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On March, 26, 2012, the Food and Drug Administration approved dosing recommendations for INTELENCE® (etravirine) for treatment-experienced pediatric patients 6 to 18 years of age and weighing at least 16 kg. In addition a new scored 25 mg tablet was approved for use in pediatric patients. Listed below are the major changes to the product labeling.
The Dosage and Administration section includes the following:
2.2 Pediatric Patients (6 years to less than 18 years of age)
The recommended dose of Intelence for pediatric patients 6 years to less than 18 years of age and weighing at least 16 kg is based on body weight not exceeding the recommended adult dose. Intelence tablet(s) should be taken orally, following a meal. The type of food does not affect the exposure to etravirine. The safety and efficacy of Intelence have not been established in children less than 6 years of age.
Healthcare professionals should pay special attention to the accurate dose selection of Intelence, the transcription of the medication order, the dispensing information and the dosing instructions to minimize the risk of medication errors, overdosing, and underdosing.
2.3 Method of Administration
Patients should be instructed to swallow the Intelence tablet(s) whole with a liquid such as water. Patients who are unable to swallow the Intelence tablet(s) whole may disperse the tablet(s) in a glass of water. The patient should be instructed to do the following:
- place the tablet(s) in 5 ml (1 teaspoon) of water, or at least enough liquid to cover the medication,
- stir well until the water looks milky, if desired, add more water or alternatively orange juice or milk (patients should not place the tablets in orange juice or milk without first adding water). The use of grapefruit juice or warm (greater than 40°C) or carbonated beverages should be avoided.
- drink it immediately,
- rinse the glass several times with water, orange juice, or milk and completely swallow the rinse each time to make sure the patient takes the entire dose.
6 ADVERSE REACTIONS
6.2 Clinical Trials Experience: Pediatric Subjects (6 years to less than 18 years of age)
The safety assessment in children and adolescents is based on the Week 24 analysis of the single-arm, Phase 2 trial TMC125-C213 in which 101 antiretroviral treatment-experienced HIV-1 infected subjects 6 years to less than 18 years of age and weighing at least 16 kg received Intelence in combination with other antiretroviral agents [see Clinical Studies (14.2)]. The frequency, type and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adult subjects, except for rash which was observed more frequently in pediatric subjects. The most common adverse drug reactions in at least 2% of pediatric subjects were rash and diarrhea. Rash (greater than or equal to Grade 2) occurred in 15% of pediatric subjects. In the majority of cases, rash was mild to moderate, of macular/papular type, and occurred in the second week of therapy. Rash was self-limiting and generally resolved within 1 week on continued therapy. The discontinuation rate for rash was 4%. Rash including serious (Grade 3 or 4) events and discontinuations were more frequently observed in female subjects compared to male subjects.
8.4 Pediatric use
Treatment with Intelence is not recommended in children less than 6 years of age. The pharmacokinetics, safety, tolerability and efficacy of Intelence in children less than 6 years of age have not been established.
The safety, pharmacokinetic profile, and virologic and immunologic responses of Intelence were evaluated in treatment-experienced HIV-1-infected pediatric subjects 6 years to less than 18 years of age and weighing at least 16 kg. Frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults, except for rash.
14 CLINICAL STUDIES
14.2 Treatment-Experienced Pediatric Subjects (6 years to less than 18 years of age)
TMC125-C213, a single-arm, Phase 2 trial evaluating the pharmacokinetics, safety, tolerability, and efficacy of Intelence enrolled 101 antiretroviral treatment-experienced HIV-1 infected pediatric subjects 6 years to less than 18 years of age and weighing at least 16 kg. Subjects eligible for this trial were on an antiretroviral regimen with confirmed plasma HIV-1 RNA of at least 500 copies per mL and viral susceptibility to Intelence at screening.
The median baseline plasma HIV-1 RNA was 3.9 log10 copies per mL, and the median baseline CD4 cell count was 385 x 106 cells per mm3.
At Week 24, 52% of all pediatric subjects had HIV-1 RNA less than 50 copies per mL. The proportion of pediatric subjects with HIV-1 RNA less than 400 copies per mL was 67%. The mean CD4 cell count increase from baseline was 112 x 106 cells per mm3.
The complete updated labeling will be posted soon to Drugs@FDA, on the FDA web site.
Intelence is a non-nucleoside reverse transcriptase inhibitor (NNRTI) manufactured by Janssen Pharmaceuticals.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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