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  • CLASSES

    Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)s

    BOXED WARNING

    Hepatic disease, hepatitis, hepatitis B and HIV coinfection, hepatotoxicity

    Nevirapine has been associated with severe or life-threatening hepatotoxicity, including fatal cases. The first 18 weeks of therapy with nevirapine are the critical period during which it is essential to intensively monitor patients to detect potentially life-threatening hepatotoxicity. The greatest risk of severe hepatic events associated with skin reactions occurs in the first 6 weeks of therapy; however, the risk of any hepatic event, with or without rash, continues past this period and monitoring should continue at frequent intervals. Obtain liver function tests at baseline, at treatment week 2 (prior to dose escalation), 2 weeks post-dose escalation, and then monthly for the first 18 weeks of therapy. In addition, the 14-day lead-in period must be strictly followed. Patients with hepatic disease associated with elevated hepatic enzymes or a history of chronic hepatitis B or C are at increased risk of developing hepatic toxicity. Women appear to have a 3-fold higher risk than men for rash associated hepatic events; women with CD4 counts greater than 250 cells/mm3 at the initiation of nevirapine therapy, including pregnant women receiving chronic treatment for HIV infection, are at considerably higher risk (12-fold) for drug-induced hepatotoxicity, which may be life-threatening. Based on this higher observed risk of serious liver toxicity in female patients with higher CD4 counts prior to initiation of therapy, women with CD4 counts greater than 250 cells/mm3 should not be started on nevirapine therapy unless benefits clearly outweigh risks. Men with CD4 counts greater than 400 cells/mm3 may also be at higher risk for rash-associated hepatic events with nevirapine, and, likewise, should not be started on nevirapine therapy unless benefits clearly outweigh risks.[46638] Although certain patient populations are at increased risk, nevirapine-associated hepatotoxicity may occur in both genders, all CD4 counts, and at any time during treatment including individuals without HIV who are taking nevirapine for post-exposure prophylaxis. In some cases, patients presented with non-specific prodromal signs or symptoms of hepatitis and progressed to hepatic failure. Some events occurred after short-term exposure including individuals receiving nevirapine for post-exposure prophylaxis; as a result, the use of nevirapine for post-exposure prophylaxis is contraindicated. Patients with signs or symptoms of hepatitis must seek medical attention immediately and should be advised to discontinue nevirapine therapy. Do not restart nevirapine following severe hepatic reactions; in some cases, hepatic injury progresses despite discontinuation of treatment. Do not administer nevirapine to patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic disease as increased nevirapine concentrations and nevirapine accumulation may be observed. Carefully monitor patients with any degree of hepatic impairment for evidence of drug-induced toxicity.[42456] Additionally, all patients presenting with HIV infection should be screened for hepatitis B virus (HBV) coinfection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [46638] [34362]

    Nevirapine hypersensitivity, serious rash

    Nevirapine has been associated with severe or life-threatening cutaneous toxicity and nevirapine hypersensitivity reactions, including fatal cases. Patients developing signs or symptoms of serious rash or nevirapine hypersensitivity reactions must discontinue nevirapine therapy immediately. The first 18 weeks of therapy with nevirapine are the critical period during which is essential to intensively monitor patients to detect potentially life-threatening skin reactions. The greatest risk of severe rash occurs in the first 6 weeks of therapy; however, the risk of any cutaneous reaction continues past this period and monitoring should continue at frequent intervals. The optimal frequency of monitoring is not established. Some experts recommend clinical monitoring more frequently than once per month during the first 18 weeks of therapy. Monitoring should continue at frequent intervals thereafter. In addition, the 14-day lead-in period must be strictly followed. Risk factors for developing severe cutaneous or hypersensitivity reactions include failure to follow the initial dosing and lead-in period and delay in stopping nevirapine treatment after the onset of initial symptoms (e.g., severe rash or rash accompanied by fever, malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, and/or hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and renal dysfunction). If rash is observed during the initial lead-in period, nevirapine dosage should not be escalated until the rash has resolved. Patients should be monitored closely if a rash of any severity develops. In a clinical trial, concomitant use of prednisone (40 mg/day for the first 14 days of nevirapine administration) was associated with an increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy. Therefore, the use of prednisone to prevent nevirapine-associated rash is not recommended. Women appear to be at higher risk than men of developing skin reactions and rash-associated hepatic events with nevirapine. Nevirapine should not be restarted following severe skin or other nevirapine hypersensitivity reactions.

    DEA CLASS

    Rx

    DESCRIPTION

    Non-nucleoside reverse transcriptase inhibitor
    Used for human immunodeficiency virus (HIV) infection and for perinatal HIV prophylaxis in combination with other antiretroviral agents
    Use is associated with serious rash and sometimes fatal hepatotoxicity

    COMMON BRAND NAMES

    Viramune, Viramune XR

    HOW SUPPLIED

    Nevirapine/Viramune Oral Susp: 5mL, 50mg
    Nevirapine/Viramune Oral Tab: 200mg
    Nevirapine/Viramune XR Oral Tab ER: 100mg, 400mg

    DOSAGE & INDICATIONS

    For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents.
    NOTE: Although the FDA-approved labeling recommends reinitiation of lead-in dosing for patients who have interrupted therapy for more than 7 days, the HIV guidelines recommend that children who interrupt therapy for 14 days or less should be restarted on full-dose nevirapine. If dosing is interrupted for more than 14 days, dosing should be restarted with the lead-in dosing for 14 days, followed by full-dose escalation.
    Oral dosage (immediate-release formulations)
    Adults

    200 mg PO once daily for the first 14 days, then 200 mg PO twice daily.

    Adolescents

    200 mg PO once daily for the first 14 days, then 200 mg PO twice daily is recommended by the HIV guidelines. The FDA-approved dosage is 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for the first 14 days, then 150 mg/m2/dose (Max: 200 mg/dose) PO twice daily.

    Children 8 to 12 years

    120 to 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for the first 14 days, then 120 to 150 mg/m2/dose (Max: 200 mg/dose) PO twice daily is recommended by the HIV guidelines. The FDA-approved dosage is 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for the first 14 days, then 150 mg/m2/dose (Max: 200 mg/dose) PO twice daily.

    Infants and Children 1 to 7 years

    200 mg/m2/dose (Max: 200 mg/dose) PO once daily for the first 14 days, then 200 mg/m2/dose (Max: 200 mg/dose) PO twice daily is recommended by the HIV guidelines. The FDA-approved dosage is 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for the first 14 days, then 150 mg/m2/dose (Max: 200 mg/dose) PO twice daily. Some clinicians initiate nevirapine without a lead-in dose for children younger than 2 years to decrease the risk of suboptimal dosing and the potential for virologic failure. In addition, no rash events occurred in this age group in patients who received full dose vs. half dose nevirapine in a clinical trial.

    Term Neonates 15 to 29 days

    6 mg/kg/dose PO twice daily (no lead in phase) is recommended by the HIV guidelines. This is an investigational dose that was studied as part of the IMPAACT 1115 protocol. This study demonstrated that nevirapine dosed at 6 mg/kg/dose twice daily achieved concentrations appropriate for treatment. The FDA-approved dosage is 150 mg/m2/dose PO once daily for the first 14 days, then 150 mg/m2/dose PO twice daily.

    Term Neonates 0 to 14 days†

    6 mg/kg/dose PO twice daily (no lead in phase) is recommended by the HIV guidelines. This is an investigational dose that was studied as part of the IMPAACT 1115 protocol. This study demonstrated that nevirapine dosed at 6 mg/kg/dose twice daily achieved concentrations appropriate for treatment.

    Premature Neonates 34 to 36 weeks gestational age and older than 7 days postnatal age†

    6 mg/kg/dose PO twice daily (no lead in phase) is recommended by the HIV guidelines. This is an investigational dose that was studied as part of the IMPAACT 1115 protocol. This study demonstrated that nevirapine dosed at 4 mg/kg/dose twice daily for 1 week followed by 6 mg/kg/dose twice daily achieved concentrations appropriate for treatment.

    Premature Neonates 34 to 36 weeks gestational age and 0 to 7 days postnatal age†

    4 mg/kg/dose PO twice daily (no lead in phase) is recommended by the HIV guidelines. This is an investigational dose that was studied as part of the IMPAACT 1115 protocol. This study demonstrated that nevirapine dosed at 4 mg/kg/dose twice daily for 1 week followed by 6 mg/kg/dose twice daily achieved concentrations appropriate for treatment.

    Oral dosage (extended-release tablet)
    Adults

    400 mg PO once daily. Patients MUST first receive 200 mg/day PO of an immediate-release nevirapine formulation for 14 days or must be switched from the twice daily immediate-release formulation. After the 14-day lead-in period is completed, begin treatment with extended-release tablets.[43831]

    Children and Adolescents 6 to 17 years with BSA 1.17 m2 or greater

    400 mg PO once daily. Before administering the extended-release tablets, patients MUST first receive 150 mg/m2/dose (Max: 200 mg/dose) PO once daily of an immediate-release nevirapine formulation for 14 days or must be switched from the twice daily immediate-release formulation. After the 14-day lead-in period, begin treatment with the extended-release tablets.

    For perinatal human immunodeficiency virus (HIV) prophylaxis† in neonates at high risk for HIV acquisition.
    NOTE: Neonates with presumed HIV exposure (mothers with unknown HIV status who test HIV positive at delivery or postpartum or whose newborns have a positive HIV antibody test) or those at high risk for perinatal HIV transmission (neonates born to HIV-infected mothers: who have not received antepartum or intrapartum antiretroviral (ARV) treatment, who have received only intrapartum ARV treatment, who have suboptimal viral suppression (confirmed HIV RNA of 50 copies/mL or more) near delivery (within 4 weeks of delivery), who have acute or primary HIV infection during pregnancy or breastfeeding, or who have known ARV drug-resistant virus) should receive combination ARV prophylaxis with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) or presumptive therapy with a 3-drug combination ARV regimen, consisting of zidovudine, lamivudine, and nevirapine or raltegravir at treatment doses. If the mother has HIV-1 and HIV-2 infection, consider raltegravir in the 3-drug combination antiretroviral prophylaxis regimen since HIV-2 is not susceptible to nevirapine. ARV therapy should be initiated as close to the time of birth as possible, preferably within 6 hours of delivery.[23512] [42452]
    Oral dosage (2-Drug Combination Antiretroviral Prophylaxis Regimen)
    Neonates 32 weeks gestation and older weighing more than 2 kg

    12 mg PO for a total of 3 doses given with zidovudine for 6 weeks. Give the first nevirapine dose as soon as possible after birth (within 48 hours). Give the second nevirapine dose 48 hours after the first dose. Give the third nevirapine dose 96 hours after the second dose. The NICHD-HPTN 040/PACTG 1043 study showed an approximately 50% reduction in transmission rate in neonates receiving zidovudine plus nevirapine compared to zidovudine alone.[23512]

