Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol Solution, Inhalation:
Alvesco: 80 mcg/actuation (6.1 g); 160 mcg/actuation (6.1 g)
Pharmacology
Mechanism of Action
Ciclesonide is a nonhalogenated, glucocorticoid prodrug that is hydrolyzed to the pharmacologically active metabolite des-ciclesonide following administration. Des-ciclesonide has a high affinity for the glucocorticoid receptor and exhibits anti-inflammatory activity. The mechanism of action for corticosteroids is believed to be a combination of three important properties − anti-inflammatory activity, immunosuppressive properties, and antiproliferative actions.
Pharmacokinetics/Pharmacodynamics
Absorption
52% (lung deposition)
Distribution
Vd: Ciclesonide: 2.9 L/kg; des-ciclesonide: 12.1 L/kg
Metabolism
Ciclesonide hydrolyzed to its active metabolite, des-ciclesonide via esterases in nasal mucosa and lungs; des-ciclesonide undergoes further hepatic metabolism primarily via CYP3A4 and to a lesser extent via CYP2D6
Excretion
Feces (66%); urine (≤20% as active metabolite)
Onset of Action
>4 weeks for maximum benefit
Time to Peak
~1 hour (des-ciclesonide)
Half-Life Elimination
Ciclesonide: 0.7 hours; des-ciclesonide: 6 to 7 hours
Protein Binding
≥99%
Use in Specific Populations
Special Populations: Hepatic Function Impairment
Cmax of des-ciclesonide in patients with moderate to severe liver impairment increased 1.4- to 2.7-fold after oral inhalation.
Use: Labeled Indications
Asthma: Maintenance treatment of asthma as prophylactic therapy in patients ≥12 years of age.
Limitations of use: Not indicated for relief of acute bronchospasm.
Guideline recommendations: A low-dose inhaled corticosteroid (in addition to an as-needed, short-acting beta2-agonist) is the initial preferred long-term control medication for children, adolescents, and adult patients with persistent asthma who are candidates for treatment according to a stepwise treatment approach (GINA 2018; NAEPP 2007).
Contraindications
Hypersensitivity to ciclesonide or any component of the formulation; status asthmaticus or other acute asthma episodes requiring intensive measures
Documentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Untreated fungal, bacterial, or tuberculosis infections of the respiratory tract; moderate to severe bronchiectasis
Dosage and Administration
Dosing: Adult
Note: Titrate to the lowest effective dose once asthma stability is achieved.
Asthma: Oral inhalation: Note: To decrease the severity or duration of an asthma exacerbation, may consider temporarily quadrupling the dose (early in the course of illness) in patients with mild to moderate asthma with a mild flare in symptoms. Reserve this approach for patients with no prior history of life-threatening asthma exacerbations, and in those with good self-management skills; return to baseline dose after normalization of symptoms or at a maximum of 14 days of the quadrupled dose (Fanta 2019; GINA 2018; McKeever 2018).
US labeling: Metered-dose inhaler:
Note: Dosing based on previous asthma therapy and asthma severity. May increase dose after 4 weeks of therapy in patients who are not adequately controlled.
Prior therapy with bronchodilators alone: Initial: 80 mcg twice daily (maximum dose: 160 mcg twice daily)
Prior therapy with inhaled corticosteroids: Initial: 80 mcg twice daily (maximum dose: 320 mcg twice daily)
Prior therapy with oral corticosteroids: Initial: 320 mcg twice daily (maximum dose: 320 mcg twice daily)
Canadian labeling: Metered-dose inhaler: Initial: 400 mcg once daily; more severe asthma may require 400 mcg twice daily; maintenance: 100 to 800 mcg/day.
Asthma guidelines: Global Initiative for Asthma guidelines (GINA 2018): HFA inhaler: Metered-dose inhaler:
Low-dose therapy: 80 to 160 mcg/day in divided doses twice daily
Medium-dose therapy: >160 to 320 mcg/day in divided doses twice daily
High-dose therapy: >320 mcg/day in divided doses twice daily
Conversion: Conversion from oral to orally inhaled steroid: Initiation of oral inhalation therapy should begin in patients who have previously been stabilized on oral corticosteroids (OCS). A gradual dose reduction of OCS should begin at least 1 week after starting inhaled therapy. Manufacturer's labeling recommends reducing prednisone dose no more rapidly than ≤2.5 mg/day on a weekly basis.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Asthma:
Maintenance therapy: Note: Doses should be titrated to the lowest effective dose once asthma is controlled:
Manufacturer's labeling: Alvesco inhaler: 80 mcg/inhalation and 160 mcg/inhalation:
Children 2 to 11 years: Limited data available: Metered-dose inhaler: Oral inhalation: 40, 80, or 160 mcg once daily. Dosing from studies of childhood asthma (or wheezing in children <5 years). Efficacy results variable in children ≤6 years (Brand 2011; Gelfand 2006; Pedersen 2010).
