Approved Drug Label (PDF)
8
Use in Specific Populations
8.4 Pediatric Use
The safety and effectiveness
of RAPIVAB for the treatment of influenza has been established in pediatric patients 6 months to 17 years
of age. Use of RAPIVAB for this indication is supported by evidence
from adequate and well-controlled trials of RAPIVAB in adults with
additional data from Study 305, a
randomized, active-controlled trial of 130
adolescent and pediatric subjects
with acute uncomplicated influenza who received open-label treatment
with a single dose of RAPIVAB or 5 days of treatment with oseltamivir administered
within 48 hours of onset of symptoms of influenza [see Dosage and Administration (2.1, 2.2, 2.3), Adverse
Reactions (6.1), Clinical Pharmacology
(12.3), and Clinical Studies
(14.2)]. Study 305 included:
13
to 17 years of age: 21 subjects treated with RAPIVAB 600 mg
6 months
to 12 years of age: 86 subjects
treated with RAPIVAB 12 mg/kg (up to a maximum dose of 600 mg)
Safety
and effectiveness of RAPIVAB in pediatric patients less than 6
months of age have not been established.
No data are available for
RAPIVAB use in pediatric patients 6
months to less than 2 years with creatinine clearance less than 50 mL/min to inform a
recommendation for dosage adjustment [see Dosage and Administration (2.2) and Clinical
Pharmacology (12.3)].
8.6 Patients with Impaired Renal Function
(Newly
added information)
No data are available for RAPIVAB use in pediatric patients 6 months
to less than 2 years with creatinine
clearance less than 50 mL/min
to inform a recommendation for
dosage adjustment [see Dosage and
Administration (2.2) and Clinical
Pharmacology (12.3)].
Approved Drug Label (PDF)
6
Adverse Reactions
6.1 Clinical Trials Experience
(additions underlined)
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in practice.
Adverse Reactions in Adults (18 years of age and older)
In five randomized, double-blind, controlled trials,
1,399 subjects with acute uncomplicated influenza received a single dose of
RAPIVAB, administered intravenously or intramuscularly, at doses up to 600 mg.
Among the 664 subjects receiving RAPIVAB 600 mg (intravenous or intramuscular),
the most commonly observed adverse reaction was diarrhea, occurring at a rate
of 8% versus 7% in subjects receiving placebo. No subject receiving RAPIVAB 600
mg experienced a serious adverse event and less than 1% discontinued study
because of an adverse reaction.
Clinically significant laboratory abnormalities (DAIDS
Grade 2-4) listed in Table 3 occurred more frequently in subjects
treated with RAPIVAB 600 mg (intravenous or intramuscular) than placebo. Only
events occurring at greater than or equal to 2% are included.
Table 3: Laboratory Abnormalities Occurring in ?2% of
Subjects Treated with RAPIVAB 600 mg
(please refer to label to view Table 3)
Adverse Reactions in Adolescent and Pediatric Subjects
(2 to 17 years of age)
Assessment of adverse reactions is based on a
randomized, active-controlled study in which 110 adolescent and pediatric
subjects ages 2 to 17 years of age with acute uncomplicated influenza received
open-label treatment with a single dose of RAPIVAB (N=88), or 5 days of
treatment with oseltamivir (N=22).
The safety profile of RAPIVAB in subjects 2 to 17 years
of age was generally similar to that observed in adults. Specific adverse
reactions reported in pediatric subjects treated with RAPIVAB (occurring in
greater than or equal 2% of subjects) and not reported
in adults included vomiting (3% versus 9% for oseltamivir), fever and tympanic
membrane erythema (2% versus 0%, respectively, for each of these events). The
only clinically significant laboratory abnormality (DAIDS Grade 2) occurring in
greater than or equal to 2% of pediatric subjects treated with RAPIVAB was
proteinuria by dipstick analysis (3% versus 0% for oseltamivir).
8
Use in Specific Populations
8.1 Pregnancy
(PLLR
conversion)
Risk Summary
Limited
available data with RAPIVAB use in pregnant women are insufficient to determine
a drug- associated risk of adverse developmental outcomes. There are risks to
the mother and fetus associated with influenza in pregnancy [see Clinical Considerations]. In animal
reproduction studies, no adverse developmental effects were observed in rats
when peramivir was administered by intravenous bolus injection during
organogenesis at the maximum feasible dose, resulting in systemic drug
exposures (AUC) approximately 8 times those in humans at the recommended dose.
