Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 10/12/2022

Drug Summary

What Is Metopirone?

Metopirone (metyrapone) is a diagnostic drug for testing hypothalamic-pituitary ACTH function.

What Are Side Effects of Metopirone?

Metopirone may cause serious side effects including:

  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • rash,
  • itching, and
  • severe dizziness

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Metopirone include:

  • nausea,
  • vomiting,
  • stomach upset or pain,
  • headache,
  • dizziness,
  • drowsiness, or
  • tiredness

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Metopirone

Metopirone is usually administered as a single-dose test. Adults and children are given the same 30 mg/kg dose (maximum 3 g Metopirone) at midnight with yogurt or milk. A blood sample is taken early the following morning.

What Drugs, Substances, or Supplements Interact with Metopirone?

Metopirone may interact with acetaminophen, cyproheptadine, estrogens, and hydantoins (such as phenytoin). Do not drive, use machinery, or do any activity that requires alertness or clear vision while taking Metopirone. Avoid alcoholic beverages.

Metopirone During Pregnancy and Breastfeeding

Metopirone should be used during pregnancy only if clearly needed. It is not known if Metopirone passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Metopirone Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Drug Description


Metopirone, metyrapone USP, is an inhibitor of endogenous adrenal corticosteroid synthesis, available as 250-mg capsules for oral administration. Its chemical name is 2-methyl-l, 2-di-3-pyridyl-l-propanone, and its structural formula is

   (metyrapone) Structural Formula Illustration

Metyrapone USP is a white to light amber, fine, crystalline powder, having a characteristic odor. It is sparingly soluble in water, and soluble in methanol and in chloroform. It forms water-soluble salts with acids. Its molecular weight is 226.28.

Inactive Ingredients. Polyethylene glycol, glycerine, gelatin, sodium ethyl hydroxybenzoate, sodium propyl hydroxybenzoate, ethyl vanillin, 4-methoxyacetophenone, titanium dioxide, brown ink.

Indications & Dosage


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


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].

Assess ability of patient’s adrenals to respond to exogenous ACTH before Metopirone is employed as a test [see WARNINGS AND PRECAUTIONS].

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).

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 11­desoxycortisol. Normal values will depend on the method used to determine ACTH and 11-desoxycortisol levels. An intact HPA axis function is generally indicated by an increase in 11-desoxycortisol to over 70 mcg/L. Because of an overlap between a normal ACTH response and an abnormal ACTH response, the ACTH response alone cannot be used to distinguish between healthy individuals and those with adrenal insufficiency.


Dosage Forms And Strengths

Capsules: Metopirone 250 mg soft gelatin, white to yellowish-white, oblong, opaque, imprinted with “HRA” on one side in red ink.

Metopirone (metyrapone capsules) are supplied as 250 mg soft gelatin, white to yellowish-white, oblong, opaque capsules, imprinted with “HRA” on one side in red ink.

Bottle of 18 capsules: NDC 76336-455-18

Storage And Handling

Store Metopirone bottles at room temperature 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Keep container tightly closed and protect from heat and moisture.

Manufactured by: Catalent Germany Eberbach GmbH Eberbach, Germany. For: HRA Pharma Rare Diseases CHATILLON, France. Revised: Sep 2022

Side Effects & Drug Interactions


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.


Effect Of Other Drugs On Metopirone

Anticonvulsants, psychotropic drugs, hormone preparations, corticosteroids, antithyroid agents and cyproheptadine may affect the results of the Metopirone test.

If these drugs cannot be withdrawn, the necessity of carrying out the Metopirone test should be reviewed.

Effect Of Metopirone On Other Drugs


Metopirone inhibits the glucuronidation of acetaminophen, which may decrease elimination of acetaminophen and lead to increased risk of adverse reactions related to acetaminophen.

Avoid concomitant use of Metopirone with acetaminophen.

Warnings & Precautions


Included as part of the PRECAUTIONS section.


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.

Dizziness And Sedation

Metopirone may cause dizziness and sedation. Patients should not drive or operate machinery until these effects have passed.

Patient Counseling Information

Advise patient to read the FDA-approved labeling (PATIENT INFORMATION).

Advise patient that Metopirone may induce acute adrenal insufficiency (nausea, vomiting, abdominal pain, hypotension) [see WARNINGS AND PRECAUTION].

Advise patient that Metopirone may cause dizziness and sedation. Advise patients not to drive or operate machinery until these effects have passed [see WARNINGS AND PRECAUTION].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility


Long-term animal carcinogenicity studies have not been conducted with Metopirone.


Metyrapone was not mutagenic with or without metabolic activation in bacterial mutagenicity tests.

Impairment Of Fertility

No studies have been conducted to assess the effect of Metopirone on fertility.

Use In Specific Populations


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.


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.


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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Metopirone and any potential adverse effects on the breastfed infant from Metopirone or from the underlying maternal condition.

Pediatric Use

Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in pediatric patients [See DOSAGE AND ADMINISTRATION].

Geriatric Use

Clinical studies of Metopirone did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

Other reported clinical experience has not identified differences in responses between patients 65 years of age and older and younger adult patients.

Hepatic Impairment

Patients with cirrhosis may have an impaired response to Metopirone.

Overdose & Contraindications


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.

For a few days blood pressure and fluid and electrolyte balance should be monitored.

Consult with a regional poison control center (1-800-222-1222) for additional treatment recommendations.


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

Clinical Pharmacology


Mechanism Of Action

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. With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine. These metabolites are readily determined by measuring urinary 17-hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS). Because of these actions, Metopirone is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness. Metopirone may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.


Metopirone exposure-response relationships and the time course of pharmacodynamic response are unknown.


The mean Cmax of metyrapone following a single 750 mg is 3.7 mcg/mL falling to 0.5 mcg/mL 4 hours after administration.


The time to peak plasma concentration of metyrapone is approximately 1 hour after oral administration.


The mean (± SD) terminal elimination half-lives of metyrapone and its active metabolite metyrapol are 1.9 (± 0.7) hours and approximately 4 hours, respectively.


Metyrapone is reduced to metyrapol, an active alcohol metabolite. Both metyrapone and metyrapol are conjugated with glucuronide.

Eight hours after a single oral dose, the ratio of metyrapone to its active metabolite metyrapol in plasma is 1:1.5.


Following administration of metyrapone 750 mg every 4 hours, approximately 5.3% of the dose was excreted in urine as unchanged and 38.5% as its active metabolite metyrapol within 72 hours after the first dose.

Medication Guide


No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

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