Methacholine
/api/v1/drug/methacholineBoxed warning
SEVERE BRONCHOCONSTRICTION WARNING: SEVERE BRONCHOCONSTRICTION Severe bronchoconstriction can result from Provocholine administration (including the lowest dose). The use of Provocholine is contraindicated in pediatric and adult patients with baseline FEV1 < 60% predicted or adults with FEV1 < 1.5 L. Because of the potential for severe bronchoconstriction, the use of Provocholine in patients with clinically apparent asthma or wheezing is not recommended [ see Warnings and Precautions (5.1) ]. Emergency equipment and medication should be immediately available to treat acute respiratory distress. If severe bronchoconstriction occurs, reverse immediately with a rapid-acting inhaled bronchodilator agent (β-agonist) [ see Warnings and Precautions (5.1) ]. If baseline spirometry is not performed or is measured inaccurately, the initial FEV1 may be underestimated. In this situation, decreases in FEV1 may not be detected after administration of escalating Provocholine doses, which may result in administration of unnecessary higher doses and an increased risk for excessive bronchoconstriction [ see Warnings and Precautions (5.1) ]. WARNING: SEVERE BRONCHOCONSTRICTION See full prescribing information for complete boxed warning.
Mechanism of action
Sourced from openFDAMethacholine chloride is a cholinergic agonist. Bronchial smooth muscle contains significant parasympathetic (cholinergic) innervation.
Indications
Sourced from openFDA- Provocholine, used in a methacholine challenge test, is indicated for the diagnosis of bronchial airway hyperreactivity in adults and pediatric patients five years of age and older who do not have clinically apparent asthma.ICD-10: J45.909
Contraindications
Sourced from openFDA- Provocholine is contraindicated in the following: Hypersensitivity to methacholine or other parasympathomimetic agents. Reactions have included rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.contraindicated
Dosage & administration
Sourced from openFDAThe methacholine challenge test should be conducted in a pulmonary function laboratory or clinic, by adequately trained personnel, for safety and accuracy (2.1) Determine baseline FEV1 values to assess whether a patient is able to undergo the methacholine challenge test (2.1) Recommended dosage(s) of Provocholine in the Methacholine Challenge Test is administration of increasing concentrations of Provocholine solution via nebulization (2.2) Administer using either the 5-Breath Dosimeter Dosing Method or the 2-Minute Tidal Breathing Dosing Method with the doubling or quadrupling stepwise protocols (2.4, 2.5) See the Full Prescribing Information for the required reconstitution and dilution procedures prior to use (2.3) See the Full Prescribing Information for the calculation and interpretation of the results (2.6) 2.1 Methacholine Challenge Test Overview Provocholine should be administered in a methacholine challenge test in a pulmonary function laboratory or clinic, by adequately trained personnel, for safety and accuracy, and should be performed only under the responsibility of a healthcare practitioner trained in and thoroughly familiar with all aspects of the technique of the test and the management of respiratory distress. Emergency medication and equipment should be immediately available to treat acute respiratory distress. Only consider Provocholine use in patients on chronic asthma drugs if the accuracy of the asthma diagnosis is in doubt. In these patients, only administer Provocholine if spirometry is normal after supervised withdrawal of the asthma drugs.
Warnings & precautions
Sourced from openFDAHealthcare provider and any other personnel involved in the administration of the methacholine challenge test should take precautions to minimize inhalation of Provocholine powder and nebulized aerosol (5.2) 5.1 Risk of Severe Bronchoconstriction Severe bronchoconstriction can result from Provocholine administration (including the lowest dose). The use of Provocholine is contraindicated in pediatric and adult patients with baseline FEV 1 < 60% predicted or adults with FEV 1 < 1.5 L. Emergency equipment and medication should be immediately available to treat acute respiratory distress. Because of the potential for severe bronchoconstriction, the use of Provocholine in patients with clinically apparent asthma or wheezing is not recommended. If severe bronchoconstriction occurs, reverse immediately by the administration of a rapid-acting inhaled β-agonist. If baseline spirometry is not performed or is measured inaccurately, the initial FEV 1 may be underestimated. In this situation, decreases in FEV 1 may not be detected after escalating Provocholine doses, which may result in administration of unnecessary higher doses and an increase in the risk for excessive bronchoconstriction. 5.2 Risks to Healthcare Providers Administering Provocholine The supplied Provocholine powder or the Provocholine nebulized aerosol may cause bronchoconstriction in healthcare providers administering Provocholine in a methacholine challenge test.
Adverse reactions
Sourced from openFDAThe following adverse reactions associated with the use of Provocholine were identified in clinical studies or post marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Bronchospasm (includes symptoms such as chest tightness, cough or wheezing). Adverse reactions less commonly associated with Provocholine include headache, throat irritation, light-headedness and itching. Adverse reactions associated with Provocholine include headache, throat irritation, light-headedness and itching (6) To report SUSPECTED ADVERSE REACTIONS, contact Methapharm at 1-866-701-4636 or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch
Use in specific populations
Sourced from openFDAPregnancy: Provocholine is not recommended (8.1) 8.1 Pregnancy Risk Summary The available data from published literature on Provocholine use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies evaluating effects of methacholine chloride on embryofetal development have not been conducted. Diagnosis of bronchial airway hyperreactivity with bronchoprovocation challenge is not recommended for pregnant women because of the potential for hypoxia in the fetus. If bronchial airway hyperreactivity is suspected, consider trial of empiric treatment. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary There are no available data on the presence of methacholine chloride in human milk, the effect on the breastfed infant, or the effect on milk production.
Pharmacokinetics
Sourced from openFDA- Metabolism
- There are no metabolic and pharmacokinetic data available on methacholine chloride.
