Medication Guide App

Viramune

Generic Name: Nevirapine
Class: HIV Nonnucleoside 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

Warning(s)

  • Hepatotoxicity
  • Severe, life-threatening (and in some cases fatal) hepatotoxicity reported, particularly during first 18 weeks of therapy.1 234 In some cases, patients presented with nonspecific prodromal signs or symptoms of hepatitis and progressed to hepatic failure; these events often associated with rash.1 234 Patients with higher CD4+ T-cell counts at initiation of therapy and women are at increased risk.1 234 Women with CD4+ T-cell counts >250 cells/mm3 (including pregnant women receiving nevirapine with other antiretrovirals for treatment of HIV-1 infection) are at greatest risk, but hepatotoxicity can occur in both genders, all CD4+ T-cell counts, and at any time during treatment. 1 234 Patients with signs or symptoms of hepatitis or with increased serum transaminase concentrations in conjunction with rash or other systemic symptoms must discontinue nevirapine and immediately seek medical evaluation.1 234

  • Contraindicated for postexposure prophylaxis of HIV following occupational or nonoccupational exposures;1 234 hepatic failure reported in patients without HIV infection receiving nevirapine for postexposure prophylaxis.1 234

  • Skin Reactions
  • Severe, life-threatening skin reaction, including fatal cases, reported.1 234 Reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction.1 234 Patients with signs or symptoms of severe skin reactions or hypersensitivity must discontinue nevirapine and immediately seek medical evaluation.1 234 Immediately measure serum transaminase concentrations if rash occurs during first 18 weeks of nevirapine therapy.1 234

  • Must be initiated using a lead-in 14-day period of low dosage of conventional (immediate-release) nevirapine (200 mg once daily in adults) since this decreases the incidence of rash.1 234

  • Monitoring
  • Must monitor patients intensively during first 18 weeks of therapy to detect potential life-threatening hepatotoxicity or skin reactions.1 234 Extra vigilance warranted during first 6 weeks, the period of greatest risk.1 234

  • Do not restart nevirapine following clinical hepatitis, elevated transaminase concentrations combined with rash or other systemic symptoms, or following severe rash or hypersensitivity reactions.1 234

Introduction

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

Uses for Viramune

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.)

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For initial treatment in antiretroviral-naive adults or adolescents, experts state nevirapine not recommended since it is associated with more serious toxicities than other HIV NNRTIs and many other preferable options are available.200 Experts state the drug can be continued in patients already receiving and tolerating a suppressive regimen that includes nevirapine.200

For initial treatment in antiretroviral-naive pediatric patients, experts state that nevirapine and 2 NRTIs is an alternative (not preferred) regimen in those ≥15 days of age.201

Prevention of Perinatal HIV Transmission

Prophylaxis in neonates born to HIV-infected women;202 used as part of a multiple-drug neonatal prophylaxis regimen.202

Multiple-drug antiretroviral regimens considered the 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 decrease risk of perinatal HIV transmission, pregnant HIV-infected women with plasma HIV-1 RNA levels >1000 copies/mL (or unknown HIV-1 RNA levels) near delivery should receive an intrapartum IV zidovudine prophylaxis regimen and all neonates born to HIV-infected women (HIV-exposed neonates) should receive an oral or IV zidovudine prophylaxis regimen.202

In certain situations (e.g., infant born to a woman who did not receive antepartum or intrapartum antiretrovirals or received only intrapartum antiretrovirals), the neonate should receive a 3-dose nevirapine prophylaxis regimen given during the first week of life in addition to the usual 6-week neonatal zidovudine prophylaxis regimen.202

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

Decisions to include additional antiretrovirals for prophylaxis with the recommended intrapartum and neonatal zidovudine prophylaxis regimens should be made in consultation with a pediatric HIV specialist.202

Clinicians can 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

Viramune 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; must not be chewed, crushed, or divided.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; 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); 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 has resolved.1 234 Do not continue initial low dosage beyond 28 days; 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 based on body surface area (BSA) calculated using Mosteller formula.1 234

