Country: United States
Language: English
Source: NLM (National Library of Medicine)
AZELASTINE HYDROCHLORIDE (UNII: 0L591QR10I) (AZELASTINE - UNII:ZQI909440X), FLUTICASONE PROPIONATE (UNII: O2GMZ0LF5W) (FLUTICASONE - UNII:CUT2W21N7U)
Apotex Corp.
NASAL
PRESCRIPTION DRUG
Azelastine hydrochloride and fluticasone propionate nasal spray is indicated for the relief of symptoms of seasonal allergic rhinitis in adult and pediatric patients 6 years of age and older. None. Risk Summary Limited data from postmarketing experience with azelastine hydrochloride and fluticasone propionate nasal spray in pregnant women have not identified any drug associated risks of miscarriage, birth defects, or other adverse maternal or fetal outcomes. The individual components of azelastine hydrochloride and fluticasone propionate nasal spray have been marketed for decades. While the data regarding the use of nasal preparations of fluticasone propionate in pregnancy are limited, data from clinical studies of inhaled fluticasone propionate do not indicate an increased risk of adverse maternal or fetal outcomes. Animal reproduction studies with azelastine hydrochloride and fluticasone propionate nasal spray are not available; however, studies are available with its individual components, azelastine hydrochloride and fluticasone propionate. In animal reproduction studies, there was no evidence of fetal harm in animals at oral doses of azelastine hydrochloride approximately 10 times the clinical daily dose. Oral administration of azelastine hydrochloride to pregnant mice, rats, and rabbits, during the period of organogenesis, produced developmental toxicity that included structural abnormalities, decreased embryo-fetal survival, and decreased fetal body weights at doses 530 times and higher than the maximum recommended human daily nasal dose (MRHDID) of 0.548 mg. However, the relevance of these findings in animals to pregnant women was considered questionable based upon the high animal to human dose multiple. In animal reproduction studies, fluticasone propionate administered via nose-only 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. Teratogenicity, characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the MRHDID of 200 mcg on a mcg/m2 basis (see Data). Experience with corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. The estimated background risk of major birth defects and miscarriage for the indicated populations 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 to 4% and 15 to 20%, respectively. Data Animal Data : Azelastine Hydrochloride: In an embryo-fetal development study in mice dosed during the period of organogenesis, azelastine hydrochloride caused embryo-fetal death, structural abnormalities (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification, and decreased fetal weight at approximately 610 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day), which also caused maternal toxicity as evidenced by decreased maternal body weight. Neither fetal nor maternal effects occurred in mice at approximately 25 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 3 mg/kg/day). In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 7 to 17, azelastine hydrochloride caused structural abnormalities (oligo-and brachydactylia), delayed ossification, and skeletal variations, in the absence of maternal toxicity, at approximately 530 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Azelastine hydrochloride caused embryo-fetal death and decreased fetal weight and severe maternal toxicity at approximately 1200 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 55 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 3 mg/kg/day). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, azelastine hydrochloride caused abortion, delayed ossification and decreased fetal weight and severe maternal toxicity at approximately 1100 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 10 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 0.3 mg/kg/day). In a prenatal and postnatal development study in pregnant rats dosed from late in the gestation period and through the lactation period from gestation day 17 through lactation day 21, azelastine hydrochloride produced no adverse developmental effects on pups at maternal doses up to approximately 530 times the MRHDID (on mg/m2 basis at a maternal dose of 30 mg/kg/day). Fluticasone Propionate: 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 5 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). Neither fetal nor maternal effects occurred in rats at approximately 1 times the MRHDID (on a mg/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 1 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). Neither fetal nor maternal effects occurred in mice with a dose approximately 0.4 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day). In an embryofetal development study with pregnant rats dosed by the nose-only 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 1 times the MRHDID (on a mg/m2 basis with a maternal nose-only inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. Neither fetal nor maternal effects occurred in rats with a dose approximately 0.25 times the MRHDID (on a mg/m2 basis with a maternal nose-only 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 0.06 times the MRHDID and higher (on a mg/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 dose approximately 0.4 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). Neither fetal nor maternal effects occurred in rabbits with a dose approximately 0.01 times the MRHDID (on a mg/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 2 times the MRHDID (on a mg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day). Risk Summary There are no available data on the presence of azelastine hydrochloride or fluticasone