Mannitol

What it is used for

BRONCHITOL is indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years and older with Cystic Fibrosis. Use BRONCHITOL only for adults who have passed the BRONCHITOL Tolerance Test.

Side effects, and when to stop

The following clinically significant adverse reactions are described elsewhere in the labeling:

Bronchospasm Hemoptysis

Who should not take it

BRONCHITOL is contraindicated in the following conditions:

• Hypersensitivity to mannitol or to any of the capsule components
• Failure to pass the BRONCHITOL Tolerance Test (BTT)

Other medicines and interactions

No formal drug interaction studies have been conducted with mannitol, the active ingredient in BRONCHITOL.

2.1 Required Testing and Evaluation Prior to Prescribing BRONCHITOL (BRONCHITOL Tolerance Test)

Prior to prescribing BRONCHITOL for treatment of cystic fibrosis, the BRONCHITOL Tolerance Test (BTT) must be administered and performed under the supervision of a healthcare practitioner who is able to manage acute bronchospasm, to identify patients who are suitable candidates for BRONCHITOL maintenance therapy.

• Perform BTT to identify patients who experience bronchospasm, a decrease in FEV1, or a decrease in oxygen saturation with administration of BRONCHITOL. If a patient experiences any of these events during the BTT, the patient has failed the BTT. Do not prescribe BRONCHITOL. If a patient does not experience any of these events during BTT, the patient has passed the BTT and is a candidate for BRONCHITOL therapy.

• Ensure that rescue medication and resuscitation equipment are available for immediate use during the BTT.
• Do not perform the BTT if the patient is considered clinically unstable.

See the BTT Healthcare Practitioner (HCP) Instructions for Use (IFU) for complete instructions and to avoid medication errors associated with BTT dosing and procedures.

Do not use BRONCHITOL add-on maintenance therapy in patients who fail the BTT.

2.2 Recommended Dosage for Treatment of Cystic Fibrosis

For patients who have passed the BTT, the recommended dosage of BRONCHITOL is 400 mg twice a day by oral inhalation (the contents of 10 capsules administered individually) via the inhaler.

A short-acting bronchodilator should be administered by oral inhalation, 5-15 minutes before every dose of BRONCHITOL.

BRONCHITOL should be taken once in the morning and once in the evening, with the later dose taken at least 2-3 hours before bedtime.

2.3 Use and Maintenance of Inhaler

Instruct patients 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.

The BRONCHITOL inhaler should be discarded and replaced after 7 days of use. If the inhaler does need to be washed, the patient should allow the inhaler to thoroughly air dry before next use.

5.1 Bronchospasm

BRONCHITOL Tolerance Test BRONCHITOL can cause bronchospasm, which can be severe in susceptible individuals. Because of the risk of bronchospasm, prior to prescribing BRONCHITOL, perform the BRONCHITOL Tolerance Test (BTT), to identify patients who are appropriate for maintenance treatment with BRONCHITOL. The BTT must be administered under the supervision of a healthcare practitioner who can treat severe bronchospasm. In clinical trials, 896 adult patients with cystic fibrosis underwent the BTT and 72 patients (8%) failed or did not complete the BTT. Do not prescribe BRONCHITOL if the patient fails the BTT.

Maintenance Therapy Bronchospasm may occur during inhalation of BRONCHITOL, even in patients who have passed the BTT. An inhaled short-acting bronchodilator must be administered 5-15 minutes before administration of each dose during maintenance therapy. In clinical studies, bronchospasm or bronchial hyperreactivity was reported in 4 of 414 adult patients (1.0%) receiving BRONCHITOL as maintenance therapy and in 2 of 347 adult patients (0.6%) receiving control (50 mg inhaled mannitol), even though these patients had passed the BTT. If bronchospasm occurs following dosing of BRONCHITOL, it should immediately be discontinued and treated with an inhaled short-acting bronchodilator or as medically appropriate.

5.2 Hemoptysis

Hemoptysis may occur with BRONCHITOL use. Hemoptysis was reported in 43 (10.4%) adult patients receiving BRONCHITOL and in 33 (9.5%) adult patients receiving control (50 mg inhaled mannitol) during clinical studies. In patients aged 6 years to 17 years, hemoptysis was reported in 12 of 154 (7.8%) patients who received BRONCHITOL and in 2 of 105 (1.9%) patients who received control. BRONCHITOL has not been studied in patients with a history of episodes of significant hemoptysis (volume greater than 60 mL) in the previous 3 months. BRONCHITOL should be discontinued in the event of hemoptysis. BRONCHITOL is not indicated for use in children and adolescents.