Metopirone (Metyrapone)

• Metopirone acts on cortisol production pathways and is employed in specific endocrine conditions.
• Cushing's syndrome: reduces excess cortisol to control hypercortisolism.
• Diagnostic testing of adrenal insufficiency: facilitates assessment of adrenal reserve by inhibiting cortisol synthesis.
• Evaluation of ACTH‑dependent hypercortisolism: helps differentiate pituitary from ectopic sources during diagnostic work‑up.

• Metyrapone selectively inhibits the adrenal enzyme 11‑beta‑hydroxylase, which catalyzes the final step of cortisol biosynthesis. By blocking this conversion, the drug lowers cortisol output, resulting in decreased plasma cortisol concentrations and a feedback‑mediated increase in adrenocorticotropic hormone (ACTH) secretion, thereby modulating the hypothalamic‑pituitary‑adrenal axis.

Metyrapone may cause a range of adverse reactions, from mild to severe.

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Dizziness: transient light‑headedness, especially on standing.
• Headache: occasional tension‑type headache.
• Fatigue: generalized tiredness.
• Abdominal pain: mild discomfort in the upper abdomen.
• Hyperpigmentation: darkening of skin in some patients.

Serious or Rare Side Effects

• Adrenal crisis: acute insufficiency requiring emergency treatment.
• Severe hypotension: marked drop in blood pressure.
• Allergic reaction: rash, itching, or swelling.
• Hepatic dysfunction: elevated liver enzymes.
• Hyponatremia: low sodium levels.
• Hypoglycemia: low blood glucose, particularly in diabetics.

• Before initiating therapy, several safety considerations should be reviewed.
• Monitor cortisol levels: regular testing to avoid over‑suppression.
• Assess adrenal function: evaluate baseline ACTH and cortisol.
• Use with caution in hepatic impairment: adjust therapy as needed.
• Avoid in pregnancy unless benefits outweigh risks: limited safety data.
• Adjust dose in elderly patients: increased sensitivity to side effects.
• Store at room temperature: keep in the original pack, protect from moisture.

Metyrapone can alter the metabolism of several co‑administered drugs.

Major Interactions (Avoid)

• Ketoconazole: potent CYP3A4 inhibition may increase metyrapone exposure.
• Rifampin: strong enzyme induction reduces metyrapone effectiveness.
• Phenytoin: accelerates metabolism, decreasing therapeutic levels.

Moderate Interactions (Monitor Closely)

• Oral contraceptives: may reduce hormonal efficacy.
• Glucocorticoids: concurrent use can mask adrenal insufficiency.
• Antihypertensives: blood pressure may be affected by cortisol changes.