Azelastine and Fluticasone

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Nasal:

Ticalast: Azelastine hydrochloride 0.1% [137 mcg/spray] and fluticasone propionate 0.037% [50 mcg/spray] (23 g) & sterile saline wash (117 mL [DSC]) [contains benzalkonium chloride; 120 metered sprays]

Suspension, Nasal:

Dymista: Azelastine hydrochloride 0.1% [137 mcg/spray] and fluticasone propionate 0.037% [50 mcg/spray] (23 g) [contains benzalkonium chloride; 120 metered sprays]

Pharmacology

Mechanism of Action

Azelastine competes with histamine for H₁receptor sites on effector cells and inhibits the release of histamine and other mediators involved in the allergic response; when used intranasally, reduces hyper-reactivity of the airways; increases the motility of bronchial epithelial cilia, improving mucociliary transport.

Fluticasone belongs to a group of corticosteroids which utilizes a fluorocarbothioate ester linkage at the 17 carbon position; extremely potent vasoconstrictive and anti-inflammatory activity.

Use: Labeled Indications

Seasonal allergic rhinitis: Relief of symptoms of seasonal allergic rhinitis in patients ≥6 years of age

Contraindications

There are no contraindications listed in the US labeling.

Canadian labeling: Hypersensitivity to azelastine, fluticasone, or any component of the formulation; untreated fungal, bacterial, or tuberculosis infections of the respiratory tract.

Dosage and Administration

Dosing: Adult

Seasonal allergic rhinitis: Intranasal: One spray (137 mcg azelastine/50 mcg fluticasone) per nostril twice daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Seasonal allergic rhinitis:

Children 4 to 5 years: Limited data available; efficacy not established: Intranasal: 1 spray (137 mcg azelastine/50 mcg fluticasone) per nostril twice daily was evaluated in 61 patients as part of a larger pediatric trial, data did not fully establish efficacy; safety profile similar to older children (NCT01915823, 2014)

Children ≥6 years and Adolescents: Intranasal: 1 spray (137 mcg azelastine/50 mcg fluticasone) per nostril twice daily

Administration

For intranasal administration only. Prime pump (press 6 times until fine spray appears) prior to first use. If ≥14 days have elapsed since last use, then reprime pump with 1 spray or until a fine mist appears. Shake bottle gently before using. Blow nose to clear nostrils. Keep head tilted downward when spraying. Insert applicator tip ¹/₄ to ¹/₂ inch into nostril, keeping bottle upright, and close off the other nostril. Breathe in through nose. While inhaling, press pump to release spray. After each use, wipe the spray tip with a clean tissue or cloth and replace cap. Clean spray pump unit and dust cap at least 1 time each week in warm water and allow to completely dry before placing back on bottle. Avoid spraying directly into nasal septum, eyes or mouth. Discard after 120 medicated sprays have been used, even if bottle is not completely empty. The 10 mL bottle [Canadian product] should be discarded after 28 medicated sprays have been used.

Storage

Store at 20°C to 25°C (68°F to 77°F); do not refrigerate or freeze. Protect from light. Store in upright position with cap on.

Drug Interactions

Alcohol (Ethyl): May enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

CNS Depressants: May enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Fluticasone (Nasal). Avoid combination

Desmopressin: Corticosteroids (Nasal) may enhance the hyponatremic effect of Desmopressin. Avoid combination

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy

Adverse Reactions

Reactions/percentages reported with combination product; also see individual agents.

1% to 10%:

Central nervous system: Headache (2%)

Gastrointestinal: Dysgeusia (4%)

Respiratory: Epistaxis (4%; frequency and severity may be increased in children)

<1%, postmarketing, and/or case reports: Abnormality in thinking, ageusia, altered sense of smell, anaphylactoid reaction, anaphylaxis, angioedema, anosmia, anxiety, application site irritation, atrial fibrillation, blurred vision, bronchospasm, burning sensation, cataract, chest pain, confusion, conjunctivitis, cough, diarrhea, dizziness, drowsiness, drug tolerance, dry nose, dry throat, dyspnea, erythema, eye irritation, facial edema, facial swelling, fatigue, generalized ache, glaucoma, hoarseness, hypersensitivity reaction, hypertension, increased heart rate, increased intraocular pressure, insomnia (initial), muscle spasm, nasal discomfort, nasal obstruction, nasal septum perforation, nasal sores, nausea, nervousness, pain, palpitations, paresthesia, pruritus, restlessness, sedation, skin rash, sore throat, swelling of eye, therapeutic response unexpected, throat irritation, tongue edema, urinary retention, urticaria, vertigo, visual disturbance, voice disorder, vomiting, weight loss, wheezing, xerophthalmia

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Pediatric patients may be more susceptible to systemic toxicity. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Concurrent use of ritonavir (and potentially other strong inhibitors of CYP3A4) may increase fluticasone levels and effects on HPA suppression.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Delayed wound healing: Avoid nasal corticosteroid use in patients with recent nasal septal ulcers, nasal surgery, or nasal trauma until healing has occurred.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Exposure to chickenpox or measles should be avoided.
• Infections: Corticosteroids should be used with caution, if at all, in patients with ocular herpes simplex, latent tuberculosis, and/or TB reactivity, in patients with untreated fungal, viral, or bacterial infections, or systemic viral or parasitic infections.
• Local nasal effects: Nasal septal perforation, nasal ulceration, epistaxis, and localized Candida albicans infections of the nose and/or pharynx may occur. Monitor patients periodically for adverse nasal effects.
• Ocular disease: Increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with intranasal corticosteroid use; use with caution in patients with a history of increased intraocular pressure, cataracts, and/or glaucoma. Consider routine eye exams in chronic users or in patients who report visual changes.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Avoid using higher than recommended dosages; suppression of linear growth (ie, reduction of growth velocity), reduced bone mineral density, or hypercortisolism (Cushing syndrome) may occur; titrate to lowest effective dose. Reduction in growth velocity may occur when corticosteroids are administered to pediatric patients, even at recommended doses via intranasal route (monitor growth).

Monitoring Parameters

Growth (adolescents and children); signs/symptoms of HPA axis suppression/adrenal insufficiency; possible eosinophilic conditions (including eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]); glaucoma and/or cataracts especially in patients with a change in vision; infection; adverse nasal effects (eg, nasal septal perforation, nasal ulceration, epistaxis, localized Candida albicans infections)

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. Refer to individual monographs.

Patient Education

What is this drug used for?

• It is used to ease allergy signs.

Frequently reported side effects of this drug

• Headache
• Change in taste

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss
• Severe nose irritation
• Runny nose
• Nose crusting
• Wheezing
• Vision changes
• Eye pain
• Severe eye irritation
• Severe nosebleed
• Fatigue
• Thrush
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.