    Neonates 32 weeks gestation and older weighing 1.5 to 2 kg

    8 mg PO for a total of 3 doses given with zidovudine for 6 weeks. Give the first nevirapine dose as soon as possible after birth (within 48 hours). Give the second nevirapine dose 48 hours after the first dose. Give the third nevirapine dose 96 hours after the second dose. The NICHD-HPTN 040/PACTG 1043 study showed an approximately 50% reduction in transmission rate in neonates receiving zidovudine plus nevirapine compared to zidovudine alone.[23512]

    Oral dosage (3-Drug Combination Antiretroviral Prophylaxis Regimen)
    Neonates 37 weeks gestation and older and 0 to 6 weeks postnatal age

    6 mg/kg/dose PO twice daily in combination with zidovudine and lamivudine. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For nevirapine and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results. For infants diagnosed with HIV infection, increase the nevirapine dose to the continuation dose (i.e., 200 mg/m2/dose PO every 12 hours) after 4 weeks of age. [42452]

    Neonates 34 to 36 weeks gestation and 1 to 6 weeks postnatal age

    6 mg/kg/dose PO twice daily in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For nevirapine and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results. For infants diagnosed with HIV infection, increase the nevirapine dose to the continuation dose (i.e., 200 mg/m2/dose PO every 12 hours) after 4 weeks of age. [42452]

    Neonates 34 to 36 weeks gestation and 0 to 6 days postnatal age

    4 mg/kg/dose PO twice daily in combination with zidovudine and lamivudine. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For nevirapine and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512] [42452]

    Neonates 32 to 33 weeks gestation and 4 to 6 weeks postnatal age

    6 mg/kg/dose PO twice daily in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For nevirapine and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results. For infants diagnosed with HIV infection, increase the nevirapine dose to the continuation dose (i.e., 200 mg/m2/dose PO every 12 hours) after 4 weeks of age.

    Neonates 32 to 33 weeks gestation and 14 to 27 days postnatal age

    4 mg/kg/dose PO twice daily in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For nevirapine and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

    Neonates 32 to 33 weeks gestation and 0 to 13 days postnatal age

    2 mg/kg/dose PO twice daily in combination with zidovudine and lamivudine. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For nevirapine and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    400 mg/day PO.

    Geriatric

    400 mg/day PO.

    Adolescents

    BSA 1.17 or more: 300 mg/m2/day (Max: 400 mg/day) PO for immediate release formulations; 400 mg/day PO for extended-release tablets.
    BSA less than 1.17: 300 mg/m2/day PO for immediate release formulations; extended-release tablets not indicated.

    Children

    8 to 12 years and BSA 1.17 or more: 300 mg/m2/day (Max: 400 mg/day) PO for immediate release formulations; 400 mg/day PO for extended-release tablets.
    8 to 12 years and BSA less than 1.17: 300 mg/m2/day PO for immediate release formulations; extended-release tablets not indicated.
    6 to 7 years and BSA 1.17 or more: for immediate release formulations, doses up to 400 mg/m2/day (Max: 400 mg/day) PO are recommended in the HIV guidelines, although 300 mg/m2/day PO is recommended in the FDA-approved labeling. 400 mg/day PO for extended-release tablets.
    6 to 7 years and BSA less than 1.17: for immediate release formulations, doses up to 400 mg/m2/day PO are recommended in the HIV guidelines, although 300 mg/m2/day PO is recommended in the FDA-approved labeling. Extended-release tablets not indicated.
    1 to 5 years: for immediate release formulations, doses up to 400 mg/m2/day PO are recommended in the HIV guidelines, although 300 mg/m2/day PO is recommended in the FDA-approved labeling. Safety and efficacy of extended-release tablets not established.

    Infants

    For immediate release formulations, 12 mg/kg/day PO is recommended in the HIV guidelines for perinatal prophylaxis and treatment, although 300 mg/m2/day PO is the FDA-approved dose for treatment. Safety and efficacy of other formulations have not been established.

    Neonates

    15 days and older: for immediate release formulations, 8 mg/kg/day PO for premature neonates 32 to 33 weeks gestation and 12 mg/kg/day PO for premature neonates 34 weeks gestation and older is recommended in the HIV guidelines for perinatal prophylaxis and treatment, although 300 mg/m2/day PO is the FDA-approved dose for treatment. Safety and efficacy of other formulations have not been established.
    7 to 14 days: Safety and efficacy have not been established; however, 4 mg/kg/day PO for premature neonates 32 to 33 weeks gestation and 12 mg/kg/day PO for premature neonates 34 weeks gestation and older is recommended in the HIV guidelines for perinatal prophylaxis and treatment.
    0 to 6 days: Safety and efficacy have not been established; however, 3 doses are recommended for perinatal prophylaxis (8 mg PO once daily for weight 1.5 to 2 kg; 12 mg PO once daily for weight more than 2 kg); 4 mg/kg/day PO for premature neonates 32 to 33 weeks gestation, 8 mg/kg/day PO for premature neonates 34 to 36 weeks gestation, and 12 mg/kg/day PO for neonates 37 weeks gestation and older also recommended in the HIV guidelines for perinatal prophylaxis and treatment.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    There are no recommendations for dosage adjustments in patients with mild (Child-Pugh Class A) hepatic impairment. Do not administer nevirapine to patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. Use of the extended-release formulation has not been studied in patients with hepatic impairment.

    Renal Impairment

    No nevirapine dosage adjustments are required for patients with any degree of renal impairment that does not require hemodialysis. Use of the extended-release formulation has not been studied in patients with renal impairment.
     
    Intermittent hemodialysis
    Patients who have renal failure requiring hemodialysis should receive an additional dose of an immediate-release formulation after each dialysis treatment.

    ADMINISTRATION

    A MedGuide is available that describes the risks, benefits, and appropriate use of nevirapine therapy; dispense the MedGuide with the drug at each prescription fill or refill.
    Discontinue if patients experience hepatic toxicity, severe rash, or rash accompanied by constitutional findings or hypersensitivity reactions. Patients who develop a rash during the initial 14 days of therapy should not have their dose increased until the rash resolves.
    Restart therapy with the initial recommended dosage in any patient who interrupt dosing for more than 7 days.
    Never administer more than one form of nevirapine (e.g., immediate-release and extended-release) at the same time.

    Oral Administration

    May be administer with or without food.

    Oral Solid Formulations

    Extended-release tablet: Swallow whole. Do not chew, crush, or divide.

    Oral Liquid Formulations

    Oral suspension: Shake gently prior to administration. Use of an oral dosing syringe is recommended for administration, particularly for volumes of 5 mL or less. If a dosing cup is used, it should be thoroughly rinsed with water and the rinse should also be administered to the patient.

    STORAGE

    Viramune:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Viramune XR:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Health care providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities. [46638] [42452]

    Hepatic disease, hepatitis, hepatitis B and HIV coinfection, hepatotoxicity

    Nevirapine has been associated with severe or life-threatening hepatotoxicity, including fatal cases. The first 18 weeks of therapy with nevirapine are the critical period during which it is essential to intensively monitor patients to detect potentially life-threatening hepatotoxicity. The greatest risk of severe hepatic events associated with skin reactions occurs in the first 6 weeks of therapy; however, the risk of any hepatic event, with or without rash, continues past this period and monitoring should continue at frequent intervals. Obtain liver function tests at baseline, at treatment week 2 (prior to dose escalation), 2 weeks post-dose escalation, and then monthly for the first 18 weeks of therapy. In addition, the 14-day lead-in period must be strictly followed. Patients with hepatic disease associated with elevated hepatic enzymes or a history of chronic hepatitis B or C are at increased risk of developing hepatic toxicity. Women appear to have a 3-fold higher risk than men for rash associated hepatic events; women with CD4 counts greater than 250 cells/mm3 at the initiation of nevirapine therapy, including pregnant women receiving chronic treatment for HIV infection, are at considerably higher risk (12-fold) for drug-induced hepatotoxicity, which may be life-threatening. Based on this higher observed risk of serious liver toxicity in female patients with higher CD4 counts prior to initiation of therapy, women with CD4 counts greater than 250 cells/mm3 should not be started on nevirapine therapy unless benefits clearly outweigh risks. Men with CD4 counts greater than 400 cells/mm3 may also be at higher risk for rash-associated hepatic events with nevirapine, and, likewise, should not be started on nevirapine therapy unless benefits clearly outweigh risks.[46638] Although certain patient populations are at increased risk, nevirapine-associated hepatotoxicity may occur in both genders, all CD4 counts, and at any time during treatment including individuals without HIV who are taking nevirapine for post-exposure prophylaxis. In some cases, patients presented with non-specific prodromal signs or symptoms of hepatitis and progressed to hepatic failure. Some events occurred after short-term exposure including individuals receiving nevirapine for post-exposure prophylaxis; as a result, the use of nevirapine for post-exposure prophylaxis is contraindicated. Patients with signs or symptoms of hepatitis must seek medical attention immediately and should be advised to discontinue nevirapine therapy. Do not restart nevirapine following severe hepatic reactions; in some cases, hepatic injury progresses despite discontinuation of treatment. Do not administer nevirapine to patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic disease as increased nevirapine concentrations and nevirapine accumulation may be observed. Carefully monitor patients with any degree of hepatic impairment for evidence of drug-induced toxicity.[42456] Additionally, all patients presenting with HIV infection should be screened for hepatitis B virus (HBV) coinfection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [46638] [34362]

    Nevirapine hypersensitivity, serious rash

    Nevirapine has been associated with severe or life-threatening cutaneous toxicity and nevirapine hypersensitivity reactions, including fatal cases. Patients developing signs or symptoms of serious rash or nevirapine hypersensitivity reactions must discontinue nevirapine therapy immediately. The first 18 weeks of therapy with nevirapine are the critical period during which is essential to intensively monitor patients to detect potentially life-threatening skin reactions. The greatest risk of severe rash occurs in the first 6 weeks of therapy; however, the risk of any cutaneous reaction continues past this period and monitoring should continue at frequent intervals. The optimal frequency of monitoring is not established. Some experts recommend clinical monitoring more frequently than once per month during the first 18 weeks of therapy. Monitoring should continue at frequent intervals thereafter. In addition, the 14-day lead-in period must be strictly followed. Risk factors for developing severe cutaneous or hypersensitivity reactions include failure to follow the initial dosing and lead-in period and delay in stopping nevirapine treatment after the onset of initial symptoms (e.g., severe rash or rash accompanied by fever, malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, and/or hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and renal dysfunction). If rash is observed during the initial lead-in period, nevirapine dosage should not be escalated until the rash has resolved. Patients should be monitored closely if a rash of any severity develops. In a clinical trial, concomitant use of prednisone (40 mg/day for the first 14 days of nevirapine administration) was associated with an increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy. Therefore, the use of prednisone to prevent nevirapine-associated rash is not recommended. Women appear to be at higher risk than men of developing skin reactions and rash-associated hepatic events with nevirapine. Nevirapine should not be restarted following severe skin or other nevirapine hypersensitivity reactions.

