Metyrapone

The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary.

• Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients. Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients.

• Metopirone is contraindicated in patients with adrenal cortical insufficiency or hypersensitivity to Metopirone or to any of its excipients.contraindicated

Single-Dose Short Test: 30 mg/kg at midnight ( 2.2 ) 2.1 Important Information Before Conducting Metopirone Testing Stop drugs affecting pituitary or adrenocortical function before administration of Metopirone in accordance with half-life of the drugs (consider at least 5 half-lives to avoid any interference with Metopirone testing). [see Drug Interactions (7.1) ] . Assess ability of patient's adrenals to respond to exogenous ACTH before Metopirone is employed as a test [see Warnings and Precautions (5.1) ] . 2.2 Single-Dose Short Test- Recommended Dose and Interpretation This test, usually given on an outpatient basis, determines plasma 11-desoxycortisol and/or ACTH levels after a single dose of Metopirone. Patients with suspected adrenocortical insufficiency based on the test results previously performed should be hospitalized overnight as a precautionary measure ( see Warnings and Precaution (5.1) ). Recommended Dose In adult and pediatric patients, the recommended single dose is 30 mg/kg (maximum 3 grams of Metopirone) administered at midnight with milk/yogurt or snack. The blood sample for the assay is taken early the following morning (7:30-8:00 a.m.). After the blood sample is collected, a prophylactic dose of glucocorticoid may be considered for patients with high risk for acute adrenal insufficiency. Interpretation of 11‑desoxycortisol and ACTH Levels After Metopirone Administration Approximately 8 hours after administration of Metopirone, evaluate the values of ACTH and 11-desoxycortisol.

Adrenal Insufficiency: May induce acute adrenal insufficiency. Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test ( 5.1 ) Dizziness and Sedation: May cause dizziness and sedation. Patients should not drive or operate machinery until these effects have passed ( 5.2 ) 5.1 Adrenal Insufficiency Metopirone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity, as well as in patients with global pituitary insufficiency. The test should be performed in the hospital with close monitoring in case of suspected adrenal insufficiency. Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test. In the presence of hypo‑ or hyperthyroidism, response to the Metopirone test may be subnormal. If adrenocortical or anterior pituitary function is more severely compromised than indicated by the results of the test, Metopirone may trigger adrenal insufficiency. This can be corrected by giving appropriate doses of corticosteroids. 5.2 Dizziness and Sedation Metopirone may cause dizziness and sedation. Patients should not drive or operate machinery until these effects have passed.

The following adverse reactions associated with the use of Metopirone were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular System: Hypotension Gastrointestinal System: Nausea, vomiting, abdominal discomfort or pain Central Nervous System: Headache, dizziness, sedation Dermatologic System: Allergic rash Hematologic System: Leukopenia, anemia, and/or thrombocytopenia Adverse reactions include: hypotension, nausea, vomiting, abdominal discomfort or pain, headache, dizziness, sedation, allergic rash, leukopenia, anemia, and/or thrombocytopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Inc. at 844-597-6373 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary Available data from published case series and reports on Metopirone use in pregnant females are insufficient to identify a drug-associated risk of major birth defects or miscarriage. Metyrapone crosses the placenta and may decrease fetal cortisol production (see Data ) . Animal reproductive studies have not been conducted with metyrapone. Metyrapone can decrease reproductive hormones by targeting adrenal androgenesis. Data Human Data The Metopirone test was administered to pregnant women in their second and third trimester of pregnancy and evidence was found that the fetal pituitary responded to the enzymatic block. Transplacental transfer of Metopirone has been shown in humans and the drug can impair the biosynthesis of fetal and placental steroids. There are a few published reports of low cortisol levels at birth in infants exposed in utero following chronic use of metyrapone in pregnant females. 8.2 Lactation Risk Summary Metyrapone and its active metabolite, metyrapol, are present in human milk. There are no available data on the effects of metyrapone on the breastfed infant or the effects on milk production.

Metabolism

The mean C max of metyrapone following a single 750 mg is 3.7 mcg/mL falling to 0.5 mcg/mL 4 hours after administration. Absorption The time to peak plasma concentration of metyrapone is approximately 1 hour after oral administration.

Death occurred in a child after two doses of Metopirone 2 g. Signs and Symptoms of Overdosage The clinical picture of overdosage with Metopirone is characterized by gastrointestinal symptoms and by signs of acute adrenal insufficiency. Cardiovascular System : Cardiac arrhythmias, hypotension, dehydration. Nervous System and Muscles : Anxiety, confusion, weakness, impairment of consciousness. Gastrointestinal System: Nausea, vomiting, epigastric pain, diarrhea. Laboratory Findings: Hyponatremia, hypochloremia, hyperkalemia. In patients under treatment with insulin or oral antidiabetics, the signs and symptoms of acute overdosage with Metopirone may be aggravated or modified. Treatment and Management of Overdosage There is no specific antidote for Metopirone overdosage. Immediate treatment is essential in the management of Metopirone overdose. Treatment with activated charcoal may be considered if the overdose has been taken within 1 hour. In addition to general measures, hydrocortisone should be administered at once, together with IV saline and glucose. This should be repeated as necessary in accordance with the patient's clinical condition.

