Ghryvelin 60 mg granules for oral suspension in sachet

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

GHRYVELIN 60 mg granules for oral suspension in sachet

macimorelin

Read the entire leaflet carefully before taking this medicine, because 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 should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What GHRYVELIN is and what it is used for

The medicine contains an active substance called macimorelin. Macimorelin acts like a natural hormone and causes the pituitary gland to release growth hormone into the bloodstream.

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

2. What you need to know before using GHRYVELIN

Do not receive GHRYVELIN

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

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

Warnings and precautions

To ensure reliable test results, you must follow these guidelines:

• Fasting: You must not eat for at least 8 hours before the test and during the test.
• Physical exercise: Avoid strenuous physical activity for 24 hours before the test.
• Drinking: You may drink up to 100 ml of still (non-carbonated) water during the hour before and the hour after taking macimorelin.

Consult your doctor or nurse if:

• you have recently received treatment with growth hormone (somatotropin) or medications affecting growth hormone secretion from the pituitary gland. You will need to stop such treatment at least 1 month before undergoing the test.
• you have recently received treatment for Cushing's disease (a disorder causing high cortisol levels) or are currently receiving high-dose hydrocortisone, as the test may produce false positive results.
• your body is deficient in other hormones such as cortisol, thyroid hormones, sex hormones, or vasopressin (in case of diabetes insipidus), as these must be adequately replaced before assessing growth hormone deficiency.
• you have heart disease or have heart rhythm problems (such as congenital or acquired long QT syndrome or a history of a type of tachycardia called torsades de pointes). GHRYVELIN may cause changes in the ECG (electrocardiogram), such as QT interval prolongation, which are associated with an increased risk of arrhythmias. If such changes occur, they will be limited and brief in duration.

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

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

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

If adult growth hormone deficiency has recently developed and is due to a lesion in a part of the brain called the hypothalamus, the test result may be negative even if you actually have the condition. In such cases, it may be necessary to repeat the test.

Children and adolescents

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

Other medicines and GHRYVELIN

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

Tell your doctor if you are taking medicines that may affect heart rhythm, such as:

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

Tell your doctor if you are taking medicines that may increase the breakdown of macimorelin, such as medicines used to treat specifically:

• seizures/epilepsy (carbamazepine, eslicarbazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone)
• sleep disorders (modafinil, pitolisant)
• mild to moderate depression (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)

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

• that may directly influence pituitary growth hormone secretion, such as somatostatin, insulin, glucocorticoids, acetylsalicylic acid, or indomethacin
• that may increase growth hormone levels, such as clonidine, levodopa, or insulin
• that may reduce the growth hormone response to macimorelin, such as atropine, propylthiouracil, or growth hormone

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or nurse before receiving this medicine.

GHRYVELIN is not recommended during pregnancy. If you are a woman of childbearing potential, you should use effective contraceptive methods to ensure you are not pregnant when undergoing the test. If you are breastfeeding or planning to breastfeed, a risk to the infant cannot be excluded. Ask your doctor whether you should interrupt breastfeeding or refrain from undergoing the macimorelin test.

Driving and use of machines

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

GHRYVELIN contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

GHRYVELIN contains sodium

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

3. How to use GHRYVELIN

The preparation and use of GHRYVELIN must be supervised by a healthcare professional. Instructions on how to prepare the medicine for the test are provided at the end of this leaflet.

The description in this leaflet 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 exercise during the 24 hours before the test. You may drink up to 100 ml of still water 1 hour before and 1 hour after taking GHRYVELIN.

Dosage

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 within 30 seconds.

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

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 changes in heart rhythm, an ECG will be performed.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Frequent adverse effects (may affect up to 1 in 10 people):

• bitter or metallic taste (dysgeusia)
• tiredness
• headache
• nausea
• dizziness
• diarrhoea
• sensation of heat

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

Uncommon adverse effects (may affect up to 1 in 100 people):

• abdominal pain
• feeling cold
• hunger
• palpitations
• slower than normal heart rate (sinus bradycardia)
• somnolence
• thirst
• tremor
• vertigo

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

• changes in electrocardiogram (ECG)

Reporting of 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 leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of GHRYVELIN

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 cardboard box and on the sachet after EXP. The expiry date refers to the last day of the month indicated.

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

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

Unopened sachet

The shelf life of a sachet is 4 years.

Reconstituted suspension

The suspension must be taken within 30 minutes of preparation.

Any remaining suspension must be discarded by the doctor or nurse according to local regulations.

Medicines should not be disposed of via wastewater or household waste. This helps protect the environment.

6. Contents of the container and other information

Composition of GHRYVELIN

• The active substance is macimorelin. Each sachet 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), anhydrous colloidal silica, crospovidone type A, sodium saccharin dihydrate, and sodium stearyl fumarate (see "GHRYVELIN contains sodium" in section 2).

Presentation of the product and contents of the pack

GHRYVELIN is presented as a white or almost white granular powder for oral suspension. Each sachet contains 1.817 mg of granules. Each cardboard box contains 1 sachet.

Marketing Authorization Holder

Atnahs Pharma Netherlands B.V.

Copenhagen Towers

Ørestads Boulevard 108, 5.tv

DK-2300 København S

Denmark

Manufacturer

Aeterna Zentaris GmbH

Weismüllerstrasse 50

D-60314 Frankfurt am Main

Germany

Date of the most recent revision of this summary:

Other sources of information

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

The following information is intended for healthcare professionals only:

INSTRUCTIONS FOR PREPARATION AND USE

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

Required materials: GHRYVELIN sachet, tap water in a decanter, transparent glass or plastic graduated container, stirrer, 50 ml graduated syringe without needle, drinking glass.

Step 1

Weigh the patient.

Step 2

Determine the number of GHRYVELIN sachets required based on body weight: one sachet is required if the patient weighs up to 120 kg, or two sachets if the patient weighs more than 120 kg.

Step 3

Add the required volume of water to a graduated glass or transparent plastic container. Dissolve the entire contents of the sachet(s) in water: one sachet in 120 ml or two sachets in 240 ml, as appropriate.

Gently stir the suspension for 2 minutes (a small amount of particles may remain undissolved, resulting in a slightly cloudy suspension). The suspension should be stirred until it is slightly cloudy and no particles are visible at the bottom of the container. The suspension should be stirred again if particles settle at the bottom, for example after standing upright for some time.

Step 4

Determine the volume of suspension required to administer the recommended dose of macimorelin of 0.5 mg/kg. The volume of the suspension in milliliters corresponds to the patient's body weight in kilograms. For example, a patient weighing 70 kg will require 70 ml of macimorelin suspension.

Measure the required volume using a 50 ml graduated syringe without needle.

Transfer the measured amount to a drinking glass.

Step 5

Instruct the patient to drink the entire contents of the glass within 30 seconds.

The suspension must be used within 30 minutes of preparation. Any unused suspension must not be stored and should be discarded.

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.

Step 6

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

Step 7

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