    Pregnancy

    Antiretroviral therapy should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. In treatment-naive women, begin HAART as soon as pregnancy is recognized or HIV is diagnosed, without waiting for the results of resistance testing; subsequent modifications to the treatment regimen should be made once the test results are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; consider resistance testing if HIV RNA concentrations are more than 500 copies/mL. For women not currently receiving HAART, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing if HIV RNA concentrations are more than 500 copies/mL; treatment should be initiated prior to receiving resistance test results. According to HIV guidelines, nevirapine-containing regimens should not be initiated in pregnant women. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant women. Available data from the Antiretroviral Pregnancy Registry (APR), which includes first trimester exposures to nevirapine (more than 1,170 exposures), have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When nevirapine exposures occurred in the first trimester, the prevalence of defects was 3% (95% CI: 2.1 to 4.1). Initiating treatment with nevirapine has been associated with severe hypersensitivity reactions (i.e., skin reactions, fatal hepatotoxicities), which occur more frequently in women with CD4 counts greater than 250 cells/mm3 than in women with lower CD4 level or in men. It is unclear if pregnancy augments the risk observed in non-pregnant women. Regardless of pregnancy status, avoid the use of nevirapine in women with CD4 counts greater than 250 cells/mm3; if nevirapine must be used, monitor closely for liver toxicity during the first 18 weeks of therapy. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Women who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for women on HAART less than 2 years, women with CD4 count less than 300 cells/mm3, or women with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit, 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, then at least every 3 months during pregnancy, and at 34 to 36 weeks gestation. Perform antiretroviral resistance assay (genotypic testing, and if indicated, phenotypic testing) at baseline in all women with HIV RNA concentrations greater than 500 copies/mL, unless they have already been tested for resistance. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in women receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a woman decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to nevirapine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.[27468] [23512] [42456] [43831]

    Females

    Based on a higher observed risk of serious liver toxicity and hypersensitivity in females with higher CD4 counts prior to initiation of therapy, women with CD4 counts more than 250 cells/mm3 should not be started on nevirapine therapy unless benefits clearly outweigh risks. In reproductive toxicology studies with nevirapine, evidence of impaired fertility was seen in female rats at doses providing systemic exposure approximately equivalent to that provided with the recommended clinical dose of nevirapine. Women who become pregnant while on a nevirapine regimen may continue therapy regardless of CD4 count as pregnancy is not an independent risk factor for these toxicities.[23512] [42456]

    Black patients, Hispanic patients, human immunodeficiency virus (HIV) infection resistance

    Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. In high-income countries (e.g., US, some European countries, Australia, Japan), approximately 10% to 17% of treatment-naive individuals have resistance mutations to at least 1 antiretroviral drug; up to 8% (but generally less than 5%) of transmitted viruses will exhibit resistance to drugs from more than 1 class. Therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. As with all other antiretroviral agents, resistance can develop when nevirapine is used either alone or in combination with other agents. In patients whom a planned discontinuation or interruption of nevirapine therapy is planned, there is an increased risk of NNRTI-resistant mutations. Pharmacokinetic data demonstrate the persistence of detectable drug levels for at least 21 days after discontinuation of nevirapine; simultaneously stopping all drugs in a regimen containing nevirapine may result in functional nevirapine monotherapy due to its long half-life. This is further complicated by evidence that certain genetic polymorphisms, more common among some ethnic groups (such as in African Americans (Black patients) and in Hispanic patients), may result in slower rate of clearance. Some experts recommend stopping nevirapine before the other antiretroviral drugs, although the optimal interval between stopping nevirapine and other antiretroviral drugs is not known. An alternative strategy is to substitute the nevirapine with a PI prior to interruption of all antiretroviral drugs; if this strategy is used, the goal is to assure that the PI used also achieves complete viral suppression during this interval. Further research to determine the best approach to temporarily discontinuing nevirapine is needed. Additionally, if a patient has interrupted treatment with nevirapine for more than 7 days and is to be restarted at a later time point, nevirapine should be reintroduced with the dose escalation guidelines in initiation of therapy.

    Dialysis

    In one small pharmacokinetic study, no significant changes in nevirapine pharmacokinetics were found in HIV seronegative adults with mild (CrCl 50 to 79 mL/min), moderate (CrCl 30 to 49 mL/min), or severe (CrCl less than 30 mL/min) renal impairment not requiring hemodialysis. However, individuals with renal failure requiring hemodialysis (dialysis) exhibited a 44% reduction in nevirapine AUC over a 1 week exposure period and there was also evidence of accumulation of the nevirapine hydroxy-metabolites in plasma these subjects. Following hemodialysis treatment, an additional dose is indicated.

    Autoimmune disease, Graves' disease, Guillain-Barre syndrome, immune reconstitution syndrome

    Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of HIV treatment, patients whose immune system responds to nevirapine may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.

    Children, infants, neonates

    Safety and efficacy of extended-release nevirapine tablets have not been established in neonates, infants, or children younger than 6 years of age or in pediatric patients with body surface area less than 1.17 m2; however, the immediate-release formulations are approved for use in patients as young as 15 days old.

    Breast-feeding

    The manufacturer recommends mothers discontinue breast-feeding if they are receiving nevirapine. The Centers for Disease Control and Prevention recommend all mothers with HIV within the United States avoid breast-feeding as a method of preventing postnatal transmission of HIV. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy, including nevirapine. If a mother with HIV opts to breast-feed, the infant should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, health care workers may contact the Perinatal HIV Hotline (888-448-8765).[42452] Pooled data from 5 publications found immediate-release nevirapine is excreted in breast-milk at median drug concentrations ranging from 4,080 to 6,795 ng/mL, and a median breast-milk to maternal plasma concentration ratio of 59% to 88%. Although the estimated nevirapine daily dose of an exclusively breast-fed infant (682 to 704 microgram/kg/day) is lower than the recommended daily dose for infants, published literature have noted cases of rash and hyperbilirubinemia in infants exposed to nevirapine through breast milk. Other antiretroviral mediations whose passage into human breast milk have been evaluated include lamivudine, zidovudine, and nelfinavir.

    Hepatitis C and HIV coinfection

    HIV treatment guidelines recommend all patients presenting with HIV infection undergo testing for hepatitis C, with continued annual screening advised for those persons considered high risk for acquiring hepatitis C. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. For most patients, the benefits of concurrent therapy outweighs the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    erythema nodosum / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatic encephalopathy / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known

    Moderate

    hypercholesterolemia / Delayed / 22.0-22.0
    neutropenia / Delayed / 2.0-13.0
    elevated hepatic enzymes / Delayed / 0-9.0
    anemia / Delayed / 0-7.0
    jaundice / Delayed / 2.0-3.0
    hyperbilirubinemia / Delayed / 2.0-2.0
    thrombocytopenia / Delayed / 0-1.0
    lymphadenopathy / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    antimicrobial resistance / Delayed / Incidence not known
    hypophosphatemia / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    lipodystrophy / Delayed / Incidence not known

