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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADVAIR DISKUS 250/50 (ADVAIR DISKUS 250/50).
| Breastfeeding | Salmeterol and fluticasone are excreted in breast milk in animal studies; human data not available. M/P ratio not established. Use with caution, weighing benefit to mother against potential risk to infant, especially due to beta-agonist effects. |
| 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. |
■ 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 ingredient","Status asthmaticus or acute episodes of asthma or COPD requiring intensive measures","Primary treatment of acute bronchospasm"]
| 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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| 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. |