Macimorelin

Macimorelin stimulates GH release by activating growth hormone secretagogue receptors present in the pituitary and hypothalamus.

• MACRILEN is indicated for the diagnosis of adult growth hormone deficiency (AGHD). MACRILEN is a growth hormone (GH) secretagogue receptor agonist indicated for the diagnosis of adult growth hormone deficiency ( 1 ).

• None None ( 4 )contraindicated

• Recommended dose is 0.5 mg/kg as a single oral dose, after fasting for at least 8 hours ( 2.1 ). • See Full Prescribing Information for important preparation and administration instructions ( 2.3 ). • Discontinue therapy with strong CYP3A4 inducers, growth hormones and drugs that affect GH release for an adequate length of time before administering MACRILEN ( 2.2 ). • Adequately replace other hormone deficiencies before administering MACRILEN ( 2.2 ). 2.1 Recommended Dose The recommended dose is a single oral dose of 0.5 mg/kg of macimorelin. The dose is administered as a reconstituted solution [see Dosage and Administration ( 2.3 )] in patients fasted for at least 8 hours. 2.2 Important Recommendations Before MACRILEN Use • Discontinue strong CYP3A4 inducers prior to MACRILEN use [see Warning and Precautions ( 5.2 ) and Drug Interactions ( 7.2 )]. • Discontinue growth hormone (GH) therapy at least one week before administering MACRILEN [see Drug Interactions ( 7.3 )] . • Avoid the use of MACRILEN with drugs known to affect pituitary GH secretion [see Drug Interactions ( 7.3 )] . • For patients with deficiencies in sex hormones, thyroid hormone and/or glucocorticoid, adequately replace each of the missing hormones before administering MACRILEN. • Ensure that the patient has fasted for at least 8 hours before MACRILEN use. 2.3 Directions for Preparation and Administration Prepare and administer by a healthcare professional exactly as follows. Prepare the MACRILEN solution: a. Weigh the patient in kilograms (i.e., kg) . b.

• QT Prolongation: QT prolongation can lead to development of torsade de pointes-type ventricular tachycardia. Avoid the concomitant use of MACRILEN with drugs that are known to prolong QT interval ( 5.1 , 7.1 ). • Potential for False Positive Test Results with Use of Strong CYP3A4 Inducers: Discontinue and washout strong CYP3A4 inducers before testing ( 5.2 , 7.2 ). • Potential for False Negative Test Results in Recent Onset Hypothalamic Disease: Consider repeat testing if indicated ( 5.3 ). 5.1 QT Prolongation MACRILEN causes an increase of about 11 msec in the corrected QT (QTc) interval [see Clinical Pharmacology ( 12.2 )] . QT prolongation can lead to development of torsade de pointes-type ventricular tachycardia with the risk increasing as the degree of prolongation increases. The concomitant use of MACRILEN with drugs that are known to prolong the QT interval should be avoided [see Dosage and Administration ( 2.2 ) and Drug Interactions ( 7.1 )] . 5.2 Potential for False Positive Test Results with Use of Strong CYP3A4 Inducers Concomitant use of strong CYP3A4 inducers with MACRILEN can decrease macimorelin plasma levels significantly and thereby lead to a false positive result [see Drug Interactions ( 7.2 )] . Strong CYP3A4 inducers should be discontinued and enough time should be given to allow washout of CYP3A4 inducers prior to test administration [see Dosage and Administration ( 2.2 )].

The most common adverse reactions were dysgeusia, dizziness, headache, fatigue, nausea, hunger, diarrhea, upper respiratory tract infection, feeling hot, hyperhidrosis, nasopharyngitis, and sinus bradycardia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. The data in Table 1 are derived from an open-label, randomized, cross-over study that compared the diagnostic performance of MACRILEN to the insulin tolerance test (ITT) for the diagnosis of adult growth hormone deficiency [see Clinical Studies ( 14 )]. A total of 154 subjects with a high to low pre-test probability of having adult growth hormone deficiency received a single oral dose of 0.5 mg/kg MACRILEN. Out of 154 subjects, 58% were male, 42% female, and 86% of white origin. Median values were for age 41 years (range: 18 – 66 years) and body mass index was 27.5 kg/m 2 (range: 16 – 40 kg/m 2 ). Common adverse reactions presented in Table 1 were adverse reactions that were not present at baseline and occurred during MACRILEN dosing in at least two individuals.

