FLUTICASONE PROPIONATE HFA- fluticasone propionate aerosol, metered

Država: Sjedinjene Američke Države

Jezik: engleski

Izvor: NLM (National Library of Medicine)

Aktivni sastojci:

FLUTICASONE PROPIONATE (UNII: O2GMZ0LF5W) (FLUTICASONE - UNII:CUT2W21N7U)

Dostupno od:

A-S Medication Solutions

Administracija rute:

RESPIRATORY (INHALATION)

Tip recepta:

PRESCRIPTION DRUG

Terapijske indikacije:

Fluticasone Propionate HFA is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients aged 4 years and older. Limitations of Use Fluticasone Propionate HFA is not indicated for the relief of acute bronchospasm. Fluticasone Propionate HFA is contraindicated in the following conditions: Risk Summary There are insufficient data on the use of fluticasone propionate HFA in pregnant women. There are clinical considerations with the use of fluticasone propionate HFA in pregnant women. (See Clinical Considerations.) In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations in rats, mice, and rabbits, was observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (MRHDID) on a mcg/m2 basis. (See Data.) However, fluticasone propionate administered via inhalation to rats decreased fetal body weight but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m2 basis. (See Data.) Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. The estimated risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Data Human Data: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery. Animal Data: In embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 0.5 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). The rat no observed adverse effect level (NOAEL) was observed at approximately 0.17 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.1 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). The mouse NOAEL was observed with a dose approximately 0.04 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day). In an embryofetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.14 times the MRHDID (on a mcg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. The NOAEL was observed with a dose approximately 0.03 times the MRHDID (on a mcg/m2 basis with a maternal inhalation dose of 5.5 mcg/kg/day). In an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.006 times the MRHDID and higher (on a mcg/m2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day). Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose approximately 0.04 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). The NOAEL was observed in rabbit fetuses with a dose approximately 0.001 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day). Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits. In a pre- and post-natal development study in pregnant rats dosed from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 0.3 times the MRHDID (on a mcg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day). Risk Summary There are no available data on the presence of fluticasone propionate in human milk, the effects on the breastfed child, or the effects on milk production. Other corticosteroids have been detected in human milk. However, fluticasone propionate concentrations in plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low [see Clinical Pharmacology (12.3)] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluticasone propionate HFA and any potential adverse effects on the breastfed child from fluticasone propionate HFA or from the underlying maternal condition. Data Animal Data: Subcutaneous administration of tritiated fluticasone propionate at a dose of 10 mcg/kg/day to lactating rats resulted in measurable levels in milk. The safety and effectiveness of fluticasone propionate HFA in pediatric patients aged 4 years and older have been established [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2)] . Use of fluticasone propionate HFA in patients aged 4 to 11 years is supported by evidence from adequate and well-controlled trials in adults and adolescents aged 12 years and older, pharmacokinetic trials in patients aged 4 to 11 years, established efficacy of fluticasone propionate formulated as FLOVENT DISKUS (fluticasone propionate inhalation powder) and FLOVENT ROTADISK (fluticasone propionate inhalation powder) in patients aged 4 to 11 years, and supportive findings with fluticasone propionate HFA in a trial conducted in subjects aged 4 to 11 years. The safety and effectiveness of fluticasone propionate HFA in pediatric patients younger than 4 years have not been established. Effects on Growth Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. A reduction of growth velocity in children or teenagers may occur as a result of poorly controlled asthma or from use of corticosteroids including ICS. The effects of long-term treatment of children and adolescents with ICS, including fluticasone propionate, on final adult height are not known. Controlled clinical trials have shown that ICS may cause a reduction in growth in pediatric patients. In these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appeared to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The effects on growth velocity of treatment with orally inhaled corticosteroids for over 1 year, including the impact on final adult height, are unknown. The growth of children and adolescents receiving orally inhaled corticosteroids, including Fluticasone Propionate HFA, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including Fluticasone Propionate HFA, each patient should be titrated to the lowest dose that effectively controls his/her symptoms. Since a cross trial comparison in adult and adolescent subjects (aged 12 years and older) indicated that systemic exposure of inhaled fluticasone propionate from fluticasone propionate HFA would be higher than exposure from FLOVENT ROTADISK, results from a trial to assess the potential growth effects of FLOVENT ROTADISK in pediatric subjects (aged 4 to 11 years) are provided. A 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (FLOVENT ROTADISK) at 50 and 100 mcg twice daily was conducted in the U.S. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. The mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89). An imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. A separate subset analysis of children who remained prepubertal during the trial revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79). In children aged 8.5 years, the mean age of children in this trial, the range for expected growth velocity is: boys – 3rd percentile = 3.8 cm/year, 50th percentile = 5.4 cm/year, and 97th percentile = 7.0 cm/year; girls – 3rd percentile = 4.2 cm/year, 50th percentile = 5.7 cm/year, and 97th percentile = 7.3 cm/year. The clinical relevance of these growth data is not certain. Pediatric Patients Younger than 4 Years Pharmacokinetics: [see Clinical Pharmacology (12.3)] . Pharmacodynamics: A 12-week, double-blind, placebo-controlled, parallel-group trial was conducted in children with asthma aged 1 to younger than 4 years. Twelve-hour overnight urinary cortisol excretion after a 12-week treatment period with 88 mcg of fluticasone propionate HFA twice daily (n = 73) and with placebo (n = 42) were calculated. The mean and median change from baseline in urine cortisol over 12 hours were -0.7 and 0.0 mcg for fluticasone propionate HFA and 0.3 and -0.2 mcg for placebo, respectively. In a 1-way crossover trial in children aged 6 to younger than 12 months with reactive airways disease (N = 21), serum cortisol was measured over a 12-hour dosing period. Subjects received placebo treatment for a 2-week period followed by a 4-week treatment period with 88 mcg of fluticasone propionate HFA twice daily with an AeroChamber Plus Valved Holding Chamber (VHC) with mask. The geometric mean ratio of serum cortisol over 12 hours [AUC(0-12 h) ] following fluticasone propionate HFA (n = 16) versus placebo (n = 18) was 0.95 (95% CI: 0.72, 1.27). Safety: Fluticasone propionate HFA administered as 88 mcg twice daily was evaluated for safety in 239 pediatric subjects aged 1 to younger than 4 years in a 12-week, double-blind, placebo-controlled trial. Treatments were administered with an AeroChamber Plus VHC with mask. The following events occurred with a frequency >3% and more frequently in subjects receiving fluticasone propionate HFA than in subjects receiving placebo, regardless of causality assessment: pyrexia, nasopharyngitis, upper respiratory tract infection, vomiting, otitis media, diarrhea, bronchitis, pharyngitis, and viral infection. Fluticasone propionate HFA administered as 88 mcg twice daily was evaluated for safety in 23 pediatric subjects aged 6 to 12 months in an open-label placebo-controlled trial. Treatments were administered with an AeroChamber Plus VHC with mask for 2 weeks with placebo followed by 4 weeks with active drug. There was no discernable difference in the types of adverse events reported between subjects receiving placebo compared with the active drug. In Vitro Testing of Dose Delivery with Holding Chambers: In vitro dose characterization studies were performed to evaluate the delivery of fluticasone propionate HFA via holding chambers with attached masks. The studies were conducted with 2 different holding chambers (AeroChamber Plus VHC and AeroChamber Z-STAT Plus VHC) with masks (small and medium size) at inspiratory flow rates of 4.9, 8.0, and 12.0 L/min in combination with holding times of 0, 2, 5, and 10 seconds. The flow rates were selected to be representative of inspiratory flow rates of children aged 6 to 12 months, 2 to 5 years, and over 5 years, respectively. The mean delivered dose of fluticasone propionate through the holding chambers with masks was lower than the 44 mcg of fluticasone propionate delivered directly from the actuator mouthpiece. The results were similar through both holding chambers (see Table 2 for data for the AeroChamber Plus VHC). The fine particle fraction (approximately 1 to 5 μm) across the flow rates used in these studies was 70% to 84% of the delivered dose, consistent with the removal of the coarser fraction by the holding chamber. In contrast, the fine particle fraction for fluticasone propionate HFA delivered without a holding chamber typically represents 42% to 55% of the delivered dose measured at the standard flow rate of 28.3 L/min. These data suggest that, on a per kilogram basis, young children receive a comparable dose of fluticasone propionate when delivered via a holding chamber and mask as adults do without their use. Age Mask Flow Rate (L/min) Holding Time (seconds) Mean Medication Delivery through AeroChamber Plus Valved Holding Chamber (mcg/actuation) Body Weight 50th Percentile (kg)a Medication Delivered per Actuation (mcg/kg)b 6 to 12 Months Small 4.9 2 5 10 8.3 6.7 7.5 7.5 7.5-9.9 0.8-1.1 0.7-0.9 0.8-1.0 0.8-1.0 2 to 5 Years Small 8.0 2 5 10 7.3 6.8 6.7 7.7 12.3-18.0 0.4-0.6 0.4-0.6 0.4-0.5 0.4-0.6 2 to 5 Years Medium 8.0 2 5 10 7.8 7.7 8.1 9.0 12.3-18.0 0.4-0.6 0.4-0.6 0.5-0.7 0.5-0.7 >5 Years Medium 12.0 2 5 10 12.3 11.8 12.0 10.1 18.0 0.7 0.7 0.7 0.6 Of the total number of subjects treated with fluticasone propionate HFA in U.S. and non-U.S. clinical trials, 173 were aged 65 years or older, 19 of which were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Formal pharmacokinetic studies using fluticasone propionate HFA have not been conducted in patients with hepatic impairment. Since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. Therefore, patients with hepatic disease should be closely monitored. Formal pharmacokinetic studies using fluticasone propionate HFA have not been conducted in patients with renal impairment.

Proizvod sažetak:

Product: 50090-6053 NDC: 50090-6053-0 120 AEROSOL, METERED in a INHALER / 1 in a CARTON

Status autorizacije:

New Drug Application Authorized Generic

Svojstava lijeka

FLUTICASONE PROPIONATE HFA- FLUTICASONE PROPIONATE AEROSOL, METERED
A-S MEDICATION SOLUTIONS
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
FLUTICASONE PROPIONATE
HFA SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
FLUTICASONE PROPIONATE HFA.
FLUTICASONE PROPIONATE HFA INHALATION AEROSOL, FOR ORAL INHALATION USE
INITIAL U.S. APPROVAL: 1994
INDICATIONS AND USAGE
Fluticasone Propionate HFA is an inhaled corticosteroid indicated for:
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Limitations of use: Not indicated for relief of acute bronchospasm.
(1)
DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Inhalation aerosol:
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CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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ADVERSE REACTIONS
Most common adverse reactions (incidence >3%) are upper respiratory
tract infection or inflammation,
throat irritation, sinusitis, dysphonia, candidiasis, cough,
bronchitis, and headache. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT PRASCO LABORATORIES AT
1-866-525-0688
OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
Maintenance treatment of asthma as prophylactic therapy in adult and
pediatric patients aged 4
years and older. (1)
For oral inhalation only. (2.1)
Starting dosage is based on prior asthma therapy and disease severity.
(2.2)
Adult and adolescent patients aged 12 years and older: 88 mcg twice
daily up to a maximum dosage
of 880 mcg twice daily. (2.2)
Pediatric patients aged 4 to 11 years: 88 mcg twice daily. (2.2)
44 mcg fluticasone propionate per actuation (3)
110 mcg fluticasone propionate per actuation (3)
220 mcg fluticasone propionate per actuation (3)
Primary treatment of status asthmaticus or acute episodes of asthma
requiring intensive measures.
(4)
Hypersensitivity to any ingredient. (4)
_Candida albicans_ infection of the mouth and pharynx may occur.
Monitor patients periodically. Advise
the patient to rinse his/her mouth with water without swallowing after
inhalation to help reduce the
ri