Treatment of HIV Infection
Oral

Children ≥15 days of age (oral suspension or immediate-release tablets): 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): 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 lead-in period of low dosage oral suspension or immediate-release tablets (150 mg/m2 once daily [up to 200 mg daily]) for first 14 days; then switch to extended-release nevirapine.234

Experts suggest those <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 twice daily (up to 200 mg twice daily) in those <8 years of age and 120–150 mg/m2 twice daily (up to 200 mg twice daily) in those ≥8 years of age.201 If extended-release tablets used in those 6 to <8 years of age, these experts recommend 400 mg/m2 once daily (up to 400 mg once daily).201

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

Prevention of Perinatal HIV Transmission
Neonatal Prophylaxis
Oral

Neonate born to an HIV-infected woman who received no antiretrovirals prior to and/or during labor: 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, third dose 96 hours after second dose).202 If birth weight 1.5–2 kg, use 8 mg (nevirapine oral suspension) for each dose; if birth weight >2 kg, use 12 mg (nevirapine oral suspension) for each dose.202

Consultation with pediatric HIV specialist recommended when making decisions regarding use of multiple-drug neonatal prophylaxis regimens.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 Do not use in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1 234

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

Renal Impairment

Treatment of HIV Infection
Oral

Immediate-release nevirapine: Dosage adjustments not needed in patients with Clcr ≥20 mL/minute not undergoing dialysis.1 234 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 Viramune

Contraindications

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

  • Do not use for postexposure prophylaxis of HIV following occupational or nonoccupational exposure to the virus.1 234 199 (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.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) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1 234

Specific Populations

Pregnancy

Category B.1 234

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202 234 Pregnancy registry data to date do not indicate an increased risk for congenital abnormalities among infants born to women who received nevirapine during pregnancy compared with general population.1 234

Manufacturer states use during pregnancy only if potential benefits justify risks to the fetus.1

Experts state that nevirapine is an alternative (not preferred) NNRTI for use in multiple-drug antiretroviral regimens in antiretroviral-naive pregnant women with baseline CD4+ T-cell counts <250/mm3.202

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

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, pharmacokinetics, and efficacy evaluated in children 3 months to 18 years of age.1 Safety and pharmacokinetics evaluated in children 15 days to <3 months 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

For prevention of perinatal HIV transmission, a 3-dose regimen of immediate-release nevirapine has been recommended for neonates born to HIV-infected women who received no antiretroviral therapy prior to and/or during labor.202 (See Prevention of Perinatal HIV Transmission under Uses.)

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

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

Renal Impairment

Modification of usual dosage of immediate-release nevirapine dosage forms not necessary in patients with Clcr ≥20 mL/minute not requiring dialysis;1 234 additional dose of immediate-release nevirapine necessary following dialysis.1 234 Pharmacokinetics not evaluated in those with Clcr <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

Interactions for Viramune

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

Drug

Interaction

Comments

Abacavir

In vitro evidence of additive to synergistic antiretroviral effects1 27 234

Antacids (Maalox)

No effect on absorption of nevirapine1

Immediate-release nevirapine may be administered with antacids1

Antiarrhythmic agents (amiodarone, disopyramide, lidocaine)

Possible decreased antiarrhythmic agent concentrations1 234

Appropriate dosages for concomitant use not established1 234

Anticoagulants, oral (warfarin)

Possible altered warfarin concentrations and increased or decreased anticoagulant effects1 200 234

Closely monitor INR; adjust warfarin dosage accordingly1 200 234

Anticonvulsants (carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin)

Possible decreased anticonvulsant concentrations1 200 234

Use concomitantly with caution;1 234 monitor anticonvulsant and nevirapine concentrations and antiretroviral response;1 200 234 alternatively, consider different anticonvulsant200

Antifungals, azoles

Fluconazole: Increased nevirapine concentrations;1 234 no effect on fluconazole concentrations;1 234 possible increased risk of hepatotoxicity200

Itraconazole: Possible decreased itraconazole concentrations and reduced antifungal efficacy1 234

Ketoconazole: Possible decreased ketoconazole concentrations and reduced antifungal efficacy1 200 234

Voriconazole: Possible decreased voriconazole concentrations and increased nevirapine concentrations200

