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Azelastine Hydrochloride, Fluticasone Propionate
FDA Drug Information • Also known as: Azelastine Hydrochloride And Fluticasone Propionate
- Brand Names
- Azelastine Hydrochloride And Fluticasone Propionate
- Route
- NASAL
- Dosage Form
- SPRAY, METERED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Azelastine hydrochloride and fluticasone propionate nasal spray is formulated as a white, uniform metered-spray suspension for nasal administration. It is a fixed dose combination product containing an antihistamine (H 1 receptor antagonist) and a corticosteroid as active ingredients. Azelastine hydrochloride active ingredient occurs as a white, odorless, crystalline powder with a bitter taste. It has a molecular weight of 418.37. It is sparingly soluble in water, methanol, and propylene glycol and slightly soluble in ethanol, octanol, and glycerin. It has a melting point of 225°C and the pH of 5.2. Its chemical name is (±)-1-(2H)-phthalazinone,4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride. Its molecular formula is C 22 H 24 ClN 3 O
HCl with the following chemical structure: Fluticasone propionate active ingredient is a white powder with a melting point of 273°C, a molecular weight of 500.6, and the empirical formula is C 25 H 31 F 3 O 5 S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol. Fluticasone propionate is a synthetic corticosteroid having the chemical name S-(fluoromethyl)-6α,9α-difluoro-11β-17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, 17-propionate, and the following chemical structure: Azelastine hydrochloride and fluticasone propionate nasal spray, 137 mcg/50 mcg contains 0.1% solution of azelastine hydrochloride and 0.037% suspension of micronized fluticasone propionate in an isotonic aqueous suspension containing glycerin, microcrystalline cellulose and carboxymethylcellulose sodium, phenylethyl alcohol (2.5 mg/g), edetate disodium, benzalkonium chloride (0.1 mg/g), polysorbate 80, and purified water. It has a pH of approximately 6.0. After priming [see Dosage and Administration ( 2.2 )] , each metered spray delivers a 0.137 mL mean volume of suspension containing 137 mcg of...What Is Azelastine Hydrochloride, Fluticasone Propionate Used For?
1 INDICATIONS AND USAGE 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. Azelastine hydrochloride and fluticasone propionate nasal spray contains an H 1 -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
2 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 ) 2.1 Recommended Dosage The recommended dosage of azelastine hydrochloride and fluticasone propionate nasal spray is 1 spray (137 mcg of azelastine hydrochloride and 50 mcg of fluticasone propionate) in each nostril twice daily. 2.2 Important Administration Instructions Administer azelastine hydrochloride and fluticasone propionate nasal spray by the nasal route only. Shake the bottle gently before each use. Avoid spraying azelastine hydrochloride and fluticasone propionate nasal spray into the eyes. If sprayed in the eyes, flush eyes with water for at least 10 minutes. Priming Prime azelastine hydrochloride and fluticasone propionate nasal spray before initial use by releasing 6 sprays or until a fine mist appears. Repriming (as needed) When azelastine hydrochloride and fluticasone propionate nasal spray has not been used for 14 or more days, reprime with 1 spray or until a fine mist appears.Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:
Somnolence [see Warnings and Precautions ( 5.1 )] Local nasal effects, including epistaxis, nasal ulceration, nasal septal perforation, impaired wound healing, and Candida albicans infection [see Warnings and Precautions ( 5.2 )] Glaucoma and Cataracts [see Warnings and Precautions ( 5.3 )] Immunosuppression and Risk of Infections [see Warnings and Precautions ( 5.4 )] Hypercorticism and Adrenal Suppression, including growth reduction [see Warnings and Precautions ( 5.5 and 5.7 ), Use in Specific Populations ( 8.4 )] The most common adverse reactions (≥2% incidence) are: dysgeusia, epistaxis, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. Adults and Adolescents 12 Years of Age and Older The safety data described below in adults and adolescents 12 years of age and older reflect exposure to azelastine hydrochloride and fluticasone propionate nasal spray in 853 patients (12 years of age and older; 36% male and 64% female) with seasonal allergic rhinitis in 3 double-blind, placebo-controlled clinical trials of 2-week duration. The racial distribution for the 3 clinical trials was 80% white, 16% black, 2% Asian, and 1% other. In the 3 placebo controlled clinical trials of 2-week duration, 3411 patients with seasonal allergic rhinitis were treated with 1 spray per nostril of azelastine hydrochloride and fluticasone propionate nasal spray, azelastine hydrochloride nasal spray, fluticasone propionate nasal spray, or placebo, twice daily. The azelastine hydrochloride and fluticasone propionate comparators use the same vehicle and device as azelastine hydrochloride and fluticasone propionate nasal spray and are not commercially marketed. Overall, adverse reactions were 16% in the azelastine hydrochloride and fluticasone propionate nasal spray treatment groups, 15% in the azelastine hydrochloride nasal spray groups, 13% in the fluticasone propionate nasal spray groups, and 12% in the placebo groups. Overall, 1% of patients in both the azelastine hydrochloride and fluticasone propionate nasal spray and placebo groups discontinued due to adverse reactions. Table 1 contains adverse reactions reported with frequencies greater than or equal to 2% and more