Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Non-Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs)

Nevirapine

Last Updated: April 16, 2019; Last Reviewed: April 16, 2019

Nevirapine (NVP, Viramune)
Nevirapine (NVP, Viramune)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Tablets: Immediate-release 200 mg, extended-release (XR) 100 mg and 400 mg
Suspension: 10 mg/mL

Generic Formulations:
  • Immediate-release 200 mg tablets
  • Extended-release (XR) 400 mg tablets
Note: While the suspension formulation of brand-name nevirapine (Viramune) is available, it is not typically stocked in local pharmacies or hospitals. Have the pharmacy ask their drug wholesaler to order from the Boehringer-Ingleheim distribution center. The distribution center should be able to ship the formulation directly to the pharmacy.
Dosing Recommendations Selected Adverse Events
Note: Nevirapine is often used to prevent perinatal transmission of HIV. See Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV for information about nevirapine dosing in neonates aged ≤1 days.

Child and Adolescent Dose:
  • Note: In most situations, nevirapine is given once daily for 2 weeks to allow for autoinduction of the enzymes involved in its metabolism. This may not be necessary in children aged <2 years.a
Immediate-Release Tablets and Suspension Formulations
Gestational Age 34 Weeks–37 Weeks:
  • Nevirapine 4 mg/kg per dose twice daily for the first week, increasing to nevirapine 6 mg/kg per dose twice daily thereafter (no lead-in dosing).a
  • This is an investigational dose that is not approved by the Food and Drug Administration (FDA).
Gestational Age ≥37 Weeks to Age <1 Month:
  • Nevirapine 6 mg/kg per dose twice daily (no lead-in dosing).a
  • This is an investigational dose that is not approved by the FDA.
  • See the Special Considerations for Dosing: Neonates and Premature Infants section below.
Aged ≥1 Month to <8 Years:
  • Nevirapine 200 mg/m2 of body surface area per dose twice daily after lead-in dosing.a In children aged ≤2 years, some experts initiate nevirapine without lead-in dosing (maximum dose of immediate-release tablets is 200 mg twice daily).
Aged ≥8 Years:
  • Nevirapine 120–150 mg per m2 of body surface area per dose twice daily after lead-in dosinga (maximum dose of immediate-release tablets is nevirapine 200 mg twice daily).
  • When adjusting the dose for a growing child, the mg dose need not be decreased as the child reaches age 8 years; rather, the mg dose can be left static to achieve the appropriate mg-per-m2 dose as the child grows, as long as there are no adverse effects.
Extended-Release Tablets
Aged ≥6 Years:
  • Patients aged ≥6 years who are already taking immediate-release nevirapine twice daily can be switched to nevirapine extended release without lead-in dosing.a
Body Surface Area Dosing for Nevirapine Extended-Release Tablets
Body Surface Area Range Nevirapine Extended-Release Tablets
0.58 m2 to 0.83 m2 200 mg once daily (two 100-mg tablets)
0.84 m2 to 1.16 m2 300 mg once daily (three 100-mg tablets)
≥1.17 m2 400 mg once daily (one 400-mg tablet)


Adolescent and Adult Dose:
  • Nevirapine 200 mg twice daily or 400 mg extended release once daily after lead-in dosing.a,b
Nevirapine Used in Combination with Lopinavir/Ritonavir:
  • Rash, including Stevens-Johnson syndrome
  • Symptomatic hepatitis, including fatal hepatic necrosisb
  • Severe systemic hypersensitivity syndrome with potential for multisystem organ involvement and shock
Special Instructions
  • Shake suspension well before administering and store at room temperature.
  • Nevirapine can be given without regard to food.
  • Nevirapine-associated skin rash usually occurs within the first 6 weeks of therapy. If rash occurs during the initial 14 day lead-in period, do not increase dose until rash resolves (see Major Toxicities below).
  • Nevirapine extended-release tablets must be swallowed whole. They cannot be crushed, chewed, or divided.
  • If nevirapine dosing is interrupted for >14 days, nevirapine should be restarted with once-daily dosing for 14 days, followed by escalation to the full, twice-daily regimen (see Dosing Considerations: Lead-In Requirement below).
  • Most cases of nevirapine-associated hepatic toxicity occur during the first 12 weeks of therapy; frequent clinical and laboratory monitoring, including liver function tests, is important during this period (see Major Toxicities below).
Metabolism/Elimination
  • Nevirapine is a substrate and inducer of cytochrome P450 (CYP) 3A4 and CYP2B6. More than 80% of a nevirapine dose is eliminated in urine as UGT-derived glucuronidated metabolites
Nevirapine Dosing in Patients with Renal Failure Who Are Receiving Hemodialysis:
  • An additional dose of nevirapine should be given following each dialysis session.
Nevirapine Dosing in Patients with Hepatic Impairment:
  • Nevirapine should not be administered to patients with moderate or severe hepatic impairment.
a Nevirapine is usually initiated at a lower dose that is increased in a stepwise fashion. Nevirapine induces CYP metabolizing enzymes, which results in increased drug clearance. The stepwise increase in dose decreases the occurrence of rash. Clinicians should initiate therapy with the immediate-release formulation once daily instead of twice daily for the first 14 days of therapy. If there are no rash or other adverse effects after 14 days of therapy, increase the dose of nevirapine to the age-appropriate full dose of the immediate-release formulation administered twice daily. For example, the recommended oral dose for pediatric patients aged ≥1 month to <8 years is nevirapine 200 mg per m2 of body surface area once daily for the first 14 days, followed by nevirapine 200 mg per m2 of body surface area twice daily thereafter. However, in children aged ≤2 years, some experts initiate nevirapine without lead-in dosing (see Dosing Considerations: Lead-In Requirement and Special Considerations for Dosing: Neonates and Premature Infants below). In patients who are already receiving the full twice-daily dose of immediate-release nevirapine, extended-release tablets can be used without the lead-in period. Patients must swallow nevirapine extended-release tablets whole. They must not be chewed, crushed, or divided. Patients must never take more than one form of nevirapine at the same time. The dose should not exceed 400 mg daily.

b Symptomatic hepatitis, including fatal hepatic necrosis, occurs at a significantly higher frequency in antiretroviral (ARV)-naive women with pre-nevirapine CD4 T lymphocyte (CD4) cell counts >250 cells/mm3 and in ARV-naive men with pre-nevirapine CD4 counts >400 cells/mm3. Nevirapine should not be initiated in these patients unless the benefit clearly outweighs the risk.

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