Metopirone

Frequency Not Defined

Abdominal discomfort

Bone marrow depression (rare)

Decr leukocyte count (rare)

Dizziness

Fall in arterial blood pressure

Headache

Nausea

Pulse rate incr

Sedation

Vertigo

Cardiovascular System: Hypotension

Gastrointestinal System: Nausea, vomiting, abdominal discomfort or pain.

Central Nervous System: Headache, dizziness, sedation.

Dermatologic System: Allergic rash.

Hematologic System: Rarely, decreased white blood cell count or bone marrow depression.

Read the entire FDA prescribing information for Metopirone (Metyrapone)

In the U.S.

• Metopirone

Available Dosage Forms:

• Capsule
• Tablet

Therapeutic Class: Diagnostic Agent, Pituitary Function

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Irregular heartbeat

Check with your doctor as soon as possible if any of the following side effects occur:

• Skin rash

• Enlargement of clitoris
• muscle cramps or pain
• sore throat or fever
• swelling of feet or lower legs
• unusual bleeding or bruising
• unusual tiredness or weakness
• weight gain (rapid)

• Abdominal or stomach pain (severe)
• confusion
• decrease in consciousness
• diarrhea (severe)
• nausea (severe)
• nervousness
• unusual thirst
• vomiting (severe)
• weakness (sudden)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dizziness
• drowsiness
• headache
• lightheadedness
• nausea

• Confusion or mental slowing
• excessive hair growth
• greater-than-normal loss of scalp hair
• increased sweating
• loss of appetite
• upper abdominal or stomach pain
• vomiting
• worsening of acne

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Metopirone is a diagnostic drug for testing hypothalamic-pituitary ACTH function.

Single-Dose Short Test

This test, usually given on an outpatient basis, determines plasma 11-desoxycortisol and/or ACTH levels after a single dose of Metopirone. The patient is given 30 mg/kg (maximum 3 g Metopirone) at midnight with yogurt or milk. The same dose is recommended in children. The blood sample for the assay is taken early the following morning (7:30-8:00 a.m.). The plasma should be frozen as soon as possible. The patient is then given a prophylactic dose of 50 mg cortisone acetate.

Normal values will depend on the method used to determine ACTH and 11-desoxycortisol levels. An intact ACTH reserve is generally indicated by an increase in plasma ACTH to at least 44 pmol/L (200 ng/L) or by an increase in 11-desoxycortisol to over 0.2 µmol/L (70 µg/L). Patients with suspected adrenocortical insufficiency should be hospitalized overnight as a precautionary measure.

Multiple-Dose Test

Day 1: Control period - Collect 24-hour urine for measurement of 17-OHCS or 17-KGS.

Day 2: ACTH test to determine the ability of adrenals to respond - Standard ACTH test such as infusion of 50 units ACTH over 8 hours and measurement of 24-hour urinary steroids. If results indicate adequate response, the Metopirone test may proceed.

Day 3-4: Rest period.

Day 5: Administration of Metopirone: Recommended with milk or snack.

Adults: 750 mg orally, every 4 hours for 6 doses. A single dose is approximately equivalent to 15 mg/kg.

Children: 15 mg/kg orally every 4 hours for 6 doses. A minimal single dose of 250 mg is recommended.

Day 6: After administration of Metopirone - Determination of 24-hour urinary steroids for effect.

ACTH Test

The normal 24-hour urinary excretion of 17-OHCS ranges from 3 to 12 mg. Following continuous intravenous infusion of 50 units ACTH over a period of 8 hours, 17-OHCS excretion increases to 15 to 45 mg per 24 hours.

Normal response: In patients with a normally functioning pituitary, administration of Metopirone is followed by a two- to four-fold increase of 17-OHCS excretion or doubling of 17-KGS excretion.

Subnormal response: Subnormal response in patients without adrenal insufficiency is indicative of some degree of impairment of pituitary function, either panhypopituitarism or partial hypopituitarism (limited pituitary reserve).

1. Panhypopituitarism is readily diagnosed by the classical clinical and chemical evidences of hypogonadism, hypothyroidism, and hypoadrenocorticism. These patients usually have subnormal basal urinary steroid levels. Depending upon the duration of the disease and degree of adrenal atrophy, they may fail to respond to exogenous ACTH in the normal manner. Administration of Metopirone is not essential in the diagnosis, but if given, it will not induce an appreciable increase in urinary steroids.

2. Partial hypopituitarism or limited pituitary reserve is the more difficult diagnosis as these patients do not present the classical signs and symptoms of hypopituitarism. Measurements of target organ functions often are normal under basal conditions. The response to exogenous ACTH is usually normal, producing the expected rise of urinary steroids (17-OHCS or 17-KGS).

The response, however, to Metopirone is subnormal; that is, no significant increase in 17-OHCS or 17-KGS excretion occurs.

This failure to respond to metyrapone may be interpreted as evidence of impaired pituitary-adrenal reserve. In view of the normal response to exogenous ACTH, the failure to respond to metyrapone is inferred to be related to a defect in the CNS-pituitary mechanisms which normally regulate ACTH secretions. Presumably the ACTH secreting mechanisms of these individuals are already working at their maximal rates to meet everyday conditions and possess limited “reserve” capacities to secrete additional ACTH either in response to stress or to decreased cortisol levels occurring as a result of metyrapone administration.

Subnormal response in patients with Cushing’s syndrome is suggestive of either autonomous adrenal tumors that suppress the ACTH-releasing capacity of the pituitary or nonendocrine ACTH-secreting tumors.

Excessive response: An excessive excretion of 17-OHCS or 17-KGS after administration of Metopirone is suggestive of Cushing’s syndrome associated with adrenal hyperplasia. These patients have an elevated excretion of urinary corticosteroids under basal conditions and will often, but not invariably, show a “supernormal” response to ACTH and also to Metopirone, excreting more than 35 mg per 24 hours of either 17-OHCS or 17-KGS.