AZELASTINE HYDROCHLORIDE AND FLUTICASONE PROPIONATE
Clinical safety rating: safe
Strong CYP3A4 inhibitors like ketoconazole may increase systemic exposure Rinse mouth after inhalation to prevent oral candidiasis.
Azelastine is a histamine H1-receptor antagonist that inhibits histamine release from mast cells; fluticasone propionate is a corticosteroid that suppresses inflammatory mediators including cytokines, prostaglandins, and leukotrienes, reducing nasal inflammation.
| Metabolism | Azelastine is metabolized via CYP450 enzymes (primarily CYP3A4 and CYP2D6) and undergoes first-pass metabolism; fluticasone propionate undergoes extensive hepatic metabolism via CYP3A4 to inactive metabolites. |
| Excretion | Azelastine: 75% renal (as unchanged drug and metabolites), 25% fecal. Fluticasone propionate: primarily fecal after IV (90%), renal <5%; after intranasal, significant first-pass hepatic metabolism to inactive metabolites excreted in bile and feces. |
| Half-life | Azelastine: ~25 hours (range 22-27 h). Fluticasone propionate: ~7.8 hours intranasal; 7-8 hours IV; context: intranasal dosing achieves steady-state in 1-2 weeks. |
| Protein binding | Azelastine: ~88-90% bound primarily to albumin. Fluticasone propionate: ~91% bound primarily to albumin; extensively bound to corticosteroid-binding globulin. |
| Volume of Distribution | Azelastine: ~14.5 L/kg (range 12-16 L/kg), indicating extensive tissue distribution. Fluticasone propionate: ~4.5 L/kg (4.2-4.9 L/kg), suggesting moderate tissue distribution. |
| Bioavailability | Azelastine: intranasal ~40% (range 30-50%) due to local absorption and first-pass metabolism. Fluticasone propionate: intranasal <1% due to limited absorption and extensive first-pass metabolism; oral bioavailability negligible (<1%). |
| Onset of Action | Intranasal: Azelastine – within 15-30 minutes for nasal symptoms; fluticasone – symptomatic improvement within 12-24 hours, max effect ≤2 weeks. |
| Duration of Action | Azelastine: ~12 hours allowing twice-daily dosing. Fluticasone: once-daily dosing effective for 24 hours with regular use; early doses provide relief up to 24 hours. |
| Molecular Weight | Azelastine HCl: 418.4 Da; Fluticasone propionate: 500.6 Da |
| Action Class | Inhaled Corticosteroid and Antihistamine Combination |
1 spray per nostril twice daily (137 mcg azelastine hydrochloride and 50 mcg fluticasone propionate per spray).
| Dosage form | SPRAY, METERED |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Not recommended for children under 6 years; for ages 6-11, 1 spray per nostril twice daily. |
| Geriatric use | No specific dose adjustment; use with caution due to potential increased systemic exposure. |
| 1st trimester | Limited human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded. |
| 2nd trimester | Limited human data; consider benefits vs risks. Avoid unnecessary use. |
| 3rd trimester | Use only if clearly needed; potential for preterm labor with fluticasone (inhaled) not established with nasal route. |
Clinical note
Strong CYP3A4 inhibitors like ketoconazole may increase systemic exposure Rinse mouth after inhalation to prevent oral candidiasis.
| FDA category | Animal |
| Placental transfer | Fluticasone propionate crosses the placenta; azelastine likely crosses but limited data. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Common Effects | COPD |
| Serious Effects | Epistaxis, Nasal ulceration, Candidiasis of the nose and throat, Impaired wound healing, Glaucoma and cataracts (with long-term use), Adrenal suppression (with high doses or prolonged use), Hypersensitivity reactions (e.g., anaphylaxis, angioedema), Growth retardation in children |
Hypersensitivity to any component
| Precautions | Avoid use in patients with recent nasal surgery or trauma, Monitor for signs of hypercortisolism and adrenal suppression with prolonged use, Possible growth suppression in pediatric patients, Caution in patients with active or quiescent tuberculosis, untreated fungal, bacterial, or viral infections, or ocular herpes simplex, May cause epistaxis, nasal ulceration, or nasal septal perforation |
| Food/Dietary |
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| Both azelastine and fluticasone are excreted into breast milk in low amounts. No reported adverse effects in infants; however, caution is advised due to potential for systemic effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C for fluticasone propionate (azelastine is Category C). No adequate human studies; animal studies show corticosteroid-induced cleft palate, intrauterine growth restriction, and fetal resorption at high doses. First trimester: theoretical risk of cleft lip/palate (corticosteroid exposure). Second and third trimesters: potential for adrenal suppression, low birth weight, and preterm birth. Avoid unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, blood glucose (fluticasone may cause hyperglycemia), and fetal growth via ultrasound (risk of intrauterine growth restriction in chronic high-dose use). Assess for adrenal insufficiency in neonates if maternal use was prolonged or high-dose. |
| Fertility Effects | Azelastine: no known effect on fertility. Fluticasone propionate: animal studies show reduced conception rates and impaired spermatogenesis at high doses (oral). Human data lacking; likely minimal due to low systemic absorption via intranasal route. |
| No specific food interactions reported. Grapefruit juice does not significantly alter pharmacokinetics of fluticasone propionate or azelastine. Avoid alcohol if it exacerbates allergic symptoms (e.g., nasal congestion). |
| Clinical Pearls | Prime the nasal spray before first use (6 actuations) or if unused for >7 days (2 actuations). Avoid contact with eyes; if occurs, rinse with water. Counsel patients to shake the bottle gently before each use. Optimal effect may require several days of regular use. Use with caution in patients with nasal septal ulcers, recent nasal surgery, or trauma. Monitor for signs of adrenal insufficiency when switching from systemic corticosteroids. Growth velocity monitoring recommended in pediatric patients. |
| Patient Advice | Use regularly as prescribed for best results; do not increase dose without consulting doctor. · Clean applicator tip with a dry tissue after each use and replace cap tightly. · Do not use if you have untreated nasal infections or recent nasal surgery. · Rinse mouth with water after use to reduce risk of thrush (yeast infection). · Report any signs of infection, vision changes, or persistent nosebleeds. · Inform all healthcare providers that you are using this medication. |