GHRYVELIN Granules for oral suspension Ref.[28093] Active ingredients: Macimorelin

The use of GHRYVELIN must be supervised by a physician or healthcare professional experienced in diagnosing growth hormone deficiency.

Posology

Adult population

The dose is calculated based on the patient’s body weight. The recommended single dose of the reconstituted suspension is 500 micrograms macimorelin per kg body weight. The growth hormone release is to be evaluated with three blood samples collected at 45, 60 and 90 minutes after the administration of the medicinal product.

Discontinuation of therapy with growth hormone (GH) or medicinal products directly affecting the pituitary secretion of somatotropin

Patients on replacement therapy with growth hormone (GH, somatotropin) or on medicinal products directly affecting the pituitary secretion of somatotropin (e.g. somatostatin analogues, clonidine, levopoda and dopamine agonists) should be advised to discontinue such treatment at least 1 month before receiving macimorelin. These substances could lead to unreliable GH stimulation results (see also section 4.4 and 4.5).

Renal and/or hepatic impairment

The safety and efficacy of macimorelin in patients with renal and/or hepatic impairment have not been established (see also section 5.2). No data are available. If macimorelin is administered to patients with renal and/or hepatic impairment, the potential for an increased macimorelin plasma concentration cannot be excluded. It is unknown whether this may affect QTc. Therefore, ECG controls may be indicated prior to the administration of macimorelin and 1 hour, 2 hours, 4 hours and 6 hours after administration of macimorelin (see also section 4.4). Based on current understanding, this potential is unlikely to decrease the specificity of the test.

Elderly

Growth hormone secretion normally decreases with age. The efficacy of macimorelin in patients aged over 65 years has not been established. In patients with age up to 60 years, diagnostic performance of MAC and ITT were comparable. In the age group 60 years up to 65 years, the limited data available do not indicate the need for a separate cut-off point.

Paediatric population

The safety and efficacy of macimorelin in children and adolescents below 18 years have not yet been established (see also section 5.2). No data are available.

Method of administration

Oral use.

GHRYVELIN granules are to be reconstituted with water and must be used within 30 minutes after preparation. Reconstituted suspension should be administered orally to patients fasting for at least 8 hours and who did not have strenuous physical exercises 24 hours before the test, since both could affect growth hormone levels.

The number of test sachets needed is based on body weight. One sachet will be required for a patient ≤120 kg, two sachets will be required if the patient weighs more than 120 kg. The entire contents of one sachet is dissolved in 120 mL, and two sachets are dissolved in 240 mL, as applicable.

The volume of suspension in mL needed for the recommended macimorelin dose of 0.5 mg/kg equals the patient’s body weight in kg. For example, a 70 kg patient will require 70 mL of the macimorelin suspension.

Assessment of fasted condition and lack of prior strenuous physical exercise

Before using GHRYVELIN it is important to ensure that the patient is in fasting condition for at least 8 hours and did not have strenuous physical exercises 24 hours before the test, since both could affect GH levels. If either of these conditions is not met, the growth hormone stimulation test must be re-scheduled for a new test day.

During the test, the patient needs to stay fasted until the end of the blood sampling. Fluid intake of no more than 100 mL of non-carbonated water is allowed each within 1 hour pre-dose, as well as within 1 hour post-dose (see section 4.4).

Long-term use

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

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

No specific recommendations after overdose are given. In the event of an overdose, symptomatic and supportive measures should be employed. Further possible undesirable effects in case of overdosing could include headache, nausea, vomiting and diarrhoea. In patients with a QTc >500 ms, an ECG monitoring should be applied (see section 4.4 and 5.1).

Unopened sachet:

The shelf life of a sachet is 4 years.

Reconstituted suspension:

The suspension must be administered within 30 minutes after preparation.

Residual suspension must be discarded according to local regulations.

Store in the original package, in order to protect from light and moisture.

Store in a refrigerator (2°C-8°C).

For storage conditions after reconstitution of the medicinal product, see section 6.3.

One LDPE/Alu/LDPE/paper sachet containing 1,817 mg granules placed in cardboard box.

Each cardboard box contains 1 sachet.

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

Items needed: GHRYVELIN sachet, tap water in decanter, graduated glass or transparent plastic container, stirring device, 50 mL graduated syringe without needle, drinking glass

Step 1:

Weigh the patient.

Step 2:

Determine the number of test sachets needed based on body weight: one sachet will be required for a patient weighing up to 120 kg, two sachets will be required if the patient weighs more than 120 kg.

Step 3:

Add required volume of water in a graduated glass or transparent plastic container. Dissolve the entire contents of the sachet in water: one sachet in 120 mL, two sachets in 240 mL, as applicable.

Stir the suspension gently for 2 minutes (a small amount of undissolved particles will remain giving a slightly turbid suspension). The suspension should be stirred until it is slightly turbid without particles at the bottom of the container. The suspension should be stirred again, when some particles settle at the bottom of the container for example after the suspension is left standing for some time.

Step 4:

Determine the volume of suspension needed for the recommended macimorelin dose of 0.5 mg/kg. The suspension volume in mL equals the patient’s body weight in kg. For example, a 70 kg patient will require 70 mL of the macimorelin suspension.

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

Transfer the measured amount to a drinking glass.

Step 5:

Have the patient drink the entire content of the drinking glass within 30 seconds.

The suspension must be used within 30 minutes after preparation. Any suspension that remains must not be stored and must be discarded.

Any unused medicinal product or waste material should be disposed in accordance with local requirements.

Step 6:

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

Step 7:

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