Azeflo

Azeflo Uses, Dosage, Side Effects, Food Interaction and all others data.

Azelastine, a phthalazinone derivative, exhibits histamine H1 receptor antagonist activity in isolated tissues, animal models and humans. It is administered as a racemic mixture with no difference in pharmacologic activity noted between the enantiomers in invitro studies. The major metabolite, desmethylazelastine, also possesses H1-receptor antagonist activity.

Azelastine antagonizes the actions of histamine, resulting in the relief of histamine-mediated allergy symptoms. Onset of action occurs within 15 minutes with intranasal formulations and as quickly as 3 minutes with ophthalmic solutions. Intranasal formulations have a relatively long-duration of action, with peak effects observed 4-6 hours after the initial dose and efficacy maintained over the entirety of the standard 12 hour dosing interval.

Fluticasone propionate is a glucocorticoid with high topical anti-inflammatory potency, but a low HPA-axis suppressive activity after dermal administration. It, therefore, has a therapeutic index which is greater than most of the commonly available steroids. Fluticasone propionate has a high degree of selectivity for the glucocorticoid receptor. In vitro studies show that fluticasone propionate has a strong affinity for, and agonist activity at, human glucocorticoid receptors. This receptor is believed to be responsible for the anti-inflammatory properties of glucocorticoids.

Fluticasone propionate has weak affinity for the progesterone receptor, and virtually no affinity for the mineralocorticoid, estrogen, or androgen receptors. The therapeutic potency of glucocorticoids is related to the half-life of the glucocorticoid-receptor complex. The half-life of the Fluticasone propionate glucocorticoid-receptor complex is approximately 10 hours.

Systemically, in vitro experiments show Fluticasone furoate activates glucocorticoid receptors, inhibits nuclear factor kappa b, and inhibits lung eosinophilia in rats. Fluticasone propionate performs similar activity but is not stated to affect nuclear factor kappa b. Fluticasone propionate as a topical formulation is also associated with vasoconstriction in the skin.

Trade Name Azeflo
Generic Fluticasone + Azelastine
Weight 50mcg
Type Nasal Spray
Therapeutic Class
Manufacturer Lupin
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Azeflo
Azeflo

Uses

Azelastine nasal spray is used for the treatment of the symptoms of seasonal allergic rhinitis such as rhinorrhea, sneezing, and nasal pruritus in adults and children 5 years and older, and for the treatment of the symptoms of vasomotor rhinitis, such as rhinorrhea, nasal congestion and postnasal drip in adults and children 12 years and older.

Fluticasone Propionate is used for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive eczema or dermatitis.

Azeflo 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 RhinitisAsthma, Bronchostenosis, Skin discomfort, Moderate, severe Chronic Obstructive Pulmonary Disease (COPD)

How Azeflo 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 furoate and Fluticasone propionate work through an unknown mechanism to affect the action of various cell types and mediators of inflammation. In vitro experiments show Fluticasone furoate activating glucocorticoid receptors, inhibiting nuclear factor kappa b, and inhibiting lung eosinophilia in rats. Fluticasone propionate performs similar activity but is not stated to affect nuclear factor kappa b.

Dosage

Azeflo dosage

Adult and children 12 years and older: 2 sprays in each nostril twice daily.

Children 5-11 years of age: 1 spray in each nostril twice daily.

Cream: Apply a thin layer of Fluticasone propionate cream to the affected skin areas once daily.

Ointment: Apply a thin layer of Fluticasone propionate Ointment to the affected skin areas twice daily.

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

Headache, dizziness, sneezing, nosebleed, nausea, stinging or itching in nose, dry mouth, sore throat, bitter taste etc.

The fluticasone propionate preparations are usually well tolerated; local burning and pruritus have been reported. If signs of hypersensitivity appear, application should be stopped immediately. Prolonged and intensive treatment with potent corticosteroid preparations may cause local atrophic changes in the skin such as thinning, striae, dilatation of the superficial blood vessels, hypertrichosis and hypopigmentation.

Secondary infection, particularly when occlusive dressings are used or when skin folds are involved and allergic contact dermatitis have also been reported with corticosteroid use. Exacerbation of the signs and symptoms of the dermatoses have been reported with corticosteroid use.