    Mild

    rash / Early / 2.0-21.0
    nausea / Early / 1.0-9.0
    fatigue / Early / 0-5.0
    headache / Early / 1.0-4.0
    anorexia / Delayed / 2.0-3.0
    vomiting / Early / 2.0-3.0
    diarrhea / Early / 0-2.0
    abdominal pain / Early / 0-2.0
    myalgia / Early / 0-1.0
    fever / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    malaise / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    drowsiness / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    Cushingoid features / Delayed / Incidence not known
    breast enlargement / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Major) Avoid concurrent use of dolutegravir with nevirapine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Nevirapine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Addition of nevirapine to a regimen of zidovudine, ZDV and didanosine showed nevirapine reduced the bioavailability of ZDV by about 30%. Zidovudine had no effect on the pharmacokinetics of nevirapine. This interaction has not been found to be clinically significant; no dosage adjustments are required.
    Abemaciclib: (Major) Avoid coadministration of nevirapine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with nevirapine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If nevirapine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Nevirapine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of oxycodone as needed. If nevirapine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Adefovir: (Major) Patients who are concurrently taking adefovir with non-nucleoside reverse transcriptase inhibitors are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
    Alfentanil: (Moderate) Drugs that induce cytochrome P450 3A4, including nevirapine, may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome 3A4 isoenzyme. Induction of alfentanil metabolism may take several days.
    Aliskiren; Amlodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Alprazolam: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system including alprazolam. Patients should be monitored closely for loss of clinical effects.
    Amiodarone: (Moderate) Nevirapine is an inducer of CYP3A4 and decreased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. Coadministration of nevirapine with amiodarone should be done with caution. Therapeutic monitoring of amiodarone concentrations is recommended.
    Amlodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Amlodipine; Atorvastatin: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments. (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including atorvastatin.
    Amlodipine; Benazepril: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Amlodipine; Celecoxib: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Amlodipine; Olmesartan: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Amlodipine; Valsartan: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of nevirapine and clarithromycin significantly decreases clarithromycin serum concentrations. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking nevirapine.
    Amprenavir: (Minor) Nevirapine has the potential to decrease serum concentrations of amprenavir. Appropriate doses of nevirapine or amprenavir for coadministration have not been determined.
    Apalutamide: (Moderate) Concomitant use of apalutamide with nevirapine should be undertaken with caution due to potential decreased nevirapine concentrations, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Nevirapine is primarily a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nevirapine exposure by greater than 50%.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if nevirapine and aprepitant or fosaprepitant are used concurrently, and monitor for a possible decrease in the efficacy of aprepitant. Nevirapine is a moderate CYP3A4 inducer and aprepitant is a CYP3A4 substrate.
    Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration with a CYP3A4 inducer such as nevirapine. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. Adjust the aripiprazole dose if necessary. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Artemether; Lumefantrine: (Major) Nevirapine is a substrate/inducer and both components of artemether; lumefantrine are substrates of the CYP3A4 isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations. Concomitant use warrants caution due to a possible reduction in antimalarial activity.
    Artesunate: (Moderate) Monitor for a decrease in antimalarial efficacy if artesunate is coadministered with nevirapine. Coadministration of oral artesunate with nevirapine resulted in a decrease in the AUC of the active metabolite of artesunate, dihydroartemisinin, by 68%.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with nevirapine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If nevirapine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Nevirapine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of oxycodone as needed. If nevirapine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Atazanavir: (Contraindicated) Do not coadminister atazanavir and nevirapine. Coadministration leads to substantially decreased atazanavir conentrations and increased nevirapine concentrations, which could lead to toxicity.
    Atazanavir; Cobicistat: (Contraindicated) Coadministration of nevirapine with regimens containing cobicistat and atazanavir are contraindicated; use of nevirapine with regimens containing cobicistat and darunavir are also not recommended. Nevirapine is a substrate and inducer of CYP3A4, cobicistat is a substrate/inhibitor of CYP3A4, while atazanavir are darunavir are CYP3A4 substrates. If these drugs are used together, the concentrations of nevirapine may increase and the concentrations of atazanavir, darunavir, and cobicistat may decrease; thereby, increasing the risk for nevirapine-associated adverse reactions and potentally decreasing the antiretroviral efficacy of atazanavir and darunavir. (Contraindicated) Do not coadminister atazanavir and nevirapine. Coadministration leads to substantially decreased atazanavir conentrations and increased nevirapine concentrations, which could lead to toxicity.
    Atogepant: (Major) Use an atogepant dose of 30 or 60 mg PO once daily if coadministered with nevirapine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and nevirapine is a moderate CYP3A inducer.
    Atorvastatin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including atorvastatin.
    Atorvastatin; Ezetimibe: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including atorvastatin.
    Avacopan: (Major) Avoid concomitant use of avacopan and nevirapine due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and nevirapine is a moderate CYP3A inducer.
    Avanafil: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as nevirapine, may decrease avanafil plasma levels. Concomitant use is not recommended.
    Avapritinib: (Major) Avoid coadministration of avapritinib with nevirapine due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
    Axitinib: (Major) Avoid coadministration of axitinib with nevirapine if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and nevirapine is a moderate CYP3A4 inducer.
    Barbiturates: (Moderate) Coadministration of nevirapine with barbiturates, which induce the activity of CYP3A, would be expected to increase the clearance of nevirapine, thereby decreasing nevirapine plasma concentrations. However, since nevirapine also induces CYP3A enzymes, decreases in anticonvulsant serum concentrations may be noted with the possibility of new seizure activity. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral drugs and barbiturates are unknown. If used concomitantly, the patient should be observed for changes in the clinical efficacy and concentrations of the antiretroviral and anticonvulsant regimens.
    Bedaquiline: (Major) Avoid concurrent use of nevirapine with bedaquiline. Nevirapine is a CYP3A4 inducer, which may result in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
    Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with nevirapine may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of nevirapine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If nevirapine is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Nevirapine is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
    Bepridil: (Major) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as bepridil, may require dosage adjustments.
    Boceprevir: (Major) Nevirapine and boceprevir should not be coadministered due to the potential for boceprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nevirapine and boceprevir. Plasma concentrations of boceprevir may be decreased due to induction of CYP3A4/5 by nevirapine.
    Bortezomib: (Minor) Agents that induce cytochrome P450 3A4 may decrease the exposure to bortezomib and possibly decrease the efficacy of the drug; however, bortezomib is also metabolized by other CYP isoenzymes. Therefore, the clinical significance of concurrent administration of bortezomib with CYP3A4 inducers is not known.
    Brentuximab vedotin: (Moderate) Concomitant administration of brentuximab vedotin and nevirapine may decrease the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin. MMAE is a CYP3A4 substrate and nevirapine is a potent CYP3A4 inducer; therefore, the efficacy of brentuximab may be reduced.
    Brexpiprazole: (Moderate) Because brexpiprazole is partially metabolized by CYP3A4, co-administration of a CYP3A4 inducer, such as nevirapine, may decrease systemic brexpiprazole exposure. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy.
    Brigatinib: (Major) Avoid coadministration of brigatinib with nevirapine due to decreased plasma exposure to brigatinib which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with nevirapine, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of nevirapine, resume the brigatinib dose that was tolerated prior to initiation of nevirapine. Brigatinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
    Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and nevirapine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; nevirapine is a moderate inducer of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Budesonide: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by nevirapine may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Budesonide; Formoterol: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by nevirapine may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by nevirapine may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by CYP3A4. Nevirapine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Bupivacaine: (Minor) Bupivacaine is metabolized by CYP3A4. Nevirapine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Bupivacaine; Epinephrine: (Minor) Bupivacaine is metabolized by CYP3A4. Nevirapine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Bupivacaine; Lidocaine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as lidocaine, may require dosage adjustments. (Minor) Bupivacaine is metabolized by CYP3A4. Nevirapine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Bupivacaine; Meloxicam: (Minor) Bupivacaine is metabolized by CYP3A4. Nevirapine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Buprenorphine: (Moderate) Inducers of CYP3A4 such as nevirapine, may induce the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after buprenorphine therapy has begun. Buprenorphine doses may need to be increased if any of these agents are added.
    Buprenorphine; Naloxone: (Moderate) Inducers of CYP3A4 such as nevirapine, may induce the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after buprenorphine therapy has begun. Buprenorphine doses may need to be increased if any of these agents are added.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Cabotegravir; Rilpivirine: (Major) Coadministration of nevirapine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Nevirapine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
    Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
    Calcium-channel blockers: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Capmatinib: (Major) Avoid coadministration of capmatinib and nevirapine due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
    Carbamazepine: (Major) Use carbamazepine and nevirapine together with caution due to the potential for loss of virologic response and possible resistance to nevirapine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Nevirapine may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and nevirapine plasma concentrations; adjust the anticonvulsant dose as necessary or consider alternative treatment. Nevirapine and carbamazepine are both substrates and inducers of CYP3A4 and CYP2B6.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as nevirapine, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
    Caspofungin: (Major) Consider dosing caspofungin as 70 mg IV once daily in adult patients and 70 mg/m2 IV once daily (Max: 70 mg/day) in pediatric patients receiving nevirapine. Administering inducers of hepatic cytochrome P450, such as nevirapine, concurrently with caspofungin may reduce the plasma concentrations of caspofungin.
    Ceritinib: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with ceritinib is necessary. Nevirapine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
    Chlordiazepoxide: (Moderate) Hepatic inducers, such as nevirapine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Amitriptyline: (Moderate) Hepatic inducers, such as nevirapine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Clidinium: (Moderate) Hepatic inducers, such as nevirapine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with nevirapine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If nevirapine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Nevirapine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with nevirapine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If nevirapine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Nevirapine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Cinacalcet: (Moderate) Coadministration of cinacalcet with a CYP3A4 enzyme inducer, such as nevirapine, may result in a decreased effect of cinacalcet.
    Cisapride: (Moderate) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Inducers of CYP3A4, such as nevirapine, may increase the clearance of cisapride.
    Clarithromycin: (Major) Coadministration of nevirapine and clarithromycin significantly decreases clarithromycin serum concentrations. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking nevirapine.
    Clevidipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Clonazepam: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system, including clonazepam.
    Clorazepate: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system, including clorazepate.
    Clozapine: (Moderate) Concurrent use of clozapine and nevirapine may decrease the therapeutic effects of clozapine since nevirapine is an inducer of CYP3A4 and clozapine is partially metabolized by this isoenzyme. According to the manufacturer, patients receiving clozapine in combination with a weak to moderate CYP3A4 inducer should be monitored for loss of effectiveness. Consideration should be given to increasing the clozapine dose if necessary. If the inducer is discontinued, monitor for adverse reactions, and consider reducing the clozapine dose if necessary.
    Cobicistat: (Contraindicated) Coadministration of nevirapine with regimens containing cobicistat and atazanavir are contraindicated; use of nevirapine with regimens containing cobicistat and darunavir are also not recommended. Nevirapine is a substrate and inducer of CYP3A4, cobicistat is a substrate/inhibitor of CYP3A4, while atazanavir are darunavir are CYP3A4 substrates. If these drugs are used together, the concentrations of nevirapine may increase and the concentrations of atazanavir, darunavir, and cobicistat may decrease; thereby, increasing the risk for nevirapine-associated adverse reactions and potentally decreasing the antiretroviral efficacy of atazanavir and darunavir.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with nevirapine due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and nevirapine is a moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
    Codeine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with nevirapine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a moderate CYP3A4 inducer.
    Conjugated Estrogens; Medroxyprogesterone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Cyclosporine: (Major) Nevirapine may induce cyclosporine metabolism, thereby increasing the clearance of cyclosporine. If nevirapine is added to an existing cyclosporine regimen, monitor cyclosporine concentrations closely to avoid loss of clinical efficacy until a new steady-state concentration is achieved. Conversely, if nevirapine is discontinued, cyclosporine concentrations could increase.
    Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as nevirapine. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
    Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with nevirapine is necessary. Dapsone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
    Darunavir: (Moderate) Concurrent administration of darunavir with nevirapine may result in increased nevirapine concentrations and decreased darunavir concentratation. Nevirapine is a substrate and inducer of CYP3A4; darunavir is a substrate and inhibitor of CYP3A4.
