FLUTICASONE PROPIONATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Glucocorticoid receptor agonist; binds to cytosolic glucocorticoid receptors, leading to inhibition of inflammatory mediators (e.g., cytokines, prostaglandins, leukotrienes) and suppression of immune cell activity.
| Metabolism | Hepatic via CYP3A4; undergoes extensive first-pass metabolism; main metabolite is 17β-carboxylic acid derivative (inactive). |
| Excretion | Primarily hepatic metabolism via CYP3A4 to inactive metabolites; <5% excreted unchanged in urine; biliary/fecal elimination accounts for >90% of metabolites. |
| Half-life | Terminal elimination half-life is approximately 7.8 hours after intravenous administration; extends to 10-14 hours following intranasal or inhaled routes due to slow absorption from the lung/nasal mucosa. |
| Protein binding | 99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 4.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Intranasal: <2% due to mucociliary clearance and hepatic first-pass metabolism; Inhaled: approximately 15-20% reaching systemic circulation; Oral: negligible (<1%). |
| Onset of Action | Intranasal: 2-4 hours; Inhaled: 24 hours for peak effect, with some improvement noted within 12 hours. |
| Duration of Action | Intranasal: 24 hours with once-daily dosing; Inhaled: 12-24 hours, typically dosed once or twice daily. |
Inhalation: 88-440 mcg twice daily for asthma (DPI: 100-500 mcg twice daily; HFA: 44-220 mcg twice daily). Intranasal: 2 sprays (50 mcg/spray) per nostril once daily (total 200 mcg/day). Topical: Apply thin layer to affected area 1-2 times daily.
| Dosage form | OINTMENT |
| Renal impairment | No dose adjustment required. Renal impairment does not significantly alter pharmacokinetics due to minimal renal excretion. |
| Liver impairment | Use with caution in severe hepatic impairment (Child-Pugh Class C). No specific dose guidelines; monitor for systemic effects. |
| Pediatric use | Inhalation (asthma): 4-11 years: 88 mcg twice daily (DPI 100-200 mcg twice daily; HFA 88 mcg twice daily). Intranasal: 2-11 years: 1 spray (50 mcg) per nostril once daily (total 100 mcg/day). Topical: Use lowest potency formulation; apply sparingly. |
| Geriatric use | No specific dose adjustments, but initiate at lower end of dosing range and monitor for increased risk of adverse effects (e.g., adrenal suppression, osteoporosis). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors like ketoconazole may increase systemic exposure Rinse mouth after inhalation to prevent oral candidiasis.
| Breastfeeding | Fluticasone propionate is excreted into human breast milk in negligible amounts due to low systemic bioavailability after inhalation. The milk/plasma ratio is unknown. No adverse effects in breastfed infants have been reported. Inhaled fluticasone is considered compatible with breastfeeding. |
| Teratogenic Risk | Fluticasone propionate is an inhaled corticosteroid. Data from large prospective cohort studies and meta-analyses do not indicate a significantly increased risk of major congenital malformations. In the first trimester, risk is low and no specific pattern of defects identified. Second and third trimester exposure may slightly increase risk of preterm birth and low birth weight, but underlying maternal asthma itself is a confounder. Animal studies show fetal harm only at high systemic doses. |
■ FDA Black Box Warning
None.
| Common Effects | COPD |
| Serious Effects |
["Hypersensitivity to fluticasone or any component","Status asthmaticus (not for acute bronchospasm)","Primary treatment of acute asthma exacerbation"]
| Precautions | ["Risk of adrenal insufficiency with systemic absorption","Increased susceptibility to infections (e.g., chickenpox, measles)","Potential for growth retardation in children","Oropharyngeal candidiasis with inhaled use","Monitor for glaucoma and cataracts with long-term use","Avoid in patients with active tuberculosis or untreated fungal/bacterial/viral infections"] |
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| Fetal Monitoring | Monitor maternal asthma control (peak expiratory flow, symptoms, rescue inhaler use). Assess fetal growth (serial ultrasound) if asthma is poorly controlled or if high doses are used for prolonged periods. No specific fetal monitoring required for fluticasone itself. |
| Fertility Effects | Fluticasone propionate at therapeutic inhaled doses is not associated with impaired fertility in humans. Animal studies at high systemic doses showed reduced fertility, but these doses far exceed clinical inhalation exposure. No clinical evidence of fertility effects in women or men. |