Dosing & Uses
Dosage Forms & Strengths
capsule, powder for oral inhalati
- 40mg (Bronchitol)
dry powder capsules for inhalation
- 0mg, 5mg, 10mg, 20mg, and 40mg per kit (Aridol)
- Each kit contains one, single patient use, dry powder inhaler device and 3 consecutively numbered foil blister packs containing 19 capsules of graduated doses of mannitol for oral inhalation
Bronchial Hyperresponsiveness Assessment
Aridol only
Indicated for the assessment of bronchial hyperresponsiveness in patients who do not have clinically apparent asthma
Administer sequentially increasing doses via inhalation while measuring forced expiratory volume in 1 second (FEV1)
A positive response is achieved when FEV1 is reduced by 15% from (0 mg) baseline (or a 10% incremental reduction in FEV1 between consecutive doses)
Patients with either a positive response to bronchial challenge testing or significant respiratory symptoms should receive a standard dose of a short-acting inhaled beta-agonist and monitored until fully recovered to within baseline
Sequential doses
- Increased sequential dosing continues until a positive response observed or 635 mg cumulative dose is administered without response (negative test)
- Dose #1: 0 mg
- Dose #2: 5 mg
- Dose #3: 10 mg (cumulative dose 15 mg)
- Dose #4: 20 mg (cumulative dose 35 mg)
- Dose #5: 40 mg (cumulative dose 75 mg)
- Dose #6: 80 mg (cumulative dose 155 mg)
- Dose #7: 160 mg (cumulative dose 315 mg); may repeat this dose if needed 2 more times for a cumulative dose of 635 mg
Cystic Fibrosis
Bronchitol only
Indicated as add-on maintenance therapy to improve pulmonary function in adults aged 18 years and older with cystic fibrosis
Only use for adults who have passed the Bronchitol tolerance test (BTT); see prescribing information instructions for BTT healthcare practitioner
Required testing before initiation
- Perform BTT to identify patients who experience bronchospasm, a decrease in FEV1, or a decrease in oxygen saturation with administration
- If any of these events occur during BTT, patient has failed the BTT; do not prescribe
- If none of these events during BTT, the patient is a candidate for therapy
- Ensure that rescue medication and resuscitation equipment are available for immediate use during the BTT
- Do not perform if the patient is considered clinically unstable
Add-on maintenance dose
- 400 mg (10 capsules) BID by oral inhalation; inhale contents of each capsule individually
- Administer short-acting bronchodilator 5-15 minutes before every dose
Dosage Modifications
Renal or hepatic impairment
- Clinical trials did not include patients with hepatic or renal impairment
- No specific dose recommendations for these patient populations are available
- 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
Dosing Considerations
Limitations of use
-
Aridol
- Not a stand-alone or screening test for asthma
- Use bronchial challenge testing only as part of the overall assessment of asthma
Dosage Forms & Strengths
kit, inhalation
- 0mg, 5mg, 10mg, 20mg, and 40mg per kit (Aridol)
- Each kit contains one, single patient use, dry powder inhaler device and 3 consecutively numbered foil blister packs containing 19 capsules of graduated doses of mannitol for oral inhalation
Bronchial Hyperresponsiveness Assessment
Aridol only
Indicated for the assessment of bronchial hyperresponsiveness in patients who do not have clinically apparent asthma
<6 years: Safety and efficacy not established
≥6 years
- Administer sequentially increasing doses via inhalation while measuring forced expiratory volume in 1 second (FEV1)
- 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)
- Patients with either a positive response to bronchial challenge testing or significant respiratory symptoms should receive a standard dose of a short-acting inhaled beta-agonist and monitored until fully recovered to within baseline
-
Sequential doses
- Increased sequential dosing continues until a positive response observed or 635 mg cumulative dose is administered without response (negative test)
- Dose #1: 0 mg
- Dose #2: 5 mg
- Dose #3: 10 mg (cumulative dose 15 mg)
- Dose #4: 20 mg (cumulative dose 35 mg)
- Dose #5: 40 mg (cumulative dose 75 mg)
- Dose #6: 80 mg (cumulative dose 155 mg)
- Dose #7: 160 mg (cumulative dose 315 mg); may repeat this dose if needed 2 more times for a cumulative dose of 635 mg
Dosage Modifications
Renal or hepatic impairment
- Clinical trials did not include patients with hepatic or renal impairment
- No specific dose recommendations for these patient populations are available
- 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
Dosing Considerations
Limitations of use
-
Aridol
- Not a stand-alone or screening test for asthma
- Use bronchial challenge testing only as part of the overall assessment of asthma
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
Bronchitol
- Cough (15%)
- Hemoptysis (10.4%)
1-10%
Aridol
-
Adults
- Headache (6%)
- Pharyngolaryngeal pain (2%)
