Nevirapine

HIV Infection (combination therapy)
1. NNRTIs carry a high risk of induced HIV resistance
2. Never use NNRTIs as monotherapy in HIV Infection

Immediate Release Tablets: 200 mg
Immediate Release Suspension: 50 mg/5 ml
Extended Release (XR) Tablets: 100 mg, 400 mg
1. Do not chew, crush or split XR tablets

Use as combination therapy with other Antiretrovirals
Immediate Release
1. Start: 200 mg orally daily for 14 days or until any rash resolves, then
2. Next: 200 mg orally twice daily (if NO rash or hepatotoxicity)
  1. May switch to Nevirapine XR formulation at any time after initial 14 day dose titration
  2. Restart at daily immediate dose if medication is stopped for >7 days
Extended Release (Nevirapine XR)
1. Take 400 mg orally once daily
Renal Dosing
1. Give supplemental 200 mg immediate dose after Hemodialysis

Use as combination therapy with other Antiretrovirals
Immediate Release (age >15 days old)
1. Start: 150 mg/m2 (max 200 mg) orally daily for 14 days or until any rash resolves, then
2. Next: 150 mg/m2 (max 200 mg) orally twice daily (if NO rash or hepatotoxicity)
  1. Age 2 to 8 years old may need dose increase to 200 mg/m2 (max 200 mg) twice daily
  2. May switch to Nevirapine XR formulation at any time after initial 14 day dose titration
  3. Restart at daily immediate dose if medication is stopped for >7 days
Extended Release (Nevirapine XR, age >=6 years)
1. BSA 0.58 to 0.83 m2: Give 200 mg orally once daily
2. BSA 0.84 to 1.16 m2: Give 300 mg orally once daily
3. BSA >1.16 m2: Give 400 mg orally once daily (adult dose)

See NNRTI for class related adverse effects
Acute Life-threatening Hypersensitivity Skin Reaction
1. Stop Nevirapine and do not rechallenge if signficant drug rash develops
2. Rash is less likely if starting at lower daily dose
Hepatotoxicity
1. Severe hepatoxicity risk
  1. Acute, rapid, severe liver failure has been described after only a few weeks of treatment
2. Risk factors
  1. Pre-treatment CD4 >400 in men or >250 in women
  2. First 6 weeks of therapy
  3. Pre-existing liver disease (e.g. Hepatitis B, Hepatitis C or baseline elevated LFTs)
    1. Contraindicated in moderate to severe liver disease (Child-Pugh B or C)
3. Monitoring
  1. Obtain LFTs at baseline, and at least once montly (as well as 2 weeks after each dose change)
  2. Monitor LFTs closely for first 18 weeks of treatment
  3. Stop Nevirapine and do not rechallenge if signficant hepatotoxicity occurs

Avoid in Lactation
Pregnancy
1. Not recommended as a first-line NNRTI in pregnancy
2. However, may be used in pregnancy if risk outweighs benefit
3. Has been used off-label for single dose prevention of vertical transmission in labor (or to delivered newborn)
4. Pregnancy registry exists

Granulocytopenia
1. More common in children coadministered Zidovudine
CYP3A4 Inducer
1. Avoid with Atazanavir, Ketoconazole, Oral Contraceptives or St Johns Wort
Methadone
1. Nevirapine may reduce Methadone effects

Original studies showed good efficacy when combined with 2 Nucleoside Reverse Transcriptase Inhibitors (nRTIs)