Side Effects of Alvesco (ciclesonide)

Alvesco (ciclesonide) is a man-made steroid for inhalation in the glucocorticoid family. It is related to the naturally-occurring steroid hormone, cortisol or hydrocortisone, produced by the adrenal glands. 

The body converts ciclesonide to des-ciclesonide, which is the active form of the drug. Glucocorticoid steroids have potent anti-inflammatory actions. When used as an inhaler, Alvesco travels to the airways in the lung. 

In people with asthma, the suppression of inflammation within the airways reduces the spasm of muscle cells that surround the airways as well as the accumulation of fluid and cells that accompanies the inflammation which lead to narrowing of the airways. 

The narrowing makes it difficult to get air into and out of the lungs. When used in lower doses, very little Alvesco is absorbed into the body. When higher doses are used, Alvesco is absorbed and may cause side effects elsewhere in the body.

Common side effects of Alvesco include

• unpleasant taste in the mouth,
• dry mouth,
• burning or irritation in the mouth,
• runny or stuffy nose,
• sore throat,
• hoarseness,
• mild itching or skin rash,
• joint pain,
• back pain, and
• headache.

Serious side effects of Alvesco include

• bronchospasm and
• worsening of existing viral, bacterial, fungal, or parasitic infections such as
  • tuberculosis,
  • measles,
  • chicken pox, or
  • herpes.

Drug interactions of Alvesco include drugs such as ketoconazole that reduce the activity of liver enzymes that breakdown drugs may increase the levels of des-ciclesonide, which is the active form of Alvesco, and lead to increased exposure of the body to des-ciclesonide and more side effects. 

Use of Alvesco during pregnancy has not been adequately evaluated. 

It is unknown if Alvesco is secreted in breast milk. Other medications in this class are secreted into breast milk. 

It is unknown if the small amounts of Alvesco that may appear in breast milk have an effect on the infant. Consult your doctor before breastfeeding. 

WARNING

• Ciclesonide may cause bronchospasm.
• Ciclesonide should not be used for treatment of acute asthmatic attacks.
• Ciclesonide may worsen existing viral, bacterial, fungal, or parasitic infections such as
  • tuberculosis,
  • measles,
  •  chicken pox, or
  • herpes.

Systemic and local corticosteroid use may result in the following:

• Candida albicans infection
• Immunosupression
• Hypercorticism and adrenal suppression
• Growth effects
• Glaucoma and cataracts

Clinical Trial Experience

• The safety data described below for adults and adolescents 12 years of age and older reflect exposure to Alvesco in doses ranging from 80 mcg to 640 mcg twice daily in five double-blind placebo-controlled clinical trials.
• Studies with once daily dosing are omitted from the safety database because the doses studied once daily are lower than the highest recommended twice daily doses.
• The five studies were of 12 to 16 weeks treatment duration, one of which included a safety extension follow up of one year. In the 12 to 16 week treatment studies, 720 patients (298 males and 422 females) aged 12 years and older were exposed to Alvesco.
• In the long-term safety trial, 197 patients (82 males and 115 females) with severe persistent asthma from one of the 12-week trials were re-randomized and treated for up to one year with Alvesco 320 mcg twice daily. Safety information for pediatric patients 4 to 11 years of age, is obtained from once daily dosing studies.
• Two of these studies were designed with a 12-week double-blind treatment period followed by a long-term open label safety extension of one year, and one study was an open label safety study of one year duration.
• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adult and Adolescent 12 Years of Age and Older

• Four of the five trials included a total of 624 patients ages 12 years and older (359 females and 265 males) with asthma of varying severity who were treated with Alvesco 80 mcg, 160 mcg, or 320 mcg twice daily for 12 to 16 weeks.
• These studies included patients previously using either controller therapy (predominantly inhaled corticosteroids) or reliever therapy (bronchodilator therapy alone).
• In these trials, the mean age was 39.1 years, and the majority of the patients (79.0%) were Caucasian.
• In these trials, 52.3%, 59.8% and 54.1% of the patients in the Alvesco 80 mcg, 160 mcg, and 320 mcg treatment groups, respectively, had at least one adverse event compared to 58.0% in the placebo group.
• Table 1 includes adverse reactions for the recommended doses of Alvesco that occurred at an incidence of ≥ 3% in any of the Alvesco groups and which were more frequent with Alvesco compared to placebo.

Table 1: Adverse Reactions with ≥ 3% Incidence Reported in Patients ≥ 12 Years of Age with Alvesco in US Placebo-Controlled Clinical Trials in Patients Previously on Bronchodilators and/or Inhaled Corticosteroids

The following adverse reactions occurred in these clinical trials using Alvesco with an incidence of less than 1% and occurred at a greater incidence with Alvesco than with placebo.

• Infections and Infestations: Oral candidiasis
• Respiratory Disorders: Cough
• Gastrointestinal Disorders: Dry mouth, nausea
• General disorders and administrative site conditions: Chest discomfort
• Respiratory, Thoracic, and Mediastinal Disorders: Dysphonia, dry throat

The fifth study was a 12-week clinical trial in asthma patients 12 years of age and older who previously required oral corticosteroids (average daily dose of oral prednisone of 12 mg/day), in which the effects of Alvesco 320 mcg twice daily (n = 47) and 640 mcg twice daily (n = 49) were compared with placebo (n = 45) for the frequency of reported adverse reactions.

The following adverse reactions occurred at an incidence of ≥ 3% in the Alvesco-treated patients and were more frequent compared to placebo:

• sinusitis,
• hoarseness,
• oral candidiasis,
•  influenza,
• pneumonia,
• nasopharyngitis,
• arthralgia,
• back pain,
• musculoskeletal chest pain,
• headache,
• urticaria,
• dizziness,
• gastroenteritis,
• face edema,
• fatigue, and
•  conjunctivitis.

Pediatric Patients less than 12 Years of Age

• The safety of Alvesco in pediatric patients 4 to 11 years of age was evaluated in two studies in which Alvesco 40 mcg, 80 mcg, and 160 mcg was administered once daily for 12 weeks and in one study in pediatric patients 2 to 6 years of age in which Alvesco 40 mcg, 80 mcg, and 160 mcg was administered once daily for 24 weeks.
• Studies have not been conducted in patients less than 2 years of age.

Long-Term Clinical Trials Experience

• A total of 197 patients 12 years of age and older (82 males and 115 females) from one of the 12-week treatment placebo-controlled studies were re-randomized to ciclesonide 320 mcg twice daily and followed for one year.
• The safety profile from the one-year follow up was similar to that seen in the 12- and 16-week treatment studies.
• Long term safety information for pediatric patients 4 to 11 years of age is obtained from three open label one year safety studies.

Post-marketing Experience

In addition to adverse reactions identified from clinical trials, the following adverse reactions have been identified during worldwide post-marketing use of ciclesonide oral inhalation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Immune System Disorders: Immediate or delayed hypersensitivity reactions such as angioedema with swelling of the lips, tongue and pharynx.

• In clinical studies, concurrent administration of ciclesonide and other drugs commonly used in the treatment of asthma (albuterol, formoterol) had no effect on pharmacokinetics of desciclesonide.
• In vitro studies and clinical pharmacology studies suggested that des-ciclesonide has no potential for metabolic drug interactions or protein binding-based drug interactions.
• In a drug interaction study, co-administration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of desciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged.