Metopirone

Generic name:

Metopirone (Metyrapone)

Drug class:

Adrenocortical steroid inhibitor; 11-beta-hydroxylase inhibitor

Dosage form:

• Tablets
• Oral capsules (varies by manufacturer)

Root of administration:

Oral

Dose:

• Typical diagnostic dose: 30 mg/kg as a single dose, often divided into three doses over 24 hours
• Therapeutic dosing varies; often 250 mg every 6 hours (1 gram/day) up to 6 grams/day in divided doses
• Dose adjustments based on clinical response and cortisol levels
• Varies by indication; consult label

Mechanism of action:

Metyrapone inhibits the enzyme 11-beta-hydroxylase in the adrenal cortex, blocking the final step in cortisol biosynthesis. This inhibition reduces cortisol production, leading to a compensatory increase in adrenocorticotropic hormone (ACTH) secretion.

Drug usage cases:

• Diagnosis of adrenal insufficiency by assessing hypothalamic-pituitary-adrenal (HPA) axis function
• Treatment of Cushing’s syndrome and Cushing’s disease to reduce excess cortisol production
• Preoperative preparation for adrenalectomy in Cushing’s syndrome
• Off-label use in ectopic ACTH syndrome management
• Occasionally used in congenital adrenal hyperplasia (CAH) resistant to other treatments

Drug contra indications:

• Hypersensitivity to metyrapone or any component of the formulation
• Acute adrenal insufficiency or Addisonian crisis without adequate glucocorticoid replacement
• Patients with severe hepatic impairment (caution advised)
• Pregnancy and breastfeeding unless benefits outweigh risks (consult label)

Side effects:

• Gastrointestinal disturbances: nausea, vomiting, abdominal pain
• Dizziness and headache
• Hypotension
• Hirsutism and acne due to increased androgen precursors
• Salt retention leading to edema and hypertension
• Allergic reactions: rash, pruritus
• Adrenal insufficiency symptoms: fatigue, weakness, hypotension
• Elevated liver enzymes (rare)
• Vertigo

Warnings:

• Monitor for signs of adrenal insufficiency, especially with rapid dose escalation or discontinuation
• Regular assessment of liver function tests advised during prolonged therapy
• May cause increased androgenic effects due to shunting of steroid precursors
• Use caution in patients with cardiovascular disease due to risk of hypotension and fluid retention
• Avoid abrupt withdrawal to prevent adrenal crisis
• May interfere with pituitary function testing; timing and interpretation require specialist input
• Careful dose titration necessary; monitor cortisol and ACTH levels

Use during pregnancy or breastfeeding:

Limited data are available regarding the use of metyrapone during pregnancy. Animal studies have shown some risk of adverse fetal effects, and metyrapone crosses the placenta. Use during pregnancy should be avoided unless the potential benefits justify the potential risks to the fetus. In cases where Cushing’s syndrome treatment is necessary, use under strict medical supervision is essential.

During breastfeeding, it is unknown whether metyrapone is excreted in human milk. Potential effects on the nursing infant are not well documented. Breastfeeding while using metyrapone is generally not recommended unless the benefits outweigh the risks. Consult healthcare provider before use.