Fluticasone

1. Drug Name

• Generic Name: Fluticasone

• Brand Names: Flonase, Flovent, Arnuity Ellipta, Cutivate, Veramyst

2. Drug Classification

• Class: Corticosteroid (Glucocorticoid)

• Subclass: Inhaled corticosteroid (ICS), Nasal corticosteroid

3. Mechanism of Action

• Fluticasone is a synthetic corticosteroid that exerts anti-inflammatory effects by binding to glucocorticoid receptors in the cytoplasm of target cells, such as those found in the lungs and nasal passages.

• Anti-inflammatory Action: Once bound to the receptor, fluticasone enters the nucleus, where it regulates gene expression and inhibits the production of pro-inflammatory mediators, including cytokines, chemokines, and eicosanoids (like prostaglandins and leukotrienes).

• Airway Inflammation: In the lungs, fluticasone reduces inflammation by inhibiting the activation of inflammatory cells such as mast cells, eosinophils, and neutrophils, leading to reduced airway hyperresponsiveness.

• Reduction of Mucus Production: In the nasal passages, it reduces swelling and mucus production, which is beneficial in managing allergic rhinitis.

• Bronchodilation: While fluticasone is not a direct bronchodilator, its anti-inflammatory effects indirectly lead to better airway patency and reduced asthma symptoms over time.

4. Pharmacokinetics

• Absorption:

  • Bioavailability: Fluticasone has very low oral bioavailability (~1%) due to extensive first-pass metabolism in the liver when taken orally. However, when inhaled, it has a higher bioavailability (approximately 10–20%).

  • Tmax (Time to Peak Plasma Concentration): Peak plasma concentrations of fluticasone after inhalation occur within 1–2 hours.

• Distribution:

  • Volume of Distribution (Vd): Fluticasone is widely distributed, primarily in the lungs, and minimally in the plasma due to its low systemic absorption.

  • Protein Binding: Fluticasone is highly protein-bound in the plasma (approximately 91%).

• Metabolism:

  • Fluticasone undergoes hepatic metabolism via the cytochrome P450 enzyme CYP3A4, primarily forming inactive metabolites.

  • The liver is the primary site of metabolism, which means drugs that inhibit CYP3A4 can increase fluticasone levels.

• Excretion:

  • Half-life (t½): The half-life of fluticasone is approximately 7.8 hours after inhalation.

  • Excretion: Fluticasone is excreted primarily in the feces (~65%) and to a lesser extent in the urine (~35%).

• Special Considerations: In patients with liver dysfunction, metabolism may be impaired, potentially increasing systemic exposure.

5. Indications

• Primary Indications:

  • Asthma: Fluticasone is used for the maintenance treatment of asthma. It is often prescribed as a controller medication to reduce inflammation, improve lung function, and prevent asthma exacerbations.

  • Chronic Obstructive Pulmonary Disease (COPD): Used as part of combination therapy for COPD to reduce inflammation and frequency of exacerbations.

  • Allergic Rhinitis: Fluticasone nasal spray is used to treat symptoms of seasonal and perennial allergic rhinitis, including nasal congestion, sneezing, and itching.

• Off-Label Uses:

  • Cystic Fibrosis: Occasionally used to reduce airway inflammation in cystic fibrosis, though this is not a first-line treatment.

  • Eczema and Dermatitis: Topical formulations (e.g., Cutivate) may be used for inflammatory skin conditions.

• Special Populations:

  • Pediatrics: Approved for use in children as young as 4 years old for asthma management (Flovent), and for allergic rhinitis in children over 2 years of age (Flonase).

  • Geriatrics: Elderly patients may be more susceptible to corticosteroid side effects such as osteoporosis, cataracts, and diabetes. Careful monitoring is recommended.

6. Dosage and Administration

• Adult Dosing:

  • Asthma:

    • Inhalation (Flovent): Typically 44–220 mcg twice daily, with a maximum dose of 880 mcg/day depending on the severity of asthma.

    • Combination Therapy (Advair, AirDuo): In combination with a long-acting beta-agonist (LABA), doses range from 100/50 mcg to 500/50 mcg twice daily.

  • COPD:

    • Inhalation (Flovent): 250 mcg twice daily for maintenance therapy. The combination with a LABA may be considered.

  • Allergic Rhinitis:

    • Nasal Spray (Flonase): 1–2 sprays (50–100 mcg) per nostril once daily, with a maximum of 2 sprays per nostril.

• Pediatric Dosing:

  • Asthma (ages 4–11): Flovent 44 mcg twice daily, up to 88 mcg if needed for asthma control.

  • Allergic Rhinitis: Flonase nasal spray is approved for children aged 2 years and older.

