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  • CLASSES

    Diagnostic Hormonal Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Oral diagnostic agent
    Used to evaluate hypothalamic-pituitary ACTH function and used off-label for Cushing's syndrome
    Contraindicated for use in adrenal insufficiency

    COMMON BRAND NAMES

    Metopirone

    HOW SUPPLIED

    Metopirone Oral Cap: 250mg

    DOSAGE & INDICATIONS

    For hypothalamic-pituitary-adrenal (HPA) suppression diagnosis.
    Single-dose short test.
    Oral dosage
    Adults, Adolescents and Children

    A dose of 30 mg/kg (maximum of 3 g) PO at midnight (12 AM) with yogurt or milk is recommended. Plasma ACTH and 11-desoxycortisol determination is drawn the following morning between 7:30 AM and 8:00 AM. After the blood sample has been taken, it is recommended to administer a prophylactic dose of cortisone acetate 50 mg.
    INTERPRETATION: An increase in ACTH to >= 44 pmol/L (200 ng/mL) or in 11-desoxycortisol to > 0.2 mcmol/L (70 mcg/ml) indicates an intact ACTH reserve. This regimen can be given to outpatients; however, If adrenal insufficiency is suspected, hospitalization is recommended.

    Multiple-dose test.
    Oral dosage
    Adults

    The recommended dose is 750 mg (approximately 15 mg/kg) PO every 4 hours for 6 doses. Administer with milk or a snack. See INTERPRETATION for full dosage regimen.
    INTERPRETATION: Four (4) days prior to administration of metyrapone (day 1), a control 24-hour urine should be assayed for 17-hydroxycorticosteroids (17-OHCS) and 17-ketogenic steroids (17-KGS); normal excretion of 17-OHCS is 3—12 mg/24 hours. Three (3) days prior (day 2), an ACTH test (e.g., infusion of 50 units of ACTH over 8 hours) should be performed to determine if there is an adequate response. If the response is adequate (urinary excretion amount of 17-OHCS of 15—45 mg/24 hours), after 2 additional days of rest, the 6-dose regimen of metyrapone should be given (day 5). On day 6, after the 6 doses of metyrapone have been taken, a 24-hour urine collection should be analyzed for 17-OHCS and 17-KGS. A normal response is 2—4 fold increase in 17-OHCS excretion or a doubling of 17-KGS excretion. A subnormal response is indicative of impaired pituitary function. In patients with panhypopituitarism, diagnosis is usually made by classic symptoms of hypogonadism, hypothyroidism, and hypoadrenocorticism plus low basal urinary steroids. Patients may not respond to the ACTH test, and when given metyrapone, an increase in urinary steroid excretion usually does not occur. For partial hypopituitarism, patients lack the classic signs and symptoms of hypopituitarism, and the response to the ACTH test is usually normal. However, an increase in urinary steroid excretion does not usually occur after metyrapone is administered. This type of pituitary impairment is thought to be secondary to a defect in CNS-pituitary mechanisms that normally regulate ACTH secretion. If a patient with Cushing's exhibits a subnormal response, autonomous adrenal tumors that suppress ACTH-releasing capacity of the pituitary or non-endocrine ACTH-secreting tumors are thought to cause the subnormal response. In patients with an excessive increase in urinary steroid excretion, Cushing's with adrenal hyperplasia should be suspected. These patients tend to excrete excessive amounts of urinary steroids at baseline and often have an exaggerated response to the ACTH test and the metyrapone test as evidenced by excretion of > 35 mg of either 17-OHS or 17-KGS/24 hours.

    Children

    The recommended dose is 15 mg/kg PO every 4 hours for 6 doses. The manufacturer recommends a minimum of 250 mg be administered per dose. Metyrapone should be administered with milk or a snack. See INTERPRETATION for full dosage regimen.
    INTERPRETATION: Four (4) days prior to administration of metyrapone (day 1), a control 24-hour urine should be assayed for 17-hydroxycorticosteroids (17-OHCS) and 17-ketogenic steroids (17-KGS); normal excretion of 17-OHCS is 3—12 mg/24 hours. Three (3) days prior (day 2), an ACTH test (e.g., infusion of 50 units of ACTH over 8 hours) should be performed to determine if there is an adequate response. If the response is adequate (urinary excretion amount of 17-OHCS of 15—45 mg/24 hours), after 2 additional days of rest, the 6-dose regimen of metyrapone should be given (day 5). On day 6, after the 6 doses of metyrapone have been taken, a 24-hour urine collection should be analyzed for 17-OHCS and 17-KGS. A normal response is 2—4 fold increase in 17-OHCS excretion or a doubling of 17-KGS excretion. A subnormal response is indicative of impaired pituitary function. In patients with panhypopituitarism, diagnosis is usually made by classic symptoms of hypogonadism, hypothyroidism, and hypoadrenocorticism plus low basal urinary steroids. Patients may not respond to the ACTH test, and when given metyrapone, an increase in urinary steroid excretion usually does not occur. For partial hypopituitarism, patients lack the classic signs and symptoms of hypopituitarism, and the response to the ACTH test is usually normal. However, an increase in urinary steroid excretion does not usually occur after metyrapone is administered. This type of pituitary impairment is thought to be secondary to a defect in CNS-pituitary mechanisms that normally regulate ACTH secretion. If a patient with Cushing's exhibits a subnormal response, autonomous adrenal tumors that suppress ACTH-releasing capacity of the pituitary or non-endocrine ACTH-secreting tumors are thought to cause the subnormal response. In patients with an excessive increase in urinary steroid excretion, Cushing's with adrenal hyperplasia should be suspected. These patients tend to excrete excessive amounts of urinary steroids at baseline and often have an exaggerated response to the ACTH test and the metyrapone test as evidenced by excretion of > 35 mg of either 17-OHS or 17-KGS/24 hours.

