"The US Food and Drug Administration has approved AstraZeneca's Symbicort inhalation aerosol (80/4.5 mcg) for children aged 6 to 12 years with asthma that is not well controlled with an inhaled corticosteroid, the company has announced.
Mannitol, the active ingredient in ARIDOL (mannitol inhalation powder) , is a sugar alcohol that may cause severe bronchospasm in susceptible subjects [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
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.
The safety population for the ARIDOL (mannitol inhalation powder) bronchial challenge test consisted of 1,082 subjects (577 females and 505 males) including patients with asthma, symptoms suggestive of asthma, and healthy individuals from 6 to 83 years of age who participated in the two clinical trials (Studies 1 and 2). The racial distribution of subjects was 84% Caucasian, 5 % Asian, 4 % Black, and 7 % Other. Children and adolescents comprised 23% of the total study population with 118 children aged 6-11 years and 128 adolescents aged 12-17 years.
Adverse reactions were reported at the time of the testing procedure and for one day thereafter. No serious adverse reactions were reported following bronchial challenge testing with ARIDOL (mannitol inhalation powder) in either trial.
Five adult subjects (0.6%) discontinued from the studies within a day following bronchial challenge testing with ARIDOL (mannitol inhalation powder) because of cough, decreased lung function, feeling jittery, sore throat, and throat irritation. One adult subject (0.3%) discontinued following the methacholine bronchial challenge test because of dizziness. One pediatric subject (0.4%) discontinued from the studies within a day following bronchial challenge testing with ARIDOL (mannitol inhalation powder) because of retching.
Table 2 displays the combined common adverse reactions ( ≥ 1%) within a day after bronchial challenge testing with ARIDOL (mannitol inhalation powder) or methacholine in the overall population for Studies 1 and 2.
Table 2: Adverse reactions with an incidence ≥ 1% within
a day after bronchial challenge testing (overall population, Studies 1 and 2
|ARIDOL (mannitol inhalation powder)
|Headache||59 (6)||4 (1)|
|Pharyngolaryngeal pain||25 (2)||0|
|Throat irritation||19 (2)||1 ( < 1)|
|Cough||17 (2)||8 (2)|
|Dyspnea||15 (1)||21 (5)|
|Chest discomfort||13 (1)||18 (4)|
|Wheezing||8 (1)||6 (1)|
|Dizziness||5 (1)||13 (3)|
The maximum reduction in FEV1 following bronchial challenge testing with ARIDOL (mannitol inhalation powder) was 46%, compared to 54% for exercise testing and 67% for the methacholine challenge. The incidences in decreases in FEV1 ≥ 30% and ≥ 60% following ARIDOL (mannitol inhalation powder) , methacholine, and exercise challenges for Studies 1 and 2 is shown in Table 3.
Table 3: Incidence of decreases in FEV1 ≥ 30%
or ≥ 60% (overall population, Studies 1 and 2)
|Challenge||No. Exposed||N (%) with Fall in FEV1 ≥ 30%||N (%) with Fall in FEV1 ≥ 60%|
|Methacholine||420||51 (12%)||3 (1%)|
|ARIDOL asthmatics||536||23 (4%)||0|
There were no differences in the incidence of adverse reactions based on gender or race. The clinical trials did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently compared to subjects below 65 years of age.
Children and Adolescent Aged 6 to 17 Years
Overall, the types and severities of adverse reactions in children were similar to those observed in the adult population. As in the adult population, the adverse reactions of pharyngolaryngeal pain, nausea, and headache were the more common with incidences of 4%, 3%, and 3%, respectively. There were no major differences in the types of adverse reactions observed in children 6-11 years of age compared to adolescents 12-17 years old.
The decrease in FEV1 in children and adolescents who received the ARIDOL (mannitol inhalation powder) bronchial challenge test was similar to that of the adult population with 5%, 15% and 9% of pediatric subjects who had bronchial challenge testing with ARIDOL (mannitol inhalation powder) , methacholine and exercise, respectively, experiencing reduction in FEV1 ≥ 30%. No patient who had bronchial challenge testing with ARIDOL (mannitol inhalation powder) or exercise had a decrease in FEV1 ≥ 60%, whereas, one adolescent patient (aged 12 years) who received methacholine had a decrease in FEV1 ≥ 60%.
The following adverse reactions have been identified post approval outside the U.S. of the ARIDOL (mannitol inhalation powder) bronchial challenge test kit: cough, gagging, wheeze, and decreased forced expiratory volume. 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.
Read the Aridol (mannitol inhalation powder) Side Effects Center for a complete guide to possible side effects
No formal drug-drug interaction studies were conducted with mannitol, the active ingredient in ARIDOL (mannitol inhalation powder) .This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/29/2010
Additional Aridol Information
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