Fluticasone | Pharmacology Mentor

Generic Name

Fluticasone

Mechanism

Fluticasone exerts its effect by:
• Binding to intracellular glucocorticoid receptors (GR) with high affinity.
• Forming a fluticasone‑GR complex that translocates to the nucleus and binds glucocorticoid response elements (GREs).
• Transactivating anti‑inflammatory genes (e.g., lipocortin‑1) and transrepressing pro‑inflammatory transcription factors (NF‑κB, AP‑1).
• Reducing cytokine, chemokine, and adhesion‑molecule production, leading to decreased eosinophil recruitment and airway hyperresponsiveness.

Because of its high receptor affinity and poor systemic bioavailability, *fluticasone* achieves local anti‑inflammatory action with minimal systemic exposure.

Pharmacokinetics

Parameter	Inhaled (e.g., Diskus®)	Nasal Spray (e.g., Flixonase®)	Topical (creams)
Absorption	~2–6 % systemic (via pulmonary and GI tract).	Limited systemic absorption; primarily local.	Poor systemic uptake; mainly topical.
Distribution	Highly protein‑bound (>99 %); extensive tissue binding in lungs.	Local tissue; minimal systemic distribution.	Local, no significant systemic spread.
Metabolism	Hepatic via CYP3A4 → inactive metabolites (e.g., 11‑O‑acetyl‑fluticasone).	Liver first‑pass metabolism; negligible systemic levels.	Minimal systemic metabolism.
Half‑life	Intrinsic drug: ~8–10 h; systemic: 5 h.	Systemic: <1 h.	Not relevant.
Elimination	Renal (urine) and biliary excretion of metabolites.	Urine.	Dermal, negligible systemic.
Special Populations	CYP3A4 inhibitors can ↑ plasma levels; caution in renal/ hepatic impairment.	Similar cautions for CYP3A4 inhibitors.	No major alterations.

Indications

Inhaled:
Persistent asthma (maintenance).
COPD exacerbations (maintenance).
Asthma–COPD overlap.
Nasal Spray:
All‑season and seasonal allergic rhinitis.
Vasomotor rhinitis.
Topical (creams, ointments):
Chronic eczema, psoriasis, atopic dermatitis, and other inflammatory dermatoses.

(Check local formularies for approved dosing regimens.)

Contraindications

Contraindicated:
Known hypersensitivity to fluticasone or any excipients.
Active, untreated infections (unless combined with appropriate therapy).
Systemic fungal infections when given orally.
Warnings:
Adrenal suppression – especially with high doses or long courses.
Growth suppression in children (monitor height, weight).
Ocular side effects (cataract, glaucoma) with nasal or topical use.
Osteoporosis risk with systemic absorption; monitor with high‑dose use.
Infections – immunosuppression may worsen viral/bacterial infections.

Dosing

Form	Typical Adult Dose	Administration Tips	Pediatric Note
Inhaled Diskus® (Pulmicort®)	200 µg twice daily (≤ 400 µg/day) or 400 µg twice daily (≤ 800 µg/day)	• Use spacer with mouthpiece. • Rinse mouth after each actuation.	200 µg BID for ages 4–11 yrs; 400 µg BID for ≥ 12 yrs.
Low‑dose Dry Powder (Beclomethasone)	100 µg QID (≈ 400 µg total).	• Same inhaler technique.	2.5 µg QID for < 6 yrs; 5 µg QID for ≥ 6 yrs.
Nasal Spray (Flixonase®)	2 sprays each nostril BID	• Tilt head slightly forward. • Avoid nose wiping; rinse mouth post‑spray.	1 spray each nostril BID for < 2 yrs; 2 sprays BID for ≥ 2 yrs.
Topical Cream (e.g., Cutimize®)	Use for 1–2 hrs daily, then wash off	• Apply thin layer to affected area only.	Similar dosing after consultation.

Note: Switch to oral steroids only for severe exacerbations; gradual tapering is advised to avoid adrenal crisis.

Adverse Effects

Localized:
Oral candidiasis (inhaled).
Nasal irritation or epistaxis (nasal spray).
Skin atrophy, striae, telangiectasia (topical).
Systemic:
Hypoadrenalism.
Growth delay.
Osteoporosis.
Glaucoma, cataract (especially with chronic nasal use).
Immunosuppression leading to opportunistic infections.
Serious (rare):
Acute adrenal crisis.
Severe cutaneous adverse reactions.
Secondary bacterial infections.

Monitoring

Parameter	Frequency	Rationale
Adrenal axis (ACTH, cortisol)	After 4–6 weeks on > 600 µg/day.	Detect suppression early.
Height/Weight	Every visit in pediatrics.	Monitor growth.
Pulmonary function (FEV₁)	Every 3–6 months.	Ensure therapeutic benefit.
Ocular exam	Every 12 months (if nasal/ocular use).	Detect cataract/glaucoma.
Serum calcium, phosphorus, bone density	After 6–12 months on high doses or in risk groups.	Evaluate osteoporosis risk.
Signs of infection	At each visit.	Early detection of immunosuppression.

Clinical Pearls

Use a spacer with the Diskus® to maximize lung deposition and minimize oral thrush.
Rinse mouth immediately after inhalation →↓ candidiasis.
Patient education: Explain that flare‑ups may still occur on low‑dose maintenance; rescue inhaler is separate.
Combine with low‑dose SABA in asthma for optimal bronchodilation.
For nasal use: a second spray during early morning for persistent symptoms; avoid over‑use > 10 days to reduce the risk of ocular side effects.
Switching formulations: if poor response to inhaled fluticasone, consider adding a long‑acting β₂‑agonist rather than escalating dose.
Check drug interactions: potent CYP3A4 inhibitors (ketoconazole, ritonavir) can raise systemic fluticasone levels → monitor for adrenal suppression.
Topical use caution: high‑potency steroid formulations can thin skin; avoid prolonged use over joints and pressure areas.

*Fluticasone* remains a cornerstone of inhaled corticosteroid therapy due to its high potency, low systemic exposure, and proven efficacy in asthma, COPD, and allergic rhinitis. Proper technique, patient education, and vigilant monitoring are essential to maximize benefit and minimize risk.