1 Indications and Usage 1.2 Pediatric Patients
The indication for treatment‑experienced pediatric patients 3 to less than 18 years of age is based on 24-week analyses of plasma HIV-1 RNA levels and CD4+ cell counts from two open-label Phase 2 trials in antiretroviral treatment‑experienced pediatric subjects. The indication for treatment‑naïve pediatric patients or antiretroviral treatment‑experienced patients with no darunavir resistance associated substitutions is based on one open-label Phase 2 trial of 48 weeks duration in antiretroviral treatment-naïve subjects 12 to less than 18 years of age and pharmacokinetic modeling and simulation for patients 3 to less than 12 years of age.
2 Dosage and Administration subsection: 2.2 Pediatric Patients (age 3 to less than 18 years)
Dosing recommendations for treatment‑naïve pediatric patients or antiretroviral treatment‑experienced pediatric patients with no darunavir resistance associated substitutions
- · Pediatric patients weighing at least 10 kg but less than 15 kg
|
Table 2: Recommended
dose for pediatric patients weighing 10 kg to less than 15 kg who are
treatment‑naïve or treatment‑experienced with no darunavir resistance
associated substitutions* |
|
|
Body weight (kg) |
Formulation: PREZISTA oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
|
|
Dose: once daily with food |
|
Greater than or equal to 10 kg to less than 11 kg |
PREZISTA 3.6 mL‡ (350 mg) with ritonavir 0.8 mL (64 mg) |
|
Greater than or equal to 11 kg to less than 12 kg |
PREZISTA 4 mL‡ (385 mg) with ritonavir 0.8 mL (64 mg) |
|
Greater than or equal to 12 kg to less than 13 kg |
PREZISTA 4.2 mL (420 mg) with ritonavir 1 mL (80 mg) |
|
Greater than or equal to 13 kg to less than 14 kg |
PREZISTA 4.6 mL‡ (455 mg) with ritonavir 1 mL (80 mg) |
|
Greater than or equal to 14 kg to less than 15 kg |
PREZISTA 5 mL‡ (490 mg) with ritonavir 1.2 mL (96 mg) |
|
* darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V ‡ The 350 mg, 385 mg, 455 mg and 490 mg darunavir dose for the specified weight groups were rounded up for suspension dosing convenience to 3.6 mL, 4 mL, 4.6 mL and 5 mL, respectively. |
|
Pediatric patients weighing at least 15 kg can be dosed with PREZISTA oral tablet(s) or solution using the following table:
|
Table 3:
Recommended dose for pediatric patients weighing at least 15 kg who
are treatment-naïve or treatment‑experienced with no darunavir
resistance associated substitions* |
||
|
Body Weight (kg) |
Formulation: PREZISTA tablet(s) and ritonavir capsules or tablets (100 mg) |
Formulation: PREZISTA oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
|
|
Dose: once daily with food |
Dose: once daily with food |
|
Greater than or equal to 15 kg to less than 30 kg |
PREZISTA 600 mg with ritonavir 100 mg |
PREZISTA 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) |
|
Greater than or equal to 30 kg to less than 40 kg |
PREZISTA 675 mg with ritonavir 100 mg |
PREZISTA 6.8 mL§∫ (675 mg) with ritonavir 1.25 mL (100 mg) |
|
Greater than or equal to 40 kg |
PREZISTA 800 mg with ritonavir 100 mg |
PREZISTA 8 mL∫ (800 mg) with ritonavir 1.25 mL (100 mg) |
|
* darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V § The 675 mg dose using darunavir tablets for this weight group is rounded up to 6.8 mL for suspension dosing convenience. ∫ The 6.8 mL and 8 mL darunavir dose should be taken as two (3.4 mLor 4 mL, respectively) administrations with the included oral dosing syringe |
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6 Adverse Reactions: subsection 6.5 Clinical Trials Experience: Pediatric Patients
PREZISTA/ritonavir has been studied in combination with other antiretroviral agents in 3 Phase II trials. TMC114-C212, in which 80 antiretroviral treatment-experienced HIV-1-infected pediatric subjects 6 to less than 18 years of age and weighing at least 20 kg were included, TMC114-C228, in which 21 antiretroviral treatment-experienced HIV-1-infected pediatric subjects 3 to less than 6 years of age and weighing at least 10 kg were included, and TMC114-C230 in which 12 antiretroviral treatment‑naïve HIV‑1 infected pediatric patients aged from 12 to less than 18 years and weighing at least 40 kg were included. The TMC114-C212 and C228 trials evaluated PREZISTA/ritonavir twice daily dosing and the TMC114-C230 trial evaluated PREZISTA/ritonavir once daily dosing.
