METRODIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for METRODIN (METRODIN).
Comprehensive clinical and safety monograph for METRODIN (METRODIN).
Treatment of infertility: controlled ovarian hyperstimulation in assisted reproductive technology (ART)Ovulation induction in anovulatory women
Nausea, Headache, Dryness in mouth, Metallic taste
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. |
| Molecular Weight | 34000 |
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 | Urofollitropin is contraindicated in pregnancy. If administered inadvertently during early pregnancy, there is potential for fetal harm based on animal studies and mechanism of action. Use only if clearly needed for ovulation induction, not for sustaining pregnancy. |
| 2nd trimester | Contraindicated: placental transfer likely, but data lacking. Should not be used during second trimester for any indication. |
| 3rd trimester | Contraindicated: no approved use in third trimester; theoretical risk of ovarian hyperstimulation or hormonal effects. |
Clinical note
Comprehensive clinical and safety monograph for METRODIN (METRODIN).
| Placental transfer | Urofollitropin is a large glycoprotein (MW ~34,000 Da) and placental transfer is expected to be minimal; however, due to its hormonal activity, potential fetal exposure cannot be ruled out. Animal studies have shown fetotoxicity. |
| Breastfeeding | Urofollitropin is not indicated during breastfeeding. It may suppress lactation or be excreted in milk. Due to lack of human data and potential for serious adverse effects in the infant, breastfeeding is not recommended during treatment. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
■ FDA Black Box Warning
Ovarian hyperstimulation syndrome (OHSS) and multiple births; increased risk of ovarian neoplasms.
| Serious Effects |
PregnancyHigh levels of FSH indicating primary ovarian failureUncontrolled thyroid or adrenal dysfunctionOrganic intracranial lesion (e.g., pituitary tumor)Abnormal uterine bleeding of undetermined originOvarian cyst or enlargement not due to polycystic ovary syndromeHypersensitivity to urofollitropin or any excipientsSex hormone-dependent tumors (e.g., ovarian, breast, uterine)
| Precautions | Ovarian hyperstimulation syndrome (OHSS), multiple gestation, ovarian torsion, pulmonary embolism, hypersensitivity reactions, and monitoring of ovarian response via ultrasound and estradiol levels. |
| Food/Dietary | Avoid all alcoholic beverages and any foods or medications containing alcohol (e.g., vinegar sauces, kombucha, some desserts) during therapy and for 48 hours post-treatment to prevent disulfiram-like reaction. No other significant food interactions. |
| Clinical Pearls | METRODIN (metronidazole) is a nitroimidazole antibiotic effective against anaerobic bacteria and protozoa. It achieves high concentrations in CNS and bone. Use with caution in patients with Cockayne syndrome due to risk of severe hepatotoxicity. Monitor INR closely in patients on warfarin as metronidazole potentiates anticoagulant effect. Dose adjustment required in severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take exactly as prescribed; do not miss doses. Complete the full course even if you feel better. · Avoid alcohol and any products containing alcohol (e.g., mouthwash, cough syrup) during treatment and for at least 48 hours after last dose to prevent disulfiram-like reaction (nausea, vomiting, headache). · May cause metallic taste, dark urine, or gastrointestinal upset; these are usually harmless. · Inform your doctor if you have a history of liver disease, Cockayne syndrome, or are taking blood thinners (warfarin). · If you experience numbness/tingling in hands/feet, seizures, or confusion, seek medical attention immediately. |
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