ALVESCO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALVESCO (ALVESCO).
Ciclesonide is a prodrug that is converted to the active metabolite des-ciclesonide, which has anti-inflammatory activity by binding to glucocorticoid receptors, thereby inhibiting inflammatory mediators such as cytokines and leukotrienes.
| Metabolism | Ciclesonide is hydrolyzed by esterases in the lungs to the active metabolite des-ciclesonide. It is further metabolized by CYP3A4 and CYP2D6 to inactive metabolites. |
| Excretion | Primarily hepatic metabolism (CYP3A4) to less active metabolites; renal excretion accounts for <10% unchanged; fecal excretion as metabolites ~80%. |
| Half-life | Terminal elimination half-life is approximately 2-3 hours for the systemically absorbed fraction; however, the receptor occupancy half-life is significantly longer due to lipophilic tissue binding, providing therapeutic duration of 12 hours. |
| Protein binding | Binding to plasma proteins is approximately 87%, primarily to albumin. |
| Volume of Distribution | Volume of distribution is large, approximately 4.5 L/kg, indicating extensive tissue distribution and lung deposition. |
| Bioavailability | Absolute bioavailability via oral inhalation is approximately 25-35% due to first-pass metabolism; orally ingested fraction has bioavailability <1%. |
| Onset of Action | Oral inhalation: Bronchodilation effect within 1-2 hours; maximal benefit may require several days of regular use. |
| Duration of Action | Bronchodilation effect persists for approximately 12 hours after inhalation, supporting twice-daily dosing. |
Inhalation: 160 mcg twice daily (morning and evening). May be increased to 320 mcg twice daily if inadequate response. Maximum 640 mcg twice daily.
| Dosage form | AEROSOL, METERED |
| Renal impairment | No dose adjustment required for renal impairment. Pharmacokinetics unchanged in renal failure. |
| Liver impairment | No specific dose adjustment required based on Child-Pugh classification. Clinical monitoring advised in severe hepatic impairment. |
| Pediatric use | Children 5-11 years: 80 mcg twice daily. Adolescents ≥12 years: same as adult dosing. |
| Geriatric use | No dose adjustment necessary. Titrate to lowest effective dose to minimize adverse effects; monitor for oropharyngeal candidiasis and dysphonia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALVESCO (ALVESCO).
| Breastfeeding | Excretion into human milk is unknown; M/P ratio not established. Inhaled corticosteroids are poorly absorbed systemically; risk to breastfed infant is expected to be negligible. Use with caution, monitoring infant for signs of adrenal suppression. |
| Teratogenic Risk | Pregnancy Category C. Inhaled corticosteroids (ICS) are generally considered low risk; however, high doses in animal studies show increased risk of cleft palate and fetal growth restriction. First trimester: theoretical risk of orofacial clefts with systemic exposure, but inhaled route minimizes systemic absorption. Second/third trimesters: no consistent human evidence of major malformations; potential for fetal adrenal suppression with prolonged high doses. |
■ FDA Black Box Warning
None
| Serious Effects |
["Primary treatment of status asthmaticus or acute asthma attacks","Hypersensitivity to ciclesonide or any component of the formulation"]
| Precautions | ["Risk of adrenal insufficiency in patients transferring from systemic corticosteroids","Localized oral and pharyngeal Candida infections","Potential for paradoxical bronchospasm","Increased susceptibility to infections"] |
| Food/Dietary | No known significant food interactions. Avoid grapefruit juice if taking concomitant CYP3A4 inhibitors, though ciclesonide is not metabolized by CYP3A4. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor maternal asthma control and lung function. No specific fetal monitoring required; standard prenatal care including ultrasound for growth if high dose therapy. Monitor for maternal hypercorticism or adrenal suppression with prolonged high-dose use. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment at clinical doses. |
| ALVESCO (ciclesonide) is a prodrug converted to active metabolite des-ciclesonide in the lungs. It requires activation by esterases, so not all patients may respond if esterase activity is deficient. Instruct patients to use a spacer for better lung deposition and to rinse mouth after inhalation to prevent oral candidiasis. |
| Patient Advice | Use exactly as prescribed; do not stop suddenly. · Rinse mouth with water after each use to prevent thrush. · Not a rescue inhaler; use a separate quick-relief inhaler for acute attacks. · Shake inhaler well before each use. · Store at room temperature away from moisture. |