Prolonged use of large amounts of corticosteroids, or treatment of extensive areas, can result in sufficient systemic absorption to produce the features of hypercorticism. This effect is more likely to occur in infants and children, and if occlusive dressings are used. In infants, the napkin may act as an occlusive dressing.

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 furoate administered nasally may be associated with adrenal suppression or an increase in QTc interval though the association has not been well demonstrated in studies. Fluticasone furoate requires no dosage adjustment in renal impairment but must be used in caution in hepatic impairment due to the elimination mechanisms. Fluticasone furoate is not associated with carcinogenicity, mutagenicity, or impairment of fertility. There are no well controlled studies in pregnancy or lactation though animal studies have shown teratogenicity and hypoadrenalism in the offspring of treated mothers and other corticosteroids are known to be excreted in breast milk. Generally, there are no reported adverse effects with fluticasone in pregnancy. Pediatric patients should be given the lowest possible dose and monitored for reduction in growth velocity. There is insufficient evidence to determine whether geriatric patients respond differently to other patients. Systemic exposure may be 27-49% higher in Japanese, Korean, and Chinese patients compared to Caucasian patients. Caution should be exercised in these patients and the benefit and risk should be assessed before deciding on a treatment.

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

In clinical trials, the occurrence of somnolence has been reported in some patients taking Azelastine nasal spray; due caution should therefore be exercised when driving a car or operating potentially dangerous machinery. Concurrent use of this nasal spray with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur.

Fluticasone propionate has a very low propensity for systemic absorption, nevertheless, prolonged application of high doses to large areas of body surface, especially in infants and small children might lead to adrenal suppression. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity.

The face, more than other areas of the body, may exhibit atropic changes after prolonged treatment with potent topical corticosteroids. This must be borne in mind when treating severe eczema.

Appropriate antimicrobial therapy should be used whenever treating inflammatory lesions which have become infected. Any spread of infection requires withdrawal of topical corticosteroid therapy and systemic administration of antimicrobial agents. Bacterial infection is encouraged by the warm, moist conditions induced by occlusive dressing, and so the skin should be cleansed before a fresh dressing is applied.

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.

608L at steady state for intravenous administration of Fluticasone furoate. Other reports suggest the mean volume of distribution at steady state is 661L. A study of 24 healthy Caucasian males showed a volume of distribution at steady state of 704L following intravenous administration.

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.

["\"Fluticasone Propionate (Flonase) Nasal Spray FDA Label\" href=\"#reference-F4358Fluticasone 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%.<\/p>\n"]

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.

15.1 hours for intranasal Fluticasone furoate and 24 hours for the inhaled formulation. A study of 24 healthy Caucasian males showed a half life of 13.6 hours following intravenous administration and 17.3-23.9 hours followed inhalation.

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.

57.8L/h for Fluticasone furoate. A study of 24 healthy Caucasian males showed a clearance of 71.8L/h following intravenous administration.

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

Contraindication

Contraindicated in patients with a known hypersensitivity to Azelastine or any of its components.

Fluticasone propionate is contraindicated in Rosacea, Acne vulgaris, Peri-oral dermatitis, Primary cutaneous viral infections (e.g., herpes simplex, chicken pox), Hypersensitivity to any of the ingredients, Perianal and genital pruritus, etc. The use of Fluticasone propionate is not indicated in the treatment of primarily infected skin lesions caused by infection with fungi or bacteria and dermatoses in children under one year of age, including deramtitis and napkin eruptions.

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

Acute overdosage is very unlikely to occur, however, in case of cronic overdosage or misuse the features of hypercorticism may appear, and in this situation, as with any corticosteroid, application should be discontinued. Overdosage by ingestion of fluticasone propionate cream or ointment is extremely unlikely to occur due to the very low oral bioavailability of fluticasone propionate.

Storage Condition

Keep out of reach of children. Store in a cool and dry place protected from light. Do not freeze.

Store below 30˚ C. Do not freeze.


*** Taking medicines without doctor's advice can cause long-term problems.
Share