Ghryvelin

Package leaflet: Information for the patient

GHRYVELIN 60 mg granules for oral suspension in sachet

macimorelin
Please read 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet

1. What GHRYVELIN is and what it is used for
2. What you need to know before taking GHRYVELIN
3. How GHRYVELIN is administered
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 stimulates the pituitary gland to release growth hormone (somatotropin) into the bloodstream.
GHRYVELIN is used in adults to test the body's ability to produce growth hormone. It is used when your doctor thinks you may not have enough growth hormone (adult growth hormone deficiency). This is not a treatment for patients who do not have enough growth hormone. It is a test that helps the doctor diagnose this condition.

2. What you need to know before receiving GHRYVELIN

Do not take GHRYVELIN

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

If you have any doubts, consult your doctor or nurse before taking GHRYVELIN.
Warnings and precautions
To ensure reliable test results, you must follow the rules below.

• Fasting: you must not eat for at least 8 hours before and during the test.
• Physical exercise: avoid intense physical activity 24 hours before the test.
• Drinking: up to 100 mL of plain water is allowed within 1 hour before and within 1 hour after taking macimorelin.

Consult your doctor or nurse if:

• you have recently been treated with growth hormone (somatropin) or medicines affecting pituitary growth hormone secretion. Such treatment must be discontinued at least 1 month before the test;
• you have recently been treated for Cushing's disease (a condition causing high levels of cortisol hormone) or are receiving a high dose of hydrocortisone-containing medicine: the test may lead to false-positive results;
• your body lacks any other hormone, e.g. cortisol, thyroid hormones, sex hormones, or vasopressin (in diabetes insipidus); such hormones must be adequately replaced before performing the growth hormone deficiency test. Untreated hormonal deficiencies may lead to inaccurate results in the growth hormone stimulation test;
• you have a heart condition or heart rhythm problems (including congenital or acquired long QT syndrome or a history of so-called torsades de pointes tachycardia). GHRYVELIN may cause ECG (electrocardiogram) changes, including QT interval prolongation, associated with an increased risk of arrhythmias. If they occur, such changes are time-limited and do not last long.

If any of the above situations apply to you, or if you are unsure, 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.
The test may need to be repeated in the early stages of the disease
If adult growth hormone deficiency is in its early phase and is caused by a lesion in a
brain region called the hypothalamus, the test result may be negative even if you have the
condition. In such a case, repeating the test may be necessary.
Children and adolescents
GHRYVELIN must not be used in children and adolescents under 18 years of age, as
its safety and efficacy in these groups have not yet been established.
Other medicines and GHRYVELIN
Inform your doctor if you are taking, have recently taken, or might take any other
medicine.
Inform your doctor if you are taking medicines that may alter heart rhythm, such as:

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

Inform your doctor if you are taking medicines that may increase the breakdown of
macimorelin, such as specific medicines for the treatment of:

• seizures/epilepsy (carbamazepine, eslicarbazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone)
• sleep disorders (modafinil, pitolisant)
• mild to moderate depressive episodes [St. John’s wort ( Hypericum perforatum )]
• cystic fibrosis (lumacaftor)
• infections (antibiotics such as rifabutin, rifampicin)
• HIV (efavirenz, nevirapine)
• type II diabetes (pioglitazone)
• cancer (dabrafenib, enzalutamide)

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

• that may directly influence pituitary growth hormone secretion: e.g. somatostatin, insulin, glucocorticoids, acetylsalicylic acid, indomethacin
• that may increase growth hormone levels: e.g. clonidine, levodopa, insulin
• that may reduce the growth hormone response to macimorelin: e.g. atropine, propylthiouracil, growth hormone-containing medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding,
please consult your doctor or nurse before receiving this medicine.
GHRYVELIN is not recommended during pregnancy. If you are a woman of childbearing potential, you must use effective contraceptive methods to ensure you are not pregnant at the time of testing.
If you are breastfeeding or intend to breastfeed, the risk to the infant cannot be excluded. Ask your
doctor whether to discontinue breastfeeding or to refrain from the macimorelin test.
Driving and using machines
Dizziness may occur with GHRYVELIN. If this occurs, do not drive or operate
machinery.
GHRYVELIN contains lactose
If you have been diagnosed by your doctor with an intolerance to certain sugars, contact him/her before taking
this medicine.
GHRYVELIN contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per sachet, i.e. is essentially
“sodium-free”.

