The FDA recently approved bronchitol (inhaled mannitol) for maintenance therapy in cystic fibrosis patients aged 18 years or above. Only individuals who have successfully completed the inhaled mannitol bronchial provocation test should use it as an add-on maintenance therapy.

Bronchitol use in Adults:

Before administering bronchitol (inhaled mannitol), bronchial provocation testing with mannitol inhalation should be performed. Patients with a positive bronchial provocation test should not be advised of mannitol inhalational therapy. A positive test is a drop in the FEV-1, severe chest-related symptoms, or hypoxemia. See inhaled mannitol for bronchial provocation testing.

Furthermore, the inhaler should be used in settings where severe bronchospasm can be managed and should be administered by experienced physicians. Patients who are clinically unstable or those who are at risk of developing severe bronchospasm should not undergo bronchial tolerance testing.

Bronchitol Dosage for the Treatment of Cystic Fibrosis:

When administering the dose, administer a short-acting beta-agonist 5 - 15 minutes before each dose. Patients must have passed the bronchial tolerance test. The suggested dosage for oral inhalation is 400 mg twice daily.The suggested dosage for oral inhalation is 400 mg twice daily.

Since each capsule contains 40 mg of the drug, 400 mg is equivalent to 10 capsules. Each capsule should be inhaled separately. The drug should be taken twice daily (morning and evening), with the evening dose being consumed at least two to three hours prior to going to bed.

Use in Children:

Children under the age of 18 should not use it for the treatment of cystic fibrosis. Children under the age of six should not take the bronchial tolerance test.

Pregnancy Risk Factor C

• It has not been tested in human and animal pregnancies.
• It is possible to use it if the potential risks to the fetus outweigh its benefits.

Use of inhaled Mannitol 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. However, since medication excretion through the kidneys is the main method of drug removal, people with kidney illness are at a higher risk of drug exposure.

Dose in Liver disease:

In the manufacturer's labeling, no specific dosage adjustment has been provided.

Side Effects of Bronchitol (Inhaled Mannitol):

• Cardiovascular:

  • Chest discomfort

• Gastrointestinal:

  • Queasiness
  • Vomiting
  • Throat irritation
  • Retching

• Respiratory:

  • Cough
  • Pharyngolaryngeal pain
  • Rhinorrhea
  • Dyspnea
  • Wheezing
  • hemoptysis
  • Oropharyngeal pain
• Central nervous system:
  • Headache
  • Dizziness

• Others:

  • Fever
  • Arthralgias

Contraindications to Bronchitol (Inhaled Mannitol):

It is contraindicated for the following patients:

• Patients who fail to pass the Bronchial Tolerance Test
• Allergy to Mannitol or any other component of the formulation.

Warnings and precautions

• Bronchospasm

  • Inhaled Mannitol may cause severe bronchospasm in some people.
  • A bronchial tolerance test must be completed before prescribing bronchitol. The drug can be prescribed to those who pass the test.
  • It is crucial to conduct the bronchial tolerance testing under supervision and in an environment where severe bronchospasm can easily be managed.
  • Some patients may develop bronchospasm after passing the bronchial probe test. Inhaled bronchodilators should be administered five to fifteen minutes prior to each dose.
  • Bronchospasm patients should stop taking any medication and immediately take a short-acting bronchodilator.

• Hemoptysis

  • Inhaled Mannitol may cause hemoptysis.
  • The clinical trials did not include patients who had hemoptysis within the last three months.
  • Patients who have hemoptysis or are at high risk shouldn't be given the medication.

Monitoring parameters:

• Standard spirometry and FEV-1 before treatment initiation and at regular intervals.

How to administer Bronchitol (Inhaled Mannitol)?

• Instruct the patient to use the inhaler device as provided by the manufacturer.
• The suggested dosage is 400 mg, or 10 capsules, taken twice day. The evening dose needs to be taken at least two to three hours prior to going to bed.The suggested dosage is 400 mg, or 10 capsules, taken twice day. 
• The capsule should only be punctured once and should not be swallowed.
• A nose clip may be used by some patients for better inhalation of the medicine.
• The patient should be asked to exhale deeply and then take a deep breath while keeping the mouth place of the inhaler in the mouth. The breath should be held for at least five seconds and then exhaled via the mouth.
• Ten capsules should be inhaled one by one.
• After seven days, the inhaler equipment should be thrown away and replaced. Before administering the subsequent dose, the inhaler should be air-dried if necessary.

Mechanism of action of Bronchitol (Inhaled Mannitol):

According to the manufacturer, the exact mechanism of the drug's use in cystic fibrosis treatment is unknown. It is believed to lower the viscosity of sputum by osmotically drawing water out from the cells into the secretions. This causes the bronchial secretions to become less viscous, making them easier to expectorate.

Half-life elimination:

• Terminal: 4.7 hours

Metabolism:

• It undergoes CYP-independent metabolism through the glycolytic route, where it is converted to fructose through dehydrogenation.

Bioavailability:

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

Excretion:

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

Time to peak, plasma:

• Inhaled: 1.5 hours

International Brand Names of Inhaled Mannitol:

• Aridol
• Bronchitol
• Osmohale

Inhaled Mannitol Brand Names in Pakistan:

Not available in Pakistan.