Fluvate0.005%

Fluvate is a synthetic corticosteroid used topically (intranasally, by oral inhalation, or by nebulisation) for its local anti-inflammatory effect. In Bangladesh it is marketed as a nasal spray, a pressurized/dry powder inhaler, and a nebuliser suspension.

Established / FDA-approved and guideline-supported uses

• Allergic rhinitis (nasal spray): Prophylaxis and treatment of symptoms of seasonal and perennial allergic rhinitis (sneezing, nasal congestion, rhinorrhoea, itching) in adults and children.
• Nasal polyps (nasal spray, higher strength): Treatment of chronic rhinosinusitis with or without nasal polyps, and prevention of polyp recurrence after surgical removal.
• Asthma - maintenance/prophylaxis (inhaler and nebuliser suspension): Regular maintenance treatment of mild, moderate, and severe persistent asthma in adults and children, including patients previously controlled on bronchodilators alone or on other inhaled corticosteroids.

Uses requiring combination therapy

• In patients with more severe or poorly controlled asthma, Fluvate is often combined with a long-acting beta-agonist (LABA, e.g. salmeterol or formoterol) as part of a step-up regimen, rather than used alone.

Important exclusion

Fluvate inhaler/nebuliser suspension is not indicated for the relief of acute bronchospasm or as a rescue treatment for status asthmaticus or other acute asthma episodes; a fast-acting bronchodilator ("reliever" inhaler) is required for that purpose.

Each formulation contains Fluticasone Propionate as the active ingredient:

• Nasal spray: Fluticasone Propionate 50 mcg or 93 mcg per metered spray, in an aqueous suspension with excipients such as microcrystalline cellulose, carboxymethylcellulose sodium, dextrose, and preservatives (e.g. benzalkonium chloride, phenylethyl alcohol).
• Metered-dose inhaler: Fluticasone Propionate 50, 125, or 250 mcg per actuation with a hydrofluoroalkane (HFA) propellant.
• Nebuliser suspension: Fluticasone Propionate 0.5 mg/2 mL or 2 mg/2 mL for use with a jet nebuliser.

Fluvate is a synthetic, halogenated trifluorinated glucocorticoid with potent local anti-inflammatory activity and very low systemic bioavailability when used as directed, because most of the swallowed portion undergoes extensive first-pass hepatic metabolism.

It is chemically related to other topical corticosteroids and is formulated for local delivery to the nasal mucosa (allergic rhinitis) or the lower airways (asthma), rather than for systemic use. It has no bronchodilator activity and does not provide immediate relief of acute breathing difficulty.

Fluvate belongs to the class of inhaled/intranasal corticosteroids (topical glucocorticoids), used as anti-inflammatory, anti-allergic agents for respiratory and nasal conditions.

Fluticasone Propionate is a corticosteroid with high topical (glucocorticoid receptor) anti-inflammatory potency and minimal mineralocorticoid activity. At the cellular level it suppresses the recruitment and activation of inflammatory cells (eosinophils, mast cells, lymphocytes, macrophages), reduces production of inflammatory mediators (cytokines, prostaglandins, leukotrienes), decreases mucosal oedema and mucus secretion, and stabilises capillary and lysosomal membranes.

In allergic rhinitis, this reduces nasal mucosal inflammation, congestion, and hyperreactivity. In asthma, it reduces airway inflammation, bronchial hyperresponsiveness, and the frequency and severity of exacerbations, but does not relax airway smooth muscle acutely and therefore has no role in relieving an acute attack.

Systemic absorption occurs mainly via pulmonary/nasal mucosal absorption and swallowed drug; the swallowed fraction undergoes extensive first-pass hepatic metabolism (via CYP3A4) to an inactive metabolite, giving very low oral bioavailability (<1%) and largely accounting for the drug's favourable safety profile at recommended doses.

Nasal spray: Shake well, prime if new/unused for >7 days, insert nozzle just inside the nostril away from the septum, close the other nostril, and spray while inhaling gently.

Inhaler: Shake before use, breathe out fully, seal lips around the mouthpiece, inhale slowly and deeply while actuating, hold breath ~10 seconds, then rinse mouth with water and spit out afterward.

Nebuliser suspension: Shake gently, do not mix with other nebuliser solutions unless advised by a physician, and administer via a jet nebuliser with a face mask or mouthpiece as directed.

Strong CYP3A4 inhibitors: Co-administration of Fluvate with potent CYP3A4 inhibitors such as ritonavir or ketoconazole markedly increases systemic exposure to Fluvate and can cause clinically significant adrenal suppression/Cushing's syndrome; concurrent use is generally not recommended unless the benefit outweighs the risk of systemic corticosteroid side effects, and patients require monitoring.

Other systemic corticosteroids: Concurrent use with other corticosteroid-containing products (oral, systemic, or other topical steroids) increases the risk of additive systemic corticosteroid effects, including HPA-axis suppression; total corticosteroid burden should be assessed.

Other moderate CYP3A4 inhibitors (e.g. itraconazole, erythromycin) may also increase systemic Fluvate exposure to a lesser degree; caution is advised.

