Viramune

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)s

Never administer more than one form of nevirapine (e.g., immediate-release and extended-release) at the same time.
Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.

Oral Administration

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.

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

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.

Viramune, Viramune Suspension, Viramune XR

Rx

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

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, 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) Adults

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

Adolescents

200 mg PO once daily for 14 days, then 200 mg PO twice daily. The FDA-approved dose is 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for 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 14 days, then 120 to 150 mg/m2/dose (Max: 200 mg/dose) PO twice daily. The FDA-approved dose is 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for 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 14 days, then 200 mg/m2/dose (Max: 200 mg/dose) PO twice daily. The FDA-approved dose is 150 mg/m2/dose (Max: 200 mg/dose) PO once daily for 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.

Neonates 37 weeks gestation and older and 15 to 29 days postnatal age

6 mg/kg/dose PO twice daily. 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 dose is 150 mg/m2/dose PO once daily for 14 days, then 150 mg/m2/dose PO twice daily.

Neonates 37 weeks gestation and older and 0 to 14 days postnatal age†

6 mg/kg/dose PO twice daily. 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.

Neonates 34 to 36 weeks gestation and older than 4 weeks postnatal age†

200 mg/m2/dose PO twice daily.

Neonates 34 to 36 weeks gestation and 1 to 4 weeks postnatal age†

6 mg/kg/dose PO twice daily. 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.

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

4 mg/kg/dose PO twice daily. 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.

Neonates 32 to 33 weeks gestation and older than 6 weeks postnatal age†

200 mg/m2/dose PO twice daily.

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

6 mg/kg/dose PO twice daily. This is an investigational dose based on PK modeling and simulation data from IMPAACT P1106 and P1115 trials.

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

4 mg/kg/dose PO twice daily. This is an investigational dose based on PK modeling and simulation data from IMPAACT P1106 and P1115 trials.

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

2 mg/kg/dose PO twice daily. This is an investigational dose based on PK modeling and simulation data from IMPAACT P1106 and P1115 trials.

Oral dosage (extended-release) Adults

400 mg PO once daily for persons switching from twice daily immediate-release nevirapine or once daily nevirapine after lead-in dosing for 14 days.[43831]

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

400 mg PO once daily for persons switching from twice daily immediate-release nevirapine or once daily nevirapine after lead-in dosing for 14 days.

For perinatal human immunodeficiency virus (HIV) prophylaxis† in neonates at high risk for HIV acquisition.
NOTE: Presumptive therapy with a 3-drug combination antiretroviral (ARV) regimen, consisting of zidovudine, lamivudine, and either nevirapine or raltegravir at treatment doses, is recommended for 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) and neonates born to HIV-infected mothers who have not received ARV treatment, who have received only intrapartum ARV treatment, who have suboptimal viral suppression (defined as at least 2 consecutive tests with HIV RNA less than 50 copies/mL obtained at least 4 weeks apart within 4 weeks of delivery), or who have acute or primary HIV infection during pregnancy or breastfeeding. Consider raltegravir use in the 3-drug combination ARV prophylaxis regimen if the mother has HIV-1 and HIV-2 infection, since HIV-2 is not susceptible to nevirapine. A 2-drug ARV prophylaxis regimen with 3 doses of nevirapine (prophylaxis dosage) and 6 weeks of zidovudine may also be considered based on clinical scenario.
NOTE: The ARV regimen for newborns born to mothers with known or suspected drug resistance should be determined in consultation with a pediatric HIV specialist before delivery or through consultation via the National Perinatal HIV hotline (1-888-448-8765). Additionally, no evidence exists that shows that neonatal prophylaxis regimens customized based on presence of maternal drug resistance are more effective than standard neonatal prophylaxis regimens. Oral dosage (3-Drug Combination Antiretroviral Prophylaxis Regimen) Neonates 37 weeks gestation and older and 0 to 4 weeks

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, including breastfeeding. 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.

Neonates 34 to 36 weeks gestation and 1 to 4 weeks

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, including breastfeeding. 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.

Neonates 34 to 36 weeks gestation and 0 to 6 days

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, including breastfeeding. 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 4 to 6 weeks

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, including breastfeeding. 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.

