Adult: Initially, 250-1,500 mg daily depending on the severity and cause of the disorder. Adjust the daily dose after a few days with the goal of reducing the mean plasma/serum cortisol levels and/or the 24-hour urinary free-cortisol levels to normal target value or until Max tolerated metyrapone dose is reached. Usual maintenance dose: 500-6,000 mg daily in 3 or 4 divided doses.
Oral Resistant oedema
Adult: In combination with glucocorticoids for the treatment of cases due to elevated aldosterone secretion in patients with cirrhosis, nephrosis, and CHF: Usual dose: 3,000 mg daily in divided doses.
Oral Diagnostic agent
Adult: Short single-dose test: For diagnosis of ACTH insufficiency: 30 mg/kg (Max: 3,000 mg) at midnight. Multiple-dose test: For diagnosis of ACTH insufficiency and differential diagnosis of ACTH-dependent Cushing's syndrome: 750 mg 4 hourly for 6 doses. Dosage recommendations may vary among countries and between individual products. Refer to local or specific product guidelines for further information or interpretation of the test. Child: Short single-dose test: For diagnosis of ACTH insufficiency: Same as adult dose. Multiple-dose test: For diagnosis of ACTH insufficiency and differential diagnosis of ACTH-dependent Cushing's syndrome: 15 mg/kg (minimum single dose of 250 mg) 4 hourly for 6 doses. Dosage recommendations may vary among countries and between individual products. Refer to local or specific product guidelines for further information or interpretation of the test.
Administration
Metyrapone Should be taken with food.
Contraindications
Adrenocortical insufficiency.
Special Precautions
Patient with gross hypopituitarism, reduced adrenal secretory activity, thyroid dysfunction, liver cirrhosis, preexisting cardiac disease and electrolyte disturbances. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Hypercortisolism or suppression of HPA axis that may lead to adrenal crisis; hypertension (long-term use), hypokalaemia. Gastrointestinal disorders: Nausea, abdominal pain, vomiting, diarrhoea. General disorders and administration site conditions: Asthenic conditions, peripheral oedema. Immune system disorders: Hypersensitivity reactions (e.g. rash, pruritus, urticaria). Metabolism and nutrition disorders: Decreased appetite. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia. Nervous system disorders: Headache, dizziness, sedation. Skin and subcutaneous tissue disorders: Hirsutism, acne. Vascular disorders: Hypotension.
This drug may cause dizziness and sedation, if affected, do not drive or operate machinery.
Monitoring Parameters
When used as a diagnostic agent: Obtain 11-deoxycortisol concentrations; a value of <70 mcg/L is diagnostic for adrenal insufficiency. When used for Cushing's syndrome: Monitor cortisol levels (either serum cortisol or 24-hour urinary free cortisol at baseline, day 3, then weekly for dosage adjustment, and periodically thereafter); potassium levels (before treatment initiation and periodically thereafter); blood pressure. Assess for signs or symptoms of acute adrenal insufficiency (e.g. severe weakness, fatigue, fever, anorexia, hypotension, CNS changes) and oedema.
Management: Symptomatic and supportive treatment. Administer activated charcoal if ingestion is within 1 hour. Large dose of hydrocortisone must be given at once, together with IV saline and glucose; repeat as necessary according to patient's clinical condition. Monitor blood pressure, fluid and electrolyte balance for a few days.
Drug Interactions
May increase the serum levels of paracetamol. Concomitant use with anticonvulsants (e.g. phenytoin, barbiturates), neuroleptics (e.g. chlorpromazine), antidepressants (e.g. amitriptyline), corticosteroids, antithyroid agents, cyproheptadine, and hormones that affect the hypothalamic-pituitary axis (e.g. estrogens, progestogens) may interfere with the results of metyrapone test.
Lab Interference
May give falsely elevated cortisol readings in immunoassays of cortisol due to cross-reaction.
Action
Description: Overview: Metyrapone, a synthetic pyrimidine base, is an adrenal steroid synthesis inhibitor. Mechanism of Action: Metyrapone is a competitive inhibitor of 11β-hydroxylase, the enzyme responsible for the synthesis of cortisol, corticosterone, and aldosterone. In the adrenal cortex, metyrapone inhibits the 11β-hydroxylation reaction of 11-desoxycortisol (compound S), 11-desoxycorticosterone (DOC), and aldosterone precursors, thereby preventing the conversion of compound S to hydrocortisone (cortisol), DOC to corticosterone, and aldosterone precursors into aldosterone. Pharmacodynamics: Inhibition of cortisol synthesis leads to the removal of its strong inhibitory feedback mechanism, resulting in increased ACTH production by the pituitary gland. Continued blockade of the enzymatic processes involved in cortisol and corticosterone synthesis results in a marked increase in adrenocortical secretion of their immediate precursors (11-desoxycortisol and 11-desoxycorticosterone), which weakly suppress ACTH release, with a corresponding increase in plasma levels of these steroids and their metabolites in the urine. Additionally, metyrapone may cause mild natriuresis due to inhibition of aldosterone synthesis. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1 hour. Distribution: Crosses the placenta and enters breast milk. Metabolism: Metabolised via rapid reduction into metyrapol (main active metabolite); both metyrapone and metyrapol undergo glucuronide conjugation. Excretion: Via urine (approx 38% as metyrapol [mainly as glucuronide conjugate], approx 5% as unchanged drug [mainly as glucuronide conjugate]). Elimination half-life: 1.9 ± 0.7 hours (metyrapone); approx. 4 hours (metyrapol).
Chemical Structure
Metyrapone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4174, Metyrapone. https://pubchem.ncbi.nlm.nih.gov/compound/Metyrapone. Accessed Jan. 28, 2026.
Storage
Store between 15-30°C. Protect from moisture and heat.
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