ADVAIR DISKUS 250/50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADVAIR DISKUS 250/50 (ADVAIR DISKUS 250/50).
Fluticasone propionate is a corticosteroid that binds to glucocorticoid receptors, inhibiting inflammatory mediators. Salmeterol xinafoate is a long-acting beta2-adrenergic agonist that relaxes bronchial smooth muscle by increasing cyclic AMP.
| Metabolism | Fluticasone propionate is metabolized primarily by CYP3A4. Salmeterol xinafoate is metabolized by CYP3A4 via hydroxylation. |
| Excretion | Fluticasone propionate: <5% renal (as metabolites), majority biliary/fecal. Salmeterol: 57% renal (as metabolites), 30% fecal. |
| Half-life | Fluticasone propionate: 14-17 hours (terminal). Salmeterol: 5.5 hours (terminal). The fluticasone half-life supports twice-daily dosing with potential accumulation. |
| Protein binding | Fluticasone propionate: 99.7% (primarily albumin). Salmeterol: 94-96% (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Fluticasone propionate: 4.2 L/kg (very high, extensive tissue distribution). Salmeterol: 7.6 L/kg (large, indicating extravascular distribution). |
| Bioavailability | Inhaled: Absolute bioavailability ~14% for fluticasone propionate (due to high first-pass metabolism); for salmeterol, systemic absorption is minimal (<1% of inhaled dose reaches systemic circulation via lungs, and oral fraction is nearly completely metabolized). |
| Onset of Action | Inhalation: 30-60 minutes for bronchodilation (salmeterol component). Anti-inflammatory effect (fluticasone) begins within 24 hours but maximal effect may take 1-2 weeks. |
| Duration of Action | Inhalation: Approximately 12 hours for bronchodilation; clinical trials show sustained bronchodilation for 12 hours. Anti-inflammatory effect persists with regular use. |
| Molecular Weight | Fluticasone propionate: 500.57 Da; Salmeterol: 415.57 Da (as base) |
1 inhalation (fluticasone propionate 250 mcg and salmeterol 50 mcg) twice daily, approximately 12 hours apart, via oral inhalation.
| Dosage form | POWDER |
| Renal impairment | No dosage adjustment required for renal impairment. Pharmacokinetics of fluticasone propionate and salmeterol are not significantly altered in renal insufficiency. |
| Liver impairment | Use with caution in patients with hepatic impairment. For Child-Pugh Class B or C, reduce dose to lowest effective strength (e.g., 100/50 or 250/50) and monitor for corticosteroid and beta-agonist adverse effects. Specific guidelines for Child-Pugh A: no adjustment typically needed. |
| Pediatric use | Approved for children aged 12 years and older: 1 inhalation of 250/50 twice daily. For children aged 4-11 years, use ADVAIR DISKUS 100/50 (fluticasone propionate 100 mcg and salmeterol 50 mcg) 1 inhalation twice daily. Not indicated for children under 4 years. |
| Geriatric use | No specific dosage adjustment required solely based on age. However, elderly patients may have increased sensitivity; initiate at lowest effective dose and monitor for systemic corticosteroid effects and cardiovascular events due to beta-agonist. |
| 1st trimester | Limited data; avoid unless benefit outweighs risk. Inhaled corticosteroids are preferred due to lower systemic absorption. |
| 2nd trimester | Use with caution; monitor fetal growth. Fluticasone propionate and salmeterol are generally considered safe when used at recommended doses. |
| 3rd trimester | Use with caution; risk of neonatal hypoglycemia and respiratory depression with beta-agonists close to delivery. |
Clinical note
Comprehensive clinical and safety monograph for ADVAIR DISKUS 250/50 (ADVAIR DISKUS 250/50).
| Placental transfer | Fluticasone propionate: extensive placental transfer; salmeterol: crosses placenta but extent unknown. |
| Breastfeeding | Fluticasone propionate and salmeterol are excreted in breast milk in small amounts. Use with caution, especially in preterm infants or those with respiratory issues. |
■ FDA Black Box Warning
Long-acting beta2-adrenergic agonists (LABAs) increase the risk of asthma-related death. Therefore, ADVAIR DISKUS is contraindicated for the treatment of asthma without concomitant use of a long-term asthma control medication, such as an inhaled corticosteroid. It should not be used for acute deterioration of asthma.
| Serious Effects |
Hypersensitivity to any componentStatus asthmaticus or acute asthma exacerbationSevere hypersensitivity to milk proteins (lactose component)
| Precautions | Increased risk of asthma-related death with LABA use, Candidiasis of the mouth and throat, Pneumonia in patients with COPD, Increased susceptibility to infections, Adrenal insufficiency during stress or withdrawal, Reduced bone mineral density with long-term use, Hypersensitivity reactions including anaphylaxis, Hypercorticism and suppression of hypothalamic-pituitary-adrenal axis, Cardiovascular effects (tachycardia, hypertension, QT prolongation), Paradoxical bronchospasm, Systemic eosinophilic conditions, Monitoring for reduced growth in pediatric patients |
| Food/Dietary |
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| Lactation Rating | L3: Limited data, probably compatible. |
| Teratogenic Risk | Inhaled corticosteroids and long-acting beta-agonists are not associated with major congenital malformations. Limited data for combination product; animal studies show no teratogenic risk at clinically relevant doses. No increased risk of orofacial clefts with inhaled corticosteroids. Use only if benefit outweighs risk, especially during first trimester. |
| Fetal Monitoring | Monitor maternal respiratory function (peak flow, FEV1), fetal growth and well-being (ultrasound for growth restriction), and signs of preterm labor. Assess for maternal glucose intolerance (steroid effect) and blood pressure changes. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility at clinically relevant doses for either component. |
| No known significant food interactions. Avoid grapefruit juice as it may affect drug metabolism? (Note: Grapefruit interaction is minimal for inhaled corticosteroids and LABAs, but general caution advised.) |
| Clinical Pearls | ADVAIR DISKUS 250/50 is a fixed-dose combination of fluticasone propionate (250 mcg, an inhaled corticosteroid) and salmeterol (50 mcg, a long-acting beta-2 agonist) indicated for maintenance treatment of asthma and COPD. It is not for acute bronchospasm. Rinse mouth after use to prevent oral candidiasis. Monitor for increased asthma-related deaths with LABA use. Not for patients with severe asthma exacerbation. Taper slowly if discontinuing. |
| Patient Advice | Use exactly as prescribed; do not use for sudden breathing problems. · Rinse mouth with water and spit after each use to prevent thrush. · Do not stop abruptly; taper under doctor's guidance. · Call doctor if symptoms worsen or need more short-acting rescue inhaler. · Keep track of dose counter on device. · Avoid allergens and triggers; do not exceed prescribed dose. |