MACRILEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MACRILEN (MACRILEN).
MACRILEN (macimorelin) is a synthetic growth hormone secretagogue receptor (GHS-R) agonist that stimulates growth hormone (GH) release from the anterior pituitary. It mimics the action of ghrelin, enhancing GH secretion through GHS-R activation.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C19. Also undergoes amide hydrolysis. |
| Excretion | Primarily renal; approximately 90% of the administered dose is excreted unchanged in urine within 24 hours. Less than 5% is metabolized, with metabolites also eliminated renally. Fecal excretion is negligible (<2%). |
| Half-life | Terminal elimination half-life is approximately 3 hours (range 2.5–4.5 hours) in healthy adults. This short half-life supports its use for diagnostic testing, with rapid clearance after stimulation of growth hormone release. |
| Protein binding | Approximately 40% bound to serum proteins, primarily albumin. Binding is moderate and non-saturable at therapeutic concentrations. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.4 L/kg (range 0.3–0.5 L/kg), indicating distribution primarily into extracellular fluid and limited tissue penetration. This is consistent with its hydrophilic nature. |
| Bioavailability | Subcutaneous injection: absolute bioavailability is approximately 90% (range 80–100%) due to complete absorption after SC administration. No oral formulation exists; oral bioavailability is negligible due to first-pass metabolism. |
| Onset of Action | Subcutaneous injection: peak serum concentrations are achieved within 30–60 minutes, with clinical effect (stimulation of growth hormone release) observed within 15–30 minutes. |
| Duration of Action | Duration of growth hormone elevation is approximately 2–4 hours after subcutaneous administration, sufficient for diagnostic sampling (typically 60–120 minutes post-dose). Effects subside as the drug is cleared. |
1 mg subcutaneously once daily, titrated as needed to a maximum of 2 mg daily.
| Dosage form | FOR SOLUTION |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Not recommended in ESRD (GFR <15 mL/min) or on dialysis. |
| Liver impairment | No specific guidelines. Use with caution in severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No dose adjustment required, but monitor for adverse effects due to potential age-related sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MACRILEN (MACRILEN).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not established. Because many drugs are excreted in human milk, caution is advised. Consider developmental benefits of breastfeeding vs. potential exposure risk. |
| Teratogenic Risk | Pregnancy Category C. No adequate controlled studies in pregnant women. In animal studies, macimorelin did not cause malformations at doses up to 10 mg/kg/day (human equivalent dose 0.5 mg/kg/day) but embryofetal toxicity (reduced fetal weight, increased postimplantation loss) was observed at maternally toxic doses. Risk cannot be ruled out. Use only if potential benefit justifies risk. |
■ FDA Black Box Warning
N/A
| Common Effects | Constipation Nausea Vomiting Dizziness Insomnia difficulty in sleeping Allergic reaction |
| Serious Effects |
["Known hypersensitivity to macimorelin or any component of the formulation.","Use of medications that strongly prolong the QT interval (e.g., class IA and III antiarrhythmics, certain antipsychotics, macrolide antibiotics).","Severe hepatic impairment (Child-Pugh class C)."]
| Precautions | ["Hypersensitivity reactions including angioedema, urticaria, and rash.","Potential for QT interval prolongation; avoid use in patients with known QTc prolongation or those taking QTc-prolonging drugs.","Interference with growth hormone stimulation tests: false-negative results may occur if patients have taken glucocorticoids, somatostatin analogs, or other drugs affecting GH release.","Not recommended for patients with severe hepatic impairment."] |
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| Fetal Monitoring | Monitor maternal response via growth hormone stimulation test results. Assess for maternal adverse events (e.g., QT prolongation via ECG, changes in blood glucose, injection site reactions). In fetus, monitor growth parameters if drug used during pregnancy. |
| Fertility Effects | Reproductive studies in rats showed no adverse effects on male or female fertility at doses up to 100 mg/kg/day (human equivalent dose 8.1 mg/kg/day). No human data available. |