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. |
| Molecular Weight | 540.65 |
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 | Insufficient human data; based on animal studies, there is evidence of teratogenicity (cleft palate, skeletal anomalies) at high systemic exposures. Use only if potential benefit outweighs risk. |
| 2nd trimester | Insufficient human data; animal studies show fetal harm at high doses. Consider using with caution. |
| 3rd trimester | Insufficient human data; potential for adrenal suppression in neonate with long-term use. Avoid prolonged use near term. |
Clinical note
Comprehensive clinical and safety monograph for ZETONNA (ZETONNA).
| Placental transfer | Ciclesonide and its active metabolite des-ciclesonide cross the placenta in animal studies; human data are lacking. The degree is likely low due to high protein binding and low systemic availability after intranasal use. |
| Breastfeeding | Intranasal administration results in negligible systemic absorption; it is unlikely to pass into breast milk. Use with caution, especially in nursing mothers of preterm infants. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to ciclesonide or any ingredientUntreated localized nasal infections (e.g., fungal, bacterial, viral)
| 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 |
| Food/Dietary | No significant food interactions. Take with or without food. Avoid grapefruit juice as it may affect metabolism (though clinically not significant for intranasal ciclesonide). No known dietary restrictions. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | ZETONNA (ciclesonide) is a prodrug converted to active metabolite des-ciclesonide in the lungs. It has high topical potency and low oral bioavailability, minimizing systemic side effects. Administer as two inhalations once daily. Prime pump with four test sprays before first use or if not used for more than seven days. Rinsing mouth after use reduces risk of oral candidiasis. Not for acute asthma attacks; use short-acting beta-agonist for rescue. |
| Patient Advice | Use ZETONNA exactly as prescribed—two sprays in each nostril once daily. Do not use more often. · Prime the spray by pumping four test sprays into the air before first use or if not used for a week or more. · Avoid spraying into eyes. · Clean the applicator weekly by wiping with a dry cloth; do not wash. · Do not stop using suddenly; consult your doctor before discontinuing. · Tell your doctor if you have nasal sores, recent nasal surgery, or tuberculosis. · Rinse your mouth with water after use to prevent thrush. |