Fluconazole: Use concomitantly with caution;1 234 closely monitor for nevirapine adverse effects;1 200 234 consider alternative antiretroviral200

Itraconazole: Concomitant use not recommended;1 234 if used, monitor itraconazole concentrations and adjust itraconazole dosage accordingly200

Ketoconazole: Concomitant use not recommended1 200 234

Voriconazole: Monitor frequently for adverse effects or toxicity and response to voriconazole; monitor voriconazole plasma concentrations200

Antimalarial agents

Fixed combination of artemether and lumefantrine (artemether/lumefantrine): Decreased AUC of artemether and active metabolite of artemether (dihydroartemisinin); possible increased AUC of lumefantrine200

Artemether/lumefantrine: Clinical importance unknown; monitor for antimalarial efficacy and lumefantrine toxicity200

Antimycobacterials (rifabutin, rifampin, rifapentine)

Bedaquiline: No effect on bedaquiline AUC200

Rifabutin: Increased rifabutin concentrations (high intersubject variability, some patients may experience large increases in rifabutin exposure); decreased nevirapine concentrations1 234

Rifampin: Decreased nevirapine concentrations1 200 234

Bedaquiline: Dosage adjustments not needed 200

Rifabutin: Use concomitantly with caution;1 200 234 dosage adjustment not needed200

Rifampin: Concomitant use not recommended200

Rifapentine: Concomitant use not recommended200

Atazanavir

Ritonavir-boosted atazanavir: Decreased atazanavir concentrations and AUC; increased nevirapine concentrations and AUC1 200 203 234

In vitro evidence of additive to synergistic antiretroviral effects;1 234 no in vitro evidence of antagonistic antiretroviral effects203

Atazanavir (with or without low-dose ritonavir): Do not use concomitantly1 200 203 234

Avanafil

Data not available200

Concomitant use not recommended200

Benzodiazepines

Alprazolam: Data not available200

Alprazolam: Monitor for therapeutic effectiveness of the benzodiazepine200

Boceprevir

Possible decreased boceprevir concentrations and reduced efficacy1 234

Do not use concomitantly1 234

Buprenorphine

No clinically important pharmacokinetic interactions200

Dosage adjustments not needed200

Calcium-channel blocking agents (diltiazem, nifedipine, verapamil)

Possible decreased concentrations of the calcium-channel blocking agent1 200 234

Appropriate dosages for concomitant use not established;1 234 if used concomitantly, titrate dosage of calcium-channel blocking agent based on clinical response200

Cisapride

Possible decreased cisapride concentrations1

Appropriate dosages for concomitant use not established1 234

Corticosteroids

Dexamethasone: Possible decreased nevirapine concentrations200

Prednisone: Concomitant use during first 14 days of nevirapine has been associated with increased incidence and severity of rash during first 6 weeks of nevirapine1 234

Dexamethasone: Monitor antiretroviral response;200 consider alternative corticosteroid for long-term therapy200

Cyclophosphamide

Possible decreased cyclophosphamide concentrations1 234

Appropriate dosages for concomitant use not established1 234

Darunavir

Ritonavir-boosted darunavir: Increased darunavir concentrations and AUC;1 200 204 234 increased nevirapine concentrations and AUC200 204 234

Ritonavir-boosted darunavir: Dosage adjustment not needed if used concomitantly with nevirapine200 204 234

Delavirdine

Possible altered delavirdine concentrations1 234

Do not use concomitantly1 200 234

Didanosine

No effect on nevirapine or didanosine pharmacokinetics1 234

In vitro evidence of additive to synergistic antiretroviral effects1 27 234

Dolutegravir

Possible decreased dolutegravir concentrations200 236

No in vitro evidence of antagonistic antiretroviral effects236

Do not use concomitantly;200 236 data insufficient to make dosage recommendations236

Efavirenz

Decreased efavirenz concentrations and AUC;1 234 increased incidence of adverse effects and no improvement in efficacy1 234

Do not use concomitantly;1 200 234 appropriate dosages for concomitant use with respect to safety and efficacy not established1 234

