Viramune

Generic Name: Nevirapine
Class: 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

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

  
  


• 
  

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

  
  


• 
  

  Essential that patients are monitored intensively during the first 18 weeks of nevirapine therapy to detect potential life-threatening hepatotoxicity or skin reactions.¹ Extra vigilance needed during first 6 weeks since this is period of greatest risk.¹

  
  


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  Hepatic injury has progressed despite discontinuation of nevirapine in some patients.¹

  
  


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  Do not restart nevirapine following severe hepatic, skin, or hypersensitivity reactions.¹

  
  


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  Strictly follow the recommendations regarding use of a low initial nevirapine dosage (Adults: 200 mg once daily for the first 14 days).¹ Initiating therapy with this dosage reduces frequency of rash.¹

  
  

REMS:

FDA approved a REMS for nevirapine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiretroviral; nonnucleoside reverse transcriptase inhibitor (NNRTI).^{1 21 42}

Uses for Viramune

Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.¹

Because of risk of potentially life-threatening hepatotoxicity, do not initiate nevirapine therapy in adult women with pretreatment CD4⁺ T-cell counts >250/mm³ or in men with CD4⁺ T-cell counts >400/mm³ unless potential benefits clearly outweigh risks.^{1 51 96} (See Hepatic Effects under Cautions.)

Prevention of Maternal-fetal Transmission of HIV

Prevention of maternal-fetal transmission of HIV†.^{58 59 60 61 68}

Has been used in a single-dose nevirapine regimen that involves a dose given to the mother at onset of labor and a dose given to the neonate within 72 hours after birth.^{58 59 60 61 68} However, this regimen is associated with development of nevirapine-resistant HIV.⁶⁸

The intrapartum/neonatal nevirapine regimen can be used in conjunction with the intrapartum and neonatal zidovudine regimen (intrapartum zidovudine in the mother and 6-week zidovudine regimen in the neonate) in HIV-infected women in labor who received no prior antiretroviral therapy.⁶⁸ If this regimen is used, some clinicians suggest that consideration be given to adding a zidovudine and lamivudine regimen in the mother (initiated intrapartum and continued for 7 days) to reduce development of nevirapine resistance.⁶⁸

Viramune Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.^{1 51}

Agitate nevirapine oral suspension prior to each dose.¹

Administer the oral suspension using the calibrated dosing syringe for volumes <5 mL.¹ Alternatively, administer using the dosing cup, then rinse cup with water and administer the rinse to the patient.¹

Dosage

Available as nevirapine and nevirapine hemihydrate; dosage expressed in terms of nevirapine.¹

Must be given in conjunction with other antiretrovirals.¹ If used with indinavir, lopinavir, or saquinavir, adjustment in the treatment regimen necessary.^{1 51} (See Specific Drugs under Interactions.)

Therapy should be initiated using a low dosage for the first 14 days since this appears to reduce frequency of rash.^{1 48 49 67} If mild to moderate rash without constitutional symptoms occurs during this initial period, dosage should not be increased until the rash has resolved.¹ Do not continue the initial low dosage beyond 28 days; discontinue nevirapine and select alternative therapy.¹

If nevirapine therapy has been interrupted for >7 days for any reason, therapy should be restarted using the recommended initial dosage.^{1 51}

Pediatric Patients

Treatment of HIV Infection

Children ≥15 days of age: Dosage of nevirapine is based on body surface area.¹ Do not exceed adult dosage.¹

Oral

Children ≥15 days of age: 150 mg/m² once daily for the first 14 days of therapy, followed by 150 mg/m² twice daily.¹

Prevention of Maternal-fetal Transmission of HIV†

Oral

Neonate when used in conjunction with a single intrapartum dose of nevirapine given to the mother: 2 mg/kg as a single dose at 2–3 days of age.⁶⁸

Neonate when mother did not receive an intrapartum dose of nevirapine: 2 mg/kg as a single dose at birth.⁶⁸

Adults

Treatment of HIV Infection

Oral

200 mg once daily for the first 14 days, followed by 200 mg twice daily.^{1 51}

Prevention of Maternal-fetal Transmission of HIV†

Oral

200 mg given at the onset of labor.^{58 59 60 61 68} Maternal dose usually used in conjunction with a single dose given to the neonate after birth.^{58 59 60 61 68} (See Pediatric Patients under Dosage and Administration.)

