Metyrapone


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO As a diagnostic test in differentiating pituitary and ectopic production of ACTH in patients with ACTH-dependent Cushing's syndrome For single-dose test: 30 mg/kg at midnight. Max: 3 g. For multiple-dose test: 750 mg every 4 hours for 6 doses. Cushing's syndrome 250 mg to 6,000 mg daily in divided doses, adjusted according to patient’s requirement. Resistant oedema Combined with glucocorticoid: 3,000 mg daily in divided doses.
Dosage Details
Oral
Diagnostic test in differentiating pituitary and ectopic production of ACTH in patients with ACTH-dependent Cushing's syndrome
Adult: For single-dose test: 30 mg/kg at midnight. Max: 3 g. For multiple-dose test: 750 mg every 4 hours for 6 doses.
Child: For single-dose test: Same as adult dose. For multiple-dose test: 15 mg/kg (Min 250 mg and Max 750 mg) every 4 hours for 6 doses.

Oral
Resistant oedema
Adult: In combination with glucocorticoid: 3,000 mg daily in divided doses.

Oral
Cushing's syndrome
Adult: 250 mg to 6,000 mg daily in divided doses, adjusted according to patient’s requirement.
Administration
Should be taken with food. Take w/ milk or yoghurt or after a meal.
Contraindications
Adrenal cortical insufficiency.
Special Precautions
Patient with hypo-or hyperthyroidism, reduced adrenal secretory capacity, gross hypopituitarism, ectopic Cushing’s syndrome. Hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Acute adrenal insufficiency, hypertension (long-term use), opportunistic infections (e.g. P. Jirovecii pneumonia).
Endocrine disorders: Hirsutism.
Gastrointestinal disorders: Abdominal pain/discomfort, nausea, vomiting.
Nervous system disorders: CNS depression (e.g. dizziness, sedation), headache.
Skin and subcutaneous tissue disorders: Rash.
Vascular disorders: Hypotension.
Patient Counseling Information
This drug may cause dizziness and sedation, if affected, do no drive or operate machinery.
MonitoringParameters
Monitor for signs and symptoms of acute adrenal insufficiency.
Overdosage
Symptoms: Gastrointestinal symptoms (e.g. vomiting, nausea, epigastric pain, diarrhoea), acute adrenocortical insufficiency, cardiac arrhythmias, hypotension, dehydration, anxiety, confusion, weakness, impairment of consciousness, hyponatremia, hypochloraemia, hyperkalaemia. Management: Perform gastric lavage, forced emesis and administration of large dose hydrocortisone, together with IV saline and glucose infusion to reduce drug absorption. Repeat if necessary according to patient’s condition. Monitor blood pressure, fluid and electrolyte imbalance.
Drug Interactions
Decreased serum concentration with phenytoin. May increase serum concentration and potentiate acetaminophen toxicity. Amitriptyline, chlorpromazine, barbiturates, corticosteroids, cyproheptadine may affect the result of metyrapone test.
Action
Description: Metyrapone is a diagnostic agent that inhibits 11β-hydroxylase enzyme in the adrenal cortex hence, blocking the synthesis of cortisol and corticosterone production resulting to increase adrenocorticotropic hormone (ACTH) production thereby, increasing cortisol precursors in the urine (17-hyroxycorticosteroids [17-OHCS] and 17-ketogenic steroids [17-KGS]).
Onset: Peak steroid secretion: Within 24 hours.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1 hour.
Distribution: Enters breast milk.
Metabolism: Metabolised in the liver via rapid reduction of the ketone to active metabolite, metyrapol. Both parent drug and metabolite also undergoes glucuronide conjugation.
Excretion: Mainly via urine (approx 5%, as metyrapone; approx 38%, as metyrapol). Elimination half-life: Approx 1.9 hours.
Chemical Structure

Chemical Structure Image
Metyrapone

Source: National Center for Biotechnology Information. PubChem Database. Metyrapone, CID=4174, https://pubchem.ncbi.nlm.nih.gov/compound/Metyrapone (accessed on Jan. 22, 2020)

Storage
Store below 30°C. Protect from moisture and heat.
ATC Classification
V04CD01 - metyrapone ; Belongs to the class of diagnostic agents used to test for pituitary function.
References
Anon. Metyrapone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/12/2017.

Buckingham R (ed). Metyrapone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/12/2017.

Joint Formulary Committee. Metyrapone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/12/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Metyrapone. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/12/2017.

Metopirone Capsule, Gelatin Coated (Laboratoire HRA Pharma). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/12/2017.

Disclaimer: This information is independently developed by MIMS based on Metyrapone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in