    For the treatment of Cushing's syndrome†.
    Oral dosage
    Adults

    Limited data indicate that an initial dose of 0.5—1 g/day PO divided into 2—4 doses may be effective. The dose may subsequently be increased every few days; doses of up to 6 g/day in 2—4 divided doses have been reported. However, additional clinical effect is usually not evident when given in doses > 2 g/day PO.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    For HPA suppression diagnosis, 3 g PO as a single dose or 4.5 g PO total dose for 24-hour regimen.

    Elderly

    For HPA suppression diagnosis, 3 g PO as a single dose or 4.5 g PO total dose for 24-hour regimen.

    Adolescents

    For HPA suppression diagnosis, 3 g PO as a single dose or 4.5 g PO total dose for 24-hour regimen.

    Children

    For HPA suppression diagnosis, 15 mg/kg or 3 g PO as a single dose or 15 mg/kg/dose or 4.5 g PO total dose for 24-hour regimen.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Administer with milk, yogurt, or a snack.

    STORAGE

    Metopirone:
    - Avoid exposure to heat
    - Protect from moisture
    - Store below 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Metyrapone is contraindicated for use in patients with a known metyrapone hypersensitivity or hypersensitivity to any of the formulation components.

    Adrenal insufficiency

    Metyrapone is contraindicated in patients with adrenal insufficiency. Furthermore, in patients with reduced adrenal secretory capacity, metyrapone may cause acute adrenal insufficiency. Therefore, prior to the administration of metyrapone, adrenal function should be assessed via an ACTH test. A normal response to the ACTH test should be demonstrated prior to giving the metyrapone test.

    Hyperthyroidism, hypothyroidism

    Patients with hypothyroidism or hyperthyroidism may have an impaired response to the metyrapone diagnostic test.

    Driving or operating machinery

    Metyrapone has been reported to cause dizziness and sedation; thus, patients should utilize caution when driving or operating machinery.

    Geriatric

    Since geriatric patients are more likely to have multiple disease states including hepatic impairment, renal impairment and/or decreased cardiac function, caution should be utilized when metyrapone is used in this patient population. Adequate numbers of patients >= 65 years of age were not included in clinical studies to determine whether there is a difference in response between elderly and younger patients.

    Pregnancy

    Metyrapone is classified in FDA pregnancy risk category C. Pregnant women may have a reduced response to the metyrapone test. When metyrapone is administered to pregnant women in their second or third trimester, the fetal pituitary gland has been found to respond to the reduction in cortisol and corticosterone production induced by metyrapone. Use during pregnancy only when the benefit outweighs the potential for fetal risk.

    Breast-feeding

    The manufacturer recommends metyrapone be used with caution during breast feeding. In a single case study, average breast milk concentrations of metyrapone and its metabolite at steady-state in a woman receiving 1000 mg/day were 11 mcg/L and 48.5 mcg/L respectively. The authors calculated that a fully breast fed infant would receive 0.1% of the weight-adjusted maternal dose, which would be unlikely to significantly effect the infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Corticosteroid therapy

    Discontinue all medications that affect pituitary or adrenocortical function, including all corticosteroid therapy, prior to and during testing with metyrapone.