Neonates 32 to 33 weeks gestation and 14 to 27 days

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, including breastfeeding. 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

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, including breastfeeding. 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]

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]

For human immunodeficiency virus (HIV) prophylaxis† to prevent mother-to-child transmission (MTCT) during breastfeeding. For human immunodeficiency virus (HIV) prophylaxis† in infants at low risk of HIV acquisition during breastfeeding.
NOTE: Nevirapine is recommended as an optional postnatal prophylaxis regimen for infants at low risk of HIV acquisition during breastfeeding. If prescribed, these simplified doses can be given from birth after confirmation of a negative infant NAT test. Optimal treatment duration has not been established. Some recommend only 6 weeks of nevirapine treatment while others recommend continuing nevirapine treatment throughout breastfeeding. Treatment can be given for 1 to 4 weeks after weaning.
Oral dosage (suspension) Infants and Children 9 to 24 months

40 mg PO once daily.

Infants 6 to 9 months

30 mg PO once daily.

Infants 6 weeks to 6 months

20 mg PO once daily.

Infants younger than 6 weeks

15 mg PO once daily.

Neonates

15 mg PO once daily.

For human immunodeficiency virus (HIV) prophylaxis† in infants at high risk of HIV acquisition during breastfeeding.
NOTE: Extended postnatal prophylaxis with nevirapine is recommended for infants of women with unsuppressed viral load who choose to breastfeed. If prescribed, these simplified doses should start after confirmation of a negative infant NAT test and after completion of 6 weeks of presumptive HIV therapy. Treatment should continue during breastfeeding and for 1 to 4 weeks after weaning to minimize the risk of transmission.
Oral dosage (suspension) Infants and Children 9 to 24 months

40 mg PO once daily.

Infants 6 to 9 months

30 mg PO once daily.

Infants 6 weeks to 6 months

20 mg PO once daily.

†Indicates off-label use

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.