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Children ≥15 days of age: Dosage based on body surface area (maximum 400 mg daily).¹

Special Populations

Hepatic Impairment

Data insufficient to make dosage recommendation.⁵¹ Do not use in patients with moderate or severe hepatic impairment.^{1 51}

Renal Impairment

Treatment of HIV Infection

Oral

Dosage adjustment not needed in patients with Cl_cr ≥20 mL/minute.¹

Administer 200 mg after each dialysis treatment.¹

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

Cautions for Viramune

Contraindications

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

  
  

Warnings/Precautions

Warnings

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

Patient Monitoring

Intensive monitoring required during the first 18 weeks of therapy to detect potentially life-threatening hepatic events and skin reactions; extra vigilance is warranted during the first 6 weeks (the period of greatest risk).¹ Optimum frequency not established; clinical and laboratory monitoring more often than once monthly and liver function tests at baseline, prior to dose escalation, and at 2 weeks after dose escalation recommended.^{1 86}

After the initial 18-week period, frequent clinical and laboratory monitoring should continue.¹

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 Hepatic events can occur at any time during therapy.¹ Risk of hepatic events (regardless of severity) greatest during the first 6 weeks of therapy; substantial risk continues through 18 weeks of therapy.¹

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 Fever and flu-like symptoms accompany some of these hepatic events.¹ 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}

Patients with higher CD4 counts and women are at increased risk of these hepatic events.¹ 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 Increased liver enzymes and/or HBV or HCV infection associated with increased risk.¹

Intensive clinical and laboratory monitoring essential.¹ (See Patient Monitoring under Cautions.)

Hepatotoxicity should be considered 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

Hepatic injury has progressed despite discontinuation of nevirapine in some patients.¹

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} 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}

Interactions

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

Sensitivity Reactions

Skin Reactions

Severe, life-threatening skin reaction (including some fatalities) reported.¹ Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction (including hepatic failure) have been reported.¹

Patients with signs or symptoms of severe skin reactions 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 nelfinavir and seek immediate medical evaluation.¹

Therapy must be initiated with nevirapine 200 mg daily (150 mg/m² daily for pediatric patients) for the first 14 days; initiating therapy with this dosage reduces the frequency of rash.¹ If mild to moderate rash without constitutional symptoms occurs during the initial 14 days, the dose should not be increased until the rash has resolved.¹ Do not continue the initial low dosage beyond 28 days; discontinue nevirapine and select alternative therapy.¹

Monitor closely if isolated rash of any severity occurs.¹

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

Women appear to be at higher risk of developing rash than men.¹

Prednisone not recommended for the prevention of nevirapine-associated rash; not effective.¹

Nevirapine should not be restarted following a hypersensitivity reaction, severe rash, or rash in conjunction with increased serum transaminase concentrations or other symptoms.¹

General Precautions

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

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 jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.^{1 101}

Specific Populations

Pregnancy

Category B.¹

Antiretroviral Pregnancy Registry at 800-258-4263.¹ Pregnancy registry data indicate no increased risk for congenital abnormalities among infants born to women who received nevirapine during pregnancy compared with general population.¹

The preferred NNRTI for use in multiple-drug antiretroviral regimens in pregnant women.⁶⁸

Because of risk of potentially life-threatening hepatotoxicity, do not initiate nevirapine in adult women, including pregnant women, with pretreatment CD4⁺ T-cell counts >250/mm³ unless potential benefits outweigh risks.^{1 51 96} (See Hepatic Effects under Cautions.)

Lactation

Distributed into milk.^{1 58 65}

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

Pediatric Use

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

When given to neonates as part of a regimen for prevention of maternal-fetal transmission of HIV†,^{58 59 60 61 68} generally well tolerated; rash and anemia reported rarely.^{59 60 61}

