Metopirone Drug Information

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.

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). . Assess ability of patient's adrenals to respond to exogenous ACTH before Metopirone is employed as a test .

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 ). 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.

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.

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.

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.

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.

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.

Pediatric Use Metopirone is indicated, in combination with other diagnostic tests, for the diagnosis of adrenal insufficiency in pediatric patients.

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 Hypersensitivity to Metopirone or to any of its excipients

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.