    Darunavir; Cobicistat: (Contraindicated) Coadministration of nevirapine with regimens containing cobicistat and atazanavir are contraindicated; use of nevirapine with regimens containing cobicistat and darunavir are also not recommended. Nevirapine is a substrate and inducer of CYP3A4, cobicistat is a substrate/inhibitor of CYP3A4, while atazanavir are darunavir are CYP3A4 substrates. If these drugs are used together, the concentrations of nevirapine may increase and the concentrations of atazanavir, darunavir, and cobicistat may decrease; thereby, increasing the risk for nevirapine-associated adverse reactions and potentally decreasing the antiretroviral efficacy of atazanavir and darunavir. (Moderate) Concurrent administration of darunavir with nevirapine may result in increased nevirapine concentrations and decreased darunavir concentratation. Nevirapine is a substrate and inducer of CYP3A4; darunavir is a substrate and inhibitor of CYP3A4.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of nevirapine with regimens containing cobicistat and atazanavir are contraindicated; use of nevirapine with regimens containing cobicistat and darunavir are also not recommended. Nevirapine is a substrate and inducer of CYP3A4, cobicistat is a substrate/inhibitor of CYP3A4, while atazanavir are darunavir are CYP3A4 substrates. If these drugs are used together, the concentrations of nevirapine may increase and the concentrations of atazanavir, darunavir, and cobicistat may decrease; thereby, increasing the risk for nevirapine-associated adverse reactions and potentally decreasing the antiretroviral efficacy of atazanavir and darunavir. (Moderate) Concurrent administration of darunavir with nevirapine may result in increased nevirapine concentrations and decreased darunavir concentratation. Nevirapine is a substrate and inducer of CYP3A4; darunavir is a substrate and inhibitor of CYP3A4.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Concurrent administration of nevirapine with dasabuvir; ombitasvir; paritaprevir; ritonavir is contraindicated. Taking these drugs together could result in elevated nevirapine plasma concentrations and decreased plasma concentrations of paritaprevir, ritonavir, and dasabuvir, which may affect antiviral efficacy. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Paritaprevir and dasabuvir (minor) are also metabolized by CYP3A4. (Moderate) Concurrent administration of nevirapine with ritonavir may result in elevated nevirapine plasma concentrations and decreased concentrations of ritonavir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Caution and close monitoring for antiviral efficacy and adverse effects are advised if these drugs are administered together.
    Dasatinib: (Moderate) Dasatinib is metabolized by CYP3A4. Concurrent administration of CYP3A4 inducers like nevirapine may decrease concentrations of dasatinib. If dasatinib must be administered with an inducer of CYP3A4, an increased dose of dasatinib should be considered.
    Deflazacort: (Major) Avoid concomitant use of deflazacort and nevirapine. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; nevirapine is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
    Delavirdine: (Major) The combined use of two NNRTIs has not been shown to be beneficial; thus, nevirapine and delavirdine should not be coadministered.
    Desogestrel; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Dextromethorphan; Quinidine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as quinidine, may require dosage adjustments as the concentration may be decreased.
    Diazepam: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system, including diazepam.
    Dienogest; Estradiol valerate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with nevirapine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If nevirapine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Nevirapine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Diltiazem: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Disopyramide: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as disopyramide, may require dosage adjustments.
    Docetaxel: (Minor) Docetaxel is metabolized by cytochrome P450 3A (CYP3A4 and CYP3A5) enzymes. In vitro studies have shown drugs that induce CYP3A enzymes, like nevirapine, can significantly affect the metabolism of docetaxel.
    Dofetilide: (Minor) Coadministration of dofetilide with inducers of CYP3A4, such as nevirapine, may increase the metabolism of dofetilide.
    Dolutegravir: (Major) Avoid concurrent use of dolutegravir with nevirapine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Nevirapine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Dolutegravir; Lamivudine: (Major) Avoid concurrent use of dolutegravir with nevirapine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Nevirapine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Dolutegravir; Rilpivirine: (Major) Avoid concurrent use of dolutegravir with nevirapine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Nevirapine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme. (Major) Coadministration of nevirapine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Nevirapine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
    Donepezil: (Minor) The elimination of donepezil may be increased by concurrent administration of certain in vitro inducers of the hepatic isoenzymes CYP2D6 and CYP3A4 including nevirapine. The clinical effect of these interactions on the efficacy of donepezil has not been determined. Observe patients for evidence of reduced donepezil efficacy if any of these agents are prescribed concurrently.
    Donepezil; Memantine: (Minor) The elimination of donepezil may be increased by concurrent administration of certain in vitro inducers of the hepatic isoenzymes CYP2D6 and CYP3A4 including nevirapine. The clinical effect of these interactions on the efficacy of donepezil has not been determined. Observe patients for evidence of reduced donepezil efficacy if any of these agents are prescribed concurrently.
    Doravirine: (Contraindicated) Concurrent treatment with nevirapine and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together may result in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; nevirapine is a CYP3A4 inducer.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent treatment with nevirapine and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together may result in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; nevirapine is a CYP3A4 inducer.
    Doxercalciferol: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as nevirapine, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Doxorubicin Liposomal: (Major) Nevirapine is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of nevirapine and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Doxorubicin: (Major) Nevirapine is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of nevirapine and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with nevirapine is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; nevirapine is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Dronedarone: (Major) The concomitant use of dronedarone and CYP3A4 inducers should be avoided. Dronedarone is metabolized by CYP3A. Nevirapine induces CYP3A4. Coadministration of CYP3A4 inducers, such as nevirapine, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy.
    Drospirenone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Drospirenone; Estetrol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Drospirenone; Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Drospirenone; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Duvelisib: (Major) Avoid concomitant use of duvelisib with nevirapine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When nevirapine has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with nevirapine. Duvelisib is a CYP3A substrate; nevirapine is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
    Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, one study with etravirine did not show a significant effect of Echinacea on drug exposure. More study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
    Efavirenz: (Major) Avoid concurrent use of efavirenz with nevirapine as the combination has been associated with increased adverse reactions without improved efficacy. Coadministration may result in decreased efavirenz AUC (22%), Cmin (36%), and Cmax (17%). The pharmacokinetics of nevirapine appear to be unaffected. The clinical implications of this interaction are not known.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid concurrent use of efavirenz with nevirapine as the combination has been associated with increased adverse reactions without improved efficacy. Coadministration may result in decreased efavirenz AUC (22%), Cmin (36%), and Cmax (17%). The pharmacokinetics of nevirapine appear to be unaffected. The clinical implications of this interaction are not known.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of efavirenz with nevirapine as the combination has been associated with increased adverse reactions without improved efficacy. Coadministration may result in decreased efavirenz AUC (22%), Cmin (36%), and Cmax (17%). The pharmacokinetics of nevirapine appear to be unaffected. The clinical implications of this interaction are not known.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with nevirapine. Nevirapine is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. (Major) If possible, avoid concurrent administration of grazoprevir with nevirapine. Nevirapine is a moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response. Conversely, concentrations of nevirapine (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
    Elvitegravir: (Major) Avoid coadministration of elvitegravir with nevirapine, as concurrent use is expected to decrease elvitegravir plasma concentrations. Nevirapine is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of nevirapine with regimens containing cobicistat and atazanavir are contraindicated; use of nevirapine with regimens containing cobicistat and darunavir are also not recommended. Nevirapine is a substrate and inducer of CYP3A4, cobicistat is a substrate/inhibitor of CYP3A4, while atazanavir are darunavir are CYP3A4 substrates. If these drugs are used together, the concentrations of nevirapine may increase and the concentrations of atazanavir, darunavir, and cobicistat may decrease; thereby, increasing the risk for nevirapine-associated adverse reactions and potentally decreasing the antiretroviral efficacy of atazanavir and darunavir. (Major) Avoid coadministration of elvitegravir with nevirapine, as concurrent use is expected to decrease elvitegravir plasma concentrations. Nevirapine is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of nevirapine with regimens containing cobicistat and atazanavir are contraindicated; use of nevirapine with regimens containing cobicistat and darunavir are also not recommended. Nevirapine is a substrate and inducer of CYP3A4, cobicistat is a substrate/inhibitor of CYP3A4, while atazanavir are darunavir are CYP3A4 substrates. If these drugs are used together, the concentrations of nevirapine may increase and the concentrations of atazanavir, darunavir, and cobicistat may decrease; thereby, increasing the risk for nevirapine-associated adverse reactions and potentally decreasing the antiretroviral efficacy of atazanavir and darunavir. (Major) Avoid coadministration of elvitegravir with nevirapine, as concurrent use is expected to decrease elvitegravir plasma concentrations. Nevirapine is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
    Empagliflozin; Linagliptin: (Moderate) Concomitant use of linagliptin with nevirapine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; nevirapine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Concomitant use of linagliptin with nevirapine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; nevirapine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Coadministration of nevirapine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Nevirapine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Coadministration of nevirapine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Nevirapine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
    Enalapril; Felodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Encorafenib: (Major) Avoid coadministration of encorafenib and nevirapine due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
    Entrectinib: (Major) Avoid coadministration of entrectinib with nevirapine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
    Enzalutamide: (Moderate) Concomitant use of enzalutamide with nevirapine should be undertaken with caution due to potential decreased nevirapine concentrations, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Nevirapine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nevirapine exposure by greater than 50%.
    Erdafitinib: (Major) If coadministration of erdafitinib and nevirapine is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If nevirapine must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If nevirapine is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Erlotinib: (Moderate) There may be a risk of reduced erlotinib efficacy when coadministered with nevirapine; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and nevirapine is a moderate CYP3A4 inducer.
    Erythromycin: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including erythromycin, may require dosage adjustments.
    Erythromycin; Sulfisoxazole: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including erythromycin, may require dosage adjustments.
    Estazolam: (Moderate) Nevirapine is a hepatic inducers and can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, possibly leading to reduced benzodiazepine concentrations.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Estradiol; Levonorgestrel: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Estradiol; Norethindrone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Estradiol; Norgestimate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Estradiol; Progesterone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Estrogens affected by CYP3A inducers: (Moderate) Women taking both estrogens and nevirapine should report breakthrough bleeding to their prescribers. Nevirapine may decrease plasma concentrations of hormonal contraceptives. However, despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on nevirapine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and nevirapine is a moderate CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Ethinyl Estradiol; Norgestrel: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Ethosuximide: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as ethosuximide, may require dosage adjustments.
    Ethotoin: (Major) Coadministration of nevirapine with phenytoin, an inducer of CYP3A, would be expected to increase the clearance of nevirapine. Since nevirapine also induces CYP3A enzymes, decreases in phenytoin serum concentrations may also be noted.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Etonogestrel: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Etonogestrel; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Etravirine: (Major) Etravirine and nevirapine should not be coadministered. Concomitant use of etravirine and nevirapine may cause a significant decrease in etravirine plasma concentrations and, thus, a loss of therapeutic effect. Additionally, the combined use of two non-nucleoside reverse transcriptase inhibitors (NNRTIs) has not been shown to be beneficial.
    Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if coadministration with nevirapine is necessary. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations.
    Ezetimibe; Simvastatin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Fedratinib: (Major) Avoid coadministration of fedratinib with nevirapine as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer. Coadministration of fedratinib with another moderate CYP3A4 inducer decreased the overall exposure of fedratinib by 47%.
    Felodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of nevirapine is necessary. If nevirapine is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like nevirapine with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
    Finerenone: (Major) Avoid concurrent use of finerenone and nevirapine due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and nevirapine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
    Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as nevirapine, is not recommended.
    Fluconazole: (Moderate) Coadministration of fluconazole and nevirapine results in increased nevirapine plasma concentrations. If fluconazole and nevirapine are to be coadministered, use caution and closely monitor patients for nevirapine-associated adverse events.
    Flurazepam: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system. Patients receiving flurazepam should be monitored closely for loss of clinical effects.
    Food: (Moderate) The pharmacokinetic parameters of anti-retroviral medications (anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs), anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs), anti-retroviral nucleotide reverse transcriptase inhibitors, and anti-retroviral protease inhibitors) metabolized through the CYP isoenzyme system are slightly altered by smoked and oral marijuana. Despite this interaction, marijuana is not expected to adversely affect anti-retroviral efficacy. However, the incidence of marijuana associated adverse effects may change following coadministration with anti-retroviral drugs. Many anti-retrovirals are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with anti-retrovirals, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Fosamprenavir: (Major) Coadministration of nevirapine and fosamprenavir without ritonavir is not recommended as significant decreases in amprenavir concentrations (active metabolite) may occur. If fosamprenavir and ritonavir, given as the twice daily dosage regimen, are administered with nevirapine, no dosage adjustments are needed.
