Fluticasone - Drug Monograph

Introduction

Fluticasone is a synthetic corticosteroid with potent anti-inflammatory properties that belongs to the glucocorticoid class of medications. It is widely used in various formulations including nasal sprays, inhalers, and topical preparations for managing inflammatory conditions primarily affecting the respiratory system and skin. First approved by the FDA in the 1990s, fluticasone has become a cornerstone therapy in the management of asthma, allergic rhinitis, and various dermatological conditions due to its high potency and favorable safety profile when used appropriately.

Mechanism of Action

Fluticasone exerts its therapeutic effects through binding to glucocorticoid receptors in target cells. This binding initiates a complex cascade of events:

• Induces synthesis of lipocortin, which inhibits phospholipase A2, reducing production of inflammatory mediators including prostaglandins and leukotrienes
• Inhibits cytokine production (IL-1, IL-2, IL-6, TNF-α) and decreases eosinophil chemotaxis
• Reduces mucus secretion and airway hyperresponsiveness
• Stabilizes cell membranes and decreases vascular permeability

The drug demonstrates particularly high affinity for glucocorticoid receptors and minimal mineralocorticoid activity, resulting in potent anti-inflammatory effects with reduced systemic side effects compared to older corticosteroids.

Indications

• Asthma maintenance treatment (inhaled formulation)
• Allergic and non-allergic rhinitis (nasal spray)
• Atopic dermatitis/eczema (topical cream/ointment)
• Prevention of asthma exacerbations (combination products with long-acting beta agonists)

• Chronic obstructive pulmonary disease (COPD) maintenance
• Eosinophilic esophagitis (oral topical suspension)
• Oral lichen planus
• Prevention of nasal polyps recurrence

Dosage and Administration

• Adults: 88-880 mcg twice daily (dose varies by product)
• Children 4-11 years: 88 mcg twice daily
• Administration: Shake well, exhale fully, administer dose while inhaling slowly

• Adults: 2 sprays (50 mcg each) per nostril once daily or 1 spray twice daily
• Children ≥4 years: 1 spray per nostril once daily

• Apply thin film to affected area 1-2 times daily
• Use lowest effective dose for shortest duration necessary

• Hepatic impairment: Use caution; may require dose adjustment
• Renal impairment: No dosage adjustment typically needed
• Elderly: Start at lower end of dosing range
• Pediatrics: Safety established for children ≥4 years (nasal) and ≥12 years (inhaled)

Pharmacokinetics

• Minimal systemic absorption from respiratory tract (inhaled: <20%; nasal: <2%)
• Topical absorption depends on application site, skin integrity, and formulation

• High protein binding (>91%)
• Volume of distribution: Approximately 4.2 L/kg
• Poor penetration across blood-brain barrier

• Extensive first-pass metabolism via CYP3A4 in liver and gut
• Hydrolyzed to inactive 17β-carboxylic acid derivative

• Primarily excreted in feces (<5% in urine)
• Elimination half-life: Approximately 8-14 hours

Contraindications

• Hypersensitivity to fluticasone or any component of formulation
• Primary treatment of status asthmaticus or other acute episodes requiring intensive measures
• Active or quiescent tuberculosis infections of respiratory tract
• Untreated fungal, bacterial, or viral infections
• Ocular herpes simplex

Warnings and Precautions

Drug Interactions

• Ketoconazole, ritonavir, clarithromycin
• Significantly increase fluticasone exposure
• Avoid concomitant use or consider alternative therapy

Adverse Effects

• Nasal: Epistaxis, nasal irritation, headache
• Inhalation: Oropharyngeal candidiasis, hoarseness, throat irritation
• Topical: Burning, itching, skin dryness

• Anaphylaxis
• Severe bronchospasm
• Adrenal suppression
• Vision changes (glaucoma, cataracts)
• Reduced bone mineral density
• Eosinophilic conditions

Monitoring Parameters

• Pulmonary function tests (asthma patients)
• Height and weight in pediatric patients
• Signs of HPA axis suppression
• Ophthalmic exams with long-term use
• Bone mineral density with prolonged high-dose therapy
• Signs of local infections (oral, nasal, dermatological)
• Symptom control and quality of life measures

Patient Education

• Demonstrate correct use of inhaler/nasal spray
• Rinse mouth after inhaled corticosteroid use
• Use spacer device if recommended

• Explain that fluticasone is a controller medication, not for acute symptoms
• Emphasize regular use even when asymptomatic

• Report any vision changes, persistent sore throat, or signs of infection
• Seek immediate care for worsening respiratory symptoms

• Clean inhaler/nasal device regularly as directed
• Do not exceed recommended dosage

• Symptoms not improving or worsening
• Need for increasing rescue medication use
• Signs of systemic corticosteroid effects

References

1. Barnes PJ. Inhaled corticosteroids. Pharmaceuticals (Basel). 2010;3(3):514-540. 2. Derendorf H, Meltzer EO. Molecular and clinical pharmacology of intranasal corticosteroids. Clin Pharmacokinet. 2008;47(5):275-282. 3. FDA Prescribing Information: Fluticasone Propionate Inhalation Powder. 2022. 4. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2023. 5. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy. Arch Intern Med. 1999;159(9):941-955. 6. Nayak AS, Ellis MH, Gross GN, et al. The effects of triamcinolone acetonide and fluticasone propionate on the hypothalamic-pituitary-adrenal axis. J Allergy Clin Immunol. 1998;101:157-162. 7. Patel D, Garadi R, Brubaker M, et al. Onset and duration of action of nasal sprays in seasonal allergic rhinitis. Clin Ther. 2007;29(5):816-827. 8. Szefler SJ, Martin RJ, King TS, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002;109(3):410-418.