Metopirone (Metyrapone)

Metopirone acts on adrenal steroidogenesis and is used in conditions related to excess cortisol or adrenal function assessment.

• Cushing's syndrome: reduces cortisol production to help control hypercortisolism.
• Diagnostic testing for adrenal insufficiency: blocks cortisol synthesis to evaluate adrenal reserve during stimulation tests.
• Preoperative adrenal function assessment: used to evaluate cortisol reserve before adrenal surgery.

• Metyrapone selectively inhibits the mitochondrial enzyme 11‑beta‑hydroxylase (CYP11B1) in the adrenal cortex. This enzyme catalyzes the conversion of 11‑deoxycortisol to cortisol, the final step in glucocorticoid synthesis. By blocking this step, metyrapone decreases cortisol output while allowing accumulation of precursor steroids, which can be measured to assess adrenal responsiveness. The resulting rise in 11‑deoxycortisol also provides a biochemical marker of enzyme inhibition, and the shift in steroid profile can influence mineralocorticoid activity.

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

Common Side Effects

• Nausea: mild to moderate stomach upset.
• Headache: transient cranial discomfort.
• Dizziness: light‑headed sensation, especially upon standing.
• Fatigue: general tiredness or weakness.

Serious or Rare Side Effects

• Adrenal insufficiency: severe cortisol deficiency leading to hypotension and shock.
• Hypertension: elevated blood pressure due to mineralocorticoid excess.
• Allergic reaction: rash, itching, swelling, or anaphylaxis.

When prescribing metyrapone, clinicians should observe several precautionary measures to ensure patient safety.

• Monitor cortisol levels: check serum cortisol before and during therapy.
• Assess blood pressure: watch for hypertension or hypotension.
• Evaluate electrolytes: especially potassium and sodium balance.
• Use cautiously in hepatic impairment: liver function may affect metabolism.
• Avoid in known hypersensitivity: discontinue if allergic signs appear.
• Store at ambient temperature: keep in original packaging, protect from moisture.

Metyrapone can interact with other medicines, altering its effectiveness or increasing adverse effects.

Major Interactions (Avoid)

• Ketoconazole: strong CYP3A4 inhibition may increase metyrapone levels.
• Rifampicin: enzyme induction can markedly reduce metyrapone efficacy.
• Exogenous glucocorticoids: may counteract the cortisol‑lowering effect.

Moderate Interactions (Monitor Closely)

• Antihypertensives: blood pressure changes may require dose adjustment.
• Diuretics: electrolyte disturbances can be amplified.
• Oral contraceptives: steroid metabolism may be affected, monitor hormonal balance.