Azelastine hydrochloride and fluticasone propionate Spray, Metered

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 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)].

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)] 

• 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)

].

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.

Nasal spray: 137 mcg of azelastine hydrochloride and 50 mcg of fluticasone propionate per spray.

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.