FDA notifications
FDA notifications
FDA provides important information for clinicians serving hurricane victims
Some HIV-infected patients may have interrupted their antiretroviral therapy and other medications due to the recent hurricane disasters. The following link provides some guidance to the general practitioners attending to the medical needs of displaced HIV-infected adult or pediatric patients who have not yet secured HIV care in the local area.
Management of antiretroviral therapy is complex and should best be done with the assistance of specialized clinicians.
To see the recommendations go to: http://aidsinfo.nih.gov/guidelines/disaster/2EssentialsforManagingHIV1ap.pdf
Medical consultation may also be available at specific local or regional HIV clinics or via the 24-hour NIH Medical Consultation Services at 1-866-887-2842 or the National HIV Telephone Consultation Service: at 1-800-933-3413.
The recommendations were prepared by: The Panel on Clinical Practices for Treatment of HIV Infection (Adult and Adolescent HIV Treatment Guidelines Panel),
The Perinatal HIV Guidelines Working Group, The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, and USPHS/IDSA Prevention and Treatment of Opportunistic Infections Working Groups.
FDA approves pediatric dosing for ritonavir
On October 6, 2006, The Food and Drug Administration approved dosing recommendations for ritonavir (Norvir) in pediatric patients one month to two years of age. The major revisions to the package insert include the following:
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 two 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
Ritonavir 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 ritonavir 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.
Adult Treatment Guidelines Updated
The "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" has been revised to include up-to-date drug information, including updated information on nevirapine hepatotoxicity risks, the interaction between rifampin and ritonavir-boosted saquinavir, new pregnancy data for efavirenz, and new contraindications and warnings for ritonavir and lopinavir/ritonavir use. Also included in the updated document is a new table, Table 30, providing information on the tipranavir expanded access program.
All changes to the document are highlighted in yellow. The updated guidelines document is available at the AIDSinfo Web site: www.aidsinfo.nih.gov/guidelines/default_db2.asp?id=50
You can view, order hard copies of the guidelines, or request them by email at the web site.
The AIDSinfo website is also a useful source of other information related to HIV/AIDS, including other treatment and prevention guidelines, downloadable databases for PDAs (Personal Digital Assistants), and HIV/AIDS-related clinical trials information.
Accelerated approval of tipranavir
On June 22, 2005, the FDA granted accelerated approval of tipranavir (Aptivus), a protease inhibitor. Tipranavir, co-administered with 200 mg of ritonavir, is indicated for use as part of combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. FDA reviewed and approved tipranavir within a six-month time frame.
The approval of tipranavir/ritonavir is based on analyses of plasma HIV-1 RNA levels in two controlled phase III studies of tipranavir/ritonavir of 24 weeks duration. Both studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy. The results of the two phase III studies showed a statistically significant greater percentage of HIV-positive patients taking tipranavir/ritonavir achieved treatment response versus the comparator group (40% vs. 18%). Treatment response was defined as a confirmed 1 log10 or greater decrease in HIV RNA from baseline.
The approved dose of tipranavir is 500 mg taken with 200 mg of ritonavir, twice daily with food. Tipranavir must be co-administered with 200 mg of ritonavir to exert its therapeutic effect. Failure to correctly co-administer tipranavir with ritonavir will result in reduced plasma levels of tipranavir that will be insufficient to achieve the desired antiviral effect. Taking the drug with food improves absorption.
Some HIV-infected patients may have interrupted their antiretroviral therapy and other medications due to the recent hurricane disasters. The following link provides some guidance to the general practitioners attending to the medical needs of displaced HIV-infected adult or pediatric patients who have not yet secured HIV care in the local area.Subscribe Now for Access
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