Methacholine chloride

Preparation and Administration Overview Provocholine powder for inhalation solution requires reconstitution and dilution prior to use [see Dosage and Administration]. Provocholine inhalation solution in a ready-to-use kit does not require reconstitution and/ or silution prior to use. Provocholine inhalation solution 16 mg/mL in a single-dose vial requires dilution prior to use [see Dosage and Administration] .

For safety and accuracy, administer Provocholine during a methacholine challenge test in a pulmonary function laboratory or clinic, by an adequately trained personnel. Only healthcare providers trained in and thoroughly familiar with all aspects of the test’s technique and management of respiratory distress should perform the test.

Emergency medication and equipment should be immediately available to treat acute respiratory distress. 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.

Provocholine is not recommended for use in patients with clinically apparent asthma or wheezing. Before starting a methacholine challenge test, baseline spirometry must be performed. For a patient to be able to undergo the test, he or she must present with baseline FEV 1 (Forced Expiratory Volume in 1 second) greater than or equal to 60% of the predicted value (in adults and children) and greater than or equal to

Reconstitution and/or Dilution Instructions for Provocholine Powder for Inhalation Solution and Provocholine Inhalation Solution 16 mg/mL (in Single-Dose Vial) Reconstitution and Dilution of Provocholine Powder for Inhalation Solution Reconstitute Provocholine Powder for Inhalation Solution by adding 6.25 mL of 0.9% Sodium Chloride Injection to the supplied vial(s) containing 100 mg of Provocholine powder.

Shake the vial to obtain a clear solution. Dilute the reconstituted Provocholine solution, using sterile, empty USP Type 1 borosilicate glass vials. Dilute the reconstituted Provocholine solution with 0.9% Sodium Chloride Injection based on Table 1 to obtain doubling strengths or Table 2 to obtain quadrupling strengths.

After adding the 0.9% Sodium Chloride Injection, shake each vial to obtain a clear solution. If not used immediately, refrigerate the reconstituted and diluted solutions at 36°F to 46°F (2°C to 8°C) for up to 2 weeks. Since the temperature of the solution affects nebulizer output, take the diluted solutions out of the refrigerator and allow them to equilibrate to room temperature (approximately 30 minutes) before use. [See table below.] [See table below.] Dilution of Provocholine Inhalation Solution 16 mg/mL (in a Single-Dose Vial) Transfer the contents of the specified number of 3 mL vials (as per Tables 3 or 4) of Provocholine inhalation solution 16 mg/mL (in Single-Dose Vial) into a sterile, empty USP Type 1 borosilicate glass vial.

Swirl the glass vial gently to mix. Dilute the solution with 0.9% Sodium Chloride Injection based on Table 3 (to obtain doubling strengths) or Table 4 (to obtain quadrupling strengths). After adding 0.9% Sodium Chloride Injection, shake each vial to obtain a clear solution. If not used immediately, refrigerate the diluted solutions at 36oF to 46oF (2oC to 8oC) for up to 2 weeks.

Since the temperature of the solution affects nebulizer output, take the diluted solutions out of the refrigerator and allow them to equilibrate to room temperature (approximately 30 minutes) before use. [See table below.] [See table below.]

Determination of Post-Diluent FEV1 and Administration of Provocholine Using the 5-Breath Dosimeter Dosing Method Determination of Post-Diluent FEV 1 Prior to Administration of Provocholine Prior to administration of Provocholine, determine thepost-diluent FEV 1 value required for the methacholine challenge test. Instill diluent (sterile 0.9% Sodium Chloride Injection) or base solution into the nebulizer.

If using Provocholine powder for inhalation solution or Provocholine inhalation solution 16 mg/mL (in single-dose vial), using a 3 mL syringe and needle, draw up 2 to 3 mL of diluent (sterile 0.9% Sodium Chloride Injection), and instill the 0.9% Sodium Chloride Injection into the nebulizer using a sterile bacterial-retentive filter (porosity 0.22 μm).

If using the Provocholine inhalation solution ready-to-use kit, instill the contents of the base solution (contains no methacholine chloride) into the nebulizer. 2. Instruct the patient to hold the nebulizer upright with the mouthpiece in his/her mouth. The patient should wear a nose clip while inhaling from the nebulizer. 3.

At the end of exhalation during tidal breathing (functional residual capacity), instruct the patient to inhale slowly and deeply through the mouthpiece. Trigger the dosimeter soon after oral inhalation begins. Encourage the patient to continue inhaling slowly (about 5 seconds to complete the inhalation) and to hold the breath at total lung capacity (TLC) for another 5 seconds. 4.

Repeat Step 3 for a total of five inspiratory capacity inhalations. Take no more than 2 minutes to perform these 5 inhalations. 5. Perform spirometry and measure the FEV 1 30 and 90 seconds after the fifth inhalation from the nebulizer to obtain the post-diluent FEV 1 value. These values may be left at ambient (spirometer) temperature pressure saturated (ATPS).

If the FEV 1 value is not of acceptable quality, repeat the procedure. If the post-diluent FEV 1 falls by ≥ 20% from baseline FEV 1 , do not proceed with administration with Provocholine and administer an inhaled β-agonist [see Dosage and Administration]. If the post-diluent FEV 1 falls by< 20% from baseline FEV1, proceed to Step 6.

Administer of Provocholine Using the 5-Breath Dosimeter Dosing Method 6. Instill Provocholine solution into the nebulizer If using Provocholine powder for inhalation solution or Provocholine inhalation solution 16 mg/mL (in single-dose vial), using a 3 mL syringe and needle, draw up at least 2 mL of the recommended Provocholine strength based on the dose doubling or quadrupling protocol in Table 5 [see Dosage and Administration] and instill into the nebulizer using a sterile bacterial-retentive filter (porosity 0.22 μm).

Refer to Tables 1, 2, 3 or 4 for preparation of the doubling or quadrupling strengths of Provocholine [see Dosage and Administration] . If using the Provocholine inhalation solution ready-to-use kit, instill at least 2 mL of the recommended Provocholine strength based on the dose quadrupling protocol in Table 5 [see Dosage and Administration] into the nebulizer. 7.

Repeat Steps 2 through 5 for each Provocholine strength, emptying the nebulizer between each strength. To keep the cumulative effect of Provocholine relatively constant, the time interval between the end of one strength and beginning of the subsequent strength should not be more than 5 minutes. 8. Stop dosing if the FEV 1 has fallen ≥ 20% from the post-diluent FEV 1 , or the highest Provocholine strength (16 mg/mL) has been administered (whichever comes first).

Do not administer additional Provocholine doses if severe bronchoconstriction occurs [see Warnings and Precautions ]. After the test is completed, administer an inhaled β-agonist to the patient [see Dosage and Administration]. 9. Wash and clean reusable nebulizers thoroughly according to manufacturer's recommendations.

Determination of Post-Diluent FEV 1 and Administration of Provocholine Using the 1-Minute Tidal Breathing Dosing Method Determination of Post-Diluent FEV 1 Prior to Administration of Provocholine Prior to administration of Provocholine, determine the post-diluent FEV 1 required for the methacholine challenge test. Instill diluent (sterile 0.9% Sodium Chloride Injection) or base solution into the nebulizer.

If using Provocholine powder for inhalation solution or Provocholine inhalation solution 16 mg/mL (in single-dose vial), using a 3 mL syringe and needle, draw up 2 to 3 mL of diluent (sterile 0.9% Sodium Chloride Injection). Instill the 0.9% Sodium Chloride Injection into the nebulizer using a sterile bacterial-retentive filter (porosity 0.22 μm).

Attach the nebulizer and necessary tubing to the dry compressed air source. If using the Provocholine inhalation solution ready-to-use kit, instill the contents of the base solution (contains no methacholine chloride) into the nebulizer. 2. Place the face mask loosely over the nose and mouth or the mouthpiece in the mouth (with a nose clip) of the patient.

Instruct the patient to hold the nebulizer to avoid warming the solution. Keep the nebulizer upright and vertical. 3. Set the pressure regulator to 50 lb/in 2 (psi) and start the nebulizer by setting the flow controller to a flow rate of

Recommended Administration of Inhaled β-agonist after Methacholine Challenge Test After the methacholine challenge test is completed, administer an inhaled β-agonist to the patient to expedite the return of the FEV1 to within 90% of baseline and to relieve any discomfort (the majority of patients revert to normal pulmonary function within 10 to 20 minutes after β-agonist administration; in contrast the majority of patients revert to normal pulmonary function within 30-45 minutes without β-agonist administration).

Wait 10 minutes and measure the FEV1 and Vital Capacity. Do not allow patients to leave the laboratory or clinic until their FEV1 has returned to within 90% of baseline.