8.1 Pregnancy Risk summary There are no available data with MACRILEN use in pregnant women to inform a drug associated risk for adverse developmental outcomes. Animal reproduction studies have not been conducted with MACRILEN. MACRILEN is indicated as a single dose which limits the risk of adverse developmental outcomes from exposure to MACRILEN. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. 8.2 Lactation Risk Summary There are no data on the presence of macimorelin in human or animal milk, the effects on the breastfed infant or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of MACRILEN to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for MACRILEN and any potential adverse effects on the breastfed infant from MACRILEN or the underlying maternal condition. 8.4 Pediatric Use The safety and efficacy of MACRILEN in pediatric patients have not been established.

Metabolism

The mean plasma macimorelin concentrations are similar between patients with AGHD and healthy subjects for 1.5 hours following administration of a single oral dose of 0.5 mg macimorelin/kg body weight. Absorption The maximum plasma macimorelin concentrations (C max ) were observed between 0.5 hour and 1.5 hours following oral administration of 0.5 mg macimorelin/kg body weight to patients with AGHD under fasting for at least 8 hours.

In the event of an overdose, symptomatic and supportive measures should be employed.

• Dec 20, 2017NDANDA205598Aeterna Zentaris

1. 1Bradycardia120%
2. 2Dizziness120%
3. 3Dysgeusia120%
4. 4Fatigue120%
5. 5Feeling Hot120%
6. 6Fluid Retention120%
7. 7Flushing120%
8. 8Nausea120%
9. 9Off Label Use120%
10. 10Product Communication Issue120%
11. 11Therapeutic Product Effect Variable120%
12. 12Wrong Technique In Product Usage Process120%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Macimorelin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Research Study of How Well Macimorelin Works to Find Out if Children Have a Lack of Growth Hormone and How Safe it is
  Completed · Phase 3 · Interventional · 101 enrolled · AEterna Zentaris
  NCT04786873updated 2024-08-12
• Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia
  Completed · Phase 2 · Interventional · 15 enrolled · Garcia, Jose M., MD, PhD
  NCT01614990updated 2024-03-20
• Copeptin After an Oral Stimulation With Macimorelin in Healthy Volunteers
  Completed · Interventional · 28 enrolled · University Hospital, Basel, Switzerland
  NCT03844217updated 2019-08-08
• Investigation of a New, Oral Growth Hormone Secretagogue, AEZS-130 as a Growth Hormone Stimulation Test.
  Completed · Phase 3 · Interventional · 101 enrolled · AEterna Zentaris
  NCT00448747updated 2019-07-23
• Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency
  Completed · Phase 3 · Interventional · 157 enrolled · AEterna Zentaris
  NCT02558829updated 2018-04-10
• Oral Ghrelin Agonist in Healthy Subjects
  Completed · Phase 1 · Interventional · 42 enrolled · University Hospital, Basel, Switzerland
  NCT00377377updated 2007-05-03

Frequently asked questions

How does Macimorelin work?

Macimorelin stimulates GH release by activating growth hormone secretagogue receptors present in the pituitary and hypothalamus.

What is Macimorelin used for?

According to FDA labeling, Macimorelin carries indications including: MACRILEN is indicated for the diagnosis of adult growth hormone deficiency (AGHD). MACRILEN is a growth hormone (GH) secretagogue receptor agonist indicated for the diagnosis of adult growth hormone deficiency ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Macimorelin?

Macimorelin is classified as Tests for pituitary function, Growth Hormone Secretagogue Receptor Agonist, Growth Hormone Secretagogue Receptor Agonists, Increased Growth Hormone Secretion.

What are the contraindications for Macimorelin?

Macimorelin labeling lists contraindications including: None None ( 4 ). Always consult the full prescribing information and a clinician.