Methacholine Dosage

Usual Adult Dose for Diagnostic

The recommended dose of powder for inhalation (requiring reconstitution and dilution) or inhalation solution (in a ready-to-use kit) is administered in increasing concentrations of solution using either the 5-Breath Dosimeter Dosing Method or the 2-Minute Tidal Breathing Dosing Method with doubling or quadrupling dosing concentrations:

Doubling Dose Increments:

• Concentration: 0.0625 mg/mL; Dose: 1.484 mcg
• Concentration: 0.125 mg/mL; Dose: 2.969 mcg
• Concentration: 0.25 mg/mL; Dose: 5.938 mcg
• Concentration: 0.5 mg/mL; Dose: 11.875 mcg
• Concentration: 1 mg/mL; Dose: 23.75 mcg
• Concentration: 2 mg/mL; Dose: 47.5 mcg
• Concentration: 4 mg/mL; Dose: 95 mcg
• Concentration: 8 mg/mL; Dose: 190 mcg
• Concentration: 16 mg/mL; Dose: 380 mcg

Quadrupling Dose Increments:

• Concentration: 0.0625 mg/mL; Dose: 1.484 mcg
• Concentration: 0.25 mg/mL; Dose: 5.938 mcg
• Concentration: 1 mg/mL; Dose: 23.75 mcg
• Concentration: 4 mg/mL; Dose: 95 mcg
• Concentration: 16 mg/mL; Dose: 380 mcg

MAXIMUM DOSE: 16 mg/mL (380 mcg)

DURATION OF THERAPY:

• Stop dosing if the Forced Expiratory Volume (FEV1) has declined by 20% or more from the post-diluent FEV1 or if the maximum concentration (16 mg/mL) has been administered, whichever comes first.

Comments:

• Baseline pulmonary function tests must be performed prior to challenge initiation.
• A patient must have an FEV1 of at least 60% of the predicted value to undergo this challenge.
• Refrain from administering additional concentrations in cases of severe bronchoconstriction.
• Upon completion of the test, provide the patient with an inhaled beta-agonist to expedite the return of the FEV1 to within 90% of the baseline and alleviate any discomfort. Typically, the majority of patients regain normal pulmonary function within 5 minutes after beta-agonist administration, while most patients achieve normal pulmonary function within 30-45 minutes without beta-agonist administration. Wait for 10 minutes and then measure the FEV1 and Vital Capacity. Patients should not be allowed to leave the laboratory until their FEV1 has returned to within 90% of the baseline.
• Refer to manufacturer provided information for detailed process of administration using the 5-Breath Dosimeter Dosing Method or the 2-Minute Tidal Breathing Dosing Method.
• Refer to manufacturer product information for calculation and interpretation of methacholine challenge test results.

Use: Diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma

Usual Pediatric Dose for Diagnostic

Age 5 years and older:
The recommended dose of powder for inhalation (requiring reconstitution and dilution) or inhalation solution (in a ready-to-use kit) is administered in increasing concentrations of solution using either the 5-Breath Dosimeter Dosing Method or the 2-Minute Tidal Breathing Dosing Method with doubling or quadrupling dosing concentrations:

Doubling Dose Increments:

• Concentration: 0.0625 mg/mL; Dose: 1.484 mcg
• Concentration: 0.125 mg/mL; Dose: 2.969 mcg
• Concentration: 0.25 mg/mL; Dose: 5.938 mcg
• Concentration: 0.5 mg/mL; Dose: 11.875 mcg
• Concentration: 1 mg/mL; Dose: 23.75 mcg
• Concentration: 2 mg/mL; Dose: 47.5 mcg
• Concentration: 4 mg/mL; Dose: 95 mcg
• Concentration: 8 mg/mL; Dose: 190 mcg
• Concentration: 16 mg/mL; Dose: 380 mcg

Quadrupling Dose Increments:

• Concentration: 0.0625 mg/mL; Dose: 1.484 mcg
• Concentration: 0.25 mg/mL; Dose: 5.938 mcg
• Concentration: 1 mg/mL; Dose: 23.75 mcg
• Concentration: 4 mg/mL; Dose: 95 mcg
• Concentration: 16 mg/mL; Dose: 380 mcg

DURATION OF THERAPY:

• Stop dosing if the Forced Expiratory Volume (FEV1) has declined by 20% or more from the post-diluent FEV1 or if the maximum concentration (16 mg/mL) has been administered, whichever comes first.