propionate in human milk, the effects on the breastfed infant, or the effects on milk production. Breastfed infants should be monitored for signs of milk rejection during azelastine hydrochloride and fluticasone propionate nasal spray use by lactating women (see Clinical Considerations). Fluticasone propionate is present in rat milk (see Data). Other corticosteroids have been detected in human milk. However, fluticasone propionate concentrations in plasma after nasal 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 azelastine hydrochloride and fluticasone propionate nasal spray and any potential adverse effects on the breastfed infant from azelastine hydrochloride and fluticasone propionate nasal spray or from the underlying maternal condition. Clinical Considerations Monitoring for Adverse Reactions : Breastfed infants of lactating women treated with azelastine hydrochloride and fluticasone propionate nasal spray should be monitored for possible signs of milk rejection related to the bitter taste of azelastine hydrochloride. Data Subcutaneous administration of 10 mcg/kg of tritiated fluticasone propionate to lactating rats resulted in measurable radioactivity in the milk. The safety and effectiveness of azelastine hydrochloride and fluticasone propionate nasal spray for seasonal allergic rhinitis have been established in pediatric patients aged 6 years and older. Use of azelastine hydrochloride and fluticasone propionate nasal spray for this indication in pediatric patients 6 to 11 years of age is supported by evidence from controlled clinical trials (416 patients 6 to 11 years of age with allergic rhinitis were treated with azelastine hydrochloride and fluticasone propionate nasal spray) [see Adverse Reactions(6.1) and Clinical Studies (14)] . Sixty-one patients ages 4 to 5 years of age were treated with azelastine hydrochloride and fluticasone propionate in the pediatric studies described above. Safety findings in children 4 to 5 years of age were similar to those in children 6 to 11 years of age, but effectiveness has not been established. Safety and effectiveness of azelastine hydrochloride and fluticasone propionate nasal spray have not been established in pediatric patients below the age of 4 years. Controlled clinical studies have shown that nasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been 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 nasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with nasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving nasal corticosteroids, including azelastine hydrochloride and fluticasone propionate nasal spray, 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/benefits of treatment alternatives. Clinical trials of azelastine hydrochloride and fluticasone propionate nasal spray did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Azelastine hydrochloride and fluticasone propionate nasal spray (NDC 60505-0953-3) is supplied as an amber glass bottle fitted with a metered-dose spray pump unit. The spray pump unit consists of a nasal spray pump with a white plastic actuator and translucent plastic cap. Each bottle contains a net fill weight of 23 g and will deliver 120 metered sprays after priming [see Dosage and Administration (2.2) ]. After priming [see Dosage and Administration (2.2) ], each spray delivers a suspension volume of 0.137 mL as a fine mist, containing 137 mcg of azelastine hydrochloride and 50 mcg of fluticasone propionate (137 mcg/50 mcg). The correct amount of medication in each spray cannot be assured before the initial priming and after 120 sprays have been used, even though the bottle is not completely empty. The bottle should be discarded after 120 sprays have been used. Azelastine hydrochloride and fluticasone propionate nasal spray should not be used after the expiration date “EXP” printed on the bottle label and carton. Storage Store upright with the cap in place at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light. Do not store in the freezer or refrigerator.
Abbreviated New Drug Application
AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE- AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE SPRAY, METERED APOTEX CORP. ---------- HIGHLIGHTS OF PRESCRIBING INFORMATION THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE NASAL SPRAY SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE NASAL SPRAY. AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE NASAL SPRAY INITIAL U.S. APPROVAL: 2012 INDICATIONS AND USAGE Azelastine hydrochloride and fluticasone propionate nasal spray contains an H -receptor antagonist and a corticosteroid, and is indicated for the relief of symptoms of seasonal allergic rhinitis in adult and pediatric patients 6 years of age and older. (1) DOSAGE AND ADMINISTRATION Recommended dosage: 1 spray per nostril twice daily (2.1) For nasal use only. (2.2) Prime before initial use and when it has not been used for 14 or more days. (2.2) DOSAGE FORMS AND STRENGTHS Nasal spray: 137 mcg of azelastine hydrochloride and 50 mcg of fluticasone propionate in each spray. (3) CONTRAINDICATIONS None. (4) WARNINGS AND PRECAUTIONS Somnolence: Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking azelastine hydrochloride and fluticasone propionate nasal spray. (5.1) Avoid concurrent use of alcohol or other central nervous system (CNS) depressants with azelastine hydrochloride and fluticasone propionate nasal spray because further decreased alertness and impairment of CNS performance may occur. (5.1) Epistaxis, nasal ulcerations, nasal septal perforation, impaired wound healing, _Candida albicans_ infection: Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma. (5.2) Glaucoma or posterior subcapsular cataracts: Monitor patients closely with a change in vision or with a history of increased intraocular p Read the complete document