Métyrapone (metyrapone)

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 )

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.

5 WARNINGS AND PRECAUTIONS Adrenal Insufficiency: May induce acute adrenal insufficiency. Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test ( 5.1 ) Dizziness and Sedation: May cause dizziness and sedation. Patients should not drive or operate machinery until these effects have passed ( 5.2 ) 5.1 Adrenal Insufficiency Metopirone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity, as well as in patients with global pituitary insufficiency. The test should be performed in the hospital with close monitoring in case of suspected adrenal insufficiency. Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test. In the presence of hypo‑ or hyperthyroidism, response to the Metopirone test may be subnormal. If adrenocortical or anterior pituitary function is more severely compromised than indicated by the results of the test, Metopirone may trigger adrenal insufficiency. This can be corrected by giving appropriate doses of corticosteroids. 5.2 Dizziness and Sedation Metopirone may cause dizziness and sedation. Patients should not drive or operate machinery until these effects have passed.

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 Esteve Pharmaceuticals, S.A. at 1-888-306-6259 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.