    ADVERSE REACTIONS

    Moderate

    leukopenia / Delayed / 0-1.0
    edema / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known

    Mild

    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    lethargy / Early / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    hirsutism / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    headache / Early / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Acetaminophen: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Aspirin, ASA; Caffeine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Butalbital: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Butalbital; Caffeine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Caffeine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Codeine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Dextromethorphan: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Dextromethorphan; Doxylamine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Diphenhydramine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Hydrocodone: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Oxycodone: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Pentazocine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Propoxyphene: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetaminophen; Pseudoephedrine: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Acetaminophen; Tramadol: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tramadol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Acetohexamide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Acrivastine; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Albiglutide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Alclometasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Alfentanil: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Alogliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Alogliptin; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Alogliptin; Pioglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Alpha-glucosidase Inhibitors: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Alprazolam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Amitriptyline: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Amitriptyline; Chlordiazepoxide: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Amobarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Aspirin, ASA; Carisoprodol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as carisoprodol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as carisoprodol, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Aspirin, ASA; Oxycodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with metyrapone can potentiate the CNS-depressant effects, such as drowsiness or dizziness.
    Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with metyrapone can potentiate the CNS-depressant effects, such as drowsiness or dizziness.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Azelastine; Fluticasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Barbiturates: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Beclomethasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Belladonna; Opium: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Benzhydrocodone; Acetaminophen: (Major) Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.
    Benzodiazepines: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Betamethasone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Bromocriptine: (Moderate) In patients taking insulin or other antidiabetic agents such as bromocriptine, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Brompheniramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Brompheniramine; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Budesonide: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Budesonide; Formoterol: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Butabarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Canagliflozin; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Carbetapentane; Chlorpheniramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbetapentane; Pyrilamine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbidopa; Levodopa; Entacapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as COMT inhibiotrs, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbinoxamine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbinoxamine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carbinoxamine; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Carisoprodol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as carisoprodol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlordiazepoxide: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlordiazepoxide; Clidinium: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Codeine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Dextromethorphan: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Hydrocodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpromazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Chlorpropamide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Clemastine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Clobetasol: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Clomipramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Clonazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Clorazepate: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Codeine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Codeine; Guaifenesin: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Codeine; Phenylephrine; Promethazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Codeine; Promethazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    COMT inhibitors: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as COMT inhibiotrs, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Conjugated Estrogens: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Conjugated Estrogens; Bazedoxifene: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Conjugated Estrogens; Medroxyprogesterone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Cortisone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test.
    Cyclizine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dapagliflozin; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Dapagliflozin; Saxagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Deflazacort: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test.
    Desipramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Desonide: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Desoximetasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Dexamethasone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of ocular, inhaled and topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Dexchlorpheniramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dextromethorphan; Promethazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Diazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dienogest; Estradiol valerate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Diethylstilbestrol, DES: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Diflorasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dimenhydrinate: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Diphenhydramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Diphenhydramine; Ibuprofen: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Diphenhydramine; Naproxen: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Diphenhydramine; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Doxepin: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Doxylamine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Doxylamine; Pyridoxine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Dronabinol: (Moderate) Metyrapone may cause drowsiness or dizziness. Use caution if coadministration of dronabinol with metyrapone is necessary, and monitor for additive CNS effects, such as drowsiness or dizziness.
    Droperidol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as droperidol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Drospirenone; Estradiol: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Drospirenone; Ethinyl Estradiol: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Dulaglutide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Empagliflozin; Linagliptin: (Moderate) In patients taking antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Empagliflozin; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Entacapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as COMT inhibiotrs, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Ertugliflozin; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Ertugliflozin; Sitagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Estazolam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Esterified Estrogens: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Esterified Estrogens; Methyltestosterone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estradiol: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estradiol; Levonorgestrel: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estradiol; Norethindrone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estradiol; Norgestimate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estradiol; Progesterone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estrogens: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Estropipate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Eszopiclone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as eszopiclone, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Ethinyl Estradiol: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Desogestrel: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Etonogestrel: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norelgestromin: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norethindrone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norgestimate: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Ethinyl Estradiol; Norgestrel: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Exenatide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Fentanyl: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Fludrocortisone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test.
    Flunisolide: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal or inhaled corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluocinolone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluocinolone; Hydroquinone; Tretinoin: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluocinonide: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluphenazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Flurandrenolide: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Flurazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Fluticasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluticasone; Salmeterol: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluticasone; Umeclidinium; Vilanterol: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fluticasone; Vilanterol: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Formoterol; Mometasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal and topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Fosphenytoin: (Moderate) Fosphenytoin may increase the metabolism of metyrapone. Inaccurate results may be obtained if fosphenytoin is taken within 2 weeks prior to the metyrapone test.