Study TMC114-C230
ADRs
to PREZISTA/ritonavir (all grades, greater than or equal to 3%),
excluding laboratory abnormalities reported as ADRs, were vomiting
(33%), nausea (25%), diarrhea (16.7%), abdominal pain (8.3%), decreased
appetite (8.3%), prurirtus (8.3%), and rash (8.3%).
There were no Grade 3 or 4 laboratory abnormalities considered as ADRs in this study.
In clinical trial TMC114-C230, the safety, pharmacokinetic profile and virologic and immunologic responses of PREZISTA/ritonavir administered once daily were evaluated in treatment‑naïve HIV‑1 infected pediatric subjects 12 to less than 18 years of age (12 subjects) [see Adverse Reactions (6.5), Clinical Pharmacology (12.3) and Clinical Studies (14.4)]. Frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see Adverse Reactions (6.1, 6.2)]. Once daily dosing recommendations for pediatric patients 3 to less than 12 years of age were derived using population pharmacokinetic modeling and simulation. Although a PREZISTA/ritonavir once daily dosing pediatric trial was not conducted in children less than 12 years of age, there is sufficient clinical safety data to support the predicted PREZISTA exposures for the dosing recommendations in this age group [see Clinical Pharmacology (12.3)]. Please see Dosage and Administration (2.2) for once-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg.
12.3 Pharmacokinetics: Pediatric Patients
PREZISTA/ritonavir administered once daily:
The pharmacokinetics of darunavir in combination with ritonavir in 12 antiretroviral treatment‑naïve HIV-1-infected pediatric subjects 12 to less than 18 years of age and weighing at least 40 kg receiving PREZISTA/ritonavir 800/100 mg once daily resulted in similar darunavir exposures when compared to the darunavir exposure achieved in treatment‑naive adults receiving PREZISTA/ritonavir 800/100 mg once daily. [see Dosage and Administration (2.2)].
Based on population pharmacokinetic modeling and simulation, the proposed PREZISTA/ritonavir once daily dosing regimens for pediatric patients 3 to less than 12 years of age is predicted to result in similar darunavir exposures when compared to the darunavir exposures achieved in treatment‑naïve adults receiving PREZISTA/ritonavir 800/100 mg once daily
14 Clinical Studies
Study TMC114-C230
Treatment-naïve
pediatric subjects between the ages of 12 and less than 18 years and
weighing at least 40 kg received the adult recommended dose of
PREZISTA/ritonavir 800/100 mg once daily plus background therapy
consisting of at least two non-protease inhibitor antiretroviral drugs.
The
12 randomized pediatric subjects had a median age of 14.4 years (range
12.6 to 17.3 years), and were 33.3% male, 58.3% Caucasian and 41.7%
Black. The mean baseline plasma HIV-1 RNA was 4.72 log10 copies/mL, and the median baseline CD4+ cell count was 282 cells/mm3 (range: 204 to 515 cells/mm3). Overall, 41.7% of pediatric subjects had baseline plasma HIV-1 RNA ³ 100,000 copies/mL.
All subjects completed the 48 week treatment period.
The
proportion of subjects with HIV-1 RNA less than 50 copies/mL and less
than 400 copies/mL was 83.3% and 91.7%, respectively. The mean change in
CD4+ cell count from baseline was 221 x 106 cells/L.
The revised label will be available soon on Drugs@FDA.
Prezista is a product of Janssen Therapeutics,
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
Division of Antiviral Products
Food and Drug Administration
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