frequently than placebo in patients treated with azelastine hydrochloride and fluticasone propionate nasal spray in the seasonal allergic rhinitis controlled clinical trials. Table 1. Adverse Reactions with ≥2% Incidence and More Frequently than Placebo in Placebo-Controlled Trials of 2 Weeks Duration with Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray in Adult and Adolescent Patients with Seasonal Allergic Rhinitis 1 spray per nostril twice daily Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray (N=853)* Azelastine Hydrochloride Nasal Spray † (N=851) Fluticasone Propionate Nasal Spray † (N=846) Vehicle Placebo (N=861) Dysgeusia 30 (4%) 44 (5%) 4 (1%) 2 (<1%) Headache 18 (2%) 20 (2%) 20 (2%) 10 (1%) Epistaxis 16 (2%) 14 (2%) 14 (2%) 15 (2%) *Safety population N=853, intent-to-treat population N=848 † Not commercially marketed In the above trials, somnolence was reported in <1% of patients treated with azelastine hydrochloride and fluticasone propionate nasal spray (6 of 853) or vehicle placebo (1 of 861) [see Warnings and Precautions ( 5.1 )] . Pediatric Patients 6-11 Years of Age The safety data described below in children 6-11 years of age reflect exposure to azelastine hydrochloride and fluticasone propionate nasal spray in 152 patients (6-11 years of age;...Drug Interactions
7 DRUG INTERACTIONS No formal drug interaction studies have been performed with azelastine hydrochloride and fluticasone propionate nasal spray. The drug interactions of the combination are expected to reflect those of the individual components.
Potent inhibitors of cytochrome P450 (CYP) 3A4: May increase blood levels of fluticasone propionate. Ritonavir: Coadministration is not recommended. ( 5.6 , 7.2 ) Other potent CYP3A4 inhibitors, such as ketoconazole: use caution with coadministration. ( 5.6 , 7.2 ) 7.1 Central Nervous System Depressants Concurrent use of azelastine hydrochloride and fluticasone propionate nasal spray with alcohol or other central nervous system depressants should be avoided because somnolence and impairment of central nervous system performance may occur [see Warnings and Precautions ( 5.1 )] . 7.2 Cytochrome P450 3A4 Ritonavir (a strong CYP3A4 inhibitor) significantly increased plasma fluticasone propionate exposure following administration of fluticasone propionate aqueous nasal spray, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology ( 12.3 )] . During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. Ketoconazole (also a strong CYP3A4 inhibitor), administered in multiple 200 mg doses to steady-state, increased plasma exposure of fluticasone propionate, reduced plasma cortisol AUC, but had no effect on urinary excretion of cortisol, following administration of a single 1000 mcg dose of fluticasone propionate by oral inhalation route. Caution should be exercised when azelastine hydrochloride and fluticasone propionate nasal spray is coadministered with ketoconazole and other known strong CYP3A4 inhibitors.Contraindications
4 CONTRAINDICATIONS Azelastine hydrochloride and fluticasone propionate nasal spray is contraindicated in patients with hypersensitivity to azelastine hydrochloride, fluticasone propionate, or to any other ingredients of azelastine hydrochloride and fluticasone propionate nasal spray. Reactions have included anaphylaxis [see Adverse Reactions ( 6.2 )] . Hypersensitivity to azelastine hydrochloride, fluticasone propionate, or to any ingredients of azelastine hydrochloride and fluticasone propionate nasal spray. Reactions have included anaphylaxis. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy 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/m 2 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...
Overdosage
10 OVERDOSAGE Azelastine hydrochloride and fluticasone propionate nasal spray: Azelastine hydrochloride and fluticasone propionate nasal spray contains both azelastine hydrochloride and fluticasone propionate; therefore, the risks associated with overdosage for the individual components described below apply to azelastine hydrochloride and fluticasone propionate nasal spray. Azelastine hydrochloride: There have been no reported overdosages with azelastine hydrochloride. Acute azelastine hydrochloride overdosage by adults with this dosage form is unlikely to result in clinically significant adverse reactions, other than increased somnolence, since one (1) 23 g bottle of azelastine hydrochloride and fluticasone propionate nasal spray contains approximately 23 mg of azelastine hydrochloride. General supportive measures should be employed if overdosage occurs. There is no known antidote to azelastine hydrochloride and fluticasone propionate nasal spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in children. Accordingly, azelastine hydrochloride and fluticasone propionate nasal spray should be kept out of the reach of children. Fluticasone propionate: Chronic fluticasone propionate overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions ( 5.5 )].
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied: Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray, 137 mcg/50 mcg (NDC 45802-066-01) is supplied as follows:
amber glass bottle fitted with a metered-dose spray pump unit, or white HDPE bottle fitted with a metered-dose spray pump unit The spray pump unit consists of a nasal spray pump with a white nasal adapter and clear plastic dust 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 dust cap in place at controlled room temperature 20°C to 25°C (68°F to 77°F). [see USP Controlled Temperature] Protect from light. Do not store in the freezer or refrigerator.About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.