Abacavir; Dolutegravir; Lamivudine: (Major) Avoid concurrent use of nevirapine and dolutegravir. Concomitant use may decrease plasma concentrations of dolutegravir and there are insufficient data to make dosing recommendations. Dolutegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Acetaminophen; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
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 CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with adagrasib is necessary. Nevirapine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A inhibitor may also increase nevirapine exposure.
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) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with nevirapine is necessary. If nevirapine is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A inducer like nevirapine with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Alprazolam: (Minor) Monitor for reduced efficacy of alprazolam if coadministration with nevirapine is necessary. Concomitant use may decrease alprazolam exposure. Alprazolam is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Amiodarone: (Minor) Monitor for decreased efficacy of amiodarone if coadministration with nevirapine is necessary; concomitant use may decrease amiodarone plasma concentrations. Amiodarone is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Amlodipine; Atorvastatin: (Moderate) Monitor for reduced cholesterol-lowering efficacy of atorvastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease atorvastatin exposure. Atorvastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of nevirapine and clarithromycin. 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. Additionally, the exposure of nevirapine may also be increased, leading to increased toxicity. Nevirapine is a CYP3A4 substrate and clarithromycin 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.
Apalutamide: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with apalutamide. 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 CYP3A substrate and apalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased nevirapine exposure by greater than 50%.
Aripiprazole: (Moderate) Monitor for decreased efficacy of aripiprazole if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease aripiprazole exposure. Aripiprazole is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Artemether; Lumefantrine: (Moderate) Monitor for reduced efficacy or increased toxicity of artemether; lumefantrine if coadministration with nevirapine is necessary. Concomitant use may alter the exposure of artemether and lumefantrine. Artemether and lumefantrine are CYP3A substrates and nevirapine is a weak CYP3A inducer. Coadministration with nevirapine decreased artemether exposure by 67% to 72% and lumefantrine exposure by 25% to 58%. Another study reported a 50% to 56% increase in lumefantrine exposure.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
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 CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Major) Do not coadminister atazanavir and nevirapine. Coadministration leads to substantially decreased atazanavir concentrations 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. (Major) Do not coadminister atazanavir and nevirapine. Coadministration leads to substantially decreased atazanavir concentrations and increased nevirapine concentrations, which could lead to toxicity.
Atogepant: (Major) Avoid use of atogepant and nevirapine when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with nevirapine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
Atorvastatin: (Moderate) Monitor for reduced cholesterol-lowering efficacy of atorvastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease atorvastatin exposure. Atorvastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Atorvastatin; Ezetimibe: (Moderate) Monitor for reduced cholesterol-lowering efficacy of atorvastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease atorvastatin exposure. Atorvastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Avanafil: (Major) Coadministration of avanafil with nevirapine is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and nevirapine is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Barbiturates: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with barbiturates. Concurrent use may decrease the plasma concentrations of nevirapine leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Concomitant use may also decrease the barbiturate concentration. Monitor concentrations closely during coadministration of nevirapine; dose adjustments may be needed. Nevirapine is a CYP3A substrate and weak CYP3A inducer; barbiturates are strong CYP3A inducers. Coadministration with another strong CYP3A inducer decreased nevirapine exposure by greater than 50%.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for reduced efficacy of benzhydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of benzhydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of benzhydrocodone and frequently monitor for signs of respiratory depression and sedation. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Brexpiprazole: (Moderate) Monitor for decreased efficacy of brexpiprazole if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease brexpiprazole exposure. Brexpiprazole is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Bupivacaine; Lidocaine: (Minor) Monitor for reduced efficacy of lidocaine if coadministration with nevirapine is necessary. Concomitant use may decrease lidocaine exposure. Lidocaine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with nevirapine is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If nevirapine is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A substrate and nevirapine is a CYP3A inducer.
Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with nevirapine is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If nevirapine is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A substrate and nevirapine is a CYP3A inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
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. Concomitant use may also cause a significant decrease in rilpivirine plasma concentrations and, thus, a loss of therapeutic effect. Rilpivirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Carbamazepine: (Major) Coadministration of carbamazepine and nevirapine is not recommended due to the potential for loss of virologic response and possible resistance to nevirapine. Nevirapine may also decrease plasma concentrations of carbamazepine. If concurrent use is necessary, monitor carbamazepine concentrations and virologic response. Nevirapine is a CYP3A substrate and weak CYP3A inducer; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Cariprazine: (Major) Coadministration of cariprazine with nevirapine is not recommended as the net effect of CYP3A induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Coadministration of cariprazine with CYP3A inducers has not been evaluated.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of tramadol as needed. If nevirapine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
