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 14, 2020; Last Reviewed: April 14, 2020

Nevirapine (NVP, Viramune)
Nevirapine (NVP, Viramune)
Formulations
Oral Suspension: 10 mg/mL 
Tablets: Immediate-release 200 mg tablets; extended-release (XR) 100 mg and 400 mg tablets

Generic Formulations:
  • 10 mg/ml suspension 
  • Immediate-release 200 mg tablets
  • XR 400 mg tablets
The oral suspension formulation of brand-name nevirapine (Viramune) is not typically stocked in local pharmacies or hospitals. Have the pharmacy ask their drug wholesaler to order it 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 (NVP) is often used to prevent perinatal transmission of HIV. See Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection.

Child and Adolescent Dose:
  • In most situations, NVP 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 Oral Suspension
Gestational Age of 34–37 Weeks:
  • NVP 4 mg/kg per dose twice daily for the first week, increasing to NVP 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 of ≥37 Weeks to Age <1 Month:
  • NVP 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 below.
Aged ≥1 Month to <8 Years:
  • NVP 200 mg per m2 of body surface area per dose twice daily after lead-in dosing.a In children aged ≤2 years, some experts initiate NVP without lead-in dosing (maximum dose of immediate-release tablets is NVP 200 mg twice daily).
Aged ≥8 Years:
  • NVP 120 mg to 150 mg per m2 of body surface area per dose twice daily after lead-in dosinga (maximum dose of immediate-release tablets is NVP 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 (AEs).
Extended-Release Tablets
Aged ≥6 Years:
  • Patients aged ≥6 years who are already taking immediate-release NVP tablets twice daily can be switched to extended-release NVP tablets without lead-in dosing.a
Body Surface Area Dosing for Extended-Release Nevirapine Tablets
Body Surface Area  Once-Daily Dose
0.58 m2 to 0.83 m2 NVP 200 mg (two 100-mg tablets)
0.84 m2 to 1.16 m2 NVP 300 mg (three 100-mg tablets)
≥1.17 m2 NVP 400 mg (one 400-mg tablet)


Adolescent and Adult Dose:
  • NVP 200 mg twice daily or NVP 400 mg with the extended-release tablets once daily after lead-in dosing. a,b
Nevirapine Used in Combination with Lopinavir/Ritonavir:
  • A higher dose of lopinavir/ritonavir may be needed in patients who are also receiving NVP (see the Lopinavir/Ritonavir section for more information).
  • 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 the oral suspension well before administering and store at room temperature.
  • NVP can be given without regard to food.
  • NVP-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 the dose until rash resolves (see Major Toxicities below).
  • Extended-release tablets must be swallowed whole. They cannot be crushed, chewed, or divided.
  • If NVP dosing is interrupted for >14 days, NVP 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 NVP-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
  • NVP is a substrate and inducer of cytochrome P450 (CYP) 3A4 and CYP2B6. More than 80% of an NVP dose is eliminated in urine as uridine diphosphate glucuronosyltransferase (UGT)-derived glucuronidated metabolites.
Nevirapine Dosing in Patients with Renal Failure Who Are Receiving Hemodialysis:
  • An additional dose of NVP should be given following each dialysis session.
Nevirapine Dosing in Patients with Hepatic Impairment:
  • NVP should not be administered to patients with moderate or severe hepatic impairment.
a NVP is usually initiated at a lower dose that is increased in a stepwise fashion. NVP 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 tablet formulation once daily instead of twice daily for the first 14 days of therapy. If there are no rashes or other AEs after 14 days of therapy, increase the dose of NVP to the age-appropriate full dose of the immediate-release tablet formulation administered twice daily. For example, the recommended oral dose for pediatric patients aged ≥1 month to <8 years is NVP 200 mg per m2 of body surface area once daily for the first 14 days, followed by NVP 200 mg per m2 of body surface area twice daily thereafter. However, in children aged ≤2 years, some experts initiate NVP 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 the immediate-release tablets, extended-release tablets can be used without the lead-in period. Patients must swallow extended-release tablets whole. They must not be chewed, crushed, or divided. Patients must never take more than one form of NVP at the same time. The dose should not exceed NVP 400 mg daily.

b Severe, life-threatening, and, in rare cases, fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, have occurred in patients who were taking NVP. These toxicities are less common in children than adults. The majority of cases occur during the first 12 weeks of therapy and may be associated with rash or other signs or symptoms of hypersensitivity reaction (HSR). NVP should be discontinued and not restarted in children or adults who develop symptomatic hepatitis, severe transaminase elevations, or HSRs.

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