Provocholine (Page 3 of 4)


Powder for Solution: 100 mg of white to off-white crystalline powder in amber glass vials (powder is reconstituted and then diluted prior to administration)


Provocholine is contraindicated in the following situations:

  • Hypersensitivity to methacholine or other parasympathomimetic agents. Reactions have included rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
  • Baseline FEV1 < 60% predicted (adults or pediatric patients) or <1.5 L (adults)


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 FEV1 < 60% predicted or adults with FEV1 < 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 FEV1 may be underestimated. In this situation, decreases in FEV1 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 (after reconstitution and/or dilution) may cause bronchoconstriction in healthcare providers administering Provocholine in a methacholine challenge test. Healthcare providers and any other personnel involved in the administration of Provocholine should take the following precautionary steps:

  • Do not inhale the supplied Provocholine powder
  • Do not handle the Provocholine powder if you have asthma or hay fever.
  • Apply a low resistance filter to expiratory ports of dosing apparatus, as necessary, to prevent Provocholine release in the room air

5.3 Coexisting Diseases and Conditions

Provocholine is not recommended for patients with uncontrolled hypertension, aortic aneurysm, or history of myocardial infarction or stroke diseases. Patients with epilepsy, vagotonia, peptic ulcer disease, thyroid disease, urinary tract obstruction or other condition that could be adversely affected by a cholinergic agent should undergo methacholine challenge only if the healthcare practitioner feels the benefit to the individual outweighs the potential risks.


The 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.


Beta-Adrenergic Blockers

The use of beta-adrenergic blockers may impair reversal of Provocholine-caused bronchoconstriction.

Beta-Agonists, Anticholinergics, and Theophylline
Beta-agonists, anticholinergics, and theophylline inhibit the response of airways to Provocholine; therefore, hold these drugs before Provocholine use for the following duration:

• Short-acting β-agonists (e.g., albuterol): 6 hours
• Long-acting β-agonists (e.g., salmeterol): 36 hours
• Short-acting anti-cholinergics (e.g., ipratropium): 12 hours
• Long-acting anti-cholinergics (e.g., tiotropium): ≥168 hours
• Oral theophylline: 12-48 hours

Oral or Inhaled Corticosteroids, and Inhaled Cromoglycate

Regular use of oral or inhaled corticosteroids and inhaled cromoglycate may acutely decrease bronchial responsiveness to Provocholine. However, these drugs may be continued with Provocholine use.


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 SummaryThere 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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Provocholine and any potential adverse effects on the breastfed infant from Provocholine or from the underlying maternal condition.

8.4 Pediatric Use

Provocholine is used in a methacholine challenge test for the diagnosis of bronchial airway hyperreactivity in pediatric patients 5 years of age and older who do not have clinically apparent asthma. The safety and effectiveness of Provocholine have not been established in pediatric patients below the age of 5 years.

8.5 Geriatric Use

The diagnosis of bronchial airway hyperreactivity is largely performed in pediatric and younger adult patients. Clinical studies of Provocholine did not include patients 65 years of age or older.


Methacholine chloride, the active ingredient of Provocholine, is a parasympathomimetic (cholinergic) bronchoconstrictor agent. Provocholine (methacholine chloride) powder for solution is administered by oral inhalation.

Chemically, methacholine chloride (the active ingredient) is 1-propanaminium, 2-(acetyloxy)-N,N,N,-trimethyl-, chloride. It is a white to practically white deliquescent compound, soluble in water, alcohol and chloroform and insoluble in ether. Aqueous solutions are neutral to litmus.

Methacholine chloride has an empirical formula of C8 H18 ClNO2 , a molecular weight of 195.69, and the following structural formula:

(click image for full-size original)

Each vial of Provocholine contains 100 mg of methacholine chloride powder.


12.1 Mechanism of Action

Methacholine chloride is a cholinergic agonist. Bronchial smooth muscle contains significant parasympathetic (cholinergic) innervation. Methacholine chloride agonizes the muscarinic receptors which eventually induce bronchoconstriction.

12.2 Pharmacodynamics

After oral inhalation of Provocholine, patients with asthma are more sensitive to Provocholine-induced bronchoconstriction than are healthy subjects. This difference in response is the pharmacological basis for Provocholine in the methacholine challenge test.

All resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.