    Fosphenytoin: (Major) Coadministration of nevirapine with phenytoin, an inducer of CYP3A, would be expected to increase the clearance of nevirapine. Since nevirapine also induces CYP3A enzymes, decreases in phenytoin serum concentrations may also be noted.
    Glasdegib: (Major) Avoid coadministration of glasdegib and nevirapine due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after nevirapine has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Guanfacine: (Major) Nevirapine may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if nevirapine is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If nevirapine is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and nevirapine is a moderate CYP3A4 inducer.
    Haloperidol: (Major) Coadministration of haloperidol and nevirapine may result in a significant reduction in haloperidol serum concentrations. Carefully monitor the patient's response to haloperidol if nevirapine is administered or discontinued. Adjust the haloperidol dose if necessary. Haloperidol is a CYP3A4 substrate and nevirapine is a CYP3A4 inducer. When coadministered with other CYP3A4 inducers, haloperidol concentrations were decreased.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Hydantoins: (Major) Coadministration of nevirapine with phenytoin, an inducer of CYP3A, would be expected to increase the clearance of nevirapine. Since nevirapine also induces CYP3A enzymes, decreases in phenytoin serum concentrations may also be noted.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with nevirapine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with nevirapine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and nevirapine is a moderate CYP3A inducer.
    Ibrutinib: (Moderate) Use ibrutinib and nevirapine together with caution; decreased ibrutinib levels may occur resulting in reduced ibrutinib efficacy. Monitor patients for signs of decreased ibrutinib efficacy if these agents are used together. Ibrutinib is a CYP3A4 substrate; nevirapine is a moderate CYP3A inducer. Simulations suggest that coadministration with a moderate CYP3A4 inducer may decrease ibrutinib exposure by 3-fold.
    Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of oxycodone as needed. If nevirapine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with nevirapine, a CYP3A substrate, as nevirapine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with nevirapine is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; nevirapine is a moderate CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
    Indinavir: (Moderate) Concurrent administration of indinavir and nevirapine results in significant decreases in indinavir Cmin, Cmax, and AUC. No change in nevirapine pharmacokinetic parameters occurs. It is recommended to increase the dose of indinavir to 1000 mg every 8 hours, or to administer a ritonavir enhanced or 'boosted' indinavir dose, when given in combination with nevirapine.
    Infigratinib: (Major) Avoid concurrent use of infigratinib and nevirapine. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Interferon Alfa-2a: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferon Alfa-2b: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferon Alfa-2b; Ribavirin: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately. (Major) The concomitant use of ribavirin and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Interferon Alfacon-1: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferon Alfa-n3: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferon Beta-1a: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferon Beta-1b: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferon Gamma-1b: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Interferons: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Isavuconazonium: (Major) Coadministration of isavuconazonium with nevirapine is not recommended as there is a potential for elevated nevirapine concentrations and decreased isavuconazonium concentrations. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Nevirapine is a CYP3A4 substrate/inducer. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and inhibitor of CYP3A4.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) The CDC recommends using nevirapine and rifampin in combination only if clearly indicated, if no other options exist, and when careful clinical and virologic monitoring are possible. When coadministered, the AUC and Cmin of nevirapine decreases by 20-58% and 68%, respectively. While the virologic consequences of coadministration are uncertain, the potential for additive hepatotoxicity exists; use of this combination is not recommended. If rifampin and nevirapine are used together, more frequent monitoring of HIV viral load, CD4+ counts, and hepatic function should take place.
    Isoniazid, INH; Rifampin: (Contraindicated) The CDC recommends using nevirapine and rifampin in combination only if clearly indicated, if no other options exist, and when careful clinical and virologic monitoring are possible. When coadministered, the AUC and Cmin of nevirapine decreases by 20-58% and 68%, respectively. While the virologic consequences of coadministration are uncertain, the potential for additive hepatotoxicity exists; use of this combination is not recommended. If rifampin and nevirapine are used together, more frequent monitoring of HIV viral load, CD4+ counts, and hepatic function should take place.
    Isradipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Itraconazole: (Major) Use of nevirapine is not recommended for 2 weeks before or during itraconazole therapy. Concurrent use may result in decreases in itraconazole plasma concentrations that may reduce efficacy of the drug. Itraconazole is a CYP3A4 substrate; nevirapine induces CYP3A4.
    Ivabradine: (Major) Avoid coadministration of ivabradine and nevirapine. Ivabradine is primarily metabolized by CYP3A4; nevirapine is an inducer of CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
    Ixabepilone: (Major) Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers, such as nevirapine, may lead to reduced and subtherapeutic concentrations of ixabepilone. Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered.
    Ketoconazole: (Major) Concomitant use of nevirapine and ketoconazole is not recommended. Unless the benefits outweigh the risk, these drugs should not be administered within 2 weeks of each other. If administered concurrently, monitor for breakthrough fungal infections. Ketoconazole is a substrate/inhibitor of the hepatic isoenzyme CYP3A4, nevirapine is a substrate/inducer. Coadministration results in a 15% to 30% increase in nevirapine plasma concentrations and a 63% and 40% reduction in ketoconazole AUC and Cmax, respectively.
    Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Addition of nevirapine to a regimen of zidovudine, ZDV and didanosine showed nevirapine reduced the bioavailability of ZDV by about 30%. Zidovudine had no effect on the pharmacokinetics of nevirapine. This interaction has not been found to be clinically significant; no dosage adjustments are required.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of nevirapine and clarithromycin significantly decreases clarithromycin serum concentrations. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking nevirapine.
    Lefamulin: (Major) Avoid coadministration of lefamulin with nevirapine unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer.
    Lemborexant: (Major) Avoid coadministration of lemborexant and nevirapine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer.
    Letermovir: (Major) Concurrent administration of letermovir and nevirapine is not recommended. Use of these drugs together may decrease letermovir plasma concentrations, resulting in a potential loss of letermovir efficacy. Also, an increase in the plasma concentration of nevirapine may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Nevirapine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Leuprolide; Norethindrone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Levamlodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Levobupivacaine: (Minor) Levobupivacaine is metabolized by CYP3A4 and 1A2. Known inducers of CYP3A4 or CYP1A2, such as nevirapine, may decrease the half-life of levobupivacaine.
    Levoketoconazole: (Major) Concomitant use of nevirapine and ketoconazole is not recommended. Unless the benefits outweigh the risk, these drugs should not be administered within 2 weeks of each other. If administered concurrently, monitor for breakthrough fungal infections. Ketoconazole is a substrate/inhibitor of the hepatic isoenzyme CYP3A4, nevirapine is a substrate/inducer. Coadministration results in a 15% to 30% increase in nevirapine plasma concentrations and a 63% and 40% reduction in ketoconazole AUC and Cmax, respectively.
    Levomethadyl: (Major) Inducers of CYP3A4, like nevirapine, may reduce levomethadyl serum concentrations resulting in symptoms of withdrawal in stabilized patients.
    Levonorgestrel: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Lidocaine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as lidocaine, may require dosage adjustments.
    Lidocaine; Epinephrine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as lidocaine, may require dosage adjustments.
    Lidocaine; Prilocaine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as lidocaine, may require dosage adjustments.
    Linagliptin: (Moderate) Concomitant use of linagliptin with nevirapine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; nevirapine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
    Linagliptin; Metformin: (Moderate) Concomitant use of linagliptin with nevirapine may result in decreased serum concentrations of linagliptin. Linagliptin is a substrate of hepatic isoenzyme CYP3A4; nevirapine is a moderate inducer of CYP3A4. Caution and close monitoring for decreased efficacy of linagliptin are advised if these drugs are used together.
    Lonafarnib: (Contraindicated) Coadministration of lonafarnib and nevirapine is contraindicated; concomitant use may decrease lonafarnib exposure, which may reduce its efficacy. Nevirapine exposure and the risk for nevirapine-related adverse effects may also be increased. Lonafarnib is a sensitive CYP3A4 substrate and a strong CYP3A4 inhibitor and nevirapine is a CYP3A4 substrate and a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may further increase nevirapine exposure.
    Loperamide: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with nevirapine. Loperamide is metabolized by the hepatic enzymes CYP3A4 and CYP2B6; nevirapine is an inducer of both enzymes.
    Loperamide; Simethicone: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with nevirapine. Loperamide is metabolized by the hepatic enzymes CYP3A4 and CYP2B6; nevirapine is an inducer of both enzymes.
    Lopinavir; Ritonavir: (Major) Coadministration of lopinavir and nevirapine may result in decreased concentratons of lopinavir. If coadministered, the dose of lopinavir; ritonavir must be increased and given twice daily; do not use once daily administration. Consult dosing information for recommended adjustments. (Moderate) Concurrent administration of nevirapine with ritonavir may result in elevated nevirapine plasma concentrations and decreased concentrations of ritonavir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Caution and close monitoring for antiviral efficacy and adverse effects are advised if these drugs are administered together.
    Lorlatinib: (Major) Avoid concomitant use of lorlatinib and nevirapine due to decreased plasma concentrations of lorlatinib, which may reduce its efficacy. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Lorlatinib is a CYP3A substrate and nevirapine is a moderate CYP3A inducer. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
    Lovastatin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4
    Lovastatin; Niacin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor can decrease the therapeutic efficacy of nevirapine; avoid concomitant use if possible. If concomitant use of nevirapine is necessary, monitor antiretroviral efficacy, consider the use of therapeutic drug monitoring, and adjust drug dosages as necessary. Do not exceed the maximum recommended dose. Nevirapine is a substrate of CYP3A4 and CYP2B6. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor may induce CYP2B6.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor can decrease the therapeutic efficacy of nevirapine; avoid concomitant use if possible. If concomitant use of nevirapine is necessary, monitor antiretroviral efficacy, consider the use of therapeutic drug monitoring, and adjust drug dosages as necessary. Do not exceed the maximum recommended dose. Nevirapine is a substrate of CYP3A4 and CYP2B6. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor may induce CYP2B6.
    Lumateperone: (Major) Avoid coadministration of lumateperone and nevirapine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer.
    Lurasidone: (Moderate) Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may occur when the drug is co-administered with inducers of CYP3A4. Concurrent use of lurasidone and CYP3A4 inducers, such as nevirapine, may lead to a decrease in efficacy of lurasidone. If lurasidone is used with a moderate CYP3A4 inducer, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more).
    Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and nevirapine due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and nevirapine is a moderate CYP3A inducer.
    Medroxyprogesterone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Nevirapine is an inducer of CYP3A4, and may increase the metabolism of mefloquine and reduce mefloquine plasma concentrations if coadministered.
    Mestranol; Norethindrone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Methadone: (Major) Nevirapine induces the CYP3A4 metabolism of methadone, resulting in decreased methadone AUC by 46% after 3 weeks. Clinically, patients who are stabilized on methadone-maintenance therapy may experience narcotic withdrawal symptoms within 7 days of begin nevirapine therapy. Methadone-maintained patients should be monitored for evidence of withdrawal and the methadone dose should be adjusted accordingly. In one series of patients, an average 45% increase in the methadone dose was required to prevent withdrawal symptoms in patients also receiving nevirapine.
    Midazolam: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system including midazolam. Patients should be monitored closely for loss of clinical effects.
    Mitapivat: (Major) Avoid coadministration of mitapivat with nevirapine, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and nevirapine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
    Mitotane: (Major) Concomitant use of mitotane with nevirapine should be undertaken with caution due to potential decreased nevirapine concentrations, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mitotane is a strong CYP3A4 inducer and nevirapine is primarily a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of nevirapine.
    Mobocertinib: (Major) Avoid concomitant use of mobocertinib and nevirapine. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and nevirapine is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
    Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with nevirapine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Nanoparticle Albumin-Bound Sirolimus: (Major) Monitor sirolimus serum concentrations carefully if administered with nevirapine. Nevirapine is an inducer of the CYP3A; sirolimus is extensively metabolized by this enzyme. Concomitant administration may result in decreased sirolimus blood concentrations.
    Nefazodone: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as nefazodone, may require dosage adjustments.
    Nelfinavir: (Moderate) Administering nevirapine (200 mg, daily and twice daily) with nelfinavir (750 mg, three times daily) resulted in a 32% decrease in the Cmin of nelfinavir, and decreases in the AUC, Cmax, and Cmin of the nelfinavir-M8 metabolite by 62%, 59%, and 66%, respectively. According to the manufacturer, an appropriate dose of nelfinavir when coadministered with nevirapine has not been established.
    Neratinib: (Major) Avoid concomitant use of nevirapine with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
    Niacin; Simvastatin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Nicardipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Nifedipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Nilotinib: (Moderate) Concomitant use of nilotinib, a substrate and moderate inhibitor of CYP3A4 and a CYP2B6 inducer, and nevirapine, a substrate and inducer of CYP3A4 and a CYP2B6 substrate, may result in decreased nilotinib and/or altered nevirapine levels. Use these agents together with caution; monitor patients for nevirapine side effects or decreased nilotinib or nevirapine efficacy.
    Nimodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of nevirapine with ritonavir may result in elevated nevirapine plasma concentrations and decreased concentrations of ritonavir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Caution and close monitoring for antiviral efficacy and adverse effects are advised if these drugs are administered together. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of nevirapine is necessary. Concomitant use of nirmatrelvir and nevirapine may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and nevirapine is a moderate CYP3A inducer.
    Nisoldipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Norethindrone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Norethindrone; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Norgestimate; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Norgestrel: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Olaparib: (Major) Avoid coadministration of olaparib with nevirapine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and nevirapine is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Concurrent administration of nevirapine with dasabuvir; ombitasvir; paritaprevir; ritonavir is contraindicated. Taking these drugs together could result in elevated nevirapine plasma concentrations and decreased plasma concentrations of paritaprevir, ritonavir, and dasabuvir, which may affect antiviral efficacy. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Paritaprevir and dasabuvir (minor) are also metabolized by CYP3A4. (Moderate) Concurrent administration of nevirapine with ritonavir may result in elevated nevirapine plasma concentrations and decreased concentrations of ritonavir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Caution and close monitoring for antiviral efficacy and adverse effects are advised if these drugs are administered together.
    Oritavancin: (Major) Nevirapine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of nevirapine may be reduced if these drugs are administered concurrently.
    Orlistat: (Major) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
    Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of oxycodone as needed. If nevirapine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Paclitaxel: (Minor) Metabolism of nevirapine to hydroxylated metabolites occurs primarily via the cytochrome P450 3A family of hepatic enzymes. Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as paclitaxel, may require dosage adjustments.
    Pacritinib: (Major) Avoid concurrent use of pacritinib with nevirapine due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and nevirapine is a moderate CYP3A inducer.
    Paricalcitol: (Moderate) Serum concentrations of paricalcitol may be reduced when administered with drugs known to induce the CYP3A4 enzyme, such as nevirapine. Dosage adjustments of paricalcitol may be required. Clinicians should monitor plasma PTH and serum calcium and phosphorous concentrations with this combination.
    Pazopanib: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and nevirapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of nevirapine. In addition, nevirapine is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
    Peginterferon Alfa-2a: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Peginterferon Alfa-2b: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Peginterferon beta-1a: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Pemigatinib: (Major) Avoid coadministration of pemigatinib and nevirapine due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
    Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with nevirapine due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of nevirapine occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Nevirapine is a CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
    Perindopril; Amlodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with nevirapine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Phenytoin: (Major) Coadministration of nevirapine with phenytoin, an inducer of CYP3A, would be expected to increase the clearance of nevirapine. Since nevirapine also induces CYP3A enzymes, decreases in phenytoin serum concentrations may also be noted.
    Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with moderate CYP3A4 inducers, such as nevirapine. Moderate inducers of CYP3A4 can reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
    Posaconazole: (Major) Posaconazole and nevirapine should be coadministered with caution due to an increased potential for nevirapine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of nevirapine. These drugs used in combination may result in elevated nevirapine plasma concentrations, causing an increased risk for nevirapine-related adverse events.
    Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with nevirapine, a CYP3A4 inducer, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
    Prednisone: (Moderate) In a clinical trial, concomitant use of prednisone was associated with an increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy. Therefore, the use of prednisone to prevent nevirapine-associated rash is not recommended.
    Progesterone: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Progestins: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Quinidine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as quinidine, may require dosage adjustments as the concentration may be decreased.
    Ranolazine: (Contraindicated) Ranolazine is contraindicated in patients receiving drugs known to be CYP3A inducers. Although not specifically mentioned by the manufacturer, coadministration of ranolazine with a CYP3A enzyme inducer such as nevirapine may result in decreased ranolazine plasma concentrations and decreased efficacy.
    Red Yeast Rice: (Minor) Since certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin. CYP3A4 inducers, such as nevirapine, can theoretically reduce the effectiveness of HMG-CoA reductase activity via induction of CYP3A4 metabolism.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Ribavirin: (Major) The concomitant use of ribavirin and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Ribociclib: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with ribociclib is necessary. Nevirapine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
    Ribociclib; Letrozole: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with ribociclib is necessary. Nevirapine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
    Rifampin: (Contraindicated) The CDC recommends using nevirapine and rifampin in combination only if clearly indicated, if no other options exist, and when careful clinical and virologic monitoring are possible. When coadministered, the AUC and Cmin of nevirapine decreases by 20-58% and 68%, respectively. While the virologic consequences of coadministration are uncertain, the potential for additive hepatotoxicity exists; use of this combination is not recommended. If rifampin and nevirapine are used together, more frequent monitoring of HIV viral load, CD4+ counts, and hepatic function should take place.
    Rifapentine: (Major) Avoid coadministration of nevirapine and rifapentine. Concurrent use may decrease the plasma concentrations of nevirapine leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Nevirapine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nevirapine exposure by greater than 50%.
    Rilpivirine: (Major) Coadministration of nevirapine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. If they are coadministered, close clinical monitoring is advised due to the potential for rilpivirine treatment failure. Predictions about the interaction can be made based on metabolic pathways. Nevirapine is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
    Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and nevirapine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
    Rimegepant: (Major) Avoid coadministration of rimegepant with nevirapine; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Ripretinib: (Major) Avoid coadministration of ripretinib with nevirapine. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of nevirapine. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and nevirapine is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
    Ritonavir: (Moderate) Concurrent administration of nevirapine with ritonavir may result in elevated nevirapine plasma concentrations and decreased concentrations of ritonavir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and potent inhibitor of this enzyme. Caution and close monitoring for antiviral efficacy and adverse effects are advised if these drugs are administered together.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and nevirapine may result in decreased rivaroxaban exposure and may decrease the efficacy of rivaroxaban. Nevirapine is an inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs of lack of efficacy of rivaroxaban.
    Roflumilast: (Major) Coadminister nevirapine and roflumilast cautiously as this may lead to reduced systemic exposure to roflumilast. Nevirapine induces CYP3A4 and roflumilast is a CYP3A4 substrate. In pharmacokinetic study, administration of a single dose of roflumilast in patients receiving another CYP3A4 inducer, rifampin, resulted in decreased roflumilast Cmax and AUC, as well as increased Cmax and decreased AUC of the active metabolite roflumilast N-oxide.
    Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Coadministration of a CYP3A4 inducer, like nevirapine, may decrease systemic concentrations of romidepsin. Use caution when concomitant administration of these agents is necessary.
    Ropeginterferon alfa-2b: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as nevirapine, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition.
    Saquinavir: (Major) Coadministration of saquinavir and nevirapine results in decreased saquinavir AUC and Cmax, 38% and 32%, respectively. No significant changes in nevirapine pharmacokinetics were noted. Appropriate doses for this combination are not established, but an increase in the dosage of saquinavir may be required. The interaction between nevirapine and saquinavir boosted with ritonavir has not been evaluated.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored.
    Selpercatinib: (Major) Avoid coadministration of selpercatinib and nevirapine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
    Selumetinib: (Major) Avoid coadministration of selumetinib and nevirapine due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
    Sildenafil: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as nevirapine, will decrease plasma levels of sildenafil.
    Simeprevir: (Major) Avoid concurrent use of simeprevir and nevirapine. Induction of CYP3A4 by nevirapine may reduce the plasma concentrations of simeprevir, resulting in treatment failure.
    Simvastatin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Simvastatin; Sitagliptin: (Minor) Nevirapine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Siponimod: (Moderate) Concomitant use of siponimod and nevirapine is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod up to 52% according to in silico evaluation.
    Sirolimus: (Major) Monitor sirolimus serum concentrations carefully if administered with nevirapine. Nevirapine is an inducer of the CYP3A; sirolimus is extensively metabolized by this enzyme. Concomitant administration may result in decreased sirolimus blood concentrations.
    Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4 and CYP2B6, such as nevirapine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2B6 substrate.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4 and CYP2B6, such as nevirapine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2B6 substrate. (Major) Avoid coadministration of voxilaprevir (a CYP3A4 substrate) with moderate to strong inducers of CYP3A4, such as nevirapine. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy.
    Sonidegib: (Major) Avoid the concomitant use of sonidegib and nevirapine; sonidegib levels may be decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and nevirapine is a CYP3A4 inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A4 inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
    St. John's Wort, Hypericum perforatum: (Contraindicated) St. John's wort is an inducer of CYP3A4 and may significantly decrease the plasma concentrations of nevirapine, a CYP3A4 substrate. Such reductions in plasma concentrations could lead to HIV treatment failures or the development of viral-resistance. St. John's wort in all forms, including teas, should be avoided in HIV patients treated with nevirapine.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if nevirapine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of sufentanil injection as needed. If nevirapine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Tacrolimus: (Major) Nevirapine induces CYP3A4, and thus, can decrease whole blood concentrations of tacrolimus, a CYP3A4 substrate. Monitoring tacrolimus whole blood concentrations and appropriate dose adjustments are recommended if used concurrently with nevirapine.
    Tadalafil: (Minor) Tadalafil is metabolized principally by cytochrome P450 3A4. Studies have shown that concomitant administration of CYP3A4 enzyme-inducers, such as nevirapine, will decrease plasma levels of tadalafil.
    Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and nevirapine. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as nevirapine, may reduce the efficacy of tasimelteon.
    Tazemetostat: (Major) Avoid coadministration of tazemetostat with nevirapine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Telaprevir: (Major) Nevirapine and telaprevir should not be coadministered due to an increased potential for nevirapine-related adverse events and the potential for telaprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nevirapine and telaprevir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of nevirapine may increase and the plasma concentrations of telaprevir may decrease.
    Telithromycin: (Moderate) Telithromycin is a potent inhibitor of CYP3A4 and is expected to compete with nevirapine for metabolism; administer together with caution, with careful monitoring of the patients nevirapine plasma concentrations and HIV status.
    Telmisartan; Amlodipine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Terbinafine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with nevirapine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; nevirapine induces this enzyme. Monitor patients for breakthrough fungal infections.
    Thiotepa: (Moderate) The concomitant use of thiotepa and nevirapine may increase the exposure of nevirapine; however, the clinical relevance of this interaction is unknown. Thiotepa is a CYP2B6 inhibitor in vitro; nevirapine is a CYP2B6 substrate.
    Trandolapril; Verapamil: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Triazolam: (Moderate) Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P450 system. Patients receiving triazolam should be monitored closely for loss of clinical effects.
    Trimetrexate: (Minor) Drugs such as nevirapine can increase the metabolism of trimetrexate by induction of the cytochrome P-450 system. This can lead to lower plasma concentrations of trimetrexate.
    Tucatinib: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with tucatinib is necessary. Nevirapine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
    Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with nevirapine as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer.
    Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and nevirapine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Venetoclax: (Major) Avoid the concomitant use of venetoclax and nevirapine; venetoclax levels may be decreased and its efficacy reduced. Venetoclax is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Consider alternative agents. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were decreased by 42% and 71%, respectively, following the co-administration of multiple doses of a strong CYP3A4 inducer. Use of venetoclax with a moderate CYP3A4 inducer has not been evaluated.
    Verapamil: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Voclosporin: (Major) Avoid coadministration of voclosporin with nevirapine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
    Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and nevirapine. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with nevirapine, a CYP3A inducer.
    Voriconazole: (Moderate) Monitor for an increase in nevirapine-related adverse reactions and breakthrough fungal infections if coadministration of voriconazole and nevirapine is necessary. Nevirapine is a CYP3A4 substrate and inducer. Voriconazole is a substrate and strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
    Voxelotor: (Major) Avoid coadministration of voxelotor and nevirapine as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Voxelotor is a substrate of CYP3A; nevirapine is a moderate CYP3A inducer. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
    Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with nevirapine is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Nevirapine is a moderate CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
    Zanubrutinib: (Major) Avoid the concomitant use of zanubrutinib and nevirapine. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; nevirapine is a moderate CYP3A4 inducer. The AUC of zanubrutinib is predicted to decrease by 60% when coadministered with another moderate CYP3A4 inducer.
    Zidovudine, ZDV: (Minor) Addition of nevirapine to a regimen of zidovudine, ZDV and didanosine showed nevirapine reduced the bioavailability of ZDV by about 30%. Zidovudine had no effect on the pharmacokinetics of nevirapine. This interaction has not been found to be clinically significant; no dosage adjustments are required.
    Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as nevirapine. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of significant decreases in systemic exposure and pharmacodynamics effects of zolpidem during co-administration of rifampin, a potent CYP3A4 inducer.
    Zonisamide: (Moderate) Zonisamide is metabolized by hepatic cytochrome P450 enzyme 3A4. Inducers of CYP3A4, such as nevirapine, can reduce the systemic exposure to zonisamide by increasing the metabolism of the drug.

