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: May 22, 2018; Last Reviewed: May 22, 2018

Nevirapine (NVP, Viramune)
Nevirapine (NVP, Viramune)
For additional information see Drugs@FDA: http://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
Tablets: Immediate-release 200 mg, extended-release (XR) 400 mg only
Suspension: Generic suspension is no longer available in the United States

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 directly 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
Neonate and Infant (≤14 Days) Dose for Prevention: Pediatric Dose for Treatment of HIV
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 (see footnotea and text below).

Immediate Release Tablets and Suspension Formulations
Aged <1 Month (This Investigational Dose is Not Food and Drug Administration-Approved):
  • 34–37 weeks gestational age: Nevirapine 4 mg/kg/dose twice daily for the first week, increasing to nevirapine 6 mg/kg/dose twice daily thereafter (no lead in; please see text and footnotea)
  • ≥37 weeks gestational age to age <1 month: Nevirapine 6 mg/kg/dose twice daily (no lead in; please see text and footnotea)
  • See the Special Considerations for Dosing: Neonates and Premature Infants section below.
Aged ≥1 Month to <8 Years:
  • 200 mg/m2 of body surface area (BSA)/dose twice daily after lead-in dosing.a In children aged ≤2 years, some experts initiate nevirapine without a lead-in (maximum dose of immediate-release tablets is 200 mg twice daily).
Aged ≥8 Years:
  • 120–150 mg/m2 BSA/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 is left static to achieve the appropriate mg-per-m2 dose as the child grows, as long as there are no untoward effects.
BSA Range NVP XR
0.58 m2 to 0.83 m2 200 mg once daily (2 x 100 mg)
0.84 m2 to 1.16 m2 300 mg once daily (3 x 100 mg)
≥1.17 m2 400 mg once daily (1 x 400 mg)
Key to Acronyms: BSA = body surface area; NVPXR = nevirapine extended release

Extended-Release Formulation

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
Adolescent and Adult Dose:a,b
  • 200 mg twice daily or 400 mg extended release once daily after lead-in dosing.
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.
  • 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 the Major Toxicities section below).
  • Nevirapine extended-release tablets must be swallowed whole. They cannot be crushed, chewed, or divided.
  • If nevirapine dosing is interrupted for more than 14 days, nevirapine should be restarted with once-daily dosing for 14 days, followed by escalation to the full, twice-daily regimen (see the Dosing Considerations: Lead-In Requirement section 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 the Major Toxicities section below).
  • Nevirapine should not be co-administered to patients receiving atazanavir (with or without ritonavir).
  • Nevirapine increases the metabolism of lopinavir. A dose adjustment of lopinavir is recommended (see Lopinavir/Ritonavir).
Metabolism/Elimination
  • Metabolized by cytochrome P450 (3A inducer); 80% of nevirapine dose is excreted in urine (glucuronidated metabolites).
Nevirapine Dosing in Patients with Renal Failure Who Are Receiving Hemodialysis:
  • An additional dose of nevirapine should be given following dialysis.
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 and increased in a stepwise fashion to allow for induction of cytochrome P450 metabolizing enzymes, which results in increased drug clearance. The stepwise increase in dose decreases the occurrence of rash. Clinicians should initiate therapy with the age-appropriate dose of the immediate-release formulation once daily (half-daily dose) for the first 14 days of therapy. If there is no rash or untoward effect, at 14 days of therapy, increase to the age-appropriate full dose, administered twice daily, of the immediate-release preparation. However, in children aged ≤2 years, some experts initiate nevirapine without a lead-in (see Dosing Considerations: Lead-In Requirement and Special Considerations for Dosing: Neonates and Premature Infants sections below). In patients who are already receiving full-dose, immediate-release nevirapine, extended-release tablets can be used without the 200-mg 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 1 form of nevirapine at the same time. 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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