    Glimepiride: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Glimepiride; Pioglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Glimepiride; Rosiglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Glipizide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Glipizide; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Glyburide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Glyburide; Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Guaifenesin; Hydrocodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Haloperidol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as haloperidol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Homatropine; Hydrocodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocodone; Ibuprofen: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocodone; Phenylephrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocodone; Pseudoephedrine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydrocortisone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Hydromorphone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Hydroxyzine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Ibuprofen; Oxycodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Imipramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Incretin Mimetics: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Insulin Degludec; Liraglutide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Insulin Glargine; Lixisenatide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Insulins: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Levorphanol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Linagliptin: (Moderate) In patients taking antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Linagliptin; Metformin: (Moderate) In patients taking antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified. (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Liraglutide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Lixisenatide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Lorazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Maprotiline: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as maprotiline, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Meclizine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Meglitinides: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Meperidine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Meperidine; Promethazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Mephobarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Mesoridazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Mestranol; Norethindrone: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Metformin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Metformin; Pioglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Metformin; Repaglinide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Metformin; Rosiglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Metformin; Saxagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Metformin; Sitagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Methadone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Methocarbamol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as methocarbamol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Methohexital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Methylprednisolone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test.
    Midazolam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Miglitol: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Mitotane: (Major) Mitotane suppresses the activity of the adrenal cortex, and may reduce the adrenal response to metyrapone. The manufacturer of metyrapone recommends that any drug that affects adrenal function be discontinued prior to and during metyrapone testing.
    Molindone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as molindone, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Mometasone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal and topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Morphine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Morphine; Naltrexone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Nabilone: (Moderate) Metyrapone may cause drowsiness or dizziness. Use caution if coadministration of nabilone with metyrapone is necessary, and monitor for additive CNS effects, such as drowsiness or dizziness.
    Nateglinide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Nortriptyline: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Opiate Agonists: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Oxazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Oxycodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Oxymorphone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Pentobarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Perphenazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Perphenazine; Amitriptyline: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible. (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Phenobarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Phenothiazines: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Phenylephrine; Promethazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Phenytoin: (Moderate) The metabolism of metyrapone is accelerated by phenytoin; therefore, results of the diagnostic test using metapyrone may be inaccurate in patients taking phenytoin within 2 weeks before. During use for Cushing's syndrome, phenytoin therapy may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated. Metapyrone may cause dizziness or drowsiness, which may be additive to phenytoin effects.
    Pimozide: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as pimozide, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Pioglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Pramipexole: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as pramipexole, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Pramlintide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Prednicarbate: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Prednisolone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of ocular or topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Prednisone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test.
    Primidone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Prochlorperazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Promethazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Propoxyphene: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Protriptyline: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Quazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Remifentanil: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Repaglinide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Ropinirole: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as ropinirole, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Rosiglitazone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Saxagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Secobarbital: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) A subtherapeutic response to metyrapone can be seen in patients on estrogen therapy. When metapyrone is used as a diagnostic drug for testing hypothalamic-pituitary ACTH function, the effect of estrogen may need to be considered, or, another diagnostic test chosen. If possible, consider discontinuing the use of estrogen prior to and during testing. During use for Cushing's syndrome, estrogen therapy may increase cortisol levels, which may attenuate the response to metyrapone treatment. Monitor for evidence of clinical response to treatment, and adjust treatment as clinically indicated.
    Semaglutide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Simvastatin; Sitagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Sitagliptin: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Sufentanil: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Sulfonylureas: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Suvorexant: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as suvorexant, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Temazepam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Thiazolidinediones: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Thiethylperazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Thiopental: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Thioridazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Tolazamide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Tolbutamide: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Tolcapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as COMT inhibiotrs, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Tramadol: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tramadol, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Trazodone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as trazodone, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Triamcinolone: (Severe) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Triazolam: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Tricyclic antidepressants: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Trifluoperazine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Trimipramine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as tricyclic antidepressants, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Triprolidine: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Zolpidem: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as zolpidem, should be used with caution. Additive drowsiness and/or dizziness is possible.

    PREGNANCY AND LACTATION

    Pregnancy

    Metyrapone is classified in FDA pregnancy risk category C. Pregnant women may have a reduced response to the metyrapone test. When metyrapone is administered to pregnant women in their second or third trimester, the fetal pituitary gland has been found to respond to the reduction in cortisol and corticosterone production induced by metyrapone. Use during pregnancy only when the benefit outweighs the potential for fetal risk.

    The manufacturer recommends metyrapone be used with caution during breast feeding. In a single case study, average breast milk concentrations of metyrapone and its metabolite at steady-state in a woman receiving 1000 mg/day were 11 mcg/L and 48.5 mcg/L respectively. The authors calculated that a fully breast fed infant would receive 0.1% of the weight-adjusted maternal dose, which would be unlikely to significantly effect the infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Under normal conditions, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are released from the hypothalamus. CRH stimulates the pituitary to release adrenocorticotropic hormone (ACTH), which then stimulates the adrenal gland to increase production and release cortisol. Cortisol, via negative feedback, suppresses the release of ACTH.Metyrapone inhibits the 11-beta-hydroxylase enzyme, which is responsible for