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.
Chloramphenicol: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with chloramphenicol is necessary. Nevirapine is a CYP3A4 substrate and chloramphenicol 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.
Chlorpheniramine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Cisapride: (Minor) Monitor for reduced efficacy of cisapride if coadministration with nevirapine is necessary. Concomitant use may decrease cisapride exposure. Cisapride is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Clarithromycin: (Major) Avoid coadministration of nevirapine and clarithromycin. 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. Additionally, the exposure of nevirapine may also be increased, leading to increased toxicity. Nevirapine is a CYP3A4 substrate and clarithromycin 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.
Clonazepam: (Minor) Monitor for reduced efficacy of clonazepam if coadministration with nevirapine is necessary. Concomitant use may decrease clonazepam exposure. Clonazepam is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Clozapine: (Moderate) Monitor for loss of clozapine effectiveness if coadministered with nevirapine. Consideration should be given to increasing the clozapine dose if necessary. When nevirapine is discontinued, reduce the clozapine dose based on clinical response. Nevirapine is a weak inducer of CYP3A, one of the isoenzymes responsible for the metabolism of clozapine.
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.
Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with nevirapine is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If nevirapine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Nevirapine is a weak CYP3A inducer. Concomitant use with nevirapine can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
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: (Moderate) Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with nevirapine is necessary. Concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. Cyclosporine is extensively metabolized by CYP3A and has a narrow therapeutic index; nevirapine is a weak CYP3A inducer.
Darunavir: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with darunavir is necessary. Nevirapine is a CYP3A4 substrate and darunavir 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.
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) Monitor for an increase in nevirapine-related adverse reactions if coadministration with darunavir is necessary. Nevirapine is a CYP3A4 substrate and darunavir 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.
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) Monitor for an increase in nevirapine-related adverse reactions if coadministration with darunavir is necessary. Nevirapine is a CYP3A4 substrate and darunavir 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.
Delavirdine: (Major) Coadministration of nevirapine and delavirdine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in delavirdine plasma concentrations and, thus, a loss of therapeutic effect. Delavirdine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
Dexamethasone: (Moderate) Monitor for a decrease in nevirapine efficacy during concurrent use of nevirapine and dexamethasone. If long term coadministration is required, consider using an alternative corticosteroid, such as prednisone or prednisolone. Concomitant use may decrease nevirapine exposure leading to potential loss of virologic control. Nevirapine is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
Diazepam: (Moderate) Monitor patients for decreased efficacy of diazepam if coadministration with nevirapine is necessary. Concurrent use may decrease diazepam exposure. Diazepam is a CYP3A substrate and nevirapine is a CYP3A inducer.
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.
Disopyramide: (Minor) Monitor for reduced efficacy of disopyramide if coadministration with nevirapine is necessary. Concomitant use may decrease disopyramide exposure. Disopyramide is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Dolutegravir: (Major) Avoid concurrent use of nevirapine and dolutegravir. Concomitant use may decrease plasma concentrations of dolutegravir and there are insufficient data to make dosing recommendations. Dolutegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Dolutegravir; Lamivudine: (Major) Avoid concurrent use of nevirapine and dolutegravir. Concomitant use may decrease plasma concentrations of dolutegravir and there are insufficient data to make dosing recommendations. Dolutegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Dolutegravir; Rilpivirine: (Major) Avoid concurrent use of nevirapine and dolutegravir. Concomitant use may decrease plasma concentrations of dolutegravir and there are insufficient data to make dosing recommendations. Dolutegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer. (Major) Coadministration of nevirapine and rilpivirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in rilpivirine plasma concentrations and, thus, a loss of therapeutic effect. Rilpivirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Doravirine: (Major) Coadministration of nevirapine and doravirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in doravirine plasma concentrations and, thus, a loss of therapeutic effect. Doravirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Coadministration of nevirapine and doravirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in doravirine plasma concentrations and, thus, a loss of therapeutic effect. Doravirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
