METRODIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METRODIN (METRODIN).
Gonadotropin-releasing hormone (GnRH) agonist; initially stimulates pituitary gonadotropin release, then downregulates GnRH receptors, suppressing LH and FSH secretion.
| Metabolism | Metabolized via peptidases in the liver and kidneys; metabolites are inactive. |
| Excretion | Primarily renal, with approximately 75% of a dose excreted unchanged in urine within 24 hours; biliary/fecal excretion accounts for less than 5% of elimination. |
| Half-life | Terminal elimination half-life is approximately 35 hours (range 28–48 hours) in patients with normal renal function; prolonged in renal impairment, requiring dose adjustment. |
| Protein binding | Approximately 30% bound to plasma proteins, predominantly albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 0.2 L/kg, indicating limited extravascular distribution and confinement primarily to the extracellular fluid space. |
| Bioavailability | Subcutaneous administration: absolute bioavailability is approximately 75–80% due to partial presystemic degradation; intramuscular administration: bioavailability is similar, approximately 70–80%. |
| Onset of Action | Subcutaneous administration: serum follicle-stimulating hormone (FSH) levels peak within 8–12 hours; clinical effect (follicular growth) typically observed after 4–6 days of repeated dosing. |
| Duration of Action | After a single subcutaneous dose, elevated FSH levels persist for approximately 48–72 hours, supporting once-daily dosing. Duration of effect on follicular development lasts the duration of treatment course, typically 7–14 days. |
750 mg intramuscularly twice weekly for 2-3 weeks; or 500 mg intramuscularly once weekly for 4-6 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: reduce dose to 500 mg intramuscularly twice weekly; GFR <10 mL/min: 500 mg intramuscularly once weekly. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended in pediatric patients; limited safety data available. |
| Geriatric use | Use with caution; dose adjustment based on renal function recommended; monitor for neurotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METRODIN (METRODIN).
| Breastfeeding | No data on M/P ratio. Excretion into breast milk unknown. Due to potential for serious adverse reactions (CNS depression, respiratory depression) in breastfed infants, breastfeeding is contraindicated during therapy and for at least 7 days after last dose. |
| Teratogenic Risk | Pregnancy Category X. In first trimester, risk of major congenital malformations including neural tube defects, cardiovascular anomalies, and orofacial clefts. Second and third trimester exposure associated with fetal growth restriction, oligohydramnios, and neonatal hypotonia. Avoid throughout pregnancy. |
■ FDA Black Box Warning
Ovarian hyperstimulation syndrome (OHSS) and multiple births; increased risk of ovarian neoplasms.
| Serious Effects |
Hypersensitivity to GnRH or similar compounds, ovarian enlargement or cyst not due to polycystic ovary syndrome (PCOS), undiagnosed vaginal bleeding, primary ovarian failure, estrogen-dependent tumors (e.g., breast cancer), and pregnancy.
| Precautions | Ovarian hyperstimulation syndrome (OHSS), multiple gestation, ovarian torsion, pulmonary embolism, hypersensitivity reactions, and monitoring of ovarian response via ultrasound and estradiol levels. |
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| Fetal Monitoring | Frequent ultrasound for fetal growth, amniotic fluid index, and anatomy; fetal heart rate monitoring; maternal blood pressure and renal function; adjust dose based on response. |
| Fertility Effects | May impair fertility in females via hormonal disruption; males may experience reduced sperm count. Effects are typically reversible after discontinuation. |