Cormeto

Patient Information Leaflet

Cormeto 250 mg Soft Capsules

metyrapone
Please read all of this leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What Cormeto is and what it is used for

Cormeto contains 250 mg of metyrapone. Metyrapone belongs to a group of medicines used as a
test to assess pituitary function. Metyrapone is used as a diagnostic test to
detect insufficient levels of ACTH, a hormone secreted by the pituitary gland, the gland that controls
cortisol secretion, or may be used for the diagnosis of a specific type of Cushing's syndrome.
This medicine may also be used in the treatment of signs and symptoms of endogenous Cushing's syndrome to reduce elevated levels of cortisol (a hormone produced by the adrenal glands). Cushing's syndrome is a constellation of symptoms that occur due to high levels of the hormone cortisol produced in the body by the adrenal glands.

2. What you need to know before taking Cormeto

Do not take Cormeto as a diagnostic test for ACTH deficiency if:

• you suffer from a condition known as Addison's disease, in which your adrenal glands do not produce sufficient amounts of steroid hormones, cortisol or aldosterone.

Do not take Cormeto:

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

Warnings and precautions
Talk to your doctor before taking Cormeto for a diagnostic test if:

• you have or think you may have a disease characterized by low hormone levels (e.g. reduced adrenal secretion of cortisol or severe hypopituitarism). Your doctor will need to perform a test to determine whether Cormeto is the appropriate treatment for you.
• you have liver disease or impaired liver function, which could slow down the action of the medicine.
• you are taking medicines such as glucocorticoids, as your doctor may decide not to perform the test with Cormeto because you would first need to stop taking these medicines.

During treatment with Cormeto
Cormeto may temporarily reduce levels of hormones produced by the adrenal gland (cortisol), but your doctor will correct this imbalance with appropriate hormone therapy.
If you suffer from Cushing's syndrome, your doctor may also prescribe medicines to prevent the onset of infections. However, if you develop shortness of breath and fever within a few hours or days, contact your doctor immediately, as you may have a serious lung infection.
Tests before and during treatment with Cormeto
Your doctor will examine your blood before starting treatment and regularly during treatment.
This is to detect any abnormalities in potassium levels and also to measure cortisol levels. Depending on the results, your doctor may adjust the dosage 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 Cormeto.
Contact your doctor if you experience any of the following symptoms: weakness, fatigue, dizziness, loss of appetite, nausea, vomiting, diarrhoea, abdominal pain. These symptoms, together with hypotension, high potassium levels, low sodium levels or low blood sugar, could be signs of hypocortisolism (insufficient levels of cortisol in the blood).
Therefore, your doctor will monitor your blood pressure and perform blood tests. If hypocortisolism is diagnosed, your doctor may decide to temporarily administer steroid replacement therapy (glucocorticoids) and/or reduce the dose or discontinue treatment with Cormeto.
If you take Cormeto for a long period of time
Your blood pressure may increase with the use of this medicine.
Other medicines and Cormeto
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as they could affect the results of the test performed with this medicine. The results of the Cormeto test may be altered by the following medicines:

• anticonvulsants used to control epilepsy (e.g. phenytoin, barbiturates)
• antidepressants and neuroleptics used to treat anxiety, depression or psychiatric disorders (e.g. amitriptiline, chlorpromazine, alprazolam)
• hormones acting on the hypothalamic-pituitary axis, which regulates numerous processes in the body such as stress, emotions, energy levels, digestion and immune system (e.g. cortisol, hydrocortisone, ACTH, tetracosactide)
• corticosteroids
• antithyroid agents used in the treatment of thyroid disorders (e.g. thyroxine, liotironine, carbimazole)
• cyproheptadine used in the treatment of allergies (e.g. Periactin)

Cormeto must not be taken with paracetamol without consulting your doctor.
Pregnancy, breastfeeding and fertility
Use during pregnancy
Cormeto is not recommended for women of childbearing age who are not using contraception.
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor as soon as possible to determine whether you should discontinue or continue treatment with Cormeto.
If you need to take the medicine during pregnancy, your doctor will need to monitor your baby's cortisol levels during the first week of life.
Use during breastfeeding
Breastfeeding must be discontinued during treatment with Cormeto, as metyrapone may pass into breast milk.
Driving and using machines
If you experience dizziness or drowsiness after taking this medicine, you must not drive or operate machinery until these effects have disappeared.
Cormeto contains sodium ethyl parahydroxybenzoate (E215) and sodium propyl parahydroxybenzoate (E217)
which may cause allergic reactions (including delayed reactions).
Cormeto 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 must only be administered in the presence of a healthcare professional, who will monitor your body's response to the medicine.

