Alvesco

ALVESCO is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients 12 years of age and older.

ALVESCO is not indicated for the relief of acute bronchospasm.

ALVESCO is not indicated for children under 12 years of age.

• For oral inhalation only. (
  
  
  2 DOSAGE AND ADMINISTRATION

  • For oral inhalation only.
  • Prime ALVESCO before first use or when inhaler not used for more than 10 days.

  1Prednisone should be reduced gradually, no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 week of therapy with ALVESCO. Patients should be carefully monitored for signs of asthma instability, including monitoring of serial objective measures of airflow, and for signs of adrenal insufficiency during steroid taper and following discontinuation of oral corticosteroid therapy [see Warnings and Precautions ] .
  Previous Therapy	Recommended Starting Dose	Highest Recommended Dose
  Patients ≥ 12 years who received bronchodilators alone	80 mcg twice daily	160 mcg twice daily
  Patients ≥ 12 years who received inhaled corticosteroids	80 mcg twice daily	320 mcg twice daily
  Patients ≥ 12 years who received oral corticosteroids1	320 mcg twice daily	320 mcg twice daily

  2.1 Administration Information

  • Administer ALVESCO by the orally inhaled route.
  • After administration, rinse the mouth with water and spit out without swallowing to help reduce the risk of oropharyngeal candidiasis
    [see Warnings and Precautions ]
    .

  Priming

  Prime ALVESCO before using for the first time by actuating 3 times prior to using the first dose from a new canister or when the inhaler has not been used for more than 10 days.

  2.2 Recommended Dosage

  The recommended starting dosage and the highest recommended dosage of ALVESCO are listed in Table 1

  Table 1: Recommended Dosages for Adults and Pediatric Patients 12 Years and Older

  1Prednisone should be reduced gradually, no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 week of therapy with ALVESCO. Patients should be carefully monitored for signs of asthma instability, including monitoring of serial objective measures of airflow, and for signs of adrenal insufficiency during steroid taper and following discontinuation of oral corticosteroid therapy [see Warnings and Precautions ] .
  Previous Therapy	Recommended Starting Dosage	Highest Recommended Dosage
  Patients ≥ 12 years who received bronchodilators alone	80 mcg twice daily	160 mcg twice daily
  Patients ≥ 12 years who received inhaled corticosteroids	80 mcg twice daily	320 mcg twice daily
  Patients ≥ 12 years who received oral corticosteroids1	320 mcg twice daily	320 mcg twice daily

  General Dosing Recommendations

  Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for four weeks or longer after initiation. After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the possibility of side effects. For patients who do not respond adequately to the starting dose after 4 weeks of therapy, higher doses may provide additional asthma control. Patients should not exceed the highest recommended dosage per day.
  )
  
• Prime ALVESCO before first use or when inhaler not used for more than 10 days. (
  
  
  2 DOSAGE AND ADMINISTRATION

  • For oral inhalation only.
  • Prime ALVESCO before first use or when inhaler not used for more than 10 days.

  1Prednisone should be reduced gradually, no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 week of therapy with ALVESCO. Patients should be carefully monitored for signs of asthma instability, including monitoring of serial objective measures of airflow, and for signs of adrenal insufficiency during steroid taper and following discontinuation of oral corticosteroid therapy [see Warnings and Precautions ] .
  Previous Therapy	Recommended Starting Dose	Highest Recommended Dose
  Patients ≥ 12 years who received bronchodilators alone	80 mcg twice daily	160 mcg twice daily
  Patients ≥ 12 years who received inhaled corticosteroids	80 mcg twice daily	320 mcg twice daily
  Patients ≥ 12 years who received oral corticosteroids1	320 mcg twice daily	320 mcg twice daily

  2.1 Administration Information

  • Administer ALVESCO by the orally inhaled route.
  • After administration, rinse the mouth with water and spit out without swallowing to help reduce the risk of oropharyngeal candidiasis
    [see Warnings and Precautions ]
    .

  Priming

  Prime ALVESCO before using for the first time by actuating 3 times prior to using the first dose from a new canister or when the inhaler has not been used for more than 10 days.

  2.2 Recommended Dosage

  The recommended starting dosage and the highest recommended dosage of ALVESCO are listed in Table 1

  Table 1: Recommended Dosages for Adults and Pediatric Patients 12 Years and Older

  1Prednisone should be reduced gradually, no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 week of therapy with ALVESCO. Patients should be carefully monitored for signs of asthma instability, including monitoring of serial objective measures of airflow, and for signs of adrenal insufficiency during steroid taper and following discontinuation of oral corticosteroid therapy [see Warnings and Precautions ] .
  Previous Therapy	Recommended Starting Dosage	Highest Recommended Dosage
  Patients ≥ 12 years who received bronchodilators alone	80 mcg twice daily	160 mcg twice daily
  Patients ≥ 12 years who received inhaled corticosteroids	80 mcg twice daily	320 mcg twice daily
  Patients ≥ 12 years who received oral corticosteroids1	320 mcg twice daily	320 mcg twice daily

  General Dosing Recommendations

  Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for four weeks or longer after initiation. After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the possibility of side effects. For patients who do not respond adequately to the starting dose after 4 weeks of therapy, higher doses may provide additional asthma control. Patients should not exceed the highest recommended dosage per day.
  )
  