Elvitegravir and cobicistat

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (EVG/COBI/TDF/FTC): Possible altered concentrations of elvitegravir, cobicistat, and/or nevirapine200

EVG/COBI/TDF/FTC: Do not use concomitantly200

Emtricitabine

In vitro evidence of additive to synergistic antiretroviral effects1

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Possible decreased concentrations of the ergot alkaloid;1 202 possible inadequate treatment effects202

Ergotamine: Appropriate dosages for concomitant use not established1 234

If methylergonovine used to treat postpartum hemorrhage in a woman receiving nevirapine, additional uterotonic agents may be needed202

Estrogens/Progestins

Oral contraceptives: Decreased ethinyl estradiol and norethindrone concentrations1 234

IM medroxyprogesterone acetate: No effect on concentrations of the contraceptive1 234

Do not use hormonal contraceptives (other than medroxyprogesterone acetate) as sole method of contraception;1 use alternative or additional contraceptive measures1 200 234

Oral contraceptives used for hormonal regulation: Monitor for therapeutic effects of the hormonal therapy1 234

Etravirine

Possible altered etravirine concentrations1 234

Do not use concomitantly1 200 234

Fentanyl

Possible decreased fentanyl concentrations1 234

Appropriate dosages for concomitant use not established1 234

Fosamprenavir

Fosamprenavir (without low-dose ritonavir): Decreased amprenavir (active metabolite of fosamprenavir) AUC and increased nevirapine AUC1 205 234

Ritonavir-boosted fosamprenavir (twice-daily regimen): Decreased amprenavir AUC and increased nevirapine AUC1 205 234

Ritonavir-boosted fosamprenavir (once-daily regimen): Concomitant use with nevirapine not studied205

In vitro evidence of additive antiretroviral effects205

Fosamprenavir (without low-dose ritonavir): Concomitant use with nevirapine not recommended1 205 234

RItonavir-boosted fosamprenavir (twice-daily regimen): Use usual nevirapine dosage with fosamprenavir 700 mg twice daily and ritonavir 100 mg twice daily1 205 234

HMG-CoA reductase inhibitors (statins)

Lovastatin or simvastatin: Possible decreased concentrations of the statin200

Pitavastatin: Data not available; clinically important interactions not expected200

Lovastatin or simvastatin: Titrate statin dosage based on lipid response; do not exceed maximum recommended statin dosage;200 avoid statin if nevirapine used in a regimen that includes a ritonavir-boosted PI200

Pitavastatin: Dosage adjustments not needed200

Immunosuppressive agents

Cyclosporine, sirolimus, tacrolimus: Possible decreased concentrations of immunosuppressive agents1 234

Cyclosporine, sirolimus, tacrolimus: Appropriate dosages for concomitant use not established;1 234 therapeutic drug monitoring of the immunosuppressive agent recommended and consultation with a specialist may be needed200

Indinavir

Decreased indinavir concentrations and AUC; no clinically important change in nevirapine pharmacokinetics1 234

In vitro evidence of additive to synergistic antiretroviral effects1 234

Appropriate dosages for concomitant use with respect to safety and efficacy not established1 206 234

Lamivudine

In vitro evidence of additive to synergistic antiretroviral effects1 27 234

Lopinavir/ritonavir

Decreased lopinavir concentrations and AUC1 207 234

Lopinavir/ritonavir (once-daily regimen): Not recommended with nevirapine207

Lopinavir/ritonavir (twice-daily regimen): Increased lopinavir/ritonavir dosage recommended;1 207 234 dosage depends on lopinavir/ritonavir preparation used (tablets, oral solution) and clinical characteristics of the patient207

Macrolides

Clarithromycin: Decreased clarithromycin concentration and increased 14-hydroxyclarithromycin concentration1 200 234

Monitor for efficacy of the macrolide or use an alternative (e.g., azithromycin) for treatment or prophylaxis of MAC1 200 234

Maraviroc

No effect on maraviroc AUC200

No in vitro evidence of antagonistic antiretroviral effects224

Recommended maraviroc dosage is 300 mg twice daily when used with nevirapine, provided regimen does not include a PI or other potent CYP3A inhibitor;200 224 recommended maraviroc dosage is 150 mg twice daily if used with nevirapine in a regimen that includes a PI (except ritonavir-boosted tipranavir)200 224