3. How to take Cormeto

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist. If you are being administered Cormeto for the diagnosis of Cushing's syndrome,
you must go to hospital to undergo certain tests.
Use in adults
If you are to undergo a single-dose rapid test (to assess pituitary function)
You must take the capsule(s) with yoghurt or milk around midnight. Then, the following morning, a blood
sample will be taken and examined by your doctor. The recommended dose is 30 mg/kg. This same dose is used in children.
If you are to undergo a multiple-dose test (to assess pituitary function and to diagnose a specific type of Cushing's syndrome):
Your doctor will begin collecting your urine samples 24 hours before you are administered this medicine.
Then, you will receive 2–3 capsules (500–750 mg) to be taken every 4 hours over the next 24 hours.
The capsules must be taken with milk or after a meal. Your doctor will collect further urine samples over the subsequent 24 hours.
If you are being treated for signs and symptoms of endogenous Cushing's syndrome:
Your dose will be individually calculated and may range from 1 capsule (250 mg) to 24 capsules (6 g) daily, divided into three or four separate doses.
Your doctor may periodically adjust your dose of Cormeto to restore normal cortisol levels.
You must always follow your doctor’s instructions carefully and never change the dose unless instructed by your doctor.
Use in children
For the multiple-dose test, children should receive 15 mg/kg, with a minimum dose of 250 mg every 4 hours.
For the management of Cushing's syndrome, the dose must be individually adjusted based on cortisol levels and product tolerability.
If you take more Cormeto than you should
If you take too many capsules, inform your doctor or nurse immediately or go to the nearest Emergency Department.
You may develop nausea and stomach discomfort and/or diarrhoea. You may also experience dizziness, fatigue, headache, sweating, and increased blood pressure.
Administration of activated charcoal and hydrocortisone may be necessary.
If you forget to take Cormeto
If you accidentally miss a dose of capsules, take it as soon as you remember.
If it is almost time for your next dose, do not double the dose to make up for the missed one; continue taking the capsules as usual.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Some side effects can be serious:

• Immediately inform your doctor if you experience two or more of the following symptoms: weakness, mild mental confusion, fatigue, loss of appetite, nausea, vomiting, abdominal pain, diarrhoea. These may indicate adrenal insufficiency (low cortisol levels). Adrenal insufficiency occurs when metyrapone reduces cortisol levels too much. It is more likely to occur during periods of increased metyrapone dosage or increased stress. Your doctor will correct this by using a hormonal medicine to compensate for the lack of cortisol and/or adjusting the dose of metyrapone.
• Immediately inform your doctor if you experience bleeding or bruising that lasts longer than usual, bleeding from the gums, nose or skin, and feeling tired most of the time. This may indicate a decrease in the number of red blood cells and/or white blood cells and/or platelets in the blood.

See also section 2 “During treatment with Cormeto”.
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 (mild mental confusion)
• High blood pressure (hypertension)
• Nausea (feeling unwell)
• Abdominal pain (stomach ache)
• Diarrhoea
• Allergic skin reaction [hives, rash (reddening of the skin), itching]
• Joint pain
• Swelling of limbs, hands or feet
• Asthenic conditions (tiredness, fatigue)

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

• Low potassium levels (hypokalaemia)
• Feeling tired or drowsy
• Low blood pressure (hypotension)
• Vomiting
• Acne
• Excessive growth of hair in unusual areas (hirsutism)
• Muscle pain

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

• Abnormal liver function (increased liver enzymes)
• Leucopenia, anaemia, thrombocytopenia (decrease in the number of red blood cells, white blood cells or platelets in the blood)
• Alopecia (hair loss)
• Lung infection

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cormeto

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and carton after "Exp.". The expiry date refers to the last day of that month. Use the medicine within two months of opening.
Keep the bottle tightly closed to protect the medicine from moisture.
Store below 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cormeto contains
The active substance is metyrapone. Each capsule contains 250 mg of metyrapone.

• The other components 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 printing ink (red colour) on the capsules contains: carminic acid (E120), aluminium chloride hexahydrate, sodium hydroxide, hypromellose and propylene glycol.

Description of the appearance of Cormeto and package contents
Soft gelatin capsule, opaque, oblong in shape, white to slightly yellowish-white in colour, with the inscription “HRA” printed in red ink and a viscous to gelatinous content of slightly yellowish colour. Capsule dimensions: length 18.5 mm, diameter 7.5 mm.
Each plastic bottle contains 50 capsules.

Marketing Authorisation Holder Manufacturer
DELPHARM LILLE S.A.S
Esteve Pharmaceuticals S.A. Parc d’activités Roubaix-Est
Passeig de la Zona Franca 109 Planta 4 22 Rue de Toufflers CS 50070
08038 Barcelona LYS LEZ LANNOY 59452
Spain France
+34 93 446 60 00

This medicinal product 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