Prescription Drug Information: Provocholine (Page 3 of 3)

7 DRUG INTERACTIONS

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 USE IN SPECIFIC POPULATIONS

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.

11 DESCRIPTION

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:

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

12 CLINICAL PHARMACOLOGY

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.

12.3 Pharmacokinetics

There are no metabolic and pharmacokinetic data available on methacholine chloride.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

There have been no studies with methacholine chloride that would permit an evaluation of its carcinogenic or mutagenic potential or of its effect on fertility.

16 HOW SUPPLIED/STORAGE AND HANDLING

Provocholine (methacholine chloride) powder for solution is supplied in amber glass vials that contain 100 mg of methacholine chloride powder, white to off-white in color. Cartons have 6 vials (NDC 64281-100-06).

Store the supplied powder at 59o to 86o F (15o to 30o C). Refrigerate the reconstituted and diluted solutions at 36o to 46o F (2o to 8o C) for up to 2 weeks [see Dosage and Administration (2.5)].

17 PATIENT COUNSELING INFORMATION

Risk of Severe Bronchoconstriction
Inform the patient or caregiver that severe bronchoconstriction can result from Provocholine administration [see Warnings and Precautions (5.1)].

Cough, Chest Tightness, or Shortness of Breath
Inform the patient or caregiver that Provocholine may produce mild cough, chest tightness or shortness of breath.

methapharm

Distributed by Methapharm, Inc. Coral Springs, FL 33065.
For more information visit www.provocholine.com, email sales@methapharm.com or call 1-833-887-7686.® Provocholine is a registered trademark of Methapharm Inc.

Revision: October 2020

outer-carton
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inner-label
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PROVOCHOLINE methacholine chloride powder, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64281-100
Route of Administration RESPIRATORY (INHALATION) DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
METHACHOLINE CHLORIDE (METHACHOLINE) METHACHOLINE 100 mg in 100 mg
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:64281-100-06 6 VIAL, GLASS in 1 BOX contains a VIAL, GLASS (64281-100-00)
1 NDC:64281-100-00 100 mg in 1 VIAL, GLASS This package is contained within the BOX (64281-100-06)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA019193 03/27/2013
Labeler — Methapharm Inc. (253526222)
Registrant — Methapharm Inc. (253526222)

Revised: 10/2020 Methapharm Inc.

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