    PREGNANCY AND LACTATION

    Pregnancy

    Antiretroviral therapy should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. In treatment-naive women, begin HAART as soon as pregnancy is recognized or HIV is diagnosed, without waiting for the results of resistance testing; subsequent modifications to the treatment regimen should be made once the test results are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; consider resistance testing if HIV RNA concentrations are more than 500 copies/mL. For women not currently receiving HAART, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing if HIV RNA concentrations are more than 500 copies/mL; treatment should be initiated prior to receiving resistance test results. According to HIV guidelines, nevirapine-containing regimens should not be initiated in pregnant women. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant women. Available data from the Antiretroviral Pregnancy Registry (APR), which includes first trimester exposures to nevirapine (more than 1,170 exposures), have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When nevirapine exposures occurred in the first trimester, the prevalence of defects was 3% (95% CI: 2.1 to 4.1). Initiating treatment with nevirapine has been associated with severe hypersensitivity reactions (i.e., skin reactions, fatal hepatotoxicities), which occur more frequently in women with CD4 counts greater than 250 cells/mm3 than in women with lower CD4 level or in men. It is unclear if pregnancy augments the risk observed in non-pregnant women. Regardless of pregnancy status, avoid the use of nevirapine in women with CD4 counts greater than 250 cells/mm3; if nevirapine must be used, monitor closely for liver toxicity during the first 18 weeks of therapy. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Women who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for women on HAART less than 2 years, women with CD4 count less than 300 cells/mm3, or women with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit, 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, then at least every 3 months during pregnancy, and at 34 to 36 weeks gestation. Perform antiretroviral resistance assay (genotypic testing, and if indicated, phenotypic testing) at baseline in all women with HIV RNA concentrations greater than 500 copies/mL, unless they have already been tested for resistance. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in women receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a woman decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to nevirapine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.[27468] [23512] [42456] [43831]

    The manufacturer recommends mothers discontinue breast-feeding if they are receiving nevirapine. The Centers for Disease Control and Prevention recommend all mothers with HIV within the United States avoid breast-feeding as a method of preventing postnatal transmission of HIV. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy, including nevirapine. If a mother with HIV opts to breast-feed, the infant should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, health care workers may contact the Perinatal HIV Hotline (888-448-8765).[42452] Pooled data from 5 publications found immediate-release nevirapine is excreted in breast-milk at median drug concentrations ranging from 4,080 to 6,795 ng/mL, and a median breast-milk to maternal plasma concentration ratio of 59% to 88%. Although the estimated nevirapine daily dose of an exclusively breast-fed infant (682 to 704 microgram/kg/day) is lower than the recommended daily dose for infants, published literature have noted cases of rash and hyperbilirubinemia in infants exposed to nevirapine through breast milk. Other antiretroviral mediations whose passage into human breast milk have been evaluated include lamivudine, zidovudine, and nelfinavir.

    MECHANISM OF ACTION

    Nevirapine inhibits HIV reverse transcriptase. Its mechanism differs from that of nucleoside reverse transcriptase inhibitors. Combination therapy with nevirapine and zidovudine has been shown to be synergistic against HIV replication. Nevirapine binds directly to reverse transcriptase. This binding causes disruption of the enzyme's catalytic site thereby blocking RNA-dependent and DNA-dependent DNA polymerase activities. Nevirapine does not compete with template or nucleoside triphosphates.
     
    Resistant HIV emerges rapidly and uniformly when nevirapine is administered as monotherapy. Nevirapine plus zidovudine combination therapy did not alter the emergence rate of nevirapine-resistant virus or the magnitude of nevirapine resistance in vitro; however, a different mutation pattern was observed. The clinical relevance of this finding has not been established. Rapid emergence of HIV strains that are cross-resistant to NNRTIs has been observed in vitro. Limited data indicate that nevirapine is active against zidovudine-resistant HIV isolates. Cross-resistance between nevirapine and HIV protease inhibitors is unlikely because the enzyme targets involved are different.
     
    Avoid the use of nevirapine in patients with HIV-2, as HIV-2 is intrinsically resistant to NNRTIs. To identify the HIV strain, The 2014 Centers for Disease Control and Prevention guidelines for HIV diagnostic testing recommend initial HIV testing using an HIV-1/HIV-2 antigen/antibody combination immunoassay and subsequent testing using an HIV-1/HIV-2 antibody differentiation immunoassay.

    PHARMACOKINETICS

    Nevirapine is administered orally. It is highly lipophilic and is widely distributed throughout the body. The drug readily crosses the placenta and is excreted in breast milk. Median breast milk concentrations have been found to be 59% to 88% of maternal plasma concentrations. Protein binding is approximately 60%. The cerebrospinal fluid concentration is about 45% of the corresponding plasma concentration which is approximately equal to the fraction of nevirapine not bound to plasma protein. Metabolism to hydroxylated metabolites occurs primarily via cytochrome P450 (CYP) 3A and 2B6. These metabolites are then further metabolized by glucuronide conjugation. Elimination of nevirapine and its metabolites is mainly in the urine. In radiolabeled pharmacokinetic studies, approximately 91% of a radiolabeled dose was detected in the urine and over 80% of the radioactivity in the urine consisted of glucuronide conjugates of the hydroxylated metabolites. About 10% was recovered in the feces. Less than 3% of the total dose is excreted unchanged in the urine. After a single dose, the terminal elimination half-life is about 45 hours. After multiple dosing with 200 to 400 mg/day, the elimination half-life is decreased to approximately 25 to 30 hours due to induction of hepatic CYP isoenzymes 3A and 2B6. Clearance is also increased 1.5- to 2-fold because of auto-induction. Pharmacokinetic data demonstrate the persistence of detectable drug concentrations for at least 21 days after discontinuation of nevirapine.
     
    Affected cytochrome P450 isoenzymes: CYP3A4, CYP2B6
    Nevirapine induces the hepatic enzymes CYP3A4 and CYP2B6 by approximately 20% to 25%. While primarily an inducer of these enzymes, in vitro data suggests nevirapine may also have mild inhibitory effects on CYP3A4.

    Oral Route

    After administration, nevirapine is readily absorbed with an absolute bioavailability of 91% to 93%. Peak plasma concentrations occur within 4 hours after a single 200 mg dose. After multiple doses, peak plasma concentrations increase linearly in the dose range of 200 to 400 mg/day. Nevirapine tablets and suspension have been shown to be comparably bioavailable and are interchangeable at doses up to 200 mg. Relative to the immediate release products, the bioavailability of the extended-release tablet is approximately 75%; this difference in bioavailability is not considered clinically relevant.