NEVIRAPINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to HIV-1 reverse transcriptase, causing a conformational change that inhibits enzyme activity and viral replication.
| Metabolism | Extensively metabolized by hepatic cytochrome P450 enzymes, primarily CYP3A4 and CYP2B6, to inactive metabolites. |
| Excretion | Renal: <5% unchanged; hepatic metabolism to inactive glucuronide metabolites, primarily excreted in urine (80%) and feces (10%). |
| Half-life | Terminal elimination half-life: 25-30 hours after single dose; decreases to 20-25 hours with multiple dosing due to autoinduction of CYP3A4 and CYP2B6. |
| Protein binding | 60% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 1.2 ± 0.4 L/kg; indicates extensive tissue distribution, including penetration into CSF (45-75% of plasma concentration). |
| Bioavailability | Oral: >90% (absolute bioavailability). |
| Onset of Action | Oral: Not applicable as it is not indicated for acute treatment; antiretroviral effect occurs within days, but clinical virologic suppression typically takes 2-4 weeks. |
| Duration of Action | Due to long half-life, therapeutic plasma concentrations persist for 24-48 hours after last dose; dosing interval is 12 hours to maintain trough above IC50. |
200 mg orally once daily for 14 days, then 200 mg orally twice daily (immediate-release); 400 mg orally once daily (extended-release). Administered in combination with other antiretroviral agents.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥20 mL/min. For hemodialysis patients, an additional 200 mg dose after dialysis is recommended if using immediate-release. Avoid extended-release in hemodialysis. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Contraindicated. Child-Pugh C: Contraindicated. Discontinue if severe hepatic events occur. |
| Pediatric use | For children ≥15 days and ≥4 kg: immediate-release suspension based on BSA or weight (e.g., 150 mg/m² once daily for 14 days, then 150 mg/m² twice daily). Maximum 200 mg twice daily. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related hepatic, renal, or cardiac impairment and potential for decreased tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Induces CYP3A4 decreasing levels of many drugs Can cause severe skin reactions and hepatotoxicity.
| Breastfeeding | Nevirapine is excreted into human breast milk with an M/P ratio of approximately 0.7. Breastfeeding is generally not recommended for HIV-infected mothers in settings where formula is available to avoid postnatal transmission of HIV. If breastfeeding is unavoidable, nevirapine is considered compatible with breastfeeding due to low levels in milk, but the infant should be monitored for adverse effects such as rash or hepatotoxicity. |
| Teratogenic Risk | Nevirapine is classified as FDA Pregnancy Category B. Animal studies have not shown teratogenic effects, but there are no adequate human studies in the first trimester. In the second and third trimesters, nevirapine is used for prevention of mother-to-child transmission of HIV. However, there is a risk of hepatotoxicity, especially in women with CD4 counts >250 cells/mm³, which may increase fetal risk. Overall, the benefit of preventing HIV transmission outweighs potential risks. |
■ FDA Black Box Warning
Severe, life-threatening hepatotoxicity, including fatal cases, has been reported. Severe, life-threatening skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash and organ dysfunction, have occurred.
| Common Effects | Rash |
| Serious Effects |
Hypersensitivity to nevirapine or any component of the formulation. Use in combination with other NNRTIs not recommended. Do not use in patients with moderate to severe hepatic impairment (Child-Pugh class B or C).
| Precautions | Hepatotoxicity: monitor liver function tests at baseline and during therapy. Skin reactions: discontinue if severe rash or hypersensitivity occurs. Immune reconstitution syndrome. Monitoring of HIV RNA and CD4 count recommended. |
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| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST) at baseline and frequently during pregnancy due to risk of hepatotoxicity, especially in women with CD4 >250. Monitor for signs of rash, Stevens-Johnson syndrome. Assess fetal growth and well-being via ultrasound. Monitor HIV viral load and CD4 count regularly. In neonates, monitor for nevirapine side effects if exposed in utero or via breast milk. |
| Fertility Effects | No adverse effects on fertility have been reported in animal studies. In humans, there is no evidence that nevirapine impairs fertility. However, untreated HIV infection can affect fertility; thus, antiretroviral therapy may improve fertility outcomes. |