Methadone

Decreased methadone concentrations;1 234 no change in nevirapine concentrations200

Opiate withdrawal reported200

Consider need to increase methadone dosage1 200 234

Nelfinavir

No effect on nelfinavir peak concentrations or AUC;1 234 decreased nelfinavir trough concentrations and substantially decreased concentrations and AUC of major nelfinavir metabolite (M8).1 234

In vitro evidence of synergistic antiretroviral effects1 234

Appropriate dosages for concomitant use with respect to safety and efficacy not established1 208 234

Quinupristin and dalfopristin

Possible increased nevirapine concentrations77

Raltegravir

In vitro evidence of additive to synergistic antiretroviral effects225

Dosage adjustments not necessary200

Rilpivirine

Possible altered rilpivirine concentrations1 234

Do not use concomitantly1 208 234

Ritonavir

No clinically important pharmacokinetic interaction1 234

Saquinavir

Decreased saquinavir concentrations; no change in nevirapine pharmacokinetics200

Ritonavir-boosted saquinavir: Concomitant use not evaluated1 234

In vitro evidence of additive to synergistic antiretroviral effects1 234

Ritonavir-boosted saquinavir: Appropriate dosages for concomitant use with respect to safety and efficacy not established1 200 234

Simeprevir

Decreased simeprevir concentrations expected187 200

Do not use concomitantly187 200

St. John’s wort (Hypericum perforatum)

Decreased nevirapine concentrations; possible loss of virologic response and increased risk of nevirapine resistance1 78 79 200 234

Concomitant use not recommended1 78 200 234

Stavudine

No clinically important effect on stavudine concentrations or AUC1 234

In vitro evidence of additive to synergistic antiretroviral effects1 27 234

Telaprevir

Possible decreased telaprevir concentrations and decreased telaprevir efficacy;1 234 possible increased nevirapine concentrations and increased nevirapine-associated adverse effects1 234

Do not use concomitantly1 234

Tenofovir

In vitro evidence of additive to synergistic antiretroviral effects1 234

Tipranavir

Ritonavir-boosted tipranavir: No clinically important effect on nevirapine concentrations;1 200 211 234 effect on tipranavir pharmacokinetics unknown200

In vitro evidence of additive antiretroviral effects211

Ritonavir-boosted tipranavir: Experts state dosage adjustments not needed200

Zidovudine

Decreased zidovudine concentrations1 234

In vitro evidence of additive to synergistic antiretroviral effects1 27 234

Viramune 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

Pharmacokinetics in pregnant women 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 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 milk58 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

25°C (may be exposed to 15–30°C).1 234

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

  • 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.

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

Nevirapine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

200 mg*

Nevirapine Tablets

Viramune (scored)

Boehringer Ingelheim

Tablets, extended-release

100 mg

Viramune XR

Boehringer Ingelheim

400 mg*

Nevirapine Extended-release Tablets

Viramune XR

Boehringer Ingelheim

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

Nevirapine Hemihydrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

50 mg (of nevirapine) per 5 mL*

Nevirapine Oral Suspension

Viramune

Boehringer Ingelheim

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Viramune 200MG Tablets (BOEHRINGER INGELHEIM): 60/$606.99 or 180/$1,781.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 30, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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203. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.

204. Janssen. Prezista (darunavir) oral suspension and tablets prescribing information. Titusville, NJ; 2012 Jun.

205. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Feb.

206. Merck Sharp & Dohme. Crixivan (indinavir sulfate) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

207. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

208. ViiV Healthcare. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. Research Triangle Park, NC; 2012 Apr.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2012 Apr.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

225. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets and chewable tablets prescribing information. Whitehouse Station, NJ; 2012 Apr.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

234. Boehringer Ingelheim. Viramune XR (nevirapine) extended-release tablets prescribing information. Ridgefield, CT; 2014 Jan.

236. ViiV Healthcare. Tivicay (dolutegravir) tablets prescribing information. Research Triangle Park, NC; 2014 May.

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