Local effects

• Nasal spray: Nasal dryness, irritation, unpleasant taste/smell, epistaxis (nosebleed), nasal ulceration; rarely, nasal septal perforation with prolonged use.
• Inhaler/nebuliser: Oral and throat candidiasis (thrush), hoarseness (dysphonia), throat irritation, and occasionally paradoxical bronchospasm immediately after dosing - rinse the mouth after each inhaled dose to reduce this risk.

Systemic effects (uncommon at recommended doses, more likely with high-dose or prolonged use)

• HPA-axis (adrenal) suppression, Cushingoid features
• Reduced growth velocity in children
• Reduced bone mineral density with long-term use
• Increased risk of cataracts and glaucoma with prolonged use
• Increased risk of pneumonia has been observed in patients with COPD using inhaled Fluvate-containing products

Hypersensitivity reactions (rash, angioedema, bronchospasm, anaphylaxis) are rare but can occur.

Pregnancy: There are no adequate and well-controlled studies establishing the safety of Fluvate in human pregnancy. As with other corticosteroids, it should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus; consult a physician before use. Uncontrolled asthma itself poses risks to mother and fetus, so treatment should not be stopped without medical advice.

Lactation: It is not known whether clinically relevant amounts of Fluvate are excreted in human breast milk. Caution is advised, and a physician should be consulted to weigh the benefits of treatment against any potential risk to the nursing infant.

Not for acute symptom relief: Fluvate inhaler/nebuliser suspension does not relieve acute bronchospasm and must not be used as a rescue medication; patients should have a fast-acting bronchodilator available for acute symptoms.

Local effects: Prolonged use may rarely cause nasal septal perforation (nasal form) or oral candidiasis (inhaled forms) - rinse the mouth after each inhaled dose. Avoid nasal spray use until nasal ulcers, surgery, or trauma have healed.

Systemic corticosteroid effects: High doses or prolonged use can suppress the hypothalamic-pituitary-adrenal (HPA) axis and cause Cushingoid features; monitor growth velocity regularly in children on long-term therapy. Use the lowest effective dose.

Infections: Use with caution in patients with active or quiescent tuberculosis, or untreated fungal, bacterial, viral, or parasitic infections; corticosteroids can mask or worsen infection and impair immune response. Patients should avoid exposure to chickenpox or measles if not previously immune, as these infections can be more serious in corticosteroid-treated patients.

COPD: An increased incidence of pneumonia has been reported in COPD patients using inhaled Fluvate-containing products; monitor for signs of respiratory infection.

Discontinuation: Do not stop abruptly after prolonged high-dose therapy, particularly in patients transferring from systemic (oral) corticosteroids, as this may unmask adrenal insufficiency or worsen underlying disease; withdraw gradually under medical supervision.

Acute overdose of Fluvate is unlikely to cause immediate danger because of its low systemic bioavailability, but chronic use of doses higher than recommended may lead to systemic corticosteroid effects such as HPA-axis suppression, Cushingoid features, and reduced growth in children. If excessive or accidental ingestion is suspected, or if signs of systemic corticosteroid excess develop, seek immediate medical attention or contact a poison control center; do not attempt home treatment. Management is generally supportive, with gradual dose reduction under medical supervision if chronic overuse has occurred.

Store at room temperature (below 30°C), away from light and moisture. Do not puncture, break, or burn the inhaler canister even when apparently empty, and avoid freezing. Keep out of reach of children.

Pediatric use

Fluvate nasal spray is approved for use in children 4 years and older for allergic rhinitis, and the inhaler/nebuliser suspension is used from as young as 1 year of age under specialist supervision for asthma, using age-appropriate doses (see Dosage). Growth velocity should be monitored periodically in children receiving prolonged treatment. Safety and efficacy in younger children outside these approved ranges have not been established.

Elderly

No specific dose adjustment is generally required in elderly patients; use the lowest effective dose.

Renal/hepatic impairment

No dosage adjustment is established for renal impairment. Since Fluvate undergoes extensive hepatic metabolism, patients with significant hepatic impairment may have increased systemic exposure and should be monitored for corticosteroid-related side effects.

Duration of treatment with Fluvate depends on the indication and clinical response: allergic rhinitis is usually treated for the duration of the allergen season or as long as symptoms warrant; asthma maintenance therapy is typically continued long-term, with the dose periodically reviewed and stepped down to the lowest effective level once control is achieved, under regular physician follow-up.

Fluticasone Propionate is classified as a topical/inhaled corticosteroid (glucocorticoid).

Fluticasone Propionate binds to glucocorticoid receptors in respiratory and nasal mucosal cells, altering gene transcription to reduce synthesis of pro-inflammatory mediators and increase synthesis of anti-inflammatory proteins, thereby suppressing local inflammation, mucosal oedema, and hyperreactivity without directly relaxing airway smooth muscle.

Fluvate nasal spray (50 mcg strength) is indicated for allergic rhinitis in children 4 years of age and older at a dose of 1 spray per nostril once daily (max 100 mcg/day); it should not be used in children under 4 years unless directed by a physician.

The inhaler and nebuliser suspension may be used for asthma maintenance from about 1 year of age under specialist supervision, with doses individualised by age and severity (see Dosage and Administration). Growth should be monitored regularly in children receiving long-term therapy, as intranasal and inhaled corticosteroids may cause a reduction in growth velocity. Safety and efficacy outside these established age ranges and doses have not been established.