Geriatric Use

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

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

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.¹

Common Adverse Effects

Rash, nausea, headache, fatigue, abnormal liver function test results.¹

Interactions for Viramune

Metabolized by CYP3A and CYP2B6.¹

Inhibits CYP3A and CYP2B6.¹

Induces CYP3A and CYP2B6.¹

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}

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

Specific Drugs

Drug	Interaction	Comments
Abacavir	Pharmacokinetic interaction unlikely54 In vitro evidence of additive or synergistic antiretroviral effects1 3 4 9 27 62
Antacids (Maalox)	Pharmacokinetic interaction unlikely1
Antiarrhythmic agents (amiodarone, disopyramide, lidocaine)	Possible decreased antiarrhythmic agent concentrations1	Clinical monitoring recommended1
Anticoagulants, oral (warfarin)	Possible increased warfarin concentrations1	Monitor anticoagulant activity (PT/INR)1
Anticonvulsants (carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin)	Possible decreased concentrations of the anticonvulsant1	Clinical monitoring recommended1
Antifungals, azoles (fluconazole, itraconazole, ketoconazole, voriconazole)	Fluconazole: Increased nevirapine concentrations;1 51 no effect on fluconazole concentrations;51 possible increased risk of hepatotoxicity51 Itraconazole: Possible decreased itraconazole concentrations1 and change in nevirapine concentrations51 Ketoconazole: Decreased ketoconazole concentrations and possible reduced antifungal efficacy;1 51 increased nevirapine concentrations51 Voriconazole: Possible pharmacokinetic interaction;51 95 may affect both drugs51	Fluconazole: Use concomitantly with caution;1 monitor for adverse effects associated with nevirapine1 51 Itraconazole: Clinical monitoring recommended;1 monitor nevirapine and itraconazole concentrations51 Ketoconazole: Concomitant use not recommended1 51 Voriconazole: Monitor frequently for nevirapine toxicity and for response to voriconazole51 95
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: Increased rifabutin concentrations (high intersubject variability-some patients may experience large increases in rifabutin exposure); decreased nevirapine concentrations1 51 Rifampin: Decreased nevirapine concentrations1 51	Rifabutin: Caution advised; monitor for rifabutin toxicity;1 dosage adjustment not needed51 73 Rifampin: Concomitant use not recommended51 Rifapentine: Concomitant use not recommended51
Atazanavir	Possible decreased atazanavir concentrations and increased nevirapine concentrations51 94	Concomitant use with atazanavir (with or without low-dose ritonavir) not recommended51 94
Calcium-channel blocking agents (diltiazem, nifedipine, verapamil)	Possible decreased concentrations of the calcium-channel blocking agent1	Clinical monitoring recommended1
Cisapride	Possible decreased cisapride concentrations1	Clinical monitoring recommended1
Cyclophosphamide	Possible decreased cyclophosphamide concentrations1	Clinical monitoring recommended1
Darunavir	Increased concentrations of nevirapine; no change in darunavir concentrations51 102	Dosage adjustment not needed when ritonavir-boosted darunavir used concomitantly with nevirapine51 102
Delavirdine	Not studied51	Concomitant use of NNRTIs not recommended51
Didanosine	Pharmacokinetic interactions unlikely1 In vitro evidence of additive or synergistic antiretroviral effects1 3 4 9 27 62
Efavirenz	Efavirenz AUC decreased1	Concomitant use of NNRTIs not recommended51
Emtricitabine	In vitro evidence of additive or synergistic antiretroviral effects103
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Possible decreased concentrations of the ergot alkaloid1	Clinical monitoring recommended1
Estrogens/Progestins	Hormonal contraceptives: Decreased ethinyl estradiol and norethindrone concentrations with oral contraceptive preparations1 51	Do not use hormonal contraceptives as the sole method of contraception;1 use alternative or additional contraceptive measures1 51
Etravirine	Decreased etravirine concentrations105	Concomitant use of NNRTIs not recommended51 105
Fentanyl	Possible decreased fentanyl concentrations1	Clinical monitoring recommended1
Fosamprenavir	Decreased amprenavir concentrations and increased nevirapine concentrations with fosamprenavir (without ritonavir); clinically important interaction unlikely with ritonavir-boosted fosamprenavir99	Concomitant use of fosamprenavir (without ritonavir) not recommended99 Dosage adjustment not needed when ritonavir-boosted fosamprenavir is given twice daily; ritonavir-boosted fosamprenavir given once daily not studied99
Immunosuppressive agents	Possible decreased concentrations of cyclosporine, sirolimus, or tacrolimus1	Clinical monitoring recommended1
Indinavir	Decreased peak and trough plasma concentrations and AUC of indinavir; no clinically important change in the pharmacokinetics of nevirapine1 51 In vitro evidence of additive or synergistic antiretroviral effects1 3 4	Manufacturer states appropriate dosages for concomitant use with respect to safety and efficacy not established1 Some experts state adjustment of nevirapine dosage not needed; consider increasing indinavir dosage to 1 g every 8 hours or using ritonavir-boosted indinavir51
Lamivudine	In vitro evidence of additive or synergistic antiretroviral effects1 3 4 9 27 62
Lopinavir	Decreased lopinavir concentrations1 83	Once-daily lopinavir regimen not recommended with nevirapine83 For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily83 Manufacturer recommends that adults receive dosage of 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of oral solution) twice daily1 83 For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive dosage of 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)83
Macrolides	Decreased clarithromycin concentration and increased 14-hydroxyclarithromycin concentration1 51	Monitor for efficacy of the macrolide or use an alternative anti-infective1 51
Maraviroc	Pharmacokinetic interaction51 104	If nevirapine is used with maraviroc without an HIV protease inhibitor (PI), the recommended dosage of maraviroc is 300 mg twice daily; 51 104 if nevirapine is used with maraviroc with a PI (except ritonavir-boosted tipranavir), the recommended dosage of maraviroc is 150 mg twice daily.51 104
Methadone	Decreased methadone concentrations;1 no change in nevirapine concentrations51 Opiate withdrawal reported51	Consider need to increase methadone dosage1 51
Nelfinavir	Clinically important pharmacokinetic interactions unlikely1 51 In vitro evidence of synergistic antiretroviral effects90	Dosage adjustment not needed51
Quinupristin and dalfopristin	Possible increased nevirapine concentrations77
Ritonavir	Clinically important pharmacokinetic interaction unlikely1 51	Dosage adjustment not needed51
Saquinavir	Decreased saquinavir concentrations; no change in nevirapine pharmacokinetics1 33 51 Concomitant use with ritonavir-boosted saquinavir not evaluated33 In vitro evidence of additive or synergistic antiretroviral effects1 33	Manufacturer of saquinavir states appropriate dosages for concomitant use with respect to safety and efficacy not established33 Consider saquinavir 1 g twice daily with ritonavir 100 mg twice daily with usual nevirapine dosage51
St. John’s wort (Hypericum perforatum)	Decreased nevirapine concentrations; possible loss of virologic response and increased risk of nevirapine resistance1 78 79	Concomitant use not recommended1 51 78
Stavudine	Pharmacokinetic interactions unlikely1 In vitro evidence of additive or synergistic antiretroviral effects1 3 4 9 27 62
Tenofovir	In vitro evidence of additive or synergistic antiretroviral effects98
Tipranavir	No change in nevirapine pharmacokinetics 51 100 In vitro evidence of additive antiretroviral effects100
Zidovudine	Decreased zidovudine concentrations1 In vitro evidence of additive or synergistic antiretroviral effects1 3 4 9 27 62

Viramune Pharmacokinetics

Absorption

Bioavailability

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

Steady-state trough concentrations in adults similar to concentrations in children receiving the recommended dosage.¹

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

Food

Food does not appear to affect absorption.¹

Special Populations

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

Pharmacokinetics not altered in most patients with mild to moderate hepatic impairment; 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

Distribution

Extent

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

Crosses the placenta;^{1 65} distributed into human milk^{1 58 65} 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

Suspension

25°C (may be exposed to 15–30°C).¹

Actions and Spectrum

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

  
  


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

  
  


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

  
  


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  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}

  
  


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

  
  


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  Cross-resistance between nevirapine and nucleoside reverse transcriptase inhibitors (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 26 33}

  
  

Advice to Patients

• 
  

  Critical nature of compliance with HIV therapy.¹ Importance of using nevirapine in conjunction with other antiretrovirals— not for monotherapy.¹

  
  


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  Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.¹ HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.¹

  
  


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  Possibility of severe liver disease or skin reactions.¹ 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

  
  


• 
  

  Need for periodic clinical and laboratory monitoring, including liver function tests.¹

  
  


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  Risk of rash, especially during the first 6 weeks of therapy.¹ If rash occurs during the first 2 weeks of therapy, nevirapine dosage should not be increased until the rash resolves.¹

  
  


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  Importance of reading patient package insert from manufacturer.¹

  
  


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

  
  


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

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


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  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Nevirapine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	200 mg	Viramune (scored)	Boehringer Ingelheim

Nevirapine Hemihydrate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Suspension	50 mg (of nevirapine) per 5 mL	Viramune	Boehringer Ingelheim

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. 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/$602.02 or 180/$1,769.03

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. 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.

References

1. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2008 Jun.

2. Havlir D, Cheeseman SH, McLaughlin M et al. High-dose nevirapine: Safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection. J Infect Dis. 1995; 171:537-45. [IDIS 346014] [PubMed 7533197]

3. Richman D, Rosenthal AS, Skoog M et al. BI-RG-587 is active against zidovudine- resistant human immunodeficiency virus type 1 and synergistic with zidovudine. Antimicrob Agents Chemother. 1991; 35:305-8. [PubMed 1708976]

4. Cheeseman SH, Havlir D, McLaughlin MM et al. Phase I/II evaluation of nevirapine alone and in combination with zidovudine for infection with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol. 1995; 8:141-51. [PubMed 7530585]

5. Kohlstaedt LA, Wang J, Friedman JM et al. Crystal structure at 3.5 resolution of HIV- 1 reverse transcriptase complexed with an inhibitor. Science. 1992; 256:1783-90. [PubMed 1377403]

6. D’Aquila RT, Hughes MD, Johnson VA et al. Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. Ann Intern Med. 1996; 124:1019-30. [IDIS 366146] [PubMed 8633815]

7. Anon. New drugs for HIV infection. Med Lett Drugs Ther. 1996; 38:35-7. [PubMed 8606677]

8. Lange JMA. Triple combinations: present and future. J Acquired Immune Defic Syndr Hum Retrovirol