• Dose Adjustments:

  • Renal or Hepatic Impairment: No routine dose adjustment is required. However, careful monitoring is needed for patients with severe hepatic impairment due to possible increased systemic exposure.

7. Contraindications

• Absolute Contraindications:

  • Hypersensitivity to fluticasone or any of the excipients in the formulation.

• Relative Contraindications:

  • Active Tuberculosis: Fluticasone may exacerbate latent tuberculosis or active infections, so it should be used with caution in these patients.

  • Untreated Fungal, Bacterial, or Viral Infections: Should be used with caution in patients with infections not properly treated, as corticosteroids can impair immune response.

8. Warnings and Precautions

• Adrenal Insufficiency: Long-term use of corticosteroids may suppress adrenal function, particularly when used in high doses or abruptly withdrawn. Patients should be monitored for symptoms of adrenal insufficiency (e.g., fatigue, weakness).

• Osteoporosis: Chronic use, especially at high doses, may lead to decreased bone density and an increased risk of fractures.

• Pediatric Growth Suppression: Prolonged use of inhaled corticosteroids in children may impair growth. Height should be regularly monitored.

• Eye Problems: Long-term use can increase the risk of cataracts or glaucoma. Regular eye examinations are recommended for long-term users.

9. Adverse Effects

• Common Adverse Effects:

  • Corticosteroid Side Effects: Oral candidiasis (thrush), throat irritation, hoarseness.

• Less Common but Clinically Significant:

  • Respiratory: Cough, sinusitis, nasal irritation (with nasal spray).

  • Systemic: Headache, fatigue, nausea.

• Rare/Serious:

  • Osteoporosis: Long-term use may cause decreased bone density.

  • Psychiatric: Mood changes, anxiety, depression.

  • Hyperglycemia: In high doses, fluticasone may increase blood glucose levels.

10. Drug Interactions

• CYP3A4 Inhibitors: Fluticasone is primarily metabolized by CYP3A4. Drugs that inhibit this enzyme (e.g., ketoconazole, ritonavir) may increase the systemic levels of fluticasone, increasing the risk of side effects.

• Beta-agonists (e.g., salbutamol): Combination therapy with inhaled beta-agonists may increase the bronchodilatory effect but requires careful monitoring to avoid excessive adrenergic stimulation.

• Vaccines: Caution is advised when administering live vaccines to patients on long-term corticosteroid therapy due to possible suppression of the immune response.

11. Clinical Pharmacology

• Pharmacodynamics: Fluticasone provides potent anti-inflammatory action by modulating immune cell activity and reducing the release of pro-inflammatory mediators. Its effects on the airways help reduce asthma symptoms and exacerbations, making it a cornerstone of asthma and COPD management.

• Additional Effects: In nasal formulations, it reduces nasal inflammation and congestion, providing symptomatic relief from allergic rhinitis.

12. Special Populations

• Pregnancy: FDA Category C. Fluticasone should only be used during pregnancy if the benefits outweigh the risks, particularly for asthma management where exacerbations pose a higher risk to both mother and fetus.

• Lactation: Fluticasone is excreted in breast milk in very small amounts. Caution should be exercised, especially in high-dose therapy.

• Geriatrics: Older adults may be more susceptible to corticosteroid side effects such as glaucoma and osteoporosis.

13. Therapeutic Uses

• Asthma: First-line therapy in persistent asthma as part of maintenance treatment to reduce inflammation and prevent exacerbations.

• COPD: Used in combination therapy for moderate to severe COPD, primarily to reduce exacerbations.

• Allergic Rhinitis: Commonly used for seasonal and perennial allergic rhinitis, especially when other treatments (e.g., antihistamines) are inadequate.

14. Monitoring and Follow-Up

• Pulmonary Function: Regular monitoring of lung function (spirometry) in asthma and COPD patients.

• Eye Examinations: Regular eye checks for signs of glaucoma or cataracts in long-term users.

• Bone Health: Monitoring bone density in long-term users, especially those on high doses.

15. Overdose Management

• Symptoms of Overdose: Acute overdose is unlikely due to low systemic bioavailability, but chronic overdose may result in adrenal suppression, Cushing’s syndrome, and osteoporosis.

• Management: Overdose management is primarily supportive. In case of inhalation overdose, no specific antidote is needed, but systemic effects should be monitored.

16. Patient Counseling Information

• Proper Use: Instruct patients on the correct technique for using inhalers or nasal sprays. Emphasize the importance of regular use even when symptoms are controlled.

• Side Effects: Discuss the potential for oral thrush and the need to rinse the mouth after use.

• Seek Immediate Attention: Advise patients to seek immediate medical help if they experience worsening breathing difficulties, signs of infection, or significant mood changes.