Ghryvelin 60 mg granulado para suspensiÓn oral en sobre

Product Information for the PatientInformation for the Patient

GHRYVELIN 60 mg Oral Suspension Granules in a Blister

macimorelina

Read this entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

The medication contains an active ingredient called macimorelina. Macimorelina acts as a natural hormone and causes the pituitary gland to release growth hormone into the bloodstream.

GHRYVELIN is used in adults to evaluate the body's ability to produce growth hormone. It is used when your doctor believes you may not be producing enough growth hormone (adult growth hormone deficiency). It is not a treatment for patients who do not have enough growth hormone, but rather a test that helps the doctor diagnose this condition.

Do not receive GHRYVELIN

• if you are allergic to macimorelin or any of the other components of this medication(listed in section 6).

If you are unsure, consult your doctor or nurse before receiving GHRYVELIN.

Warnings and precautions

To ensure that test results are reliable, you must follow the following guidelines:

• Fast: you will not be able to eat for at least 8 hours before the test or during its performance.
• Physical exercise: avoid intense physical activities 24 hours before the test.
• Drink: you are allowed to drink up to 100 ml of non-carbonated water in the hour before and in the hour after taking macimorelin.

Consult your doctor or nurse if:

• you have recently received treatment with growth hormone (somatotropin) or with medications that affect the secretion of growth hormone by the pituitary gland. You will need to suspend this treatment at least 1 month before the test.
• you have recently received treatment for Cushing's disease (a disorder that produces elevated cortisol levels) or are receiving a high dose of hydrocortisone, as the test may produce false positive results.
• your body is deficient in other hormones, such as cortisol, thyroid hormones, or sex hormones, vasopressin (in the case of diabetes insipidus), as they should be adequately replaced before analyzing the growth hormone deficiency.
• if you have a heart disease or have heart rhythm problems (such as congenital or acquired long QT syndrome or a history of the arrhythmias called torsades de pointes). GHRYVELIN may cause changes in the ECG (electrocardiogram), such as prolongation of the QT interval, which are associated with an increased risk of arrhythmias. In case of occurrence, such changes will have a limited and brief duration.

If any of the above situations apply to you or you have any doubts, consult your doctor or nurse before receiving this medication.

GHRYVELIN is indicated as a diagnostic test in a single dose. There is no information available on the safety and effects of macimorelin during long-term use.

Possible need to repeat the test in initial stages of the disease

If the adult growth hormone deficiency has just started and is due to a lesion in a part of the brain called the hypothalamus, the test result may be negative although you actually have the disease. In this situation, it may be necessary to repeat the test.

Children and adolescents

GHRYVELIN should not be used in children and adolescents under 18 years of age, as its safety and efficacy have not yet been established in these groups.

Other medications and GHRYVELIN

Inform your doctor if you are taking, have recently taken, or may need to take any other medication.

Inform your doctor if you are taking medications that may affect heart rhythm, such as:

• medications to treat psychosis (such as chlorpromazine or haloperidol)
• medications to treat infections (antibiotics such as erythromycin, clarithromycin, or moxifloxacin)
• medications to correct heart rhythm (antiarrhythmics such as amiodarone, procainamide, quinidine, or sotalol)
• any other medication that may prolong the QT interval or induce torsades de pointes

Inform your doctor if you are taking medications that may increase the degradation of macimorelin, such as medications specifically to treat:

• seizures/epilepsy (carbamazepine, eslicarbazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone)
• sleep disorders (modafinil, pitolisant)
• mild or moderate depression (hypericum or St. John's Wort [Hypericum perforatum])
• cystic fibrosis (lumacaftor)
• infections (antibiotics such as rifabutin or rifampicin)
• HIV infection (efavirenz, nevirapine)
• type 2 diabetes (pioglitazone)
• cancer (dabrafenib, enzalutamide)

Inform your doctor if you are taking medications that may affect the accuracy of the diagnostic test. Avoid concomitant use of medications:

• that may have a direct influence on the secretion of growth hormone by the pituitary gland, such as somatostatin, insulin, glucocorticoids, aspirin, or indomethacin
• that may increase growth hormone levels, such as clonidine, levodopa, or insulin
• that may reduce the response of growth hormone to macimorelin, such as atropine, propylthiouracil, or growth hormone

Pregnancy and lactation

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

GHRYVELIN is not recommended during pregnancy. If you are a woman and are of childbearing age, you should use effective contraceptive methods to ensure that you are not pregnant when you undergo the test. If you are breastfeeding or intend to do so, it cannot be ruled out that there may be a risk to the infant. Ask your doctor if you should stop breastfeeding or refrain from undergoing the macimorelin test.

Driving and operating machinery

GHRYVELIN may cause dizziness. If this happens, do not drive or operate machinery.

GHRYVELIN contains lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

GHRYVELIN contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially«sodium-free».

The preparation and use of GHRYVELIN must be supervised by a healthcare professional. At the end of this prospectus, instructions are provided on how to prepare the medication for the test.

