Generic: AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE
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 )
5 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 pressure, glaucoma, and/or cataracts. ( 5.3 ) Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections. ( 5.4 ) Hypercorticism and adrenal suppression with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue azelastine hydrochloride and fluticasone propionate nasal spray slowly. ( 5.5 ) Potential reduction in growth velocity in children. Monitor growth routinely in pediatric patients receiving azelastine hydrochloride and fluticasone propionate nasal spray. ( 5.7 , 8.4 ) 5.1 Somnolence In clinical trials, the occurrence of somnolence has been reported in some patients (6 of 853 adult and adolescent patients and 2 of 416 children) taking azelastine hydrochloride and fluticasone propionate nasal spray in placebo controlled trials [see Adverse Reactions (6.1)] . Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as operating machinery or driving a motor vehicle after administration of azelastine hydrochloride and fluticasone propionate nasal spray. Concurrent use of azelastine hydrochloride and fluticasone propionate nasal spray with alcohol or other central nervous system depressants should be avoided because additional reductions in alertness and additional impairment of central nervous system performance may occur [see Drug Interactions (7.1)] . 5.2 Local Nasal Effects In clinical trials of 2 to 52 weeks’ duration, epistaxis was observed more frequently in patients treated with azelastine hydrochloride and fluticasone propionate nasal spray than those who received placebo [see Adverse Reactions (6)] . Instances of nasal ulceration and nasal septal perforation have been reported in patients following the nasal application of corticosteroids. There were no instances of nasal ulceration or nasal septal perforation observed in clinical trials with azelastine hydrochloride and fluticasone propionate nasal spray. Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should avoid use of azelastine hydrochloride and fluticasone propionate nasal spray until healing has occurred. In clinical trials with fluticasone propionate administered nasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of treatment with azelastine hydrochloride and fluticasone propionate nasal spray. Patients using azelastine hydrochloride and fluticasone propionate nasal spray over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa. 5.3 Glaucoma and Cataracts Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. Glaucoma and cataract formation were evaluated with intraocular pressure measurements and slit lamp examinations in a controlled 12-month study in 612 adolescent and adult patients aged 12 years and older with perennial allergic or vasomotor rhinitis (VMR). Of the 612 patients enrolled in the study, 405 were randomized to receive azelastine hydrochloride and fluticasone propionate nasal spray (1 spray per nostril twice daily) and 207 were randomized to receive fluticasone propionate nasal spray (2 sprays per nostril once daily). In the azelastine hydrochloride and fluticasone propionate nasal spray group, one patient had increased intraocular pressure at month 6. In addition, three patients had evidence of posterior subcapsular cataract at month 6 and one at month 12 (end of treatment). In the fluticasone propionate group, three patients had evidence of posterior subcapsular cataract at month 12 (end of treatment). 5.4 Immunosuppression and Risk of Infections Persons who are using drugs, such as corticosteroids, that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective Prescribing Information for VZIG and IG). If chickenpox develops, treatment with antiviral agents may be considered. Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract; untreated local or systemic fungal or bacterial infections; systemic viral or parasitic infections; or ocular herpes simplex because of the potential for worsening of these infections. 5.5 Hypercorticism and Adrenal Suppression When nasal steroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of azelastine hydrochloride and fluticasone propionate nasal spray should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy. The concomitant use of nasal corticosteroids with other inhaled corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis. The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency, and in addition some patients may experience symptoms of withdrawal, e.g., joint and/or muscular pain, lassitude, and depression. Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In those patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms. 5.6 Use of Cytochrome P450 3A4 Inhibitors Ritonavir and other strong cytochrome P450 3A4 (CYP3A4) inhibitors can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Drug Interactions (7.2) and 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 azelastine hydrochloride and fluticasone propionate nasal spray and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. Use caution with the coadministration of azelastine hydrochloride and fluticasone propionate nasal spray and other potent CYP3A4 inhibitors, such as ketoconazole [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)] . 5.7 Effect on Growth Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely of pediatric patients receiving azelastine hydrochloride and fluticasone propionate nasal spray [see Use in Specific Populations (8.4)] .
