Important note: Information in this article was accurate in 2005. The state of the art may have changed since the publication date.
 |
Food and Drug Administration - October 6, 2005
Richard Klein, Kimberly Struble
On October 6, 2006, The Food and Drug Administration approved dosing recommendations for NORVIR (ritonavir) in pediatric patients one month to two years of age. The major revisions to the package insert include the following:
CLINICAL PHARMACOLOGY
This section was modified to include pharmacokinetic data in children 1 month to 2 years of age. The new Clinical Pharmacology section for Pediatric Patients reads as follows:
Pediatric Patients
Steady-state pharmacokinetics were evaluated in 37 HIV infected patients ages 2 to 14 years receiving doses ranging from 250 mg/m2 twice-daily to 400 mg/m2 twice daily in PACTG Study 310, and in 41 HIV-infected patients ages 1 month to 2 years at doses 350 and 450 mg/m2 twice daily in PACTG Study 345. Across dose groups, ritonavir steady-state oral clearance (CL/F/m2) was approximately 1.5 to 1.7 times faster in pediatric patients than in adult subjects. Ritonavir concentrations obtained after 350 to 400 mg/m2 twice daily in pediatric patients > 2 years were comparable to those obtained in adults receiving 600 mg (approximately 330 mg/m2) twice daily. The following observations were seen regarding ritonavir concentrations after administration with 350 or 450 mg/m2 twice daily in children < 2 years of age. Higher ritonavir exposures were not evident with 450 mg/m2 twice daily compared to the 350 mg/m2 twice daily. Ritonavir trough concentrations were somewhat lower than those obtained in adults receiving 600 mg twice daily. The area under the ritonavir plasma concentration-time curve and trough concentrations obtained after administration with 350 or 450 mg/m2 twice daily were approximately 16% and 60% lower, respectively, than that obtained in adults receiving 600 mg twice daily.
PRECAUTIONS
The following information was added under the section of Pediatric Use subsection:
Pediatric Use
In HIV-infected patients age > 1 month to 21 years, the antiviral activity and adverse event profile seen during clinical trials and through postmarketing experience were similar to that for adult patients.
ADVERSE REACTIONS
The following information was added under the section of Pediatric Use subsection. Of note, the treatment-emergent adverse events and laboratory abnormalities shown in the label reflect the summary of the adverse events and laboratory abnormalities observed in pediatric studies M95-310, PACTG 366, and PACTG 345.
Pediatrics
Treatment-Emergent Adverse Events
NORVIR has been studied in 265 pediatric patients > 1 month to 21 years of age. The adverse event profile observed during pediatric clinical trials was similar to that for adult patients.
Vomiting, diarrhea, and skin rash/allergy were the only drug-related clinical adverse events of moderate to severe intensity observed in = 2% of pediatric patients enrolled in NORVIR clinical trials.
Laboratory Abnormalities
The following Grade 3-4 laboratory abnormalities occurred in = 3% of pediatric patients who received treatment with NORVIR either alone or in combination with reverse transcriptase inhibitors: neutropenia (9%), hyperamylasemia (7%), thrombocytopenia (5%), anemia (4%), and elevated AST (3%).
DOSAGE AND ADMINISTRATION
The section of Pediatric Patients has been modified to include dosing recommendations for children > 1 month to 2 years of age. The new Dosage and Administration section for Pediatric Patients is:
Pediatric Patients
Ritonavir should be used in combination with other antiretroviral agents (see General Dosing Guidelines). The recommended dosage of ritonavir in children > 1 month is 350 to 400 mg/m2 twice daily by mouth and should not exceed 600 mg twice daily. Ritonavir should be started at 250 mg/m2 and increased at 2 to 3 day intervals by 50 mg/m2 twice daily. If patients do not tolerate 400 mg/m2 twice daily due to adverse events, the highest tolerated dose may be used for maintenance therapy in combination with other antiretroviral agents, however, alternative therapy should be considered. When possible, dose should be administered using a calibrated dosing syringe.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
051006
FD051001
SOURCE: Food and Drug Administration (FDA).
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2005. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1980, 2005. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .