METOPIRONE 250 mg SOFT CAPSULES

2. What you need to know before you take Metopirone

Do not take Metopirone as a diagnostic test for ACTH deficiency:

• if you have a condition in which the adrenal glands do not produce enough steroid hormones, cortisol or aldosterone, known as Addison's disease.

Do not take Metopirone:

• if you are allergic to metyrapone or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor before taking Metopirone for a diagnostic test

• if you have, or think you may have, a condition in which your hormone levels are low (for example, reduced cortisol production in the adrenal glands or severe hypopituitarism). Your doctor will need to perform a test to check that Metopirone is suitable for you,
• if you have liver disease or liver damage, as this may cause the medicine to act more slowly,
• if you are taking medicines such as glucocorticoids; your doctor may decide that you should not undergo the test with Metopirone, as you should stop taking them.

During treatment with Metopirone

Metopirone may temporarily decrease the amount of hormones produced by the adrenal glands (cortisol), but your doctor will correct this with appropriate hormonal medication.

If you have Cushing's syndrome, your doctor may also give you medicines to prevent the development of infections. But if you experience shortness of breath and fever for hours or days, contact your doctor immediately, as you may be developing a severe pulmonary infection.

Tests before and during treatment with Metopirone

Your doctor will perform a blood test before starting treatment and regularly during treatment. This is to detect any possible anomalies in your potassium levels and to measure your cortisol levels. Based on the results, your doctor may adjust the dose and/or prescribe corrective treatment.

Depending on your cardiac risk factors, your doctor may decide to perform an ECG before starting or during treatment with Metopirone.

Consult your doctor if you experience any of the following symptoms: weakness, fatigue, dizziness, loss of appetite, nausea, vomiting, diarrhea, or abdominal pain. These symptoms, as well as low blood pressure, high potassium levels, low sodium levels, or low blood glucose levels, may be signs of hypocortisolism (insufficient cortisol levels in the blood).

Consequently, your doctor will monitor your blood pressure and perform a blood test. If you are diagnosed with hypocortisolism, your doctor may decide to administer temporary steroid replacement therapy (glucocorticoids) and/or reduce the dose or discontinue treatment with Metopirone.

If you take Metopirone for a prolonged period

Your blood pressure may increase when taking this medicine.

Other medicines and Metopirone

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as they may influence the results of the test with this medicine. The following medicines may affect the results of the test with Metopirone:

• Anticonvulsants used to control epilepsy (e.g., phenytoin, barbiturics.
• Antidepressants and neuroleptics used to treat anxiety, depression, or psychiatric problems (e.g., amitriptyline, chlorpromazine, alprazolam).
• Hormones that affect the hypothalamic-pituitary axis, which regulates many bodily processes such as stress, emotions, energy levels, digestion, and the immune system (e.g., cortisol, hydrocortisone, ACTH, tetracosactide).
• Corticosteroids.
• Antithyroid medicines used to treat thyroid gland diseases (e.g., thyroxine, liotrix, carbimazole).
• Cyproheptadine, used to treat allergies (e.g., Periactin).

Do not take Metopirone with paracetamol without consulting your doctor.

Pregnancy, breastfeeding, and fertility

Use during pregnancy

Metopirone is not recommended in women of childbearing age who are not using contraceptive methods.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor as soon as possible to determine whether you should stop or continue taking Metopirone.

In case you take the medicine during pregnancy, if necessary, your doctor will need to monitor your baby's cortisol levels during the first week of life.

Use during breastfeeding

Breastfeeding should be discontinued during treatment with Metopirone, as there is a possibility that metyrapone may pass into the breast milk.

Driving and using machines

If you feel dizzy or drowsy after taking this medicine, do not drive or use machines until these effects have disappeared.

Metopirone contains sodium parahydroxybenzoate (E215) and propyl parahydroxybenzoate (E217), whichmay cause allergic reactions (possibly delayed).

Metopirone contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, i.e., essentially "sodium-free".

Monitoring and supervision

When used as a diagnostic test, this medicine should only be administered in the presence of a healthcare professional, as they will need to monitor your body's response to the medicine.

3. How to take Metopirone

Follow your doctor's instructions for taking this medicine exactly. If you are unsure, consult your doctor or pharmacist again. If you are going to be given Metopirone to diagnose Cushing's syndrome, you will need to go to the hospital for some tests.