3. How GHRYVELIN is administered

A healthcare professional must supervise the preparation and use of GHRYVELIN. Instructions
on how to prepare the test are provided at the end of this leaflet.
The description contained in this leaflet is intended to inform you about the test procedure.
You must fast for at least 8 hours before receiving GHRYVELIN. You must not perform intense physical
exercise within 24 hours before the test. You may drink up to 100 mL of plain water within 1 hour before and within
1 hour after taking GHRYVELIN.
Dose
The recommended dose is 0.5 mg of GHRYVELIN per kg of body weight.
This corresponds to a volume of 1 mL of the prepared suspension per kg of body weight.
You must drink the entire test dose within 30 seconds.
Three blood samples will be taken to measure growth hormone, one at a time, at 45, 60 and 90 minutes after
ingestion of the test dose.
If you take more GHRYVELIN than you should
If you take more GHRYVELIN than you should, inform your doctor or nurse. In cases of
overdose, possible adverse effects may include headache, nausea, vomiting, and diarrhea. If cardiac
rhythm disturbances occur, ECG monitoring will be performed.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common side effects (may affect up to 1 in 10 people):

• a bitter or metallic taste (dysgeusia)
• fatigue
• headache
• feeling unwell (nausea)
• dizziness
• diarrhoea
• sensation of warmth

These side effects are mostly mild, do not last long, and usually disappear quickly without treatment.
Uncommon side effects (may affect up to 1 in 100 people):

• abdominal pain
• feeling cold
• hunger
• palpitations
• heartbeat slower than normal (sinus bradycardia)
• drowsiness
• thirst
• tremor
• vertigo

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

• changes in the electrocardiogram (ECG)

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 national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How GHRYVELIN is stored

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and on the sachet after "Exp.". The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from light and moisture.
Store in a refrigerator (2 °C - 8 °C).

Intact sachet
The shelf life of a sachet is 5 years.

Reconstituted suspension
The suspension should be administered within 30 minutes after preparation.
Any remaining suspension must be disposed of by the doctor or nurse according to local regulations.

Do not dispose of any medicine via wastewater or household waste. This will help protect the environment.

6. Package contents and other information

What GHRYVELIN contains

• The active substance is macimorelin. Each sachet contains 60 mg of macimorelin (as acetate). 1 mL of reconstituted suspension contains 500 micrograms of macimorelin.
• The other components are: lactose monohydrate (see section 2, point “GHRYVELIN contains lactose”), anhydrous colloidal silica, crospovidone type A, sodium saccharin dihydrate and sodium stearil fumarate (see section 2, point “GHRYVELIN contains sodium”).

Description of the appearance of GHRYVELIN and contents of the pack
GHRYVELIN is an oral suspension granulate, white to off-white. Each sachet contains 1,817 mg of granulate. 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
Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu

The following information is intended exclusively for healthcare professionals:

INSTRUCTIONS FOR PREPARATION AND USE
The suspension must be prepared and administered by a healthcare professional.
Required materials: GHRYVELIN sachet, tap water in a jug, transparent plastic or glass container with graduated scale, stirrer, 50 mL graduated syringe without needle, glass

Step 1
Weigh the patient.

Step 2
Determine the number of GHRYVELIN sachets required based on body weight: one sachet is required for a patient weighing up to 120 kg; two sachets are required for a patient weighing more than 120 kg.

Step 3
Add the required volume of water to a transparent plastic or glass container with a graduated scale. Dissolve the entire contents of the sachet(s) in water: one sachet in 120 mL, two sachets in 240 mL, as appropriate.
Gently mix the suspension for 2 minutes (a small amount of undissolved particles may remain, resulting in a slightly turbid suspension). The suspension should be mixed until it becomes slightly turbid with no particles remaining at the bottom of the container. The suspension should be mixed again if particles settle at the bottom, for example after being left to stand for some time.

Step 4
Determine the volume of suspension required for the recommended dose of macimorelin of 0.5 mg/kg. The volume of suspension in mL is equal to the patient's body weight in kg. For example, a 70 kg patient will require 70 mL of macimorelin suspension.
Measure the required volume using a 50 mL graduated syringe without needle.
Transfer the measured amount into a glass.

Step 5
Have the patient drink the entire contents of the glass within 30 seconds.
The suspension must be used within 30 minutes of preparation. Any remaining suspension must not be stored but should be discarded.
Any unused medicine and waste material derived from this medicine must be disposed of 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.