Metopirone

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: patient information

Metopirone, 250 mg, soft capsules

Metyrapone

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Metopirone and what is it used for
• 2. Important information before taking Metopirone
• 3. How to take Metopirone
• 4. Possible side effects
• 5. How to store Metopirone
• 6. Contents of the pack and other information

1. What is Metopirone and what is it used for

Metopirone contains 250 mg of metyrapone. Metyrapone belongs to a group of medicines used in tests to assess pituitary function. Metyrapone is used in diagnostic tests to determine if a patient has insufficient levels of ACTH (a hormone produced by the pituitary gland), which regulates cortisol production. Metyrapone may also be used in tests to help diagnose a specific type of Cushing's syndrome. Additionally, the medicine may be used to treat symptoms and signs of endogenous Cushing's syndrome by reducing elevated cortisol levels (a hormone produced by the adrenal glands). Cushing's syndrome is a set of symptoms resulting from high levels of cortisol produced by the body in the adrenal glands.

2. Important information before taking Metopirone

When not to take Metopirone during diagnostic testing for ACTH deficiency:

• If the patient has Addison's disease, in which the adrenal glands do not produce sufficient amounts of steroid hormones, cortisol, or aldosterone.

When not to take Metopirone:

• If the patient is allergic to metyrapone or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before starting Metopirone for diagnostic testing, discuss with your doctor if:

• The patient has or may have a condition where hormone levels in the body are low (e.g., decreased cortisol production by the adrenal glands or severe hypopituitarism). The doctor will perform tests to ensure that taking Metopirone is suitable for the patient.
• The patient has liver disease or damage, as this may slow down the effect of the medicine.
• The patient is taking medicines such as glucocorticosteroids, as the doctor may decide not to perform the test with Metopirone until the patient has stopped taking these medicines.

During treatment with Metopirone

Metopirone may temporarily reduce the amount of hormones produced by the adrenal glands (cortisol), but the doctor will adjust this by administering the appropriate hormonal medicine. If the patient has Cushing's syndrome, the doctor may also administer a medicine to prevent infections. However, if the patient experiences shortness of breath and fever after a few hours or days, they should contact their doctor immediately, as these symptoms may indicate a severe lung infection.

Laboratory tests before and during Metopirone administration

Blood tests should be performed before starting treatment and regularly during treatment. This is to detect any possible abnormalities in potassium and cortisol levels in the patient. Depending on the results, the doctor may adjust the dosage and/or prescribe corrective treatment. Depending on the risk factors for heart disease, an EKG test should be considered before starting treatment with Metopirone or during treatment. If the patient experiences any of the following symptoms: weakness, fatigue, dizziness, loss of appetite, nausea, vomiting, diarrhea, abdominal pain, they should consult their doctor. These symptoms, as well as low blood pressure, high potassium levels, low sodium levels, or low glucose levels in the blood, may be signs of hypokortisolism (insufficient cortisol levels in the blood). Therefore, the doctor will monitor the patient's blood pressure and perform blood tests. In case of confirmed hypokortisolism, the doctor may decide to administer temporary replacement steroid therapy (glucocorticosteroid) and/or reduce the dose or discontinue Metopirone treatment.

If the patient takes Metopirone for a long time

During treatment with this medicine, blood pressure may increase.

Metopirone and other medicines

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, as they may affect the results of the test with this medicine. The following medicines may affect the results of the test with Metopirone:

• Antiepileptic medicines used to treat epilepsy (e.g., phenytoin, barbiturates);
• Antidepressant and neuroleptic medicines used to treat anxiety, depression, or psychiatric disorders (e.g., amitriptyline, chlorpromazine, alprazolam);
• Hormones that affect the hypothalamic-pituitary axis, which regulates body processes such as stress, emotions, energy levels, digestion, and the immune system (e.g., cortisol, hydrocortisone, ACTH, tetracosactide);
• Glucocorticosteroids;
• Thyroid medicines used to treat thyroid diseases (e.g., thyroxine, liothyronine, carbimazole);
• Cyproheptadine used to treat allergies (e.g., Periactin).

Do not take Metopirone with paracetamol without consulting a doctor.

Pregnancy, breastfeeding, and fertility Use during pregnancy

Metopirone is not recommended for women of childbearing age who are not using effective contraception. If the patient is pregnant, thinks they may be pregnant, or plans to have a child, they should consult their doctor as soon as possible to determine whether they should stop or continue taking Metopirone. If it is necessary to take the medicine during pregnancy, the doctor will monitor the newborn's cortisol levels for the first week of life. Use during breastfeedingBreastfeeding should be discontinued during treatment with Metopirone, as there is a possibility that metyrapone may pass into human milk.

Driving and using machines

If the patient experiences dizziness or drowsiness while taking this medicine, they should not drive a vehicle or operate machinery until these symptoms have resolved.

Metopirone contains ethyl parahydroxybenzoate sodium (E215) and propyl parahydroxybenzoate sodium

(E217), which may cause allergic reactions (which may be delayed).

Metopirone contains sodium

The medicine contains less than 1 mmol of sodium (23 mg) per capsule, which means the medicine is considered "sodium-free".

Monitoring and supervision

During diagnostic testing, the patient will receive the medicine only in the presence of a doctor, as the doctor must monitor the body's response to the administered medicine.

3. How to take Metopirone

This medicine should always be taken strictly according to the doctor's instructions. In case of doubts, consult a doctor or pharmacist. If Metopirone is administered for the diagnosis of Cushing's syndrome, the patient must be hospitalized for testing.

Use in adults

If the patient is undergoing a rapid test after a single dose (to assess pituitary function):

Around midnight, the patient will be asked to swallow the capsule(s) and drink yogurt or milk. The next morning, a blood sample will be taken, which will be examined by the doctor. The recommended dose of the medicine is 30 mg/kg of body weight. The same dose is used in children.

If the patient is undergoing testing after multiple doses of the medicine (to assess pituitary function and facilitate the diagnosis of a specific type of Cushing's syndrome):

The doctor will start collecting the patient's urine samples 24 hours before starting the administration of this medicine. Then, the patient will receive 2-3 capsules (500-750 mg) every 4 hours for the next 24 hours. The capsules should be taken with milk or after a meal. Then, over the next 24 hours, the doctor will collect additional urine samples.

If the patient is being treated for symptoms and signs of endogenous Cushing's syndrome

The dose administered to the patient will be individually determined and may range from 1 capsule (250 mg) to 24 capsules (6 g) per day in three or four divided doses. The dose of Metopirone may be periodically changed by the doctor to restore normal cortisol levels. The patient should always strictly follow the doctor's instructions and never change the dose unless advised by the doctor.

Use in children

In the case of testing after multiple doses, children should receive 15 mg/kg of body weight, with a minimum dose of 250 mg every 4 hours. In the case of treatment for Cushing's syndrome, the dose should be individually determined based on cortisol levels and the tolerated dose of the medicine.

Taking a higher dose of Metopirone than recommended

If the patient has taken too many capsules, they should immediately inform their doctor or nurse or go to the emergency department of the nearest hospital. Vomiting and abdominal pain and/or diarrhea may occur. The patient may experience dizziness, fatigue, headache, sweating, and increased blood pressure. It may be necessary to administer activated charcoal and hydrocortisone to the patient.

Missing a dose of Metopirone

If a dose is missed, the patient should take it as soon as possible. If it is almost time for the next dose, the patient should not take a double dose to make up for the missed dose, but should take the capsules at the usual time. In case of any further doubts about taking this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Metopirone can cause side effects, although not everybody gets them.

Some side effects may be serious:

• The patient should immediately inform their doctor if they experience two or more of the following symptoms: weakness, dizziness, fatigue, loss of appetite, nausea, vomiting, abdominal pain, diarrhea. This may indicate adrenal insufficiency (low cortisol levels). Adrenal insufficiency occurs when metyrapone excessively reduces cortisol levels. It is more likely to occur during periods of higher metyrapone doses or increased stress. The doctor will adjust this by administering hormonal medicine to compensate for the lack of cortisol and/or by adjusting the metyrapone dose.
• The patient should immediately inform their doctor if they experience bruising or bleeding that lasts longer than usual, blood on the gums, nose, or skin, and/or feeling tired most of the time. This may indicate a decrease in the number of red blood cells, white blood cells, and/or platelets in the blood. See also section 2 "During treatment with Metopirone".

Reporting side effects If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products Al. Jerozolimskie 181C, 02-222 Warsaw tel.: + 48 22 49 21 301 fax: + 48 22 49 21 309 website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Metopirone

The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the bottle and carton after the words "Expiry date". The expiry date refers to the last day of the month. Use within two months of opening. Store the bottle tightly closed to protect from moisture. Store below 25 °C. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Metopirone contains

• The active substance is metyrapone. One capsule contains 250 mg of metyrapone.
• The other ingredients are: ethyl vanillin, gelatin, glycerol, macrogol 400, macrogol 4000, p-methoxyacetophenone, ethyl parahydroxybenzoate sodium (E215), propyl parahydroxybenzoate sodium (E217), titanium dioxide (E171), and purified water. The ink used for printing on the capsules contains: carminic acid (E120), aluminum chloride hexahydrate, sodium hydroxide, hypromellose, and propylene glycol.

What Metopirone looks like and contents of the pack

White or yellowish-white, elongated, opaque, soft gelatin capsule with red ink printing "HRA", with a slightly yellowish, sticky or gel-like content. Capsule size: length 18.5 mm; diameter 7.5 mm. One plastic bottle contains 50 capsules.

Manufacturer

DELPHARM LILLE S.A.S Parc d’activités Roubaix-Est 22 Rue de Toufflers CS 50070 59452 LYS LEZ LANNOY France

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Metopirone: Ireland, Croatia, Czech Republic, Latvia, Denmark, Finland, Netherlands, Portugal, Poland, Spain, Sweden Metycor: Slovenia, Austria, Norway Metyrapone Esteve: France Metopiron: Germany Cormeto: Italy, Estonia, Hungary

Date of last revision of the leaflet: 03/2025

Marketing Authorization Holder

Esteve Pharmaceuticals S.A. Passeig de La Zona Franca 109 Planta 4 08038 Barcelona Spain + 34 93 446 60 00