Version July 2025
ACTH function, diagnostic test:
Single dose/overnight test:
Note: Due to possible precipitation of acute adrenal insufficiency (adrenal crisis), experts suggest that metyrapone should be used with extreme caution in an outpatient setting; consider administration in an inpatient environment (Ref).
Children and Adolescents: Oral: 30 mg/kg as a single dose given at midnight the night before the test; perform test 7.5 to 8 hours after administration; maximum dose: 3,000 mg/dose.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Metyrapone: Drug information")
Diagnostic aid, adrenal insufficiency: Oral: 30 mg/kg (maximum: 3 g) at midnight.
Cushing syndrome (off-label use): Note: Dosages based on retrospective/observational data and clinical experience. Metyrapone may be administered as monotherapy or occasionally in combination with other agents (eg, ketoconazole and/or mitotane); refer to protocols for details.
Initial: Oral: 500 mg/day to 1 g/day in 2 to 4 divided doses; higher initial doses (eg, 1.5 g/day) may be considered in patients with ectopic ACTH syndrome or adrenocortical carcinoma (Ref).
Dosage adjustment: Oral: Adjust daily dose in increments of 250 to 500 mg based on cortisol response (Ref). Usual dosage range: 500 mg/day to 4.5 g/day (Ref); maximum: 6 g/day (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer's labeling. Diagnostic response to metyrapone may be impaired in patients with cirrhosis.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions may be derived for off-label long-term use for Cushing syndrome.
Postmarketing:
Cardiovascular: Edema (including peripheral edema) (Ceccato 2018; Nieman 2015; Verhelst 1991), hypertension (Nieman 2015; Verhelst 1991), hypotension
Dermatologic: Allergic skin rash (including allergic dermatitis) (Ceccato 2018), alopecia (Ceccato 2018; Harries-Jones 1990), exacerbation of acne (Jeffcoate 1977; Nieman 2015)
Endocrine: Adrenocortical insufficiency (Daniel 2015), hirsutism (Nieman 2015; Verhelst 1991), hypokalemia (Nieman 2015; Verhelst 1991)
Gastrointestinal: Abdominal distress, abdominal pain (including upper abdominal pain) (Ceccato 2018; Mancini 2010), decreased appetite (Ceccato 2018), gastric distress (Daniel 2015), nausea (Ceccato 2018), vomiting
Hematologic & oncologic: Anemia, leukopenia, thrombocytopenia
Nervous system: Asthenia (Ceccato 2018), dizziness (Ceccato 2018), headache, sedated state
Neuromuscular & skeletal: Myalgia (Ceccato 2018; Daniel 2015)
Hypersensitivity to metyrapone or any component of the formulation; patients with adrenal cortical insufficiency.
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, which may lead to adrenal crisis. Adrenal response to exogenous ACTH should be demonstrated prior to metyrapone administration. For patients at high risk for adrenal insufficiency, consider administering a prophylactic dose of glucocorticoid after test completion.
• CNS depression and dizziness: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns:
• Hepatic impairment: Diagnostic response to metyrapone may be impaired in patients with cirrhosis.
• Reduced adrenal secretory capacity: Acute adrenal insufficiency may be induced in patients with reduced adrenal secretory capacity.
• Thyroid disease: Response to test may be subnormal in patients with hypo- or hyperthyroidism.
Other warnings and precautions:
• Appropriate use: Discontinue use of drugs affecting pituitary or adrenocortical function prior to administration; consider ≥5 half-lives to avoid interference. Prior to testing, assess the ability of the patient's adrenal glands to respond to exogenous ACTH.
Administration of metyrapone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity; for patients at high risk for adrenal insufficiency, consider administering a prophylactic dose of glucocorticoid after test completion. Use with extreme caution in an outpatient setting; consider administration in an inpatient environment. Patients should be observed closely during administration and the following day; should only be administered under the supervision of a qualified physician experienced in the use of metyrapone (Uçar 2016; manufacturer's labeling).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Metopirone: 250 mg
No
Capsules (Metopirone Oral)
250 mg (per each): $70.27
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Metopirone is available from HRA Pharma via special allocation only. Contact the manufacturer for additional information at 1-800-320-2112 (for outpatient prescriptions), 1-844-597-6373 (for hospital and institutional orders), or https://metopirone.com/.
