Antiretroviral non-nucleoside reverse transcriptase inhibitor (NNRTI), enzyme inducer
Nevirapine is an antiretroviral medicine used to treat HIV-1 infection, always in combination with other antiretrovirals (never as monotherapy). It blocks viral replication by inhibiting reverse transcriptase. It can cause severe skin rashes and liver damage, especially in the first weeks — requiring close clinical and laboratory monitoring at treatment initiation.
Also known as: Viramune
Combining Nevirapine with Warfarin reduces the anticoagulant effect of Warfarin, posing a risk of thrombotic events.
Nevirapine induces CYP3A4 and CYP2B6 and can accelerate warfarin metabolism, reducing its levels and the INR. The risk is loss of anticoagulation and thromboembolism if the dose is not adjusted; the inducing effect develops over 2–4 weeks and persists after discontinuation. The INR should be monitored frequently at nevirapine initiation and discontinuation and the warfarin dose adjusted accordingly, with vigilance for thrombosis signs.
Nevirapine induces CYP3A4/CYP2B6 and can REDUCE the effect of warfarin. Monitor the INR when starting and stopping the antiretroviral.
As a cytochrome P450 inducer, Nevirapine increases Warfarin metabolism, lowering its concentrations and its effect.
INR monitoring at start and dose changes; signs of thromboembolism.
A high INR with bleeding or signs of thrombosis requires immediate anticoagulant adjustment.
Monitor the INR and adjust the Warfarin dose whenever Nevirapine is started, stopped or changed.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fbd628db-4076-4fe0-8323-9cc33ae92e42 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Nevirapine with Ketoconazole alters the concentrations of both: it raises Nevirapine and lowers Ketoconazole.
Nevirapine, a non-nucleoside reverse transcriptase inhibitor, induces CYP3A4 and lowers ketoconazole concentrations, potentially compromising antifungal treatment; conversely, ketoconazole inhibits CYP3A4 and can raise nevirapine levels, with a higher risk of adverse effects (notably hepatotoxicity and skin rash). The nevirapine label states that ketoconazole and nevirapine should not be administered concomitantly (reduced ketoconazole may compromise antifungal efficacy) and that increased nevirapine exposure warrants close monitoring for adverse effects. If the combination is unavoidable, monitor the clinical response to the fungal infection and liver function/rash.
Ketoconazole + nevirapine: nevirapine lowers ketoconazole levels and the azole raises nevirapine levels. The label advises against the combination; monitor response and liver function.
Nevirapine (an enzyme inducer) lowers Ketoconazole concentrations; Ketoconazole (a CYP3A4 inhibitor) raises Nevirapine concentrations.
Monitor liver function and antifungal efficacy; signs of Nevirapine toxicity (skin rash, hepatitis).
Antifungal failure or raised transaminases require reassessment of the regimen.
Avoid the combination whenever possible; if needed, monitor the therapeutic response and adverse effects of both.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fbd628db-4076-4fe0-8323-9cc33ae92e42 ; approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol adds hepatotoxicity to that of nevirapine, which carries a high risk of severe liver injury.
Avoid alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6e93829-7024-48f6-8023-da6ff27dfc0a
Nevirapine can be taken with or without food, with no relevant change in absorption.
May be taken with or without food, consistently.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6e93829-7024-48f6-8023-da6ff27dfc0a
Nevirapine causes skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, especially in the first weeks.
Stop immediately with a severe rash, blistering or mucosal involvement.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6e93829-7024-48f6-8023-da6ff27dfc0a
Nevirapine causes severe hepatotoxicity, especially in the first 18 weeks and in women with high CD4 counts; prior liver disease increases the risk.
Monitor transaminases in the first weeks; stop with liver injury or hepatitis symptoms.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6e93829-7024-48f6-8023-da6ff27dfc0a
Nevirapine is used in pregnancy as part of HIV antiretroviral therapy; the hepatotoxicity risk is higher in women with high CD4 counts.
Use in pregnancy as part of the antiretroviral regimen, with close hepatic monitoring in the first weeks.
Excreted into breast milk; in HIV infection breastfeeding is not recommended regardless of treatment.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Nevirapine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6e93829-7024-48f6-8023-da6ff27dfc0a
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1, used in combination with other antiretrovirals. Serious risk of hepatotoxicity (including hepatic failure) and severe skin reactions (SJS/TEN), especially in the first weeks — requires close monitoring.
Binds directly to an allosteric site of HIV-1 reverse transcriptase, inducing a conformational change that inhibits viral polymerase activity (does not compete with nucleosides). No clinical activity against HIV-2.
Rapid absorption (>90%) after oral administration; absolute bioavailability 93±9%; plasma peak 2±0.4 mcg/mL ~4 h after 200 mg; food, antacids and didanosine do not alter absorption. Reaches ~45% of the plasma concentration in CSF; crosses the placenta and passes into breast milk.
Extensive hepatic metabolism (CYP3A4 and CYP2B6) with CYP3A4 autoinduction (accelerates its own metabolism with repeated dosing); hydroxylated metabolites excreted in urine (~80%) and faeces (~10%). Relevant pharmacokinetic interactions (CYP3A4 inducer).
Elimination half-life ~45 h after a single dose, decreasing to ~25-30 h with multiple dosing of 200-400 mg/day (enzyme autoinduction).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