Efavirenz: (Major) Coadministration of nevirapine and efavirenz is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a decrease in plasma concentrations of efavirenz and, thus, a loss of therapeutic effect. The pharmacokinetics of nevirapine appear to be unaffected. Nevirapine is a CYP3A substrate and weak CYP3A inducer. Efavirenz is a CYP3A substrate and moderate CYP3A inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of nevirapine and efavirenz is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a decrease in plasma concentrations of efavirenz and, thus, a loss of therapeutic effect. The pharmacokinetics of nevirapine appear to be unaffected. Nevirapine is a CYP3A substrate and weak CYP3A inducer. Efavirenz is a CYP3A substrate and moderate CYP3A inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of nevirapine and efavirenz is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a decrease in plasma concentrations of efavirenz and, thus, a loss of therapeutic effect. The pharmacokinetics of nevirapine appear to be unaffected. Nevirapine is a CYP3A substrate and weak CYP3A inducer. Efavirenz is a CYP3A substrate and moderate CYP3A inducer.
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) Avoid concurrent use of nevirapine and elbasvir. Concomitant use may decrease plasma concentrations of elbasvir, resulting in decreased virologic response. Elbasvir is a CYP3A substrate and nevirapine is a weak CYP3A inducer. (Major) Avoid concurrent use of nevirapine and grazoprevir. Concomitant use may decrease plasma concentrations of grazoprevir, resulting in decreased virologic response. Grazoprevir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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 concurrent use of nevirapine and elvitegravir. Concomitant use may decrease plasma concentrations of elvitegravir resulting in loss of antiviral efficacy and potentially the development of viral resistance. Elvitegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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 concurrent use of nevirapine and elvitegravir. Concomitant use may decrease plasma concentrations of elvitegravir resulting in loss of antiviral efficacy and potentially the development of viral resistance. Elvitegravir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Empagliflozin; Linagliptin: (Minor) Monitor for reduced efficacy of linagliptin if coadministration with nevirapine is necessary. Concomitant use may decrease linagliptin exposure.
Empagliflozin; Linagliptin; Metformin: (Minor) Monitor for reduced efficacy of linagliptin if coadministration with nevirapine is necessary. Concomitant use may decrease linagliptin exposure.
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. Concomitant use may also cause a significant decrease in rilpivirine plasma concentrations and, thus, a loss of therapeutic effect. Rilpivirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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. Concomitant use may also cause a significant decrease in rilpivirine plasma concentrations and, thus, a loss of therapeutic effect. Rilpivirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Enzalutamide: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with enzalutamide. 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 CYP3A substrate and enzalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased nevirapine exposure by greater than 50%.
Erythromycin: (Moderate) Monitor for nevirapine-related side effects and decreased erythromycin efficacy if nevirapine and erythromycin are coadministered. Concomitant use may increase nevirapine exposure and decrease erythromycin exposure. Nevirapine is a CYP3A substrate and weak CYP3A inducer; erythromycin is a moderate CYP3A inhibitor.
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 weak CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
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: (Minor) Monitor for reduced efficacy of ethosuximide and seizure control if coadministration with nevirapine is necessary. Concomitant use may decrease ethosuximide exposure. Ethosuximide is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Ethotoin: (Major) Coadministration of phenytoin or fosphenytoin and nevirapine is not recommended due to the potential for loss of virologic response and possible resistance to nevirapine. Nevirapine may also decrease plasma concentrations of phenytoin/fosphenytoin. If concurrent use is necessary, monitor phenytoin concentrations and virologic response. Nevirapine is a CYP3A substrate and phenytoin/fosphenytoin are strong CYP3A inducers.
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) Coadministration of nevirapine and etravirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in etravirine plasma concentrations and, thus, a loss of therapeutic effect. Etravirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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 CYP3A substrate and nevirapine is a weak CYP3A inducer.
Ezetimibe; Simvastatin: (Moderate) Monitor for reduced cholesterol-lowering efficacy of simvastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease simvastatin exposure. Simvastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
Finasteride; Tadalafil: (Moderate) Monitor for reduced efficacy of tadalafil if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease tadalafil exposure. Tadalafil is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Fluconazole: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with fluconazole is necessary. Nevirapine is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with fluconazole increased nevirapine exposure by 100%.
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. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with fosamprenavir is necessary. Nevirapine is a CYP3A4 substrate and weak CYP3A inducer; fosamprenavir is a CYP3A 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.
Fosphenytoin: (Major) Coadministration of phenytoin or fosphenytoin and nevirapine is not recommended due to the potential for loss of virologic response and possible resistance to nevirapine. Nevirapine may also decrease plasma concentrations of phenytoin/fosphenytoin. If concurrent use is necessary, monitor phenytoin concentrations and virologic response. Nevirapine is a CYP3A substrate and phenytoin/fosphenytoin are strong CYP3A inducers.
Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydantoins: (Major) Coadministration of phenytoin or fosphenytoin and nevirapine is not recommended due to the potential for loss of virologic response and possible resistance to nevirapine. Nevirapine may also decrease plasma concentrations of phenytoin/fosphenytoin. If concurrent use is necessary, monitor phenytoin concentrations and virologic response. Nevirapine is a CYP3A substrate and phenytoin/fosphenytoin are strong CYP3A inducers.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of hydrocodone as needed. If nevirapine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
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 CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with idelalisib is necessary. Nevirapine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CY

