ZETONNA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZETONNA (ZETONNA).
Ciclesonide is a prodrug that is converted to the active metabolite des-ciclesonide, which has high affinity for the glucocorticoid receptor. It inhibits inflammatory mediators such as cytokines, leukotrienes, and prostaglandins, and reduces airway hyperresponsiveness.
| Metabolism | Ciclesonide is converted to the active metabolite des-ciclesonide by esterases in the nasal mucosa; further metabolism is via CYP3A4 and possibly CYP2D6 in the liver. |
| Excretion | Following intravenous administration, ciclesonide and its active metabolite desisobutyryl-ciclesonide are excreted primarily in feces (66%) and urine (20%) as metabolites. <1% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of desisobutyryl-ciclesonide is approximately 0.4 hours (25-30 minutes) due to rapid clearance. The mean residence time is 3.5 hours for ciclesonide and 2.5 hours for the active metabolite. |
| Protein binding | Ciclesonide and desisobutyryl-ciclesonide are highly protein bound (>99%) in human plasma, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The volume of distribution for ciclesonide is approximately 203 L (or about 2.9 L/kg based on 70 kg), indicating extensive tissue distribution. For the active metabolite, Vd is approximately 931 L (13.3 L/kg). |
| Bioavailability | Absolute bioavailability of ZETONNA nasal aerosol is <1% due to minimal systemic absorption. Following intranasal administration, the systemic exposure is very low; the bioavailability relative to intravenous dosing is about 0.5% for ciclesonide and 1% for desisobutyryl-ciclesonide. |
| Onset of Action | Onset of clinical effect for ZETONNA (ciclesonide) nasal aerosol is observed within 24-48 hours after initial dosing, with maximal effect achieved after 1-2 weeks of regular use. |
| Duration of Action | Duration of action supports once-daily dosing. Clinical studies show sustained efficacy over 24 hours with regular use. The drug's effect is maintained with consistent daily administration. |
2 sprays (80 mcg) per nostril once daily. Each spray delivers 40 mcg of ciclesonide.
| Dosage form | AEROSOL, METERED |
| Renal impairment | No dose adjustment required. |
| Liver impairment | No formal studies; caution in severe hepatic impairment (Child-Pugh class C) due to potential increased systemic exposure. |
| Pediatric use | Approved for children ≥12 years: 2 sprays (80 mcg) per nostril once daily. Safety and efficacy in children <12 years not established. |
| Geriatric use | No specific dose adjustment; use same adult dose. Monitor for adrenal suppression and local effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZETONNA (ZETONNA).
| Breastfeeding | It is unknown if ciclesonide or its active metabolite des-ciclesonide are excreted in human milk. The M/P ratio is not available. Other inhaled corticosteroids are considered compatible with breastfeeding due to low systemic bioavailability. Caution is advised; use only if potential benefit justifies risk. |
| Teratogenic Risk | Ciclesonide is a corticosteroid. Animal studies show no teratogenic effects at clinically relevant doses. In humans, inhaled corticosteroids at standard doses are not associated with increased risk of major congenital malformations. However, limited data exist for ciclesonide specifically. Use only if clearly needed; monitor for potential adrenal suppression in newborns if used chronically in high doses. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to ciclesonide or any ingredient in the formulation","Untreated nasal mucosal ulceration","Recent nasal surgery or trauma (until healing has occurred)"]
| Precautions | ["Local nasal effects: epistaxis, nasal ulceration, Candida albicans infection, impaired wound healing","Hypothalamic-pituitary-adrenal axis suppression with excessive doses","Potential for growth suppression in pediatric patients","Monitor for signs of systemic corticosteroid effects when switching from systemic steroids","Avoid use in patients with active or quiescent tuberculosis, untreated fungal, bacterial, or viral infections, or ocular herpes simplex"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal adrenal function if high doses are used. No specific fetal monitoring required beyond routine prenatal care. Assess newborn for signs of adrenal suppression if mother used high-dose corticosteroids during pregnancy. |
| Fertility Effects | No adverse effects on fertility have been reported in animal studies. Human data are lacking; however, systemic corticosteroids may affect ovulation. Inhaled corticosteroids at standard doses are unlikely to impact fertility. |