Leaflet: information for the user

PROVOCHOLINE 100 mg Powder for inhalation solution for nebuliser

Metacolina hydrochloride

Read this leaflet carefully before you start using the medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others even if they have similar symptoms, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What PROVOCHOLINE 100 mg Powder for inhalation solution for nebuliser is and what it is used for

2. What you need to know before you start using PROVOCHOLINE 100 mg Powder for inhalation solution for nebuliser

3. How to use PROVOCHOLINE 100 mg Powder for inhalation solution for nebuliser

4. Possible side effects

5. Storage of PROVOCHOLINE 100 mg Powder for inhalation solution for nebuliser

6. Contents of the pack and additional information

This medication is solely for diagnostic use (performance of a test to check if a disease is present).

PROVOCHOLINE produces bronchial constriction when administered in solution, through inhalation (breathing in).

PROVOCHOLINE is indicated for the diagnosis of asthma and, if positive, determines the severity of the condition.

Individuals with asthma are much more sensitive to the bronchoconstriction produced by PROVOCHOLINE than healthy individuals. This difference in response is the pharmacological basis for diagnosing asthma with PROVOCHOLINE.

Do not use PROVOCHOLINE

• If you are allergic to the active ingredient or other parasympathomimetic agents (acetylcholine, carbachol, arecoline, pilocarpine...) or to any of the other components of this medication (listed in section 6).

• If you are asthmatic, have wheezing (jadeating) or the results of your baseline (at rest) respiratory function tests (FEV1) are equal to or less than 1-1.5 liters or 70% of the expected value.

• If you are taking beta-adrenergic blockers (medications for hypertension, circulation, or the heart), see “Other medications and PROVOCHOLINE”.

• If you have undergone a PROVOCHOLINE test, it is contraindicated to perform a second test with PROVOCHOLINE.

• If you have uncontrolled hypertension (high blood pressure) or have had a myocardial infarction (heart attack) in the last 3 months.

• If you have a condition called myasthenia gravis (muscle weakness and fatigue) and are being treated with medications that inhibit cholinesterase.

Warnings and precautions

Consult your doctor or pharmacist before undergoing the PROVOCHOLINE inhalation provocation test:

• If you have ever had a seizure, if you have any cardiovascular disease (heart and blood vessel disease), peptic ulcer, urinary tract obstruction.

• If you have recently had or have respiratory tract infections, chronic lung diseases (cystic fibrosis, sarcoidosis, tuberculosis, chronic obstructive pulmonary disease).

• If you have allergic rhinitis (inflammation of the nasal mucosa, with continuous dripping and nasal congestion) without asthma, are a smoker, or are exposed to airborne contaminants.

• If you are being treated with medications for asthma or allergies (see “Other medications and PROVOCHOLINE”).

• If you are a woman, inform your doctor if you are pregnant, or the date of your last menstruation, or the date and result of your last pregnancy test. In women of childbearing age, pregnancy must be ruled out before performing the PROVOCHOLINE test.

• It is not recommended for use in children under 5 years old, due to the absence of data on its safety.

• As a result of PROVOCHOLINE administration, severe bronchoconstriction and reduced respiratory function may occur. Patients with hyperreactivity of the airways may experience bronchoconstriction (contraction of the bronchi that makes breathing difficult) with doses as low as 0.025 mg/ml. If severe bronchoconstriction occurs, your doctor will administer a rapid-acting bronchodilator agent (beta-agonist) via inhalation to counteract it.

• The PROVOCHOLINE inhalation provocation test must be performed only under the supervision of a specialized doctor and in facilities equipped with the necessary equipment.

Other medications and PROVOCHOLINE

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

If you are taking beta-adrenergic blockers (medications for hypertension, circulation, or the heart), you should not undergo the PROVOCHOLINE inhalation provocation test, as the response to metacholine hydrochloride may be exaggerated or prolonged, and you may not respond easily to the treatment used to restore normal breathing and alleviate symptoms.

Discontinue administration of asthma and allergy medications (beta agonists, anticholinergics, and theophylline) before performing the PROVOCHOLINE test.

The use of other asthma and allergy medications such as corticosteroids, cromoglicate, and nedocromil may alter the response to PROVOCHOLINE; however, it is not necessary to interrupt treatment with these medications.

The effects of other more recent medications have not been investigated.

Use of PROVOCHOLINE with food and beverages

Avoid consuming coffee, tea, cola drinks, and chocolate on the day of the PROVOCHOLINE test.

Pregnancy and lactation

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

PROVOCHOLINE should not be used in pregnant women.

Lactation will be suspended if necessary to perform the PROVOCHOLINE test, as it is unknown whether it passes into breast milk.

Driving and operating machinery

No effects on driving or operating machinery have been described.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist.This medication should be inhaled only with a special breathing device (nebulizer) under the direct supervision of a specialized doctor. PROVOCHOLINE cannot be used orally or by injection. It must be diluted before being inhaled. Your doctor will administer different concentrations of the diluted medication by inhalation, as needed, based on the results obtained. Inform your doctor if you experience any breathing difficulties at any time during the test.

This medication should be inhaled only with a special breathing device (nebulizer) under the direct supervision of a specialized doctor. PROVOCHOLINE cannot be used orally or by injection. It must be diluted before being inhaled. Your doctor will administer different concentrations of the diluted medication by inhalation, as needed, based on the results obtained. Inform your doctor if you experience any breathing difficulties at any time during the test.

Adults and children 5 years of age and older

Before starting the test with PROVOCHOLINE, your doctor will perform baseline pulmonary function tests (at rest). You will only be able to undergo the inhalation provocation test with PROVOCHOLINE if you have a FEV1(volume that is expelled in the first second of a forced exhalation) of at least 70% of the predicted value.

The test is positive if the level of reduction in FEV1with PROVOCHOLINE is 20% compared to the value obtained in the pulmonary function test without the medication.

Standard inhalation procedure:The patient will receive a series of concentrations (from lower to higher) of PROVOCHOLINE. For each concentration, 5 inhalations will be administered in a nebulizer that allows for intermittent release every 0.6 seconds using a dosifier.

After the test with PROVOCHOLINE, your doctor may administer a medication (bronchodilator) to accelerate the return to normal of the FEV1value and alleviate discomfort. Most patients return to normal pulmonary function within 5 minutes of bronchodilator administration or 30-45 minutes without bronchodilator.

Children under 5 years of age

Not recommended for use in children under 5 years of age due to the absence of data on its safety.

If you use more PROVOCHOLINE than you should

PROVOCHOLINE is administered in solution and only by inhalation. If administered orally or by injection, a metacolina hydrochloride overdose may cause syncope (fainting), cardiac arrest, and loss of consciousness.

Severe toxic reactions should be treated with 0.5-1 mg of atropine sulfate, administered intramuscularly or intravenously.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20.

Like all medications, this medication may produce adverse effects, although not everyone will experience them.

The adverse reactions associated with PROVOCHOLINE inhalation challenge tests include the following adverse effects: Headache, throat irritation, dizziness, and itching.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Usehttp://www.notificaram.es.By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

•Unopened vials (powder):No special storage conditions are required.

•Reconstituted vials (solutions A, B, C, and D):Store in refrigerator (between 2°C and 8°C) for a maximum of 2 weeks. The stability of solutions A, B, C, and D is not affected by freezing.

•Reconstituted vial E:Prepare on the day of the provocation test.

Do not use this medication after the expiration date appearing on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that are no longer needed. This will help protect the environment.

Composition of PROVOCHOLINE

• The active ingredient is metacoline hydrochloride. Each vial of 20 ml contains 100 mg of metacoline hydrochloride in powder.
• The excipient is nitrogen.

Aspect of the product and content of the package

PROVOCHOLINE is presented in amber-colored vials of 20 ml containing 100 mg of metacoline hydrochloride in powder that are reconstituted with an injection of 0.9% sodium chloride, containing 0.4% phenol (pH = 7.0). Each package contains 6 vials.

Holder of the marketing authorization and responsible for the manufacture

DIATER LABORATORIO DE DIAGNÓSTICO Y APLICACIONES TERAPÉUTICAS, S.A.

Avda. Gregorio Peces Barba 2,

28919Leganés, Madrid

SPAIN

This information is intended solely for healthcare professionals:

Standard inhalation procedure:The patient will receive a series of concentrations (from lower to higher) of PROVOCHOLINE. For each concentration, 5 inhalations will be administered in a nebulizer that allows for intermittent release every 0.6 seconds through a dosifier.

In each of the 5 inhalations of the series of concentrations, the patient will start with a functional residual capacity (FRC) and inhale slowly and completely the released dose. At 5 minutes, the FEV1values will be determined. The procedure will end when the FEV1decreases by 20% or more of the basal value obtained with the sodium chloride solution (for example: A positive response) or if a total of 188.88 accumulated units have been administered (see the table below) and the FEV1has decreased by 14% or less (for example: A negative response). If a reduction of FEV1from 15% to 19% is observed compared to the basal value, or the test can be repeated at the same concentration, or a higher concentration can be given as long as the administration of a total of 188.88 accumulated units is not exceeded.

Before performing the inhalation provocation test, the doctor must prepare the corresponding dilutions of PROVOCHOLINE. To do this, the following instructions must be followed:

Dilutions:(Note: Do not inhale the powder. Do not handle this product if you have asthma or allergies). All dilutions must be made with 0.9% sodium chloride injectable, containing 0.4% phenol (pH = 7.0), using empty and sterile borosilicate glass Type I vials. After adding the sodium chloride solution, agitate each vial until a clear solution is obtained.

Dilution-sequence test for multiple patients (2-5 patients)

2 vials of PROVOCHOLINE are required

Dilution-sequence test for a single patient

Use a sterile filter capable of retaining bacteria (0.22 μm) to transfer the solution from each vial (of at least 2 ml) to the nebulizer.

Last review date of thisleaflet:June 2020

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)