P3A4 inhibitor may also increase nevirapine exposure.
Indinavir: (Major) Coadministration of nevirapine and indinavir may result in decreased indinavir exposure; however, an appropriate dose of indinavir when coadministered with nevirapine has not been established. Additionally, concomitant use may increase the exposure of nevirapine. Monitor for an increase in nevirapine-related adverse reactions if coadministration with indinavir is necessary. Nevirapine is a CYP3A4 substrate and weak CYP3A inducer; indinavir is a CYP3A 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.
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-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: (Moderate) Monitor for decreased efficacy of isavuconazonium if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease isavuconazonium exposure. Isavuconazonium is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of nevirapine and rifampin. Concurrent use may decrease nevirapine exposure and increase the risk for virologic failure and drug resistance. Nevirapine is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the AUC of nevirapine by greater than 50%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of nevirapine and rifampin. Concurrent use may decrease nevirapine exposure and increase the risk for virologic failure and drug resistance. Nevirapine is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the AUC of nevirapine by greater than 50%.
Isradipine: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with nevirapine is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Itraconazole: (Major) Avoid coadministration of nevirapine and itraconazole. Concurrent use may result in decreases in itraconazole plasma concentrations that may reduce efficacy of the drug. If concurrent use cannot be avoided, monitor for decreased efficacy of itraconazole and increase the dose of itraconazole as necessary. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with itraconazole is necessary. Itraconazole is a CYP3A substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and CYP3A inducer.
Ketoconazole: (Major) Avoid coadministration of nevirapine and ketoconazole. Concurrent use may result in decreases in ketoconazole plasma concentrations that may reduce efficacy of the drug. If concurrent use cannot be avoided, monitor for decreased efficacy of ketoconazole and increase the dose of ketoconazole as necessary. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with ketoconazole is necessary. Ketoconazole is a CYP3A substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and CYP3A inducer. Coadministration results in a 15% to 30% increase in nevirapine plasma concentrations and a 63% reduction in ketoconazole AUC.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of nevirapine and clarithromycin. 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. Additionally, the exposure of nevirapine may also be increased, leading to increased toxicity. Nevirapine is a CYP3A4 substrate and clarithromycin 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.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and nevirapine due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance.
Letermovir: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with letermovir and cyclosporine is necessary. 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. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
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.
Levoketoconazole: (Major) Avoid coadministration of nevirapine and ketoconazole. Concurrent use may result in decreases in ketoconazole plasma concentrations that may reduce efficacy of the drug. If concurrent use cannot be avoided, monitor for decreased efficacy of ketoconazole and increase the dose of ketoconazole as necessary. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with ketoconazole is necessary. Ketoconazole is a CYP3A substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and CYP3A inducer. Coadministration results in a 15% to 30% increase in nevirapine plasma concentrations and a 63% reduction in ketoconazole AUC.
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.
Levonorgestrel; 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.
Lidocaine: (Minor) Monitor for reduced efficacy of lidocaine if coadministration with nevirapine is necessary. Concomitant use may decrease lidocaine exposure. Lidocaine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Lidocaine; Epinephrine: (Minor) Monitor for reduced efficacy of lidocaine if coadministration with nevirapine is necessary. Concomitant use may decrease lidocaine exposure. Lidocaine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Lidocaine; Prilocaine: (Minor) Monitor for reduced efficacy of lidocaine if coadministration with nevirapine is necessary. Concomitant use may decrease lidocaine exposure. Lidocaine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Linagliptin: (Minor) Monitor for reduced efficacy of linagliptin if coadministration with nevirapine is necessary. Concomitant use may decrease linagliptin exposure.
Linagliptin; Metformin: (Minor) Monitor for reduced efficacy of linagliptin if coadministration with nevirapine is necessary. Concomitant use may decrease linagliptin exposure.
Lonafarnib: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with lonafarnib is necessary. Nevirapine is a CYP3A4 substrate and lonafarnib 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.
Lopinavir; Ritonavir: (Major) Increase the dose of lopinavir; ritonavir to 500/125 mg or 600/150 mg (tablets) or 520/130 mg (solution) twice daily in adults and pediatric patients weighing more than 45 kg if concomitant use with nevirapine is necessary; do not use once daily administration. For pediatric patients weighing less than 45 kg, use 300 mg/75 mg per m2/dose PO twice daily (solution) if concomitant use with nevirapine is necessary. Concomitant use may decrease the plasma concentrations of lopinavir, resulting in decreased efficacy. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with nevirapine. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with ritonavir is necessary. Ritonavir is a CYP3A substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and weak CYP3A inducer. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Lovastatin: (Moderate) Monitor for reduced cholesterol-lowering efficacy of lovastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease lovastatin exposure. Lovastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Lumacaftor; Ivacaftor: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with lumacaftor; ivacaftor . 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 CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased nevirapine exposure by greater than 50%.
Lumacaftor; Ivacaftor: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with lumacaftor; ivacaftor . 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 CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased nevirapine exposure by greater than 50%.
Lumateperone: (Major) Avoid coadministration of lumateperone and nevirapine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A substrate; nevirapine is a weak CYP3A inducer. Although data are unavailable for weak CYP3A inducers, coadministration with a strong CYP3A inducer significantly decreased lumateperone exposure.
Lurasidone: (Minor) Monitor for reduced efficacy of lurasidone if coadministration with nevirapine is necessary. Concomitant use may decrease lurasidone exposure. Lurasidone is a CYP3A substrate and nevirapine is a weak 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) Use mefloquine with caution if coadministration with nevirapine is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Meperidine: (Moderate) Monitor for reduced efficacy of meperidine and signs of opioid withdrawal if coadministration with nevirapine is necessary. Consider increasing the dose of meperidine as needed. If nevirapine is discontinued, consider a dose reduction of meperidine and frequently monitor for signs of respiratory depression and sedation. Meperidine is a substrate of CYP3A; nevirapine is a weak CYP3A inducer. Concomitant use can decrease meperidine exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with nevirapine is necessary. Consider increasing the dose of methadone as needed. If nevirapine is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; nevirapine is a weak CYP3A inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Midazolam: (Minor) Monitor for reduced efficacy of midazolam if coadministration with nevirapine is necessary. Concomitant use may decrease midazolam exposure. Midazolam is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Mitotane: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with mitotane. 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 CYP3A substrate and mitotane is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased nevirapine exposure by greater than 50%.
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 CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with nevirapine. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nefazodone: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with nefazodone is necessary. Nevirapine is a CYP3A4 substrate and nefazodone 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.
Nelfinavir: (Major) Coadministration of nevirapine and nelfinavir may result in decreased nelfinavir exposure; however, an appropriate dose of nelfinavir when coadministered with nevirapine has not been established. Coadministration of nevirapine and nelfinavir resulted in a 62% decrease in the AUC of nelfinavir-M8 metabolite. Additionally, concomitant use may increase the exposure of nevirapine. Monitor for an increase in nevirapine-related adverse reactions if coadministration with nelfinavir is necessary. Nevirapine is a CYP3A4 substrate and weak CYP3A inducer; nelfinavir is a CYP3A 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.
Niacin; Simvastatin: (Moderate) Monitor for reduced cholesterol-lowering efficacy of simvastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease simvastatin exposure. Simvastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nimodipine: (Moderate) Monitor for decreased efficacy of nimodipine if coadministration with nevirapine is necessary as concomitant use may decrease plasma concentrations of nimodipine. Nimodipine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nirmatrelvir; Ritonavir: (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 CYP3A inducer. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with nevirapine. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with ritonavir is necessary. Ritonavir is a CYP3A substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and weak CYP3A inducer. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with nevirapine as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and nevirapine is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
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.
Orlistat: (Major) Monitor HIV RNA concentrations frequently during concurrent use of orlistat and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Discontinue orlistat if an increased HIV viral load is confirmed. Loss of virological control has been reported in persons with HIV infection taking orlistat with antiretrovirals, including NNRTIs. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the antiretroviral agent.
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 CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paclitaxel: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with nevirapine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
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 phenytoin or fosphenytoin and nevirapine is not recommended due to the potential for loss of virologic response and possible resistance to nevirapine. Nevirapine may also decrease plasma concentrations of phenytoin/fosphenytoin. If concurrent use is necessary, monitor phenytoin concentrations and virologic response. Nevirapine is a CYP3A substrate and phenytoin/fosphenytoin are strong CYP3A inducers.
Pimavanserin: (Major) Avoid coadministration of pimavanserin with nevirapine as concurrent use may decrease pimavanserin exposure which may lead to decreased efficacy. Pimavanserin is a CYP3A4 substrate and nevirapine is a weak CYP3A4 inducer.
Posaconazole: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with posaconazole is necessary. Nevirapine is a CYP3A4 substrate and posaconazole 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.
Praziquantel: (Moderate) Monitor for reduced response to praziquantel if coadministered with nevirapine. Concomitant use may produce therapeutically ineffective concentrations of praziquantel. In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism; nevirapine is a weak CYP3A4 inducer.
Prednisone: (Major) The use of prednisone to prevent nevirapine-associated rash is not recommended. 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.
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.
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: (Moderate) The concomitant use of ribavirin and antiretroviral 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: (Major) Avoid coadministration of nevirapine and rifampin. Concurrent use may decrease nevirapine exposure and increase the risk for virologic failure and drug resistance. Nevirapine is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased the AUC of nevirapine by greater than 50%.
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. Concomitant use may also cause a significant decrease in rilpivirine plasma concentrations and, thus, a loss of therapeutic effect. Rilpivirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with nevirapine. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Additionally, monitor for an increase in nevirapine-related adverse reactions if coadministration with ritonavir is necessary. Ritonavir is a CYP3A substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and weak CYP3A inducer. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Rivaroxaban: (Major) Coadministration of rivaroxaban and nevirapine may result in decreased rivaroxaban exposure and reduced efficacy of rivaroxaban. Alternative anticoagulant therapy should be considered. Rivaroxaban is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
Saquinavir: (Major) Coadministration of saquinavir with nevirapine is not recommended as there is a potential for decreased saquinavir concentrations, which may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Additionally, the exposure of nevirapine may also be increased, leading to increased toxicity. Saquinavir is a CYP3A4 substrate and strong CYP3A inhibitor; nevirapine is a CYP3A substrate and weak CYP3A4 inducer.
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.
Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with nevirapine is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and nevirapine is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Simvastatin: (Moderate) Monitor for reduced cholesterol-lowering efficacy of simvastatin if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease simvastatin exposure. Simvastatin is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of nevirapine. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Sofosbuvir; Velpatasvir: (Major) Avoid concurrent use of nevirapine and velpatasvir. Concomitant use may decrease plasma concentrations of velpatasvir, resulting in decreased virologic response. Velpatasvir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent use of nevirapine and velpatasvir. Concomitant use may decrease plasma concentrations of velpatasvir, resulting in decreased virologic response. Velpatasvir is a CYP3A substrate and nevirapine is a weak CYP3A inducer. (Major) Avoid concurrent use of nevirapine and voxilaprevir. Concomitant use may decrease plasma concentrations of voxilaprevir, resulting in decreased virologic response. Voxilaprevir is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
St. John's Wort, Hypericum perforatum: (Major) Concomitant use of nevirapine and St. John's Wort is not recommended. 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 St. John's Wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nevirapine exposure by greater than 50%.
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 of respiratory depression and sedation. Sufentanil is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A 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: (Moderate) Monitor tacrolimus serum concentrations as appropriate if coadministration with nevirapine is necessary; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus concentrations. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range and nevirapine is a weak CYP3A4 inducer.
Tadalafil: (Moderate) Monitor for reduced efficacy of tadalafil if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease tadalafil exposure. Tadalafil is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of tramadol as needed. If nevirapine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with nevirapine is necessary; consider increasing the dose of tramadol as needed. If nevirapine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and nevirapine is a weak CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Triazolam: (Minor) Monitor for reduced efficacy of triazolam if coadministration with nevirapine is necessary. Concomitant use may decrease triazolam exposure. Triazolam is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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 weak CYP3A4 inducer.
Ulipristal: (Major) Avoid coadministration of ulipristal with nevirapine. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A and nevirapine is a CYP3A inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of nevirapine and clarithromycin. 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. Additionally, the exposure of nevirapine may also be increased, leading to increased toxicity. Nevirapine is a CYP3A4 substrate and clarithromycin 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.
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 CYP3A substrate and weak CYP3A inducer. Voriconazole is a CYP3A substrate and strong CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
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. The R-enantiomer of warfarin is a CYP3A substrate and nevirapine is a CYP3A inducer. 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.