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 Teva at 1-888-838-2872 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 to 11 Years of Age The safety data described below in children 6 to 11 years of age reflect exposure to azelastine hydrochloride and fluticasone propionate nasal spray in 152 patients (6 to 11 years of age; 57% male and 43% female) with seasonal allergic rhinitis in one double-blind, placebo-controlled clinical trial of 2-week duration. The racial distribution for the clinical trial was 69% white, 31% black, 2% Asian and 2% other. In the placebo-controlled clinical trial of 2-week duration, patients with seasonal allergic rhinitis were treated with 1 spray per nostril of azelastine hydrochloride and fluticasone propionate nasal spray or placebo, twice daily. Overall, adverse reactions were 16% in the azelastine hydrochloride and fluticasone propionate nasal spray treatment group, and 12% in the placebo group. Overall, 1% of patients in both the azelastine hydrochloride and fluticasone propionate nasal spray and placebo groups discontinued due to adverse reactions. Table 2 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 trial. Table 2. 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 Children 6 to 11 Years of Age with Seasonal Allergic Rhinitis 1 spray per nostril twice daily Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray (N=152)* Vehicle Placebo (N=152) Dysgeusia 6 (4%) 0 (0%) Epistaxis 6 (4%) 4 (3%) * Safety population N=152, intent-to-treat population N=152 In the above trial, somnolence was not reported [see Warnings and Precautions (5.1)] . Long-Term (12-Month) Safety Trial in Adults and Adolescents 12 Years of Age and Older In the 12-month open-label, active-controlled clinical trial, 404 Asian patients (240 males and 164 females) with perennial allergic rhinitis or vasomotor rhinitis were treated with azelastine hydrochloride and fluticasone propionate nasal spray, 1 spray per nostril twice daily. In the 12-month, open-label, active-controlled, long-term safety trial in adults and adolescents 12 years of age and older, 404 patients with perennial allergic rhinitis or vasomotor rhinitis were treated with azelastine hydrochloride and fluticasone propionate nasal spray 1 spray per nostril twice daily and 207 patients were treated with fluticasone propionate nasal spray, 2 sprays per nostril once daily. Overall, adverse reactions were 47% in the azelastine hydrochloride and fluticasone propionate nasal spray treatment group and 44% in the fluticasone propionate nasal spray group. The most frequently reported adverse reactions (≥2%) with azelastine hydrochloride and fluticasone propionate nasal spray were headache, pyrexia, cough, nasal congestion, rhinitis, dysgeusia, viral infection, upper respiratory tract infection, pharyngitis, pain, diarrhea, and epistaxis. In the azelastine hydrochloride and fluticasone propionate nasal spray treatment group, 7 patients (2%) had mild epistaxis and 1 patient (<1%) had moderate epistaxis. In the fluticasone propionate nasal spray treatment group 1 patient (<1%) had mild epistaxis. No patients had reports of severe epistaxis. Focused nasal examinations were performed and no nasal ulcerations or septal perforations were observed. Eleven of 404 patients (3%) treated with azelastine hydrochloride and fluticasone propionate nasal spray and 6 of 207 patients (3%) treated with fluticasone propionate nasal spray discontinued from the trial due to adverse reactions. Long-Term (3-Month) Safety Trial in Pediatric Patients 6 to 11 Years of Age In the 3-month open label active-controlled clinical trial, 264 patients (60% male, 40% female) (80% white, 19% black, 4% Asian and 2% other) with allergic rhinitis were treated with azelastine hydrochloride and fluticasone propionate nasal spray, 1 spray per nostril twice daily. In the 3-month, open label, active-controlled, safety trial in pediatric patients 6 to 11 years of age 264 patients (128 patients ≥6 to <9 years of age, and 136 patients ≥9 to <12 years of age) with allergic rhinitis (based on the Investigator’s assessment) were treated with azelastine hydrochloride and fluticasone propionate nasal spray, 1 spray per nostril twice daily and 89 patients (44 patients ≥6 to <9 years of age, and 45 patients ≥9 to <12 years of age) were treated with fluticasone propionate nasal spray, 1 spray per nostril twice daily. Overall, adverse reactions were 40% in the azelastine hydrochloride and fluticasone propionate nasal spray treatment group and 36% in the fluticasone propionate nasal spray group. The most frequently reported adverse reactions (≥2%) with azelastine hydrochloride and fluticasone propionate nasal spray were epistaxis, headache, oropharyngeal pain, vomiting, upper abdominal pain, cough, pyrexia, otitis media, upper respiratory tract infection, diarrhea, nausea, otitis externa, and urticaria. In the azelastine hydrochloride and fluticasone propionate nasal spray treatment group 23 patients (9%) had mild epistaxis and 3 patients (1%) had moderate epistaxis. In the fluticasone propionate nasal spray treatment group 8 patients (9%) had mild epistaxis. No patients had reports of severe epistaxis. Focused nasal examinations were performed and no ulcerations or septal perforations were observed. Four of 264 patients (2%) treated with azelastine hydrochloride and fluticasone propionate nasal spray and 3 of 89 (3%) treated with fluticasone propionate nasal spray discontinued from the trial due to adverse reactions. There were two reports of somnolence, one severe, among children taking azelastine hydrochloride and fluticasone propionate nasal spray [see Warnings and Precautions (5.1)] . 6.2 Postmarketing Experience The following spontaneous adverse reactions have been reported with azelastine hydrochloride and fluticasone propionate nasal spray or one of the components (azelastine and fluticasone). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders: atrial fibrillation, increased heart rate, palpitations Eye Disorder: blurred vision, cataracts, conjunctivitis, dryness and irritation, eye swelling, glaucoma, increased intraocular pressure, vision abnormal, xerophthalmia Gastrointestinal Disorders: nausea, vomiting General Disorders and Administration Site Condition: aches and pain, application site irritation, chest pain, edema of face and tongue, fatigue, tolerance Immune System Disorders: anaphylaxis Musculoskeletal and Connective Tissue Disorders: growth suppression [see Use in Specific Populations (8.4)] Nervous System Disorders: disturbance or loss of smell and/or taste, dizziness, involuntary muscle contractions, paresthesia, parosmia Psychiatric Disorders: anxiety, confusion, nervousness Renal and Urinary Disorders: urinary retention Respiratory, Thoracic and Mediastinal Disorders: bronchospasm, cough, dysphonia, dyspnea, hoarseness, nasal septal perforation, nasal discomfort, nasal dryness, nasal sores, nasal ulcer, sore throat, throat dryness and irritation, voice changes, wheezing Skin and Subcutaneous Tissue Disorder: angioedema, erythema, face swelling, pruritus, rash, urticaria Vascular Disorder: hypertension
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.