Bileni

Uses

Azelastine and Fluticasone Nasal Spray is used for the relief of symptoms of seasonal allergic rhinitis in patients 6 years of age and older who require treatment with both Azelastine Hydrochloride and Fluticasone Propionate for symptomatic relief.

Bileni is also used to associated treatment for these conditions: Allergic Eye Disease, Allergic Rhinitis (AR), Atopy Keratoconjunctivitis, Blepharitis allergic, Conjunctivitis allergic, Pollen Allergy, Seasonal Allergic Conjunctivitis, Seasonal Allergic Rhinitis, Vasomotor RhinitisAllergic Rhinitis (AR), Allergy to Mold, Allergy; Dander, Asthma, Bacterial Sinusitis, Chronic Bronchitis, Chronic Obstructive Pulmonary Disease (COPD), Chronic Sinusitis, Dermatitis, Emphysema, House Dust Mite Allergy, House dust allergy, Itching of the nose, Nasal Congestion, Nonallergic Rhinitis, Oesophagitis, Eosinophilic, Perennial Rhinitis, Pollen Allergy, Rhinitis, Rhinorrhoea, Seasonal Allergic Rhinitis, Sneezing, Moderate, severe Perennial Allergic Rhinitis (PAR), Moderate, severe Seasonal Allergic Rhinitis

How Bileni works

Azelastine is primarily a selective antagonist of histamine H1-receptors, with a lesser affinity for H2-receptors, used for the symptomatic treatment of allergies. Histamine H1-receptors are G-protein-coupled receptors with 7 transmembrane spanning domains that are found on nerve endings, smooth muscle cells, and glandular cells. Following allergen exposure in sensitized individuals, IgE-receptor cross-linking on mast cells results in the release of histamine, which binds to H1-receptors and contributes to typical allergic symptoms such as itching, sneezing, and congestion.

Though its primary mode of action is thought to be via H1-receptor antagonism, azelastine (like other second-generation antihistamines) appears to affect other mediators of allergic symptomatology. Azelastine has mast cell-stabilizing properties that prevent the release of interleukin-6, tryptase, histamine, and TNF-alpha from mast cells, and has been shown to reduce mediators of mast cell degranulation such as leukotrienes in the nasal lavage of patients with rhinitis, as well as inhibiting their production and release from eosinophils (potentially via inhibition of phospholipase A₂ and leukotriene C₄ synthase). Additionally, patients using oral azelastine were observed to have significantly reduced concentrations of substance P and bradykinin in nasal secretions, both of which may play a role in nasal itching and sneezing in patients with allergic rhinitis.

Fluticasone propionate works through an unknown mechanism to affect the action of various cell types and mediators of inflammation. Fluticasone propionate activates glucocorticoid receptors and inhibits lung eosinophilia in rats.

Dosage

Bileni dosage

Adult: The recommended dosage is one spray each nostril twice daily.

Paediatric: The safety and effectiveness of Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray has not been established for patients less than 6 years of age.

Initial pump priming requires seven sprays of the pump. If used regularly as recommended, no further priming is required. If not used more than 24 hours, the pump will require 2 sprays, or if not used for more than seven days, the pump will require 7 sprays.

Side Effects

The most common adverse reactions (>2% incidence) are: dysgeusia, epistaxis, and headache.

Toxicity

Overdosage of intranasal or ophthalmic azelastine is unlikely to result in clinically significant adverse effects aside from increased drowsiness. If overdose does occur, employ general supportive measures. Oral ingestion of antihistamines, including non-oral formulations of azelastine, can cause serious adverse effects in children - for this reason, these products should be kept out of the reach of children. The oral LD₅₀ in rats is 580 mg/kg.

Fluticasone propionate's use in specific populations has not been well studied. Fluticasone propionate is not carcinogenic, mutagenic, or clastogenic, nor did it affect fertility in animal studies. Subcutaneous fluticasone propionate has been shown to produce teratogenic effects in rats though oral administration does not. Generally, there are no reported adverse effects with fluticasone in pregnancy. Fluticasone propionate in human milk may cause growth suppression, effects on endogenous corticosteroid production, or other effects. Pediatric patients treated with fluticasone propionate ointment experienced adrenal suppression. Geriatric patients treated with fluticasone propionate did not show any difference in safety or efficacy compared to other patient groups, though older patients may be more sensitive to adverse effects. There is no difference in the clearance of fluticasone propionate across genders or race. Patients with hepatic impairment should be closely monitored due to the elimination mechanism.

Precaution

Engagement in hazardous occupations requiring complete mental alertness such as driving or operating machinery should be avoided when taking Azelastine and Fluticasone Nasal Spray. Concurrent use of alcohol or other central nervous system (CNS) depressants with this Nasal Spray should also be avoided because of further decreased alertness and impairment of CNS. Hypercorticism and adrenal suppression with very high dosages or at the regular dosage in susceptible individuals may appear. If such changes occur, the spray should be discontinued slowly.

Interaction

It is especially important to check before combining Azelastine nasal spray with Alcohol, CNS depressants, Cimetidine & Ketoconazole.

Volume of Distribution

After intravenous and oral administration, the steady-state volume of distribution is 14.5 L/kg.

The volume of distribution of intravenous fluticasone propionate is 4.2L/kg. A study of 24 healthy Caucasian males showed a volume of distribution at steady state of 577L following intravenous administration.

Elimination Route

Systemic bioavailability of azelastine hydrochloride following intranasal administration is approximately 40%, reaching Cmax within 2-3 hours. When administered at doses greater than the recommended maximum, greater than proportional increases in both Cmax and AUC were observed.

Intranasal bioavailability of fluticasone propionate is 10. Intranasal exposure results in the majority of the dose being swallowed. Topical absorption of fluticasone propionate is very low but can change depending on a number of factors including integrity of the skin and the presence of inflammation or disease. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 9.0%.

Half Life

Based on intravenous and oral administration, azelastine demonstrated an elimination half-life of 22 hours. Its primary active metabolite, desmethylazelastine, has an elimination half-life of 54 hours.

7.8 hours for intravenous fluticasone propionate. A study of 24 healthy Caucasian males shows a half life of 14.0 hours following intravenous administration and 10.8 hours following inhalation.

Clearance

Based on intravenous and oral administration, azelastine demonstrated a plasma clearance of 0.5 L/h/kg.

1093mL/min for fluticasone propionate. A study of 24 healthy Caucasian males showed a clearance of 63.9L/h following intravenous administration.

Elimination Route

After an oral dose of radio-labeled azelastine hydrochloride, approximately 75% was excreted in the feces, with less than 10% as unchanged azelastine hydrochloride.

Fluticasone propionate is mainly eliminated in the feces with 10,5.

Pregnancy & Breastfeeding use

Pregnancy category C. There are no adequate and well-controlled clinical trials of Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray, Azelastine Hydrochloride only or Fluticasone Propionate only in pregnant women. It should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when administered to a nursing woman.

Contraindication

There is no known contraindication.

Special Warning

Use in children: The safety and effectiveness of Azelastine nasal spray in patients below 5 years of age have not been established.

Acute Overdose

There have been no reported over dosages with Azelastine Hydrochloride. Acute Azelastine Hydrochloride overdosage by adults with this dosage form is unlikely to result in clinically significant adverse events, other than increased somnolence. Chronic Fluticasone Propionate overdosage may result in symptoms of hypercorticism.

Storage Condition

Store below 25° C. Protected from light. Do not store in the refrigerator. Keep out of the reach of children.

Innovators Monograph

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