Metyrapone
2-methyl-1,2-di(pyridin-3-yl)propan-1-one
Also known as: Metopirone · SU-4885 · metirapona · metyraponum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Hyperadrenocorticism | 65 mg/kg PO every 8 to 12 hours | PO | q8-12h | — | 🌎 NA |
- Hyperadrenocorticism: Alternatively, dosages ranging from 195-250 mg/cat/day (divided) have been used without observed toxicity (Bruyette 2010).
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Metyrapone is an adrenal steroid synthesis inhibitor primarily utilized in veterinary medicine for the management of feline hyperadrenocorticism (Cushing's syndrome).
- Clinical Utility: It is most frequently used as a short-term medical stabilization therapy prior to surgical intervention (adrenalectomy).
- Concurrent Diabetes: Feline hyperadrenocorticism is rare and often presents with concurrent, insulin-resistant diabetes mellitus. By resolving the hypercortisolism, metyrapone reduces insulin antagonism, which can significantly decrease or even eliminate the need for exogenous insulin therapy.
- Species Specificity: While clinical experience is limited, it appears well-tolerated in cats. It may also have potential utility in ferrets and small mammals (e.g., hamsters), though pharmacokinetic and safety data in these species are lacking.
- Human Use: In human medicine, it is used diagnostically to evaluate hypothalamic-pituitary-adrenal (HPA) axis function and off-label for Cushing's syndrome.
Mechanism of action
Metyrapone exerts its effects by directly interfering with the steroidogenic pathway within the adrenal cortex:
- Enzyme Inhibition: It reversibly inhibits the enzyme 11-β-hydroxylase (CYP11B1).
- Pathway Blockade: 11-deoxycortisol → [Blocked by Metyrapone] → Cortisol. This prevents the final hydroxylation step, leading to a rapid reduction in circulating cortisol and corticosterone levels.
- Feedback Loop: The sudden drop in cortisol removes negative feedback on the pituitary gland, leading to a compensatory surge in ACTH secretion. Over time, this ACTH surge can override the enzymatic blockade, limiting the drug's long-term efficacy.
- Mineralocorticoid Effects: It can also suppress aldosterone synthesis, causing mild natriuresis. However, long-term use leads to the accumulation of 11-desoxycorticosterone (a precursor with mineralocorticoid activity), which prevents Addisonian crises but can induce hypertension.
Safety & warnings
Contraindications
- Known hypersensitivity to metyrapone
- Primary adrenal cortical insufficiency (Addison's disease)
Adverse effects
- Nausea
- Vomiting
- Abdominal pain
- Headache (reported in humans)
- Dizziness (reported in humans)
- Sedation (reported in humans)
- Allergic rash (reported in humans)
- Bone marrow depression (rare)
Precautions
Diabetic Patients: Use with extreme caution and enhanced monitoring in cats with concurrent diabetes mellitus. As cortisol levels drop, insulin resistance resolves, and hypoglycemia can develop rapidly if insulin doses are not adjusted.
- Pregnancy: FDA Category C. Use in pregnant queens only if clearly needed. Fetal pituitary response to the enzymatic block has been detected in humans.
- Lactation: Safety is unknown; use with caution.
- Laboratory Interference: May interfere with diagnostic tests. Antidepressants, antithyroid drugs, phenothiazines, barbiturates, and exogenous hormones can alter metyrapone test results.
Drug interactions
Increased risk for acetaminophen toxicity. Note: Acetaminophen is strictly contraindicated in cats due to fatal methemoglobinemia and hepatotoxicity.
Decreases the efficacy of metyrapone by suppressing ACTH and interfering with the diagnostic or therapeutic intent.
Monitoring
- Blood glucose levels (critical in diabetic cats)
- Clinical signs of hyperadrenocorticism (to assess efficacy)
- Clinical signs of hypoadrenocorticism/Addisonian crisis (lethargy, vomiting, collapse)
- Electrolytes (sodium, potassium)
Pharmacokinetics
Absorption
In humans, well absorbed after oral administration. Peak plasma levels occur in about 1 hour, though pharmacological response is delayed.
Distribution
Rapidly cleared from the plasma.
Metabolism
Reduced to an active metabolite, metyrapol. In humans, both parent drug and metabolite are conjugated with glucuronide. Because cats are deficient in glucuronidation pathways, the exact metabolic fate in felines is unclear.
Elimination
In humans, the average elimination half-life is approximately 2 hours. The active metabolite (metyrapol) has a half-life roughly twice as long.
Overdose
Acute toxicity data indicates an oral LD50 in rats of 521 mg/kg.
Clinical Signs of Overdose:
- Gastrointestinal distress (severe vomiting/nausea)
- Acute adrenocortical insufficiency (Addisonian crisis)
- Hypoglycemia, hyponatremia, hypochloremia, hyperkalemia
- Cardiac arrhythmias, hypotension, dehydration, and altered mentation
Treatment:
- No specific antidote exists.
- Standard gastrointestinal decontamination protocols if ingestion is recent.
- Intravenous fluid therapy (saline) supplemented with glucose.
- Administration of intravenous hydrocortisone or dexamethasone to replace depleted corticosteroids.
- Intensive monitoring and supportive care for several days may be required.
Available products
Formulations
- Oral capsules
- Compounded oral suspensions or capsules (veterinary)
Human-labeled
- Metyrapone Oral Capsules: 250 mg; Metopirone® (Ciba-Geigy); (Rx)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature in a well-closed, light-resistant container.
Client information
Important: This medication is used to lower the amount of cortisol (stress hormone) your cat's body produces. Because it often needs to be custom-made (compounded) for your cat's specific size, follow the pharmacy's storage instructions carefully.
- Administration: Give this medication with food to reduce the chance of stomach upset and vomiting.
- Diabetic Cats: If your cat is also receiving insulin, watch them very closely. As this drug works, your cat's need for insulin may drop dramatically, putting them at risk for low blood sugar (hypoglycemia). Watch for weakness, wobbliness, or seizures.
- When to Call the Vet: Contact your veterinarian immediately if your cat stops eating, seems unusually weak or lethargic, vomits, has diarrhea, or shows changes in drinking or urination. These could be signs that their cortisol levels have dropped too low.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.