The description of this prospectus is for your information about the test procedure.

You must remain fasting for at least 8 hours before receiving GHRYVELIN. You must not perform intense physical exercises for 24 hours before the test. You may drink up to 100 ml of non-carbonated water 1 hour before and 1 hour after taking GHRYVELIN.

Dose

The recommended dose is 0.5 mg of GHRYVELIN per kilogram of body weight.

This corresponds to a volume of 1 ml of the prepared suspension per kilogram of body weight.

You must drink the complete dose for the test in 30 seconds.

Three blood samples will be taken to determine the growth hormone at 45, 60, and 90 minutes after taking the dose for the test.

If you receive more GHRYVELIN than you should

If you receive more GHRYVELIN than you should, inform your doctor or nurse. Possible adverse effects in case of overdose may include headache, nausea, vomiting, and diarrhea. If you experience any alterations in heart rhythm, an ECG will be performed.

If you have any other questions about the use of this medication, ask your doctor or nurse.

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

Frequent Adverse Effects(may affect up to 1 in 10 people):

• bitter or metallic taste (dysgeusia)
• fatigue
• headache
• nausea
• dizziness
• diarrhea
• sensation of heat

These adverse effects are mostly mild, do not last long, and usually disappear quickly without treatment.

Rare Adverse Effects(may affect up to 1 in 100 people):

• abdominal pain
• sensation of cold
• hunger
• palpitations
• slower than normal heart rate (sinus bradycardia)
• drowsiness
• thirst
• tremor
• dizziness

Unknown Frequency(cannot be estimated from available data):

• changes in electrocardiogram (ECG)

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.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.

Do not use this medication after the expiration date that appears on the carton box and on the blister pack after CAD. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light and moisture.

Store in the refrigerator (between 2 °C and 8 °C).

Unopened blister pack

The validity period of a blister pack is 4 years.

Reconstituted suspension

The suspension should be taken within 30 minutes of its preparation.

The doctor or nurse will dispose of any remaining suspension according to local regulations.

Medicines should not be disposed of through drains or in the trash. This will help protect the environment.

Composition of GHRYVELIN

• The active ingredient is macimorelin. Each pack contains 60 mg of macimorelin (as acetate). 1 ml of the reconstituted suspension contains 500 micrograms of macimorelin.
• The other components are: lactose monohydrate (see "GHRYVELIN contains lactose" in section 2), colloidal anhydrous silica, crospovidone type A, sodium saccharin dihydrate and stearate and sodium fumarate (see "GHRYVELIN contains sodium" in section 2).

Appearance of the product and contents of the package

GHRYVELIN is presented in the form of white or off-white granules for oral suspension. Each pack contains 1.817 mg of granules. Each carton contains 1 pack.

Marketing authorization holder

Atnahs Pharma Netherlands B.V.

Copenhagen Towers

Ørestads Boulevard 108, 5th floor

DK-2300 København S

Denmark

Responsible for manufacturing

Aeterna Zentaris GmbH

Weismüllerstrasse 50

D-60314 Frankfurt am Main

Germany

Last revision date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the European Medicines Agency website:http://www.ema.europa.eu

The following information is intended only for healthcare professionals:

PREPARATION AND ADMINISTRATION INSTRUCTIONS

The suspension must be prepared and administered by a healthcare professional.

Required items: GHRYVELIN pack, tap water in a decanter, graduated glass or plastic container, agitator, 50 ml graduated syringe without needle, drinking cup

Step 1

Weigh the patient.

Step 2

Determine the number of GHRYVELIN packs needed based on the patient's weight: one pack is needed if the patient weighs up to 120 kg, or two packs if the patient weighs more than 120 kg.

Step 3

Add the necessary volume of water to a graduated glass or plastic container. Dissolve the entire contents of the pack in water: one pack in 120 ml or two packs in 240 ml, as applicable.

Agitate the suspension gently for 2 minutes (it will remain undissolved a small amount of particles, obtaining a slightly turbid suspension). The suspension must be agitated until it is slightly turbid and no particles are observed at the bottom of the container. The suspension must be agitated again if some particles settle at the bottom of the container, as after leaving the suspension vertical for a time.

Step 4

Determine the volume of suspension needed to administer the recommended dose of macimorelin 0.5 mg/kg. The volume of the suspension in milliliters is equal to the patient's weight in kilograms. For example, a 70 kg patient will need 70 ml of macimorelin suspension.

Measure the necessary volume with a 50 ml graduated syringe without needle.

Transfer the measured amount to a drinking cup.

Step 5

Instruct the patient to drink the entire contents of the cup in 30 seconds.

The suspension must be used within 30 minutes of preparation. The remaining suspension must not be stored and must be discarded.

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Step 6

Extract venous blood samples for determination of growth hormone at 45, 60, and 90 minutes after administration.

Step 7

Prepare the plasma or serum samples and send them to a laboratory for determination of growth hormone.