METOPIRONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METOPIRONE (METOPIRONE).
Competitive inhibitor of 11β-hydroxylase, blocking conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone.
| Metabolism | Hepatic via reduction and glucuronidation; major metabolites include metyrapol (active) and N-oxide derivatives. |
| Excretion | Renal (60-70% as unchanged drug and metabolites); biliary/fecal (10-15%) |
| Half-life | Terminal elimination half-life is approximately 2-3 hours in adults with normal renal function; prolonged in hepatic impairment (up to 6-8 hours). |
| Protein binding | ~90% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.5-0.8 L/kg, indicating distribution into total body water with some tissue binding. |
| Bioavailability | Oral: approximately 50-70% due to first-pass metabolism. |
| Onset of Action | Oral: 1-2 hours; Intravenous: 15-30 minutes (when used for diagnostic testing). |
| Duration of Action | Oral: 4-6 hours (based on ACTH suppression); Intravenous: 2-4 hours (dose-dependent). |
Adult: 750 mg orally every 4 hours for 6 doses. Alternatively, 30 mg/kg intravenously over 4 hours.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment guidelines available; use with caution in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment, reduce dose by 50% and monitor response. |
| Pediatric use | Children: 15 mg/kg orally every 4 hours for 6 doses (maximum 750 mg per dose). |
| Geriatric use | Start at lower end of dosing range due to potential for decreased hepatic function and increased sensitivity; monitor for hypotension and adrenal insufficiency. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METOPIRONE (METOPIRONE).
| Breastfeeding | No human data; M/P ratio unknown. Metopirone is excreted in rat milk. Not recommended during breastfeeding due to potential neonatal adrenal suppression. |
| Teratogenic Risk | First trimester: Animal studies show teratogenicity (cleft palate, skeletal anomalies). Human data limited; avoid if possible. Second/third trimester: May cause fetal adrenal suppression, transient neonatal adrenal insufficiency. Risk of maternal adrenal crisis if used. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to metyrapone","Adrenal insufficiency","Porphyria"]
| Precautions | ["Adrenal insufficiency and acute adrenal crisis","Hypotension","Hypokalemia","Neutropenia (rare)","Precipitation of acute porphyria"] |
Loading safety data…
| Monitor maternal serum cortisol, ACTH, blood pressure, electrolytes. Fetal monitoring: ultrasound for growth, amniotic fluid index. Neonatal assessment for adrenal insufficiency after delivery. |
| Fertility Effects | May impair fertility due to hormonal disruption (inhibits cortisol synthesis, alters ACTH and sex hormones). Reversible upon discontinuation. |