In individuals without clinically obvious asthma, inhaled mannitol (Bronchitol) is administered as a dry powder formulation for the assessment of allergic airway illness. Osmotic diuretics, such as mannitol injection, are utilised. Adults with cystic fibrosis are now able to receive treatment with bronchitol (inhaled mannitol).

Mannitol Uses:

• Assessment of bronchial hyper-responsiveness:

  • It is recommended for use in adults and children aged 6 and older who do not have clinically obvious asthma to measure bronchial hyperresponsiveness.

Mannitol Dose in Adults:

Assessment of bronchial hyper-responsiveness:

• Inhalation:
  • Stepwise drug delivery is recommended, with duplicate FEV-1 measurements after each dose, until the patient responds favourably or 635 mg of mannitol have been provided, whichever comes first.
  • Positive test:
    • 15% of the patient's baseline FEV or a 10% incremental drop in FEV-1 between doses, whichever is more
  • Negative test:
    • Full dose (635 mg) administration without a FEV-1 drop sufficient to meet test-positive criteria

Administration should be as follows:

Stepwise Administration of inhaled mannitol Schedule:

Mannitol Dose in Children:

Inhaled Mannitol (Bronchitol) Dose in the assessment of Bronchial hyper-responsiveness:

• Children ≥6 years and Adolescents:

  • Oral inhalation:
    • Until the patient exhibits a good reaction or until a dose of 635 mg of mannitol has been supplied, the medication should be given progressively (measuring FEV1 in duplicate at baseline and after inhalation).
  • Positive test:
    • 15% decrease in FEV-1 from the patient's baseline or a 10% decrease in FEV-1 after two doses in a row
  • Negative test:
    • Full dose (635 mg) administration without a sufficient decrease in FEV-1 to satisfy the requirements for a positive test result.
  • Administration should be as follows:

Stepwise Administration of Inhaled Mannitol Schedule:

Pregnancy Risk Factor C

• Animal reproduction studies have not shown adverse fetal outcomes.

Mannitol use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• It is recommended that you use it with caution if you are lactating.

Dose in Kidney Disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Side Effects of Inhaled Mannitol (Bronchitol):

• Cardiovascular:

  • Chest discomfort

• Central nervous system:

  • Headache
  • Dizziness

• Gastrointestinal:

  • Nausea
  • Throat irritation
  • Retching

• Respiratory:

  • Cough
  • Pharyngolaryngeal pain
  • Rhinorrhea
  • Dyspnea
  • Wheezing

Contraindication to Inhaled Mannitol (Bronchitol):

• hypersensitivity to any ingredient in the formulation, including mannitol or gelatin.
• Repeated spirometry, induced bronchospasm and/or induced bronchospasm can compromise medical conditions such as cerebral aneurysm or aortic or cerebral angiopathy, uncontrolled hypertension, Myocardial Infarction, or cerebrovascular accident.

Warnings and precautions

• Bronchospasm - [US Boxed Warning]

  • Inhaling mannitol can cause severe bronchospasm.
  • A trained professional should perform testing for bronchial challenges.
  • Avoid use of the drug for patients with asthma or with abnormal pulmonary function tests.
  • At the testing site, short-acting beta-agonists should be available.
  • Patients with conditions that can cause bronchoconstriction, such as severe cough, ventilatory impairment, bronchoconstriction induced spirometry or pneumothorax, patients who have had recent abdominal or intraocular surgeries, unstable angina and those with a viral infection of the respiratory tract, should be cautious when using inhlaed Mannitol.
  • If they are unable to take inhaled beta-agonists, patients should be administered a short-acting beta-agonist. Patients must be closely monitored until complete recovery.
    • After taking the "0 mg" capsule, you will see a 10% reduction in FEV-1
    • Patients who have passed the positive bronchial test
    • Patients who have developed severe respiratory symptoms after inhaling the "0" mg capsule.
  • Children under 6 years old should not have bronchial provocation tested. Children may not be able to perform spirometry correctly.

Mannitol (systemic): Drug Interaction

Monitoring parameters:

• Standard spirometry before a bronchial challenge test;
• FEV-1 in duplicate 60 seconds after the administration of each step of the test.

How to administer Inhaled Mannitol?

Inhalation:

• It is administered using an inhaler supplied by the manufacturer for single use.
• The capsule should be punctured only once. The content of the capsules are only intended for inhalation. The capsule should not be swallowed.
• Patients may need to used a nose clip.
• The patient should completely exhale followed by deep inhalation from the device. After inhalation, the patient should be advised to hold breath for at least five seconds and then exhale via mouth.
• The FEV-1 may be measured twice 60 seconds after the inhalation. The dose may be repeated until the full dose (635 mg) or a full response is administered.

Mechanism of action of Mannitol:

The mechanisms of bronchoconstriction are unknown.

Metabolism:

• Minimally hepatic to glycogen

Bioavailability:

• Inhaled: 59% (relative to oral administration: 96%)

Half-life elimination:

• Terminal: 4.7 hours

Time to peak, plasma:

• Inhaled: 1.5 hours

Excretion:

• Urine (~55% to 87% as unchanged drug)

International Brand Names of Inhaled Mannitol:

• Aridol
• Bronchitol
• Osmohale

Inhaled Mannitol Brand Names in Pakistan:

Inhaled Mannitol is not available in Pakistan.