Oral: Note: Due to possible precipitation of acute adrenal insufficiency (adrenal crisis) in some patients, experts suggest that metyrapone should be used with extreme caution in an outpatient setting; consider administration in an inpatient environment (Ref).
Single dose/overnight test: Administer dose at midnight with yogurt or milk. Blood samples should be collected the following morning (7:30 to 8:00 am). For patients at high risk for adrenal insufficiency, consider administering a prophylactic dose of glucocorticoid after test samples are obtained.
Oral:
Diagnostic aid, adrenal insufficiency: Administer dose at midnight with milk/yogurt or snack. Blood samples are taken early the following morning (7:30 am to 8:00 am). May administer a prophylactic dose of glucocorticoid after samples are obtained to reduce the risk of acute adrenal insufficiency.
Cushing syndrome: Administer with food or milk to minimize GI disturbance (Ref).
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F); protect from heat. Protect from moisture.
Diagnostic agent for testing hypothalamic-pituitary ACTH function (FDA approved in pediatric patients [age not specified] and adults)
MetyraPONE may be confused with metyroSINE
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acetaminophen: MetyraPONE may increase serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk X: Avoid
Antiseizure Agents: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
Antithyroid Agents: Coadministration of Antithyroid Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antithyroid agents. Risk D: Consider Therapy Modification
Corticosteroids (Systemic): Coadministration of Corticosteroids (Systemic) and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking systemic corticosteroids. Risk D: Consider Therapy Modification
Cyproheptadine: Coadministration of Cyproheptadine and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking cyproheptadine. Risk D: Consider Therapy Modification
Estrogen Derivatives: Coadministration of Estrogen Derivatives and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking estrogen derivatives. Risk D: Consider Therapy Modification
Progestins: Coadministration of Progestins and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider Therapy Modification
Propacetamol: MetyraPONE may increase active metabolite exposure of Propacetamol. Specifically, metyrapone may increase acetaminophen exposure. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism toward the oxidative route that produces a hepatotoxic metabolite. Risk X: Avoid
Take with milk/yogurt or snack.
Metyrapone crosses the placenta (Azzola 2020).
When used as a diagnostic test during the second and third trimesters of pregnancy, the fetal pituitary responded to the enzymatic block. A subnormal response to testing may occur in pregnant patients.
Untreated Cushing syndrome during pregnancy may cause adverse events in the mother and fetus (Bronstein 2015; Brue 2018; Kamoun 2014). Information related to metyrapone for the treatment of Cushing disease (off-label use) during pregnancy is limited. Medication may be considered for patients when surgery is not an option or for symptomatic control at initial diagnosis (ES [Nieman 2015]; ESE [Luger 2021]. When medical therapy is needed, treatment is generally started in the second or third trimesters (Bronstein 2015).
Single-dose test: ACTH, cortisol and 11-deoxycortisol concentrations measured at 8 am (Uçar 2016); 11-deoxycortisol concentrations diagnostic for adrenal insufficiency:
Infants, Children, and Adolescents: <210 nmol/L (Uçar 2016).
Response to exogenous ACTH stimulation test (prior to administration); sedation; dizziness; hypotension; bone marrow suppression (leukopenia, anemia, and/or thrombocytopenia); signs of allergic reaction (rash).
Metyrapone inhibits 11 beta-hydroxylase, preventing the conversion of 11-deoxycortisol to cortisol; blockade can be measured by the urinary increase of the metabolites of cortisol precursors in the urine (17-hydroxycorticosteroids [17-OHCS] and 17-ketogenic steroids [17-KGS]).
Metabolism: Reduced to metyrapol (active metabolite); parent drug and metabolite also undergo glucuronide conjugation.
Half-life elimination: Metyrapone: 1.9 ± 0.7 hours; Metyrapol (active metabolite): ~4 hours.
Time to peak: ~1 hour.
Excretion: Urine; ~5% as metyrapone (primarily as glucuronide conjugate) and ~38% as metyrapol (primarily as glucuronide conjugate).
