Metopirone (metyrapone)

Four days prior to the metyrapone test, a control 24-hour urine specimen is collected and assayed for 17-OHCS or 17-KGS. (Alternatively, some clinicians recommend determination of urinary THS.) On the following day, a corticotropin test is performed to rule out adrenocortical insufficiency. If adrenal insufficiency is not demonstrated, the metyrapone test may begin after 2 days without medications. Adults may be given a metyrapone dose of 750 mg (approximately 15 mg/kg) orally every 4 hours for 6 doses. Children may be given a metyrapone dose of 15 mg/kg or 300 mg/m2 orally every 4 hours for 6 doses; a minimum single dose of 250 mg is recommended by the manufacturer. On the day following administration of metyrapone, another 24-hour urine specimen is collected and urinary 17-OHCS and 17-KGS are measured.

As an alternative to the multiple-dose oral metyrapone schedule, a test using a single 30 mg/kg oral dose of metyrapone, administered at midnight, has been used in adults+. Urine samples are obtained and analyzed for 17-OHCS and 17-KGS as in the multiple-dose schedule. Alternatively, plasma samples may be obtained prior to, and at 8 a.m. on the day following, administration of metyrapone and assayed for compound S. Some clinicians believe that the single dose metyrapone procedure is safer, simpler, and more reliable than the multiple-dose procedure.

Individuals with a normal pituitary-adrenal axis will respond to metyrapone with a 2- to 4-fold increase in 17-OHCS urinary excretion or doubling of 17-KGS excretion. A normal response to metyrapone produces urinary THS concentrations of greater than 500 mcg/day and plasma compound S concentrations 4-5 times greater than control concentrations. In patients without adrenal insufficiency, failure to respond to metyrapone is generally interpreted as evidence of pituitary-adrenal reserve impairment and, by inference, reflects a defect in the CNS-pituitary mechanisms governing ACTH release. Specifically, patients with hypopituitarism show no significant increase in the excretion of the urinary steroids. Panhypopituitarism can be distinguished from partial hypopituitarism, because a partial response to exogenous corticotropin is exhibited in the latter disorder while patients with panhypopituitarism fail to respond to corticotropin. Patients with Cushing's syndrome secondary to adrenal hyperplasia respond with urinary steroid increments in excess of those seen in normal patients, whereas patients with Cushing's syndrome secondary to adrenal adenoma usually exhibit no change in urinary steroids. A subnormal response to metyrapone may occur in pregnant women and in patients with hypothyroidism.

Metyrapone is administered orally. Metyrapone may be taken with milk or food to reduce GI irritation.

No dosing information is available for this tab.

No dosing information is available for this tab.

Phenytoin enhances first-pass liver metabolism of metyrapone and, thus, may invalidate metyrapone test results. Phenytoin therapy should be discontinued at least 2 weeks prior to the metyrapone test. Some clinicians suggest that the effect of phenytoin on plasma metyrapone concentrations can be overcome by doubling the oral dose of metyrapone.

Subnormal response to metyrapone may also occur in patients receiving estrogens, progestins, corticosteroids, phenothiazines, chlordiazepoxide, chlorpromazine, amitriptyline, phenobarbital, or methysergide. Estrogen-progestin oral contraceptives have been reported to both reduce and elevate response to metyrapone.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Metyrapone/Cyproheptadine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Cyproheptadine-induced decrease in ACTH response to metyrapone.

CLINICAL EFFECTS: Decreased pituitary-adrenal response to metyrapone.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue or avoid cyproheptadine administration prior to metyrapone administration for pituitary-adrenal axis assessment.

DISCUSSION: Decreased pituitary-adrenal response to metyrapone occurred during concomitant administration of cyproheptadine.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Metyrapone/Hydantoins

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Hydantoin increases the first pass metabolism of metyrapone.

CLINICAL EFFECTS: The effect of the metyrapone test may be invalidated.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue or avoid phenytoin administration prior to metyrapone administration for pituitary-adrenal axis assessment. It may be necessary to administer metyrapone intravenously or to double its dose in patients receiving phenytoin.

DISCUSSION: Invalid results to the metyrapone test have been obtained in patients receiving standard dose of metyrapone and chronic phenytoin treatment. Doubling the dose of metyrapone or administering metyrapone intravenously have produced valid results.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

• Primary adrenocortical insufficiency

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

More Frequent

• Leukopenia

Less Frequent

• Allergic dermatitis
• Skin rash

Rare or Very Rare

• Anemia
• Bone marrow depression
• Clitoral hypertrophy
• Edema
• Hypokalemia
• Thrombocytopenic disorder

More Frequent

• Dizziness
• Drowsy
• Headache disorder
• Hypotension
• Nausea
• Vomiting

Less Frequent

• Acute abdominal pain
• Sedation

Rare or Very Rare

• Acute cognitive impairment
• Alopecia
• Anorexia
• Hirsutism
• Hyperhidrosis
• Worsening acne

No enhanced messaging available.

No enhanced messaging available.

Animal reproduction studies have not been performed with metyrapone. In women who received the metyrapone test during the second or third trimester of pregnancy, there was evidence of inhibition of 11-beta-hydroxylation by the drug in fetal pituitary. The effect of the drug on reproduction is not known. Safe use of metyrapone in pregnant women has not been established, and the drug should be used during pregnancy only when clearly needed.

Since it is not known whether metyrapone distributes into milk, the drug should be used with caution in nursing women.

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