Methacholine is a cholinergic drug that activates the parasympathetic nerve endings present in the bronchi. It causes bronchoconstriction and is used primarily in the diagnosis of asthma.

Methacholine Uses:

• Asthma diagnosis:

  • used to identify bronchial airway hyperactivity in adults and children under the age of 5 without clinically obvious asthma.

Methacholine Dose in Adults:

Note: To be inhaled after mixing with the solution; powder form should not be inhaled.

Methacholine Dose in the diagnosis of Asthma: Inhalation:

Note: Baseline pulmonary function tests should be performed before inhalation; the FEV of the patient must be at least 60% of the predicted value. After completion of the challenge, an inhaled beta-agonist may be administered to expedite FEV-1 return within 90% of baseline and for relieving any discomfort. For detailed information regarding dosing, refer to the manufacturer's labeling.

• Five-breath dosimeter method:

  • Quadrupling dose protocol should be used beginning with a 0.0625 mg/mL (1.484 mcg) solution for the first dose progressing to a 16 mg/mL (380 mcg) solution if need be. If the FEV has decreased by 20% or more from the mean baseline, the dose should be stopped, the FEV is less than 1.5 L, or the maximal dose has been given, dosing should be stopped (whichever comes first).

• Two-minute tidal breathing method:

  • Doubling or quadrupling dose protocol should be used beginning with a 0.0625 mg/mL (1.484 mcg) solution for the first dose progressing to a 16 mg/mL (380 mcg) solution if need be. If the FEV has decreased by 20% or more from the mean baseline, the FEV is less than 1.5 L, or the maximal dose has been provided, dosing should be stopped (whichever comes first).

Methacholine Dose in Children:

Methacholine Dose as Diagnostic agent in the bronchial airway hyperactivity:

Note: The FEV-1 of the patient must be ≥60% of the predicted value. Drug administration and testing should be performed only in a pulmonary function laboratory or clinic, by an individual who is adequately trained. Baseline pulmonary function tests should be performed before inhalation challenge with 0.9% saline diluent or 0.9% saline with 0.4% phenol diluent; the same diluent should be used to reconstitute methacholine. After completion of the challenge, a beta-agonist via inhalational route may be administered to expedite FEV return within 90% of baseline and to relieve any discomfort.

• Children ≥5 years and Adolescents:

  • Inhalation:
    • Depending on the nebulizer device output per minute, particle size distribution (to gauge lower airway delivery), period of tidal breathing, and the ratio of inspiratory time to total breathing time, the dose is then increased progressively by doubling or quadrupling from 1 to 3 mcg.
    • Deep breathing techniques are favoured to the tidal breathing method. Results should be based on an effective dose that results in a 20% decrease in FEV. cite the institutional guidelines.
  • Manufacturer labeling:
    • This may not reflect the current practice; nebulizers that were necessary for described methodology in the prescribing information are considered obsolete and may be difficult to obtain (ie, two-minute tidal breathing protocol utilized the EnglishWright nebulizer and five-breath dosimeter method was the DeVilbiss 646 nebulizer).
  • Two-minute tidal breathing method:
    • Doubling or quadrupling dose protocol should be used beginning with a 0.0625 mg/mL solution and 1.484 mcg dose (English-Wright nebulizer; dose delivered by other devices may vary) for the first dose progressing to a 16 mg/mL solution and 380 mcg dose if required.
    • If the FEV has fallen by ≥20% from the mean baseline or the highest dose has been administered (whichever comes first), the dosing should be stopped.
    • For detailed information regarding dosing and administration, see manufacturer's labeling.
  • Five-breath dosimeter method:
    • Quadrupling dose protocol should be used beginning with a 0.0625 mg/mL solution for the first dose progressing to a 16 mg/mL solution if required. If the FEV-1 has fallen by ≥20% from the mean baseline or the 16 mg/mL dose has been administered (whichever comes first), the dosing should be stopped.
    • For detailed information regarding dosing and administration, see manufacturer's labeling.

Methacholine Pregnancy Category: C

• It is not advised to diagnose bronchial hyperactivity in pregnancy.

Use during breastfeeding:

• It is unknown if breast milk secretes it.
• The manufacturer recommends that you consider the following when deciding whether to breastfeed your infant.
  • Infant exposure is a risk
  • Breastfeeding is good for the infant
  • Mothers can reap the benefits of mother-to-child treatment

Dose in Kidney Disease:

No dosage adjustments have been provided in the manufacturer's labeling.

Dose in Liver disease:

No dosage adjustments have been provided in the manufacturer's labeling.

Side effects of Methacholine:

• Central nervous system:

  • Dizziness
  • Headache

• Dermatologic:

  • Pruritus

• Respiratory:

  • Throat irritation

Contraindications to Methacholine:

• Hypersensitivity to methacholine, parasympathomimetic drugs, or any component in the formulation
• Baseline FEV-1 lower than 60% (adults and pediatric patients) or below 1.5 L (adults only).

Warnings and precautions

• Bronchoconstriction [US Boxed Warning]

  • Methacholine administration can cause severe, even fatal, bronchoconstriction (even at the lowest dose).
  • Patients with wheezing or clinically evident asthma should not be given methacholine as it can cause severe bronchoconstriction.
  • Acute respiratory distress should be treated immediately with emergency equipment and medication.
  • For severe bronchoconstriction, a rapid-acting inhaled beta-agonist bronchodilator agent should be used immediately.
  • If baseline spirometry has not been performed correctly or is inaccurate, one could underestimate the initial FEV-1.
  • This could mean that FEV-1 decreases may not be detected after administration of increasing methacholine dosages.
  • This may cause administration of higher doses which may increase the risk of excessive bronchoconstriction.

• There is always risk

  • Patients with peptic or thyroid disease, seizures, thyroid disease and/or vagotonia should be assessed for the risk to their health.
  • If the risk does not outweigh the benefit, these people shouldn't be treated.

• Cardiovascular disease

  • It is not advisable for patients to use this drug if they have recently experienced a stroke, myocardial injury (MI), uncontrolled hypertension (systolic > 200 mm Hg or dialystolic > 100 mm Hg), a known aortic aneurysm, or any of these conditions.

• Ocular disease:

  • Use is not recommended for patients who have recently had eye surgery or are suffering from conditions that could lead to increased pressures, such as forceful exhalations.

• Respiratory disease: [US-Boxed Warning]

  • Patients with asthma or wheezing are not advised to use methacholine. It is also contraindicated for patients with a baseline FEV-1 lower than 60% or an adult with FEV-1 below 1.5 L.
  • The product should not be used by someone suffering from asthma or hay fever.

Methacholine: Drug Interaction

Monitoring parameters:

Baseline FEV-1.

How to administer Methacholine?

Oral inhalation:

• Ideally, each dose should be provided over a 2-minute period via oral inhalation using either the five-breath dosimeter dosing method or the two-minute tidal breathing dosing method.
• For detailed administration instructions see manufacturer's labeling.

Mechanism of action of Methacholine:

• A synthetic analogue of acetylcholine known as methacholine stimulates muscarinic, postganglionic parasympathetic receptors, which causes smooth muscle in the airways to contract and increases tracheobronchial secretions.

Duration:

• 30 to 45 mins
• The time is minutes if a beta-agonist is administered after a methacholine challenge.

International Brand Names of Methacholine:

• Provocholine
• Methacholine Omega
• Kenbran
• Provokit

Methacholine Brand Names in Pakistan:

No Brands Available in Pakistan.