The
U.S. Food and Drug Administration this week announced new pediatric doing recommendation
for use of the protease inhibitor atazanavir
(Reyataz) in HIV positive children ages 6 through 18.
Below is the
text of the announcement with accompanying tables:
New
pediatric dosing recommendations for Reyataz Capsules, patients ages 6 to 18 years
old
 |
Reyataz
Capsule |
Reyataz
(atazanavir) Capsule label has been updated to include the dosing recommendations
for pediatric patients 6 to 18 years of age.
Reyataz should not be administered
to pediatric patients below the age of 3 months due to the risk of kernicterus
(a type of brain damage caused by excessive levels of bilirubin).
Important
changes made to the product label include the following:
Section 2.2 Recommended
Pediatric Dosage was added to the label.
The recommended dosage of REYATAZ
for pediatric patients (6 to less than 18 years of age) is based on body weight
and should not exceed the recommended adult dosage. REYATAZ Capsules must be taken
with food. The data are insufficient to recommend dosing of REYATAZ for any of
the following: (1) patients less than 6 years of age, (2) without
ritonavir in patients less than 13 years of age, and (3) treatment-experienced
pediatric patients with body weight less than 25 kg.
Therapy-Naive
Pediatric Patients
The recommended dosage of REYATAZ with
ritonavir in treatment-naive patients at least 6 years of age is shown in Table
1.
For treatment-naive patients at least 13 years of age and at least
39 kg, who are unable to tolerate ritonavir, the recommended dose is REYATAZ 400
mg (without ritonavir) once daily with food.
| Table 1: Dosage for Treatment-Naive Pediatric Patients (6 to less
than 18 years of age) for REYATAZ Capsules with ritonavir
|
Body Weight | | ritonavir
dose [b] (mg) |
(kg) | (lbs) |
15 to less than 25 | 33 to less than 55 | 150 | 80 [c] |
25 to less than 32 | 55 to less than 70 | 200 | 100 [d] |
32 to less than 39 | 70 to less than 86 | 250 | 100 [d] |
at least 39 | at least 86 | 300 | 100 [d] |
[a] The recommended
dosage of REYATAZ can be achieved using a combination
of commercially available capsule strengths.
[b] The dosage of REYATAZ and ritonavir was calculated as follows: - 15 kg to less than 20 kg: REYATAZ 8.5 mg/kg with ritonavir 4 mg/kg once daily with food. - at least 20 kg: REYATAZ 7 mg/kg with ritonavir
4 mg/kg once daily with food not to exceed REYATAZ 300 mg and ritonavir 100 mg. [c] Ritonavir
liquid. [d] Ritonavir capsule or liquid. |
Therapy-Experienced
Pediatric Patients
The recommended dosage of REYATAZ with
ritonavir in treatment-experienced patients at least 6 years of age is shown in
Table 2.
| Table 2: Dosage for
Treatment-Experienced Pediatric Patients (6 to less than 18 years of age) for
REYATAZ Capsules with ritonavir |
Body Weight | | ritonavir
dose [b] (mg) |
(kg) | (lbs) |
25 to less than 32 | 55 to less than 70 | 200 | 100 [c] |
32 to less than 39 | 70 to less than 86 | 250 | 100 [c] |
at least 39 | at least 86 | 300 | 100 [c] |
[a] The recommended dosage of
REYATAZ can be achieved using a combination
of commercially available capsule strengths.
[b] The dosage was calculated as
REYATAZ 7 mg/kg with ritonavir 4 mg/kg once daily with
food not to exceed REYATAZ 300 mg and ritonavir 100
mg. [c] Ritonavir
capsule or liquid. |
In
section 6 Adverse Reactions subsection 6.2 Clinical Trial Experience in Pediatric
Patients was added and includes the following information:
The safety
profile of REYATAZ in pediatric patients (6 to less than 18 years of age) was
comparable to that observed in clinical studies of REYATAZ in adults. The most
common Grade 2-4 adverse events (5%, regardless of causality) reported in pediatric
patients were cough (21%), fever (19%), rash (14%), jaundice/scleral icterus (13%),
diarrhea (8%), vomiting (8%), headache (7%), and rhinorrhea (6%). Asymptomatic
second-degree atrioventricular block was reported in 2% of patients. The most
common Grade 3-4 laboratory abnormality was elevation of total bilirubin (3.2
mg/dL) which occurred in 49% of pediatric patients. All other Grade 3-4 laboratory
abnormalities occurred with a frequency of less than 3%.
In section 14
Clinical Studies, subsection 14.3 Pediatric Patients was added and includes the
following:
Assessment of the pharmacokinetics, safety, tolerability, and
efficacy of REYATAZ is based on data from the open-label, multicenter clinical
trial PACTG 1020A conducted in patients from 3 months to 21 years of age. In this
study, 182 patients (83 antiretroviral-naive and 99 antiretroviral-experienced)
received once daily REYATAZ, with or without ritonavir, in combination with two
NRTIs.
Ninety-nine patients (6 to less than 18 years of age) treated with the
REYATAZ capsule formulation, with or without ritonavir, were evaluated. In this
cohort, the overall proportions of antiretroviral-naive and -experienced patients
with HIV RNA <400 copies/mL at week 24 were 68% (28/41) and 33% (19/58), respectively.
The overall proportions of antiretroviral-naive and experienced patients with
HIV RNA <50 copies/mL at week 24 were 59% (24/41) and 24% (14/58), respectively.
The median increase from baseline in absolute CD4 count at 20 weeks of therapy
was 171 cells/mm3 in antiretroviral-naive patients and 116 cells/mm3 in antiretroviral-experienced
patients.
3/28/08
Source
R
Klein and K Struble (U.S. Food and Drug Administration). HIV/AIDS Update -New
pediatric dosing recommendations for Reyataz Capsules, patients ages 6 to 18 years
old. E-mail announcement. March 26, 2008.