Children ≥12 years and Adolescents: Metered-dose inhaler: Oral inhalation: Note: Initial dose is based on previous asthma therapy.
Prior therapy with bronchodilators alone: Initial: 80 mcg twice daily, may increase dose after 4 weeks of therapy if response inadequate; maximum daily dose: 320 mcg/day.
Prior therapy with inhaled corticosteroids: Initial: 80 mcg twice daily, may increase dose after 4 weeks of therapy if response inadequate; maximum daily dose: 640 mcg/day.
Prior therapy with oral corticosteroids: Initial: 320 mcg twice daily; maximum daily dose: 640 mcg/day.
Asthma guidelines: Global Initiative for Asthma guidelines (GINA 2018): HFA inhaler (refers to available US products): Oral inhalation: Note: Administer in divided doses twice daily:
Children 6 to 11 years:
"Low" dose: 80 mcg/day.
"Medium" dose: >80 to 160 mcg/day.
"High" dose: >160 mcg/day.
Children ≥12 years and Adolescents:
"Low" dose: 80 to 160 mcg/day.
"Medium" dose: >160 to 320 mcg/day.
"High" dose: >320 mcg/day.
Mild flare, exacerbation: Limited data available:
Children ≥12 years and Adolescents with mild to moderate asthma, no prior history of life-threatening asthma exacerbations, and with good self-management skills:
It is recommended to temporarily quadruple the inhaled corticosteroid dose early in the course of a mild flare to decrease the severity of an asthma exacerbation. After symptoms stabilize or after a maximum of 14 days of quadrupled dose, whichever occurs first, patients should be returned to their baseline dose (GINA 2019). Quadrupling the inhaled corticosteroid dose has been shown to decrease the severity of an asthma exacerbation in select patients. In a randomized trial of adolescents ≥16 years and adults (n=1,871), temporarily quadrupling the inhaled corticosteroid dose when asthma control began to deteriorate resulted in fewer severe asthma exacerbations (ie, less treatment with systemic glucocorticoids or unscheduled appointments for asthma) compared to patients who maintained their inhaled corticosteroid dose (McKeever 2018). No data for quadrupling the dose in patients <16 years of age has been published. Quintupling the dose of inhaled corticosteroids (fluticasone) in children 5 to 11 years of age was not shown to reduce the rate of severe exacerbations and may have been associated with adverse effects (decreased linear growth, particularly in patients <8 years of age) (GINA 2019; Jackson 2018).
Conversion from oral systemic corticosteroid to orally-inhaled corticosteroid: Children ≥12 years and Adolescents: Initiation of oral inhalation therapy should begin in patients who have previously been stabilized on oral corticosteroids (OCS). A gradual dose reduction of OCS should begin at least 1 week after starting inhaled therapy. Manufacturer's labeling recommends reducing prednisone dose no more rapidly than 2.5 mg/day on a weekly basis. In the presence of withdrawal symptoms, resume previous OCS dose for 1 week before attempting further dose reductions.
Canadian labeling: Maintenance therapy: Alvesco Inhaler 100 mcg/inhalation and 200 mcg/inhalation [Canadian products]: Metered-dose inhaler: Oral inhalation:
Children 6 to 11 years:
Initial: 100 to 200 mcg once daily.
Maintenance: 100 to 200 mcg/day.
Children ≥12 years and Adolescents:
Initial: 400 mcg once daily; more severe asthma may require 400 mcg twice daily.
Maintenance: 100 to 800 mcg/day.
Administration
Metered-dose inhaler: Prime inhaler by actuating 3 times before the first use or when the inhaler has not been used for >10 consecutive days; do not shake before use. Rinse mouth with water (and spit out) after inhalation. Do not wash or place inhaler in water. Clean mouthpiece using a dry cloth or tissue once weekly. Discard after the "discard by" date or when dose indicator display window reads "0", even if canister is not completely empty.
Storage
Store at 25°C (77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F). Do not use or store near open flame or heat; do not puncture canisters. Exposure to temperatures >49°C (120°F) may cause canister to burst; do not throw canister into fire or incinerator.
Drug Interactions
Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination
Amphotericin B: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy
Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Monitor therapy
Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Avoid combination
Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
Loop Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination
Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy
Thiazide and Thiazide-Like Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Headache (≤11%)
Respiratory: Nasopharyngitis (≤11%)
1% to 10%:
Cardiovascular: Facial edema (≥3%)
Central nervous system: Dizziness (≥3%), fatigue (≥3%), voice disorder (1%)
Dermatologic: Urticaria (≥3%)
Gastrointestinal: Gastroenteritis (≥3%), oral candidiasis (≥3%)
Infection: Influenza (≥3%)
Neuromuscular & skeletal: Arthralgia (≥3%), back pain (≥3%), limb pain (≥3%), musculoskeletal chest pain (≥3%)
Ophthalmic: Conjunctivitis (≥3%)
Otic: Otalgia (2%)
Respiratory: Upper respiratory tract infection (≤9%), nasal congestion (≤6%), pharyngolaryngeal pain (≤5%), hoarseness (≥3%), pneumonia (≥3%), sinusitis (≥3%), paradoxical bronchospasm (2%)
<1%, postmarketing, and/or case reports: Angioedema (with swelling of lip/pharynx/tongue), cataract, chest discomfort, increased gamma-glutamyl transferase, increased intraocular pressure, increased serum ALT, nausea, palpitations, pharyngeal candidiasis, skin rash, weight gain, xerostomia
Warnings/Precautions
Concerns related to adverse effects:
- Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections (particularly gastroenteritis), or other conditions with severe electrolyte loss. Select surgical patients on long-term, high-dose, inhaled corticosteroid (ICS), should be given stress doses of hydrocortisone intravenously during the surgical period and the dose reduced rapidly within 24 hours after surgery (NAEPP 2007).
- Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; reaction should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue ciclesonide and institute alternative therapy.
- Hypersensitivity reactions: Immediate hypersensitivity reactions (eg, angioedema, bronchospasm, rash, urticaria) may occur; discontinue use if reaction occurs.
- Immunosuppression: Prolonged use of corticosteroids may also increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use, if possible, in patients with ocular herpes, active or quiescent respiratory tuberculosis, or untreated viral, fungal, parasitic, or bacterial systemic infections. Exposure to chickenpox and measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intramuscular immunoglobulin, respectively, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
- Oral candidiasis: Local oropharyngeal Candida albicans infections have been reported; if this occurs, treat appropriately while continuing therapy. Patients should be instructed to rinse mouth with water without swallowing after each use.
- Vasculitis: Rare cases of vasculitis (eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]) or other eosinophilic conditions (eg, vasculitic rash, decreased pulmonary function, cardiac complications) can occur.
Disease-related concerns:
- Asthma: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Short-acting beta2-agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. Use is contraindicated in status asthmaticus or during other acute asthma episodes requiring intensive measures.
- Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral count such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (eg, anticonvulsants or oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.
- Ocular disease: Use with caution in patients with cataracts and/or glaucoma; blurred vision, increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in chronic users.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pediatric: Orally inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 cm per year [range: 0.3 to 1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.
Other warnings/precautions:
- Discontinuation of therapy: A gradual tapering of dose may be required prior to discontinuing therapy; there have been reports of systemic corticosteroid withdrawal symptoms (eg, joint/muscle pain, lassitude, depression) when withdrawing oral inhalation therapy.
- Transfer to oral inhaler: When transferring to oral inhalation therapy from systemic corticosteroid therapy, previously suppressed allergic conditions (rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions) may be unmasked. Withdraw systemic corticosteroid therapy by gradually tapering the dose. Monitor lung function, beta-agonist use, asthma symptoms, and for signs and symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea/vomiting, hypotension) during withdrawal.
Monitoring Parameters
FEV1, peak flow, and/or other pulmonary function tests; bone mineral density; growth (adolescents and children via stadiometry); signs/symptoms of HPA axis suppression/adrenal insufficiency; possible eosinophilic conditions (including eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]); signs/symptoms of oral candidiasis; asthma symptoms; glaucoma/cataracts
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Hypoadrenalism may occur in infants born to mothers receiving corticosteroids during pregnancy.
Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications (ACOG 2008; GINA 2018).
Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy (ACOG 2008; GINA 2018; Namazy 2016). Pregnant females adequately controlled on ciclesonide for asthma may continue therapy; if initiating treatment during pregnancy, use of an agent with more data in pregnant females may be preferred (Namazy 2016).
Patient Education
What is this drug used for?
- It is used to treat asthma.
- Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.
Frequently reported side effects of this drug
- Headache
- Stuffy nose
- Sore throat
- Sinus pain
- Common cold symptoms
- Joint pain
- Back pain
- Painful extremities
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Infection
- Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss
- Cushing syndrome like weight gain in upper back or abdomen; moon face; severe headache; or slow healing
- Trouble breathing
- Wheezing
- Cough
- Severe loss of strength and energy
- Irritability
- Tremors
- Fast heartbeat
- Confusion
- Dizziness
- Sweating
- Thrush
- Chest pain
- Bone pain
- Vision changes
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
