Revised Pediatric Dosing Recommendations for Viracept (nelfinavir)
Based on clinical and pharmacokinetic data from 5 pediatric studies, FDA has approved new dosing recommendations for VIRACEPT (nelfinavir) in patients 2 years of age or older.
In patients less than 2 years of age, VIRACEPT was found to be safe at the doses studied, but a reliably effective dose could not be established. Summary data from all pharmacokinetic (PK) studies submitted is included in the revised label for completeness. The major revisions made to the product label based on this review are described below:
1. Pediatric PK information is incorporated into the product label in a table summarizing the steady-state area under the concentration-time curve from 0 to 24 hours (AUC24) of nelfinavir observed in pediatric studies enrolling patients from birth to 13 years of age. Comments regarding the marked variability of drug exposure identified in pediatric patients are also included.
2. The basis for the pediatric indication with relevant age groups and brief descriptions of the major pediatric clinical trials available for review are incorporated. The following points are highlighted in the PEDIATRIC USE section of the label:
In pediatric patients 2 years of age and older receiving VIRACEPT as part of triple combination antiretroviral therapy in randomized studies, the proportion of patients achieving an HIV RNA level less than 400 copies/mL through 48 weeks ranged from 26% to 42%.
Response rates in children less than 2 years of age appeared to be poorer than those in patients 2 years of age and older in some studies.
Highly variable drug exposure remains a significant problem in the use of VIRACEPT in pediatric patients. Unpredictable drug exposure may be exacerbated in pediatric patients because of increased clearance compared to adults and difficulties with compliance and adequate food intake with dosing.
3. An updated description of the pediatric safety data is included, highlighting the size of the safety database, the similarity of the safety profile in adults and children, and 2 of the most commonly reported toxicities (diarrhea and neutropenia).
4. The new dosing recommendations for children are included in the DOSAGE AND ADMINISTRATION section of the label. These recommendations include tables that provide dosing guidelines for pediatric patients of different weights taking either the 250 mg tablets or the oral powder. Instructions for mixing the powder remain unchanged.
The revised dose recommendations are as follows:
"In children 2 years of age and older, the recommended oral dose of VIRACEPT oral powder or 250 mg tablets is 45 to 55 mg/kg twice daily (BID) or 25 to 35 mg/kg three times daily (TID). All doses should be taken with a meal. Doses higher than the adult maximum dose of 2500 mg per day have not been studied in children. For children unable to take tablets, VIRACEPT Oral Powder may be administered."
Viracept was originally approved for pediatric use in 1997. This supplement provides additional information, and new TID and BID dose recommendations.
A pdf file containing the revised VIRACEPT label is attached. A free copy of Adobe Acrobat Reader 5.0 can be downloaded.
Office of Special Health Issues
Food and Drug Administration
Division of Antiviral Drug Products
Food and Drug Administration