II. Indications
-
HIV Infection (combination therapy)
- NNRTIs carry a high risk of induced HIV resistance
- Never use NNRTIs as monotherapy in HIV Infection
III. Contraindications
- Moderate to severe liver disease (Child-Pugh B or C)
- Avoid in HIV Post Exposure Prophylaxis
IV. Mechanism
- See Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
- First generation NNRTI
V. Medications
- Immediate Release Tablets: 200 mg
- Immediate Release Suspension: 50 mg/5 ml
- Extended Release (XR) Tablets: 100 mg, 400 mg
- Do not chew, crush or split XR tablets
VI. Dosing: Adult
- Use as combination therapy with other Antiretrovirals
- Immediate Release
- Start: 200 mg orally daily for 14 days or until any rash resolves, then
- Next: 200 mg orally twice daily (if NO rash or hepatotoxicity)
- May switch to Nevirapine XR formulation at any time after initial 14 day dose titration
- Restart at daily immediate dose if medication is stopped for >7 days
- Extended Release (Nevirapine XR)
- Take 400 mg orally once daily
-
Renal Dosing
- Give supplemental 200 mg immediate dose after Hemodialysis
VII. Dosing: Child
- Use as combination therapy with other Antiretrovirals
- Immediate Release (age >15 days old)
- Start: 150 mg/m2 (max 200 mg) orally daily for 14 days or until any rash resolves, then
- Next: 150 mg/m2 (max 200 mg) orally twice daily (if NO rash or hepatotoxicity)
- Age 2 to 8 years old may need dose increase to 200 mg/m2 (max 200 mg) twice daily
- May switch to Nevirapine XR formulation at any time after initial 14 day dose titration
- Restart at daily immediate dose if medication is stopped for >7 days
- Extended Release (Nevirapine XR, age >=6 years)
- BSA 0.58 to 0.83 m2: Give 200 mg orally once daily
- BSA 0.84 to 1.16 m2: Give 300 mg orally once daily
- BSA >1.16 m2: Give 400 mg orally once daily (adult dose)
VIII. Adverse Effects
- See NNRTI for class related adverse effects
-
Acute Life-threatening Hypersensitivity Skin Reaction
- Stop Nevirapine and do not rechallenge if signficant drug rash develops
- Rash is less likely if starting at lower daily dose
- Hepatotoxicity
- Severe hepatoxicity risk
- Acute, rapid, severe liver failure has been described after only a few weeks of treatment
- Risk factors
- Pre-treatment CD4 >400 in men or >250 in women
- First 6 weeks of therapy
- Pre-existing liver disease (e.g. Hepatitis B, Hepatitis C or baseline elevated LFTs)
- Contraindicated in moderate to severe liver disease (Child-Pugh B or C)
- Monitoring
- Obtain LFTs at baseline, and at least once montly (as well as 2 weeks after each dose change)
- Monitor LFTs closely for first 18 weeks of treatment
- Stop Nevirapine and do not rechallenge if signficant hepatotoxicity occurs
- Severe hepatoxicity risk
IX. Safety
X. Drug Interactions
-
Granulocytopenia
- More common in children coadministered Zidovudine
-
CYP3A4 Inducer
- Avoid with Atazanavir, Ketoconazole, Oral Contraceptives or St Johns Wort
-
Methadone
- Nevirapine may reduce Methadone effects
XI. Efficacy
- Original studies showed good efficacy when combined with 2 Nucleoside Reverse Transcriptase Inhibitors (nRTIs)
XII. Resources
- Nevirapine Immediate Release Suspension or Tablet (DailyMed)
- Nevirapine Extended Release (DailyMed)