Comments:

• Baseline pulmonary function tests must be performed prior to challenge initiation.
• A patient must have an FEV1 of at least 60% of the predicted value to undergo this challenge.
• Refrain from administering additional concentrations in cases of severe bronchoconstriction.
• Upon completion of the test, provide the patient with an inhaled beta-agonist to expedite the return of the FEV1 to within 90% of the baseline and alleviate any discomfort. Typically, the majority of patients regain normal pulmonary function within 5 minutes after beta-agonist administration, while most patients achieve normal pulmonary function within 30-45 minutes without beta-agonist administration. Wait for 10 minutes and then measure the FEV1 and Vital Capacity. Patients should not be allowed to leave the laboratory until their FEV1 has returned to within 90% of the baseline.
• Refer to manufacturer provided information for detailed process of administration using the 5-Breath Dosimeter Dosing Method or the 2-Minute Tidal Breathing Dosing Method.
• Refer to manufacturer product information for calculation and interpretation of methacholine challenge test results.

Use: Diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

US BOXED WARNING(S):
SEVERE BRONCHOCONSTRICTION:

• Severe bronchoconstriction may occur, including at the lowest dose.
• Use in contraindicated in all patients with baseline forced expiratory volume (FEV1) less than 60% of predicted or in adults with FEV1 under 1.5 L.
• Use is not recommended in clinically apparent asthma or wheezing due to the potential for severe bronchoconstriction.
• Have emergency equipment and medication immediately available to treat acute respiratory distress.
• Severe bronchoconstriction should be immediately reversed with a rapid-acting bronchodilator agent (beta-agonist).

CONTRAINDICATIONS:

• Hypersensitivity to methacholine or other parasympathetic agents. Reactions include rash, itching/swelling (especially of face/tongue/throat), severe dizziness, and trouble breathing.
• All patients with baseline FEV1 less than 60% of predicted or in adults with FEV1 under 1.5 L.

Safety and efficacy have not been established in patients younger than 5 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration Advice:

• Consult the manufacturer product information for instructions on the standardized inhalation procedure.
• At each inhalation of a serial concentration, patients should begin at functional residual capacity (FRC) and slowly and completely inhale the dose delivered.
• This drug should be administered in a methacholine challenge test, which is typically conducted in a pulmonary function laboratory or clinic. This test should be conducted by personnel who have received proper training to ensure both safety and accuracy. Moreover, it should only be carried out under the supervision of a healthcare practitioner who is familiar with all aspects of the test technique and the management of respiratory distress. Immediate access to emergency medication and equipment should be ensured in case acute respiratory distress occurs.
• The use of this drug should be considered in patients who are already on chronic asthma medications only when there are doubts about the accuracy of their asthma diagnosis. In such cases, this drug should only be administered if spirometry results return to normal after supervised withdrawal of their asthma drugs. However, this drug is not recommended for patients with clinically evident asthma or wheezing.
• The powder for inhalation solution of this drug requires reconstitution and dilution before use. However, the inhalation solution, available in a ready-to-use kit, does not need any reconstitution or dilution steps.
• This drug should be administered through oral inhalation using either the 5-Breath Dosimeter Dosing Method or the 2-Minute Tidal Breathing Dosing Method, following the doubling or quadrupling stepwise protocols. Any unused solution in the nebulizer should be discarded after each administration.
• This drug can be taken with or without meals.

Spirometry test:

• Before initiating a methacholine challenge test, it is essential to conduct baseline spirometry. Patients must meet certain criteria to undergo the test, including having a baseline Forced Expiratory Volume in 1 second (FEV1) equal to or greater than 60% of the predicted value (for both adults and children) and equal to or greater than 1.5 liters (for adults). This should not be used in pediatric and adult patients whose baseline FEV1 falls below 60% of the predicted value or in adults with FEV1 less than 1.5 liters.
• At the beginning of the methacholine challenge test, prior to administering any doses of this drug via nebulization, FEV1 should be measured following exposure to a nebulized diluent or base solution that does not contain methacholine chloride. This measurement provides the post-diluent FEV1.
• The methacholine challenge test is considered positive if there is a reduction in FEV1 of 20% or more from the post-diluent FEV1 measurement. At this point, the test should be stopped, and the reduction value must be calculated and recorded before proceeding with administration of this drug.
• After a methacholine challenge test with this drug, an inhaled beta agonist should be administered to facilitate the return of FEV1 to baseline levels and alleviate any discomfort experienced by the subject. Most patients typically recover normal pulmonary function within 10 to 20 minutes following the administration of a beta agonist.

Storage Requirements:

• Unreconstituted Powder: 59F to 86F (15C to 30C).
• Refrigerate the reconstituted and diluted solutions at 36F to 46F (2C to 8C) for up to 2 weeks.
• Inhalation solution kit: Store between 59F to 86F (15C to 30C). Use immediately upon opening the vial.

Reconstitution/Preparation Techniques:

• Consult manufacturer product information.

General:

• The target level for a positive challenge is a 20% reduction in the FEV1 compared with the baseline value after inhalation.
• People with asthma or hay fever should not handle this drug.

Patient Advice:

• Inform the patient or caregiver about the potential for severe bronchoconstriction as a risk associated with administration of this drug.
• Inform the patient or caregiver that this drug may cause mild symptoms such as cough, chest tightness, or shortness of breath.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer