AdultPediatricDosage 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 Interaction CheckerEnter a drug name and mannitol inhalationNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (0)Serious - Use Alternative (0)Monitor Closely (0)Minor (0) >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 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 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 conditionPregnancy 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. 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) 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 No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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