ARIDOL® (mannitol inhalation powder)
D-mannitol (referred to throughout as mannitol), the active ingredient in ARIDOL is a hexahydric alcohol, that is a sugar alcohol, with the following chemical name (2R,3R,4R,5R)-hexane-1,2,3,4,5,6- hexol.
Mannitol is a white or almost white crystalline powder of free-flowing granules with an empirical formula of C6H14O6 and molecular weight of 182.2. Mannitol is freely soluble in water, and very slightly soluble in alcohol. Mannitol shows polymorphism
The ARIDOL Bronchial Challenge Test Kit contains one single patient use dry powder inhaler and 3 consecutively numbered foil blister packs containing a total of 19 capsules of mannitol for oral inhalation. All except the 0 mg printed hard gelatin capsules contain dry powder mannitol for oral inhalation. The accompanying dry powder inhaler is a plastic device used for inhaling the capsules. All doses are to be administered using the same device supplied with each kit without washing or sterilizing the device at anytime during the test.
Indications and usage
ARIDOL is a sugar alcohol indicated for the assessment of bronchial hyperresponsiveness in adult and pediatric patients 6 years of age or older who do not have clinically apparent asthma.
Limitations of Use: ARIDOL is not a standalone test or a screening test for asthma. Bronchial challenge testing with ARIDOL should be used only as part of a physician’s overall assessment of asthma.
Mechanism of Action
The precise mechanisms through which inhaled mannitol causes bronchoconstriction are not known.
Dosage and administration
ARIDOL is a bronchial challenge test kit containing the required capsules of dry powder mannitol for oral inhalation in graduated doses with the supplied single patient use inhaler necessary to perform one bronchial challenge test. Do not swallow ARIDOL capsules.
The airway response to bronchial challenge testing with ARIDOL is measured using forced expiratory volume in one second (FEV1).
Prior to bronchial challenge testing with ARIDOL, standard spirometry should be performed and the reproducibility of the resting FEV1 established.
An overview of the testing procedure can be found below. The ARIDOL bronchial challenge test should only be used with the provided inhaler. All remaining unused (opened and unopened) blister packs and the inhaler should be properly discarded at the completion of the test. See the ARIDOL Bronchial Challenge Test Kit instructions for complete instructions on the dosing and spirometry procedures.
- A nose clip may be used if preferred. If so, apply nose clip to the patient and direct the patient to breathe through the mouth
- Insert 0 mg capsule into inhalation device. Puncture capsule by depressing buttons on side of device slowly, and ONCE ONLY (a second puncture may fragment the capsules)
- The patient should exhale completely, before inhaling from device in a controlled deep inspiration
- At the end of deep inspiration, start 60 second timer, subject should hold breath for 5 seconds and exhale through mouth before removal of nose clip
- At the end of 60 seconds, measure the FEV1 in duplicate (the measurement after inhaling the 0 mg capsule is the baseline FEV1)
- Repeat steps a-e following the mannitol capsule dose steps from Table 1 below until the patient has a positive response or 635 mg of mannitol has been administered (negative test)
|Dose #||Dose mg||Cumulative Dose mg||Capsules per dose|
Bronchial Challenge Test Response and Patient Management A positive response is achieved when the patient experiences a 15% reduction in FEV1 from (0 mg) baseline (or a 10% incremental reduction in FEV1 between consecutive doses). The test result is expressed as a PD15.
Patients with either a positive response to bronchial challenge testing with ARIDOL or significant respiratory symptoms should receive a standard dose of a short-acting inhaled beta-agonist and monitored until fully recovered to within baseline.
ARIDOL is contraindicated in:
- Patients with known hypersensitivity to mannitol or to the gelatin used to make the capsules.
- Patients with conditions that may be compromised by induced bronchospasm or repeated spirometry maneuvers. Some examples include: aortic or cerebral aneurysm, uncontrolled hypertension, recent myocardial infarction or cerebral vascular accident
Warnings and precautions
Severe Bronchospasm: Mannitol, the active ingredient in ARIDOL, acts as a bronchoconstrictor and may cause severe bronchospasm in susceptible patients. The test should only be conducted by trained professionals under the supervision of a physician familiar with all aspects of the bronchial challenge test and the management of acute bronchospasm. Patients should not be left unattended during the bronchial challenge test. Medications and equipment to treat severe bronchospasm must be present in the testing area.
If a patient has a ≥10% reduction in FEV1 (from pre-challenge FEV1) on administration of the 0 mg capsule, the ARIDOL Bronchial Challenge Test should be discontinued and the patient should be given a dose of a short-acting inhaled beta-agonist and monitored accordingly.
Patients with either a positive response to bronchial challenge testing with ARIDOL or significant respiratory symptoms should receive a short-acting inhaled beta-agonist. Patients should be monitored until fully recovered to within baseline.
Subjects with Co-morbid: Conditions Bronchial challenge testing with ARIDOL should be performed with caution in patients with conditions that may increase sensitivity to the bronchoconstricting or other potential effects of ARIDOL such as severe cough, ventilatory impairment, spirometry-induced bronchoconstriction, hemoptysis of unknown origin, pneumothorax, recent abdominal or thoracic surgery, recent intraocular surgery, unstable angina, or active upper or lower respiratory tract infection
Most common adverse reactions (rate ≥1%) were headache, pharyngolaryngeal pain, throat irritation, nausea, cough, rhinorrhea, dyspnea, chest discomfort, wheezing, retching and dizziness.
Use in specific populations
Pregnancy: There are no available human data regarding inhaled mannitol to evaluate a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on animal reproduction studies, no evidence of structural alterations was observed when mannitol was orally administered to pregnant rats and mice during organogenesis at doses up to approximately 20 and 10 times, respectively, the maximum recommended daily inhalation dose (MRDID) in humans
Lactation: There are no data on the presence of mannitol in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ARIDOL bronchial challenge test and any potential adverse effects on the breastfed child from ARIDOL or from the underlying maternal condition.
Pediatric Use: The safety and effectiveness of ARIDOL for the assessment of bronchial hyperresponsiveness in adult and pediatric patients 6 years of age or older who do not have clinically apparent asthma have been established. The use of ARIDOL for this indication is supported by evidence from two clinical studies that included 246 pediatric patients 6 to 17 years of age.
Safety and effectiveness of ARIDOL have not been established in pediatric patients less than 6 years old. Bronchial challenge testing with ARIDOL should not be performed in children less than 6 years of age due to their inability to provide reliable spirometric measurements
Geriatric Use: Clinical studies of ARIDOL did not include sufficient numbers of patients 50 years of age and older to determine whether they respond differently from younger adult patients.
Hepatic and Renal Impairment: Formal pharmacokinetic studies with mannitol, the active ingredient, in ARIDOL, have not been conducted in patients with hepatic or renal impairment. However, an increase in systemic exposure of mannitol can be expected in patients with renal impairment based on the kidney being its primary route of elimination.
Susceptible persons may experience excessive bronchospasm from an overdosage. If such bronchospasm occurs, immediately administer a short-acting inhaled beta-agonist and other medical treatments such as oxygen, as necessary.
Store below 77°F (25°C) with excursions permitted between 59°F – 86°F (15°C – 30°C). [See USP Controlled Room Temperature]. Do not freeze. Do not refrigerate.