- Throat irritation (2%)
- Nausea (2%);
- Cough (2%)
- Rhinorrhea (2%)
- Dyspnea (1%)
- Chest discomfort (1%)
- Wheezing (1%)
- Retching (1%)
- Dizziness (1%)
-
Children
- Pharyngolaryngeal pain, children (4%)
- Headache, children (3%)
- Nausea, children (3%)
Bronchitol
- Oropharyngeal pain (7%)
- Bacterial sputum identified (6.8%)
- Pyrexia (4.6%)
- Arthralgia (3.1%)
- Vomiting (3.1%)
Postmarketing Reports
Aridol
- Cough, gagging, wheeze, and decreased forced expiratory volume
- Severe bronchospasm
Warnings
Risk of Severe Bronchospasm
Aridol only
- Mannitol, the active ingredient, acts as a bronchoconstrictor and may cause severe bronchospasm
- Bronchial challenge testing with mannitol inhalation is for diagnostic purposes only
- Bronchial challenge testing 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
- Medications (eg, short-acting inhaled beta-agonist) and equipment to treat severe bronchospasm must be present in the testing area; if severe bronchospasm occurs, treat immediately with a short-acting inhaled beta-agonist
- Owing to the potential for severe bronchoconstriction, do not perform the bronchial challenge testing in any patient with clinically apparent asthma or very low baseline pulmonary function tests (eg, FEV1 <1-1.5 L or <70% of the predicted values)
Contraindications
Hypersensitivity
Aridol only
- Conditions that may be compromised by induced bronchospasm or repeated spirometry maneuvers (eg, aortic or cerebral aneurysm, uncontrolled hypertension, recent myocardial infarction, cerebral vascular accident)
Bronchitol only
- Failure to pass the BTT
Cautions
May cause severe bronchospasm in susceptible patients; if bronchospasm occurs following dosing, discontinue immediately and treat with an inhaled short-acting bronchodilator or as medically appropriate
Aridol
- If a 10% or more reduction in FEV1 (from prechallenge FEV1) on administration of the 0 mg capsule, discontinued test administer short-acting inhaled beta-agonist and monitored accordingly
- Caution with conditions that may increase sensitivity to the bronchoconstricting or other potential effects (eg, 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)
Pregnancy & Lactation
Pregnancy
There are no adequate and well-controlled studies pregnant females
Insufficient data available on use in pregnant females to inform any drug-associated risks for major birth defects and miscarriage
Use during pregnancy only if potential benefit justifies potential risk to the mother and fetus
Animal data
- No evidence of structural alterations was observed when mannitol was administered to pregnant rats and mice during organogenesis at doses up to ~20 and 10 times, respectively, the maximum recommended daily inhalation dose in humans
Clinical considerations
- Cystic fibrosis may increase the risk for preterm delivery
Lactation
There are no data on presence of drug in human or animal milk, the effects on breastfed infant, or on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for bronchial challenge test and any potential adverse effects on breastfed child from drug or from underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Mannitol is a sugar alcohol
Precise mechanism of action for bronchoconstriction or cystic fibrosis is unknown
Absorption
- Peak plasma time: 1.5 hr
- Peak plasma concentration: 13 mcg/mL (following 635 mg cumulative dose)
- AUC: 73.15 mcg⋅hr/mL
Distribution
Vd: 34.3 L
Metabolism
Metabolized in a CYP-independent manner through the glycolytic pathway via dehydrogenation to fructose
Extent of metabolism of mannitol appears to be small
Elimination
Half-life: 4.7 hr
Clearance: 5.1 L/hr (total); 4.4 L/hr (renal)
Excretion: Urine (55%; unchanged drug)
Administration
Oral Inhalation Administration
Oral inhalation only
Aridol
- Do not swallow capsules
- Before bronchial challenge testing, preform standard spirometry and reproducibility of the resting FEV1 established
- See the complete bronchial challenge test instructions in the prescribing information
Bronchitol
- Do not swallow capsules
- Inhale capsule content once in AM and once in PM, with the later dose taken at least 2-3 hr before bedtime
- Use with provided inhaler, which is a white plastic inhaler comprised of a mouthpiece, blue piercing buttons, capsule chamber, and a removable cap
- Instruct on safe hygiene practices (clean and dry hands thoroughly) and correct inhaler use, including loading of capsules and proper inhalation technique per the Patient Instructions for Use
- Discard and replace inhaler after 7 days of use
- If inhaler does need to be washed, allow the inhaler to thoroughly air dry before next use
Storage
Bronchitol and training kit
- Store at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF)
- Do not refrigerate; do not freeze
Aridol kitº
- Store at ≤25°C (≤77ºF), excursions permitted to 15-30ºC (59-86ºF)
- Do not refrigerate; do not freeze
Images
Formulary
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