Approval history
Sourced from openFDA- Oct 31, 1986NDANDA019193Methapharm
FAERS reports
- 1Fatigue79.9%
- 2Chest Discomfort68.5%
- 3Dyspnoea68.5%
- 4Headache68.5%
- 5Dizziness57.0%
- 6Drug Ineffective57.0%
- 7Urticaria57.0%
- 8Angioedema45.6%
- 9Anxiety45.6%
- 10Asthma45.6%
- 11Benign Prostatic Hyperplasia45.6%
- 12Pain45.6%
- 13Accidental Exposure To Product34.2%
- 14Arthralgia34.2%
- 15Back Pain34.2%
Literature
Recent PubMed references pinned to Methacholine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.
- [Interpretation of standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)].Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases · 2026 · Xie YQ, Zheng JP, Gao Y, et al.PMID 42108175DOI 10.3760/cma.j.cn112147-20250903-00542
- Airway smooth muscle force adaptation on the methacholine response in asthmatic patients.American journal of physiology. Lung cellular and molecular physiology · 2025 · Henry C, Boulay MÈ, Lechasseur A, et al.PMID 41171168DOI 10.1152/ajplung.00339.2025
- Methacholine Challenge: Physiology, Methodology, and Clinical Interpretation.Clinics in chest medicine · 2025 · Satia I, Inman M, Davis BE, et al.PMID 40769591DOI 10.1016/j.ccm.2025.04.004
- Lung Tissue Compliance Interacts with Smooth Muscle and Drives Hyperresponsiveness in Mice with Experimental Asthma.Lung · 2025 · Hecht S, Rojas-Ruiz A, Boucher M, et al.PMID 40730919DOI 10.1007/s00408-025-00840-4
- Relation of Changes in PEF and FEV(1) During Salbutamol-Induced Bronchodilation After Methacholine Challenge Test.Pulmonary medicine · 2025 · Csonka LL, Tikkakoski A, Vuotari L, et al.PMID 40661699DOI 10.1155/pm/7675935
- The Advantages of FEV(1) Percent Predicted Change During Bronchial Challenge Testing.Lung · 2025 · Dean J, Beech A, Singh D, et al.PMID 40615741DOI 10.1007/s00408-025-00823-5
- Oscillometry with or without spirometry for methacholine testing.Physiological reports · 2025 · Henry C, Boucher M, Boulay MÈ, et al.PMID 40405531DOI 10.14814/phy2.70387
- Methacholine hyperresponsiveness in mice with house dust mite-induced lung inflammation is not associated with excessive airway constriction ex vivo.Experimental physiology · 2025 · Rojas-Ruiz A, Boucher M, Henry C, et al.PMID 40153804DOI 10.1113/EP092522
Clinical trials
The 10 most recently updated of 131 ClinicalTrials.gov registrations naming Methacholine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- The Effects of Iontophoresed Vasoactive Drugs on Cutaneus Blood FlowTerminated · Interventional · 31 enrolled · University Hospital, LinkoepingNCT04777383updated 2026-05-13
- Diagnosing Asthma With Clinically Accessible, Non-invasive, and Efficient Tests: a Child-inclusive Translational InvestigationRecruiting · Observational · 123 enrolled · Université de SherbrookeNCT07011394updated 2026-05-06
- Reversibility of Methacholine Induced BronchoconstrictionCompleted · Phase 4 · Interventional · 16 enrolled · University of SaskatchewanNCT05977699updated 2026-05-04
- Body Composition Related Evaluation of Airway Tone and Hyper-rEactivity Using OscillometryRecruiting · Observational · 100 enrolled · University of RochesterNCT07356310updated 2026-04-13
- Effect of Ectoin® Inhalation Solution on Subjects With Mild Bronchial AsthmaCompleted · Interventional · 18 enrolled · Bitop AGNCT01478152updated 2026-01-29
- Examining Bronchial Hyperresponsiveness in Primary Ciliary DyskinesiaRecruiting · Interventional · 40 enrolled · Indiana UniversityNCT07288827updated 2025-12-17
- Diagnostic and Translational Values of Point-of-care Blood Eosinophils and Exhaled Nitric Oxide (FeNO) in People Referred by Primary Care for Suspected AsthmaCompleted · Observational · 123 enrolled · Université de SherbrookeNCT05992519updated 2025-11-19
- A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 InclusiveRecruiting · Phase 1 · Interventional · 84 enrolled · GlaxoSmithKlineNCT06433921updated 2025-10-28
- Exercise Induced Bronchoconstriction and Field TestsCompleted · Interventional · 60 enrolled · Karolinska InstitutetNCT04275648updated 2025-08-26
- Pilot Study for the Application of Low Power External Bioelectronic Devices in the Diagnosis of Bronchial Asthma.Not yet recruiting · Observational · 50 enrolled · Acurable Ltd.NCT06836375updated 2025-08-19
Frequently asked questions
- How does Methacholine work?
- Methacholine chloride is a cholinergic agonist. Bronchial smooth muscle contains significant parasympathetic (cholinergic) innervation.
- What is Methacholine used for?
- According to FDA labeling, Methacholine carries indications including: Provocholine, used in a methacholine challenge test, is indicated for the diagnosis of bronchial airway hyperreactivity in adults and pediatric patients five years of age and older who do not have clinically apparent asthma.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Methacholine?
- Methacholine is classified as Other diagnostic agents, Cholinergic Receptor Agonist, Adrenergic beta-Antagonists, Cholinergic Agonists.
- What are the contraindications for Methacholine?
- Methacholine labeling lists contraindications including: Provocholine is contraindicated in the following: Hypersensitivity to methacholine or other parasympathomimetic agents. Reactions have included rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.. Always consult the full prescribing information and a clinician.
methacholine is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.