Use in adults

If you are going to have a short test with a single dose (to evaluate pituitary function):

You will be asked to swallow the capsule(s) with yogurt or milk, around midnight. Then, a blood sample will be taken in the morning, which will be reviewed by the doctor. The recommended dose is 30 mg/kg. In children, the same dose is used.

If you are going to have a test with multiple doses(to evaluate pituitary function and to help diagnose a specific type of Cushing's syndrome):

Your doctor will start taking urine samples 24 hours before administering this medicine. Then, you will be given 2-3 capsules (500-750 mg) every 4 hours, over the next 24 hours. You should take the capsules with milk or after a meal. Afterward, your doctor will take more urine samples over the next 24 hours.

If you are receiving treatment for the signs and symptoms of endogenous Cushing's syndrome

The dose administered to you will be specific to you and may range from 1 capsule (250 mg) to 24 capsules (6 g) per day, divided into three or four doses. Your doctor may periodically adjust the dose of Metopirone to restore normal cortisol levels.

You should always follow your doctor's instructions exactly and never change the dose unless your doctor tells you to.

Use in children

For the test with multiple doses, children should be given 15 mg/kg, with a minimum dose of 250 mg every 4 hours.

For the management of Cushing's syndrome, the dose should be adjusted individually based on cortisol levels and tolerability.

If you take more Metopirone than you should

If you take too many capsules, inform your doctor or nurse immediately or go to the emergency department. You may experience nausea and stomach pain and/or diarrhea. You may also feel dizzy, tired, have a headache, start sweating, and have high blood pressure. You may need to take activated charcoal and be given hydrocortisone.

If you forget to take Metopirone

If you accidentally forget to take a dose of capsules, take it as soon as you remember. If it is almost time for your next dose, do not take a double dose to make up for the forgotten dose, but continue taking the capsules as usual.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Some side effects can be serious:

• Tell your doctor immediately if you have two or more of these symptoms: weakness, dizziness, fatigue, loss of appetite, nausea, vomiting, abdominal pain, diarrhea. This may indicate that you have adrenal insufficiency (low cortisol levels). Adrenal insufficiency occurs when metyrapone decreases cortisol levels too much. It is more likely to occur during periods of increased metyrapone dose or increased stress. Your doctor will correct this using hormonal medication to compensate for the lack of cortisol and/or adjust the dose of metyrapone.
• Tell your doctor immediately if you have bleeding or bruising that lasts longer than usual, if you notice blood in your gums, nose, or skin, and if you feel tired most of the time. This may indicate that you have a decrease in the number of red blood cells and/or white blood cells and/or platelets.

See also in Section 2 "During treatment with Metopirone".

Side effects by frequency:

Very common side effects (may affect more than 1 in 10 people)

• Adrenal insufficiency (low cortisol levels)
• Loss of appetite
• Headache
• Dizziness (drowsiness)
• High blood pressure (hypertension)
• Nausea (vomiting)
• Abdominal pain (stomach pain)
• Diarrhea
• Allergic reactions on the skin (hives, rash, itching)
• Joint pain
• Swelling of limbs, hands, or feet
• Asthenic disorders (fatigue, tiredness)

Common side effects (may affect up to 1 in 10 people):

• Low potassium levels (hypokalemia)
• Feeling of tiredness or drowsiness
• Low blood pressure (hypotension)
• Vomiting
• Acne
• Excessive hair growth in unusual areas (hirsutism)
• Muscle pain

Frequency not known (cannot be estimated from the available data):

• Abnormal liver function (elevated liver enzymes)
• Leukopenia, anemia, thrombocytopenia (decrease in the number of red blood cells, white blood cells, or platelets in the blood)
• Alopecia (hair loss)
• Pulmonary infection

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Metopirone

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

Do not use this medicine after the expiry date which is stated on the bottle and carton after the letters EXP. The expiry date is the last day of the month shown. Use within 2 months of first opening.

Keep the bottle tightly closed to protect from moisture.

Store below 25°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of Metopirone

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

Appearance and packaging

Soft gelatin capsule, oblong, opaque, white to off-white, with "HRA" printed in red ink, with a viscous to gelatinous slightly yellowish content. Capsule size: 18.5 mm in length, 7.5 mm in diameter.

Each plastic bottle contains 50 capsules.

This medicine is authorised 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 this leaflet: 11/2024The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.