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

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; safety and efficacy have not been established for extended-release tablet.

Children

8 to 12 years and BSA 1.17 m2 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 m2: 300 mg/m2/day (Max: 400 mg/day) PO for immediate release formulations; safety and efficacy have not been established for extended-release tablet.
6 to 7 years and BSA 1.17 m2 or more: doses up to 400 mg/m2/day PO for immediate release formulations are recommended off-label, although 300 mg/m2/day PO is the FDA-approved maximum; 400 mg/day PO for extended-release tablet.
6 to 7 years and BSA less than 1.17 m2: doses up to 400 mg/m2/day PO for immediate release formulations are recommended off-label, although 300 mg/m2/day PO is the FDA-approved maximum; safety and efficacy have not been established for extended-release tablet.
1 to 5 years: doses up to 400 mg/m2/day PO for immediate release formulations are recommended off-label, although 300 mg/m2/day PO is the FDA-approved maximum; safety and efficacy have not been established for extended-release tablet.

Infants

12 mg/kg/day PO is recommended off-label for perinatal prophylaxis and treatment, although 300 mg/m2/day PO is the FDA-approved dose for treatment.

Neonates

15 days and older: Doses of 8 mg/kg/day PO for neonates 32 to 33 weeks gestation and 12 mg/kg/day PO for neonates 34 weeks gestation and older are recommended off-label for perinatal prophylaxis and treatment, although 300 mg/m2/day PO is the FDA-approved dose for treatment.
7 to 14 days: Safety and efficacy have not been established; however, doses of 4 mg/kg/day PO for neonates 32 to 33 weeks gestation and 12 mg/kg/day PO for neonates 34 weeks gestation and older are recommended off-label for perinatal prophylaxis and treatment.
0 to 6 days: Safety and efficacy have not been established; however, doses of 4 mg/kg/day PO for neonates 32 to 33 weeks gestation, 8 mg/kg/day PO for neonates 34 to 36 weeks gestation, and 12 mg/kg/day PO for neonates 37 weeks gestation and older are recommended off-label for perinatal prophylaxis and treatment. Three doses of 8 mg PO (weight 1.5 to 2 kg) or 12 mg PO (weight more than 2 kg) given within first week of life (birth, 48 hours later, and 96 hours after second dose) also recommended off-label for perinatal prophylaxis.

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.

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.

Pregnancy

Antiretroviral therapy should be provided to all patients 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. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. According to HIV guidelines, nevirapine-containing regimens should not be initiated in pregnant patients. However, it may be appropriate to continue use of the drug in some virally suppressed pregnant patients. 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. Patients 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 patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. 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 patients 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 patients 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 patients 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 patient 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.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants 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, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). 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.