Inhalation aerosol:

• 80 mcg of ciclesonide per actuation, supplied with a brown plastic actuator with a red dust cap
• 160 mcg of ciclesonide per actuation, supplied with a red plastic actuator with a red dust cap

There are no available data on ALVESCO use in pregnant women to assess a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There is low systemic exposure following ALVESCO oral inhalation administration at the recommended dose

In animal reproduction studies, ciclesonide administered by the oral route to pregnant rats during the period of organogenesis did not cause any evidence of fetal harm at doses up to 15 times the maximum recommended human daily oral inhalation dose (MRHDOID) of 640 mcg/day. Teratogenicity, characteristic of corticosteroids, decreased body weight and/or skeletal variations were observed in rabbit fetuses following administration of ciclesonide to pregnant rabbits by the subcutaneous route during the period of organogenesis at doses 0.15 times the MRHDOID and higher on a mcg/m
²basis (see Data). No evidence of fetal harm was observed in rabbits at doses of 0.03 times the MRHDOID.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

• Candida albicans
  infection of the mouth and pharynx. Monitor patients periodically for signs of adverse effects on the oral cavity. Advise patients to rinse mouth following inhalation. (
  
  
  5.1 Oropharyngeal Candidiasis

  In clinical trials, the development of localized infections of the mouth and pharynx with

  Candida albicans

  occurred in 32 of 3038 patients treated with ALVESCO. Of the 32 reported cases, 20 occurred in 1394 patients treated with a total daily dose of 320 mcg of ALVESCO or higher. Most cases of

  Candida

  infection were mild to moderate. When such an infection occurs, treat it with appropriate local or systemic (i.e., oral antifungal) therapy and discontinue ALVESCO. Patients should rinse the mouth after inhalation of ALVESCO.
  )
  
• Potential worsening of existing tuberculosis: fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with above because of the potential for worsening of these infections. (
  
  
  5.3 Immunosuppression and Risk of Infections

  Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The safety and effectiveness of ALVESCO have not been established in pediatric patients less than 12 years of age and ALVESCO is not indicated for use in this population. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See Prescribing Information for VZIG and IG.) If chickenpox develops, treatment with antiviral agents may be considered.

  Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
  )
  
• Risk of impaired adrenal function when transferring from oral steroids to inhaled corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to ALVESCO. (
  
  
  5.4 Transferring Patients from Systemic Corticosteroid Therapy

  HPA Suppression/Adrenal Insufficiency

  Particular care is needed for patients who are transferred from systemically active corticosteroids to ALVESCO because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically-available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

  Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although ALVESCO may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.

  During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.

  Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to ALVESCO. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during ALVESCO therapy

  [see Dosage and Administration ]

  . Lung function (FEV₁or AM PEFR), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.

  Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids

  Transfer of patients from systemic steroid therapy to ALVESCO may unmask allergic conditions previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions.

  Corticosteroid Withdrawal Symptoms

  During withdrawal from oral steroids, some patients may experience symptoms of systemically active steroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function.
  )
  
• Hypercorticism, suppression of hypothalamic-pituitary-adrenal (HPA) function with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue ALVESCO slowly (
  
  
  5.5 Hypercorticism and Adrenal Suppression

  ALVESCO will often help control asthma symptoms with less suppression of HPA function than therapeutically similar oral doses of prednisone. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing ALVESCO. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

  Hypercorticism and adrenal suppression may occur when corticosteroids, including ALVESCO, are used at higher-than-recommended dosages

  [see Dosage and Administration ]

  or patients at risk for such effects.
  )
  
• Suppression of growth in children. Monitor growth routinely in pediatric patients receiving ALVESCO. (
  
  
  5.7 Effect on Growth

  Orally inhaled corticosteroids, including ALVESCO, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of ALVESCO have not been established in pediatric patients less than 12 years of age and ALVESCO is not indicated for use in this population. Monitor the growth of pediatric patients receiving ALVESCO routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ALVESCO, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms

  [see Use in Specific Populations ]

  .
  )
  
• Development of glaucoma, increased intraocular pressure and posterior subcapsular cataracts. Monitor patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts closely. (
  
  
  5.8 Glaucoma and Cataracts

  Glaucoma, increased intraocular pressure, and cataracts have been reported following the administration of inhaled corticosteroids including ALVESCO. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

  In a comparator control study of one-year treatment duration, 743 patients 18 years of age and older (mean age 43.1 years) with moderate persistent asthma were treated with ALVESCO 320 mcg twice daily and 742 were treated with a labeled dose of a comparator-inhaled corticosteroid appropriate for the patient population. Patients had an ophthalmology examination that included visual acuity, intraocular pressure measurement, and a slit lamp examination at baseline, 4, 8 and 12 months. Lens opacities were graded using the Lens Opacification System III. After 52 weeks, CLASS I effects (minimally detected changes) were recorded in 36.1% of the ALVESCO-treated patients and in 38.4% of patients treated with the comparator-inhaled corticosteroid. The more severe CLASS III effects were recorded in 8.1% of the ALVESCO-treated patients and 9.2% of patients treated with the comparator-inhaled corticosteroid. Of those patients having a CLASS III effect, the incidence of posterior sub-capsular opacities was 0.9% and 0.5% in the ALVESCO- and comparator-treated patients, respectively.
  )