Asthma/COPD:

Indications for: ALVESCO

Maintenance treatment of asthma as prophylactic therapy in patients ≥12 years of age.

Limitations of Use:

Not indicated for the relief of acute bronchospasm or for children under 12 years of age.

 

Clinical Trials:

The efficacy of Alvesco was evaluated in 6 randomized, double-blind, placebo-controlled, parallel-group clinical trials in adult and adolescent patients 12 years of age and older with mild persistent to severe persistent asthma.

Patients Previously Maintained on Bronchodilator Alone

Two randomized, double-blind, placebo-controlled trials of 12-weeks duration.

Trial 1:

  • Patients with mild to moderate persistent asthma (mean baseline percent predicted FEV1 of 79%), previously maintained on predominantly inhaled corticosteroids.
  • Randomly assigned to Alvesco 160mg once daily in the AM, Alvesco 80mcg twice daily, or placebo.
  • Statistically significantly more increases in AM pre-dose FEV1 compared with placebo were seen at 12 weeks for Alvesco 160mcg once daily (0.14L or 5.7%) and Alvesco 80mcg twice daily (0.19L or 7.5%). 
  • Asthma symptoms scores, AM PEF, and decreased need for rescue albuterol remained relatively stable in the Alvesco treatment groups compared with slight worsening in the placebo. 
  • Compared with placebo, fewer patients receiving Alvesco experienced worsening of asthma.

Trial 2:

  • 257 patients with moderate to severe persistent asthma (mean baseline percent predicted FEV1 of 54%).
  • Randomly assigned to Alvesco 160mcg or 320mcg twice daily, or placebo for 12 weeks.
  • Both Alvesco doses showed statistically significantly more improvement in pre-dose FEV1 (0.11L or 8.6% and 0.18L or 11.8%), compared with placebo.
  • Other measures of asthma control, AM PEF, symptoms, and need for rescue albuterol also showed improvement compared with placebo. 
  • Fewer patients treated with Alvesco experienced worsening of asthma vs placebo.

Patients Previously Maintained on Oral Corticosteroids

  • 12-week double-blind trial that included 140 patients with severe persistent asthma who had failed prior efforts to eliminate oral prednisone and had established the lowest effective prednisone dose (average prednisone dose at baseline: ~12mg/day)
  • Randomly assigned to Alvesco 320mcg or 640mcg twice daily or placebo.
  • Patients treated with Alvesco 320mcg and 640mcg twice daily significantly reduced their prednisone requirements by 47% and 62%, respectively, compared with a 4% increase in the placebo group.
  • Patients on Alvesco maintained asthma control as reflected by lung function, symptoms, and need for rescue albuterol.
  • A significantly larger percentage of patients on Alvesco were able to reduce oral prednisone by 50% or more as compared with placebo (64% and 77% of the patients treated with 320mcg and 640mcg, respectively twice daily vs 33% of patients on placebo). 
  • There was no statistically significant difference observed with Alvesco 640mcg twice daily compared with Alvesco 320mcg twice daily.

Adult Dosage:

Previously on bronchodilators alone: initially 80mcg twice daily, max 160mcg twice daily. Previously on inhaled corticosteroids: initially 80mcg twice daily; max 320mcg twice daily. Previously on oral corticosteroids (see full labeling): 320mcg twice daily. Rinse mouth after use; avoid eyes.

Children Dosage:

<12yrs: not established.

ALVESCO Contraindications:

Primary treatment of status asthmaticus or other acute episodes of asthma requiring intensive measures.

ALVESCO Warnings/Precautions:

Do not exceed recommended dose. Risk of local infections (eg, mouth/pharynx candidiasis). Immunosuppression: active or quiescent tuberculosis, systemic infections, ocular herpes simplex. If exposed to chickenpox or measles, consider immune globulin or antiviral prophylactic therapies. Monitor for signs/symptoms of adrenal insufficiency when transferring from systemic corticosteroids. May need supplemental systemic corticosteroids during periods of stress or a severe asthma attack. May unmask previously suppressed allergic conditions. Monitor for hypercorticism and HPA axis suppression (if occurs, discontinue gradually), growth in children, change in vision or with history of increased intraocular pressure, glaucoma, and/or cataracts. Reevaluate periodically. Assess bone mineral density if risk factors exist (eg, prolonged immobilization, osteoporosis, or chronic use of drugs that can reduce bone mass [eg, anticonvulsants, oral steroids]). Discontinue if paradoxical bronchospasm occurs; use alternative therapy. Prescribe a short-acting, inhaled β2-agonist for acute symptoms; monitor. Eosinophilic conditions. Hepatic impairment. Pregnancy: monitor closely. Nursing mothers.

ALVESCO Classification:

Steroid.

Adverse Reactions:

Headache, nasopharyngitis, sinusitis, throat pain, upper respiratory infection, arthralgia, nasal congestion, back pain; hypersensitivity reactions, immunosuppression, glaucoma, cataracts, bronchospasm.

Metabolism:

Ciclesonide is hydrolyzed to a biologically active metabolite, des-ciclesonide, by esterases. Des-ciclesonide undergoes further metabolism in the liver to additional metabolites mainly by the CYP3A4 isozyme and to a lesser extent by CYP2D6.

Drug Elimination:

14C-labeled ciclesonide was predominantly excreted via the feces after intravenous administration (66%) indicating that excretion through bile is the major route of elimination. Approximately 20% or less of des-ciclesonide was excreted in the urine. The mean half-life of ciclesonide and des-ciclesonide was 0.71 hours and 6 to 7 hours, respectively. Tmax of des-ciclesonide occurs at 1.04 hours following inhalation of ciclesonide.

 

Generic Drug Availability:

NO

How Supplied:

Inhaler—6.1g (60 inh)