• Dec 4, 1961NDANDA012911Esteve

1. 1Off Label Use36338%
2. 2Nausea808.4%
3. 3Drug Ineffective656.8%
4. 4Vomiting525.4%
5. 5Fatigue495.1%
6. 6Adrenal Insufficiency404.2%
7. 7Asthenia404.2%
8. 8Dizziness404.2%
9. 9Maternal Exposure During Pregnancy353.7%
10. 10Pneumocystis Jirovecii Pneumonia343.6%
11. 11Diarrhoea323.3%
12. 12Anaemia272.8%
13. 13Death272.8%
14. 14Hypokalaemia272.8%
15. 15Premature Baby272.8%

Recent PubMed references pinned to Metyrapone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Efficacy and Tolerability of Metyrapone in Mild Autonomous Cortisol Secretion: Real-World Findings From Clinical Practice.
  Clinical endocrinology · 2026 · Berry S, Iqbal A, Newell-Price J, et al.
  PMID 41198609DOI 10.1111/cen.70056
• Effects of metyrapone in patients with mild hypercortisolism.
  European journal of endocrinology · 2025 · Musolino A, Favero V, Parazzoli C, et al.
  PMID 41102583DOI 10.1093/ejendo/lvaf216
• Prospective study of metyrapone in endogenous Cushing's syndrome (PROMPT).
  European journal of endocrinology · 2025 · Nieman LK, Boscaro M, Scaroni C, et al.
  PMID 40966724DOI 10.1093/ejendo/lvaf181
• Blood steroid hormone profile and clinical outcomes following switching from metyrapone to osilodrostat in patients with Cushing disease.
  Endocrine journal · 2025 · Yokozeki K, Kameda H, Miya A, et al.
  PMID 40887254DOI 10.1507/endocrj.EJ25-0089
• Adverse Event Profile Differences Between Metyrapone and Osilodrostat: A Pharmacovigilance Study of the FDA Adverse Event Reporting System.
  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2025 · Xia C, Hu L, Fan Y, et al.
  PMID 40825365DOI 10.1055/a-2685-7512
• Matching-Adjusted Indirect Comparison of Osilodrostat Versus Metyrapone for the Treatment of Cushing's Syndrome.
  Advances in therapy · 2025 · Hickey C, Gueron B, Schmidt F, et al.
  PMID 40439958DOI 10.1007/s12325-025-03229-0
• Differences in baseline and dynamic plasma/saliva endocrine and linear/non-linear heart measures between patients with major depression and closely-matched healthy subjects: A 3-day combined overnight dexamethasone/metyrapone challenge study.
  Journal of psychiatric research · 2025 · Agorastos A, Stiedl O, Heinig A, et al.
  PMID 40378692DOI 10.1016/j.jpsychires.2025.05.020
• Advances in pharmacological treatment of Cushing's disease.
  Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024 · Chai J, Tang Y, Liu Y, et al.
  PMID 39788490DOI 10.11817/j.issn.1672-7347.2024.240306

The 10 most recently updated of 27 ClinicalTrials.gov registrations naming Metyrapone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake
  Completed · Interventional · 23 enrolled · Eleonora Seelig
  NCT06556277updated 2026-05-22
• Sleep Loss and Circadian Misalignment - Mechanisms of Insulin Resistance
  Not yet recruiting · Phase 4 · Interventional · 48 enrolled · Washington State University
  NCT07494084updated 2026-05-15
• Effects of Metyrapone in Patients With Hypercortisolism
  Completed · Observational · 20 enrolled · Istituto Auxologico Italiano
  NCT05255900updated 2026-03-30
• Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS)
  Recruiting · Phase 4 · Interventional · 150 enrolled · Laikο General Hospital, Athens
  NCT07268222updated 2025-12-05
• Metyrapone for Mild Autonomous Cortisol Secretion (MACS)
  Active not recruiting · Phase 2 · Interventional · 30 enrolled · Mayo Clinic
  NCT06106295updated 2025-09-22
• Metyrapone Study for Patients Diagnosed With Mild Autonomous Cortisol Secretion - MACS
  Not yet recruiting · Phase 2 · Interventional · 90 enrolled · Mayo Clinic
  NCT07138274updated 2025-08-22
• Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.
  Recruiting · Phase 2 · Interventional · 24 enrolled · Maria Sklodowska-Curie National Research Institute of Oncology
  NCT05563467updated 2025-04-02
• Effect of Metyrapone on Cardiovascular Risk Factors in Patients With Adrenal Incidentalomas and Cushing's Syndrome
  Recruiting · Phase 4 · Interventional · 50 enrolled · IRCCS Azienda Ospedaliero-Universitaria di Bologna
  NCT06801249updated 2025-01-30
• The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation (Gluco-Starve)
  Completed · Early phase 1 · Interventional · 24 enrolled · Eleonora Seelig
  NCT05919992updated 2024-08-14
• Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals
  Completed · Early phase 1 · Interventional · 20 enrolled · Eleonora Seelig
  NCT05167084updated 2023-08-23

Frequently asked questions

How does Metyrapone work?

The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary.

What is Metyrapone used for?

According to FDA labeling, Metyrapone carries indications including: Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients. Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Metyrapone?

Metyrapone is classified as Tests for pituitary function, Adrenal Steroid Synthesis Inhibitor, Adrenal Steroid Synthesis Inhibitors, Adrenal Cortical Activity Alteration.

What are the brand names for Metyrapone?

Metyrapone is marketed under brand names including Metopirone.

What are the contraindications for Metyrapone?

Metyrapone labeling lists contraindications including: Metopirone is contraindicated in patients with adrenal cortical insufficiency or hypersensitivity to Metopirone or to any of its excipients.. Always consult the full prescribing information and a clinician.