However, when peramivir was administered to rats by continuous intravenous
infusion during the same gestation period, fetal abnormalities of reduced renal
papilla and dilated ureters were observed. In rabbits, administration of
peramivir during organogenesis at exposures 8 times those in humans at the
recommended dose resulted in developmental toxicity (abortion or premature
delivery) at a maternally toxic dose [see
Data].
The estimated
background risk of major birth defects and miscarriage for the indicated
population is unknown. All pregnancies have a background risk of birth defect,
loss, or other adverse outcomes. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Pregnant women
are at higher risk of severe complications from influenza, which may lead to
adverse pregnancy and/or fetal outcomes including maternal death, stillbirths,
birth defects, preterm delivery, low birthweight, and small for gestational
age.
Data
Animal Data
Reproductive
toxicity studies have been performed in rats and rabbits. In rats, peramivir
was administered once daily by intravenous bolus injection at doses of 200,
400, and 600 mg/kg/day on gestational days 6-17. No treatment-related fetal
toxicities were observed when peramivir was administered by intravenous bolus
injection at the maximum feasible dose of 600 mg/kg, resulting in exposures
approximately 8 times those in humans at the recommended dose.
Peramivir was
also administered by continuous intravenous infusion to rats at daily doses of
50, 400, and 1000 mg/kg/day on gestational days 6-17. Dose related increases in
the incidence of fetal abnormalities of reduced renal papilla and dilated
ureters were observed at 400 and 1000 mg/kg/day. The systemic drug exposure in
rats at a dose without fetal effects was less than the exposures in humans at
the recommended dose.
In rabbits,
peramivir was administered once daily by intravenous bolus injection at doses
of 25, 50, 100, and 200 mg/kg/day on gestational days 7-19. Developmental
toxicity (abortion or premature delivery) was observed at maternally toxic dose
levels (100 and 200 mg/kg/day) resulting in exposures approximately 8 times
those in humans at the recommended dose. The exposure in
rabbits at
doses without developmental toxicity was less than the exposure in humans at
the recommended dose.
RAPIVABA
pre/post-natal developmental toxicity study was performed in pregnant rats administered
peramivir once daily by intravenous infusion at doses of 50, 200, 400 and 600
mg/kg/day on gestational day 6 through lactation day 20. No significant effects
of peramivir on developmental outcomes were observed in nursing pups at up to
the highest dose tested.
8.2 Lactation
(PLLR
conversion, additions underlined)
Risk Summary
There are no
data on the presence of RAPIVAB in human milk, the effects on the breastfed
infant, or the effects on milk production. Peramivir is present in rat milk [see Data]. Limited clinical data during
lactation preclude a clear determination of the risk of RAPIVAB to an infant
during lactation; therefore, the developmental and health benefits of breastfeeding
should be considered along with the mother’s clinical need for RAPIVAB and any
potential adverse effects on the breastfed child from the drug or from the
underlying maternal condition.
StudiesData
pharmacokinetic
study was performed in lactating rats administered a single intravenous dose of
peramivir (10 mg/kg) on lactation/postpartum days 11-13. The maximum
concentration of peramivir in milk was reached at 0.75 hours post-dose. The
milk to plasma AUC ratio of peramivir was approximately 0.5.
8.4 Pediatric Use
(subsection
revised, additions underlined)
The safety and
effectiveness of RAPIVAB for the treatment of influenza has been established in
pediatric patients 2 to 17 years of age. Use of RAPIVAB for this indication is
supported by evidence from adequate and well-controlled trials of RAPIVAB in
adults with additional data from Study 305, a randomized, active-controlled
trial of 110 adolescent and pediatric subjects with acute uncomplicated
influenza who received open-label treatment with a single dose of RAPIVAB or 5
days of treatment with oseltamivir administered within 48 hours of onset of
symptoms of influenza. Study 305
included:
13 to 17 years of age: 21 subjects treated with RAPIVAB
600 mg
2 to 12 years of age: 67 subjects treated with RAPIVAB
12 mg/kg (up to a maximum dose of 600 mg)
Safety and
effectiveness of RAPIVAB in pediatric patients less than 2 years of age
have not been established.
Get Email Alerts |
Guide
