Metyrapone
FDA Drug Information • Also known as: Metopirone
- Brand Names
- Metopirone
- Drug Class
- Adrenal Steroid Synthesis Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- CAPSULE, GELATIN COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Metopirone (metyrapone capsules) is an adrenal steroid synthesis inhibitor, available as 250‑mg capsules for oral administration. Its chemical name is 2‑methyl‑1, 2‑di‑3‑pyridyl‑1‑propanone, and its structural formula is Metyrapone is a white to light amber, fine, crystalline powder, having a characteristic odor. It is sparingly soluble in water, and soluble in methanol and in chloroform. It forms water‑soluble salts with acids. Its molecular weight is 226.27. Inactive Ingredients : Ethyl vanillin, gelatin, glycerol, macrogol 400, macrogol 4000, paramethoxy acetophenone, purified water, sodium ethyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, titanium dioxide, + red ink (aluminum chloride hexahydrate, carminic acid, hypromellose, propylene glycol, sodium hydroxide). Chemical Structure
What Is Metyrapone Used For?
1 INDICATIONS AND USAGE Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients. Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in adult and pediatric patients. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Single-Dose Short Test: 30 mg/kg at midnight ( 2.2 ) 2.1 Important Information Before Conducting Metopirone Testing Stop drugs affecting pituitary or adrenocortical function before administration of Metopirone in accordance with half-life of the drugs (consider at least 5 half-lives to avoid any interference with Metopirone testing). [see Drug Interactions (7.1) ] . Assess ability of patient's adrenals to respond to exogenous ACTH before Metopirone is employed as a test [see Warnings and Precautions (5.1) ] . 2.2 Single-Dose Short Test- Recommended Dose and Interpretation This test, usually given on an outpatient basis, determines plasma 11-desoxycortisol and/or ACTH levels after a single dose of Metopirone. Patients with suspected adrenocortical insufficiency based on the test results previously performed should be hospitalized overnight as a precautionary measure ( see Warnings and Precaution (5.1) ). Recommended Dose In adult and pediatric patients, the recommended single dose is 30 mg/kg (maximum 3 grams of Metopirone) administered at midnight with milk/yogurt or snack. The blood sample for the assay is taken early the following morning (7:30-8:00 a.m.). After the blood sample is collected, a prophylactic dose of glucocorticoid may be considered for patients with high risk for acute adrenal insufficiency. Interpretation of 11‑desoxycortisol and ACTH Levels After Metopirone Administration Approximately 8 hours after administration of Metopirone, evaluate the values of ACTH and 11-desoxycortisol. Normal values will depend on the method used to determine ACTH and 11‑desoxycortisol levels. An intact HPA axis function is generally indicated by an increase in 11‑desoxycortisol to over 70 mcg/L. Because of an overlap between a normal ACTH response and an abnormal ACTH response, the ACTH response alone cannot be used to distinguish between healthy individuals and those with adrenal insufficiency.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions associated with the use of Metopirone were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular System: Hypotension Gastrointestinal System: Nausea, vomiting, abdominal discomfort or pain Central Nervous System: Headache, dizziness, sedation Dermatologic System: Allergic rash Hematologic System: Leukopenia, anemia, and/or thrombocytopenia Adverse reactions include: hypotension, nausea, vomiting, abdominal discomfort or pain, headache, dizziness, sedation, allergic rash, leukopenia, anemia, and/or thrombocytopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Inc. at 844-597-6373 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
7 DRUG INTERACTIONS Anticonvulsants, psychotropic, hormone preparations, corticosteroids, antithyroid agents, cyproheptadine: may affect the results of the metyrapone test. ( 7.1 ) Acetaminophen: Avoid concomitant use with Metopirone. ( 7.2 ) 7.1 Effect of Other Drugs on Metopirone Anticonvulsants, psychotropic drugs, hormone preparations, corticosteroids, antithyroid agents and cyproheptadine may affect the results of the Metopirone test. If these drugs cannot be withdrawn, the necessity of carrying out the Metopirone test should be reviewed. 7.2 Effect of Metopirone on Other Drugs Acetaminophen Metopirone inhibits the glucuronidation of acetaminophen, which may decrease elimination of acetaminophen and lead to increased risk of adverse reactions related to acetaminophen. Avoid concomitant use of Metopirone with acetaminophen.
Contraindications
4 CONTRAINDICATIONS Metopirone is contraindicated in patients with adrenal cortical insufficiency or hypersensitivity to Metopirone or to any of its excipients. In patients with adrenal cortical insufficiency ( 4 ) Hypersensitivity to Metopirone or to any of its excipients ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from published case series and reports on Metopirone use in pregnant females are insufficient to identify a drug-associated risk of major birth defects or miscarriage. Metyrapone crosses the placenta and may decrease fetal cortisol production (see Data ) . Animal reproductive studies have not been conducted with metyrapone. Metyrapone can decrease reproductive hormones by targeting adrenal androgenesis. Data Human Data The Metopirone test was administered to pregnant women in their second and third trimester of pregnancy and evidence was found that the fetal pituitary responded to the enzymatic block. Transplacental transfer of Metopirone has been shown in humans and the drug can impair the biosynthesis of fetal and placental steroids. There are a few published reports of low cortisol levels at birth in infants exposed in utero following chronic use of metyrapone in pregnant females.
Overdosage
10 OVERDOSAGE Death occurred in a child after two doses of Metopirone 2 g. Signs and Symptoms of Overdosage The clinical picture of overdosage with Metopirone is characterized by gastrointestinal symptoms and by signs of acute adrenal insufficiency. Cardiovascular System : Cardiac arrhythmias, hypotension, dehydration. Nervous System and Muscles : Anxiety, confusion, weakness, impairment of consciousness. Gastrointestinal System: Nausea, vomiting, epigastric pain, diarrhea. Laboratory Findings: Hyponatremia, hypochloremia, hyperkalemia. In patients under treatment with insulin or oral antidiabetics, the signs and symptoms of acute overdosage with Metopirone may be aggravated or modified. Treatment and Management of Overdosage There is no specific antidote for Metopirone overdosage. Immediate treatment is essential in the management of Metopirone overdose. Treatment with activated charcoal may be considered if the overdose has been taken within 1 hour. In addition to general measures, hydrocortisone should be administered at once, together with IV saline and glucose. This should be repeated as necessary in accordance with the patient's clinical condition. For a few days blood pressure and fluid and electrolyte balance should be monitored. Consult with a regional poison control center (1-800-222-1222) for additional treatment recommendations.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Metopirone (metyrapone capsules) are supplied as 250 mg soft gelatin, white to yellowish‑white, oblong, opaque capsules, imprinted with "HRA" on one side in red ink. Bottle of 18 capsules: NDC 76336-455-18 Storage and Handling Store Metopirone bottles at room temperature 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Keep container tightly closed and protect from heat and moisture.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.