on reverse transcriptase and have difference mechanisms of action.¹ Cross-resistance between nevirapine and HIV protease inhibitors (PIs) unlikely since the drugs have different target enzymes and mechanisms of action.¹

Advice to Patients

• Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.^{1 234} Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.^{1 234}

• Importance of using in conjunction with other antiretrovirals— not for monotherapy.^{1 234}

• Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.^{1 234}

• Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.²⁰⁰ Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.^{1 234 200}

• Importance of reading patient information provided by the manufacturer.^{1 234}

• If a dose is missed, the next dose should be taken as soon as possible.^{1 234} If a dose is skipped, do not take a double dose to make up for the missed dose.^{1 234}

• Possibility of severe liver disease or skin reactions (potentially fatal).^{1 234} Importance of discontinuing nevirapine and seeking immediate medical attention if signs or symptoms of liver disease (fatigue, malaise, anorexia, nausea, jaundice, acholic stools, liver tenderness, hepatomegaly) or severe skin or hypersensitivity reactions (rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis) occur.^{1 234}

• Need for intensive clinical and laboratory monitoring, including liver enzymes, during first 18 weeks of therapy (especially first 6 weeks) and importance of frequent monitoring throughout nevirapine treatment.^{1 234}

• Risk of rash, especially during first 6 weeks of therapy.^{1 234} If rash occurs during first 2 weeks of therapy, do not increase nevirapine dosage and do not switch to extended-release tablets until rash resolves.^{1 234}

• Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.^{1 234}

• Advise patients to immediately contact a clinician if they have any signs or symptoms of infection since inflammation from previous infections may occur soon after antiretroviral therapy is initiated.^{1 234}

• To avoid overdosage, do not use immediate-release nevirapine (tablets or oral suspension) and extended-release nevirapine (tablets) concomitantly.^{1 234}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.^{1 234}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 234} Advise HIV-infected women not to breast-feed.^{1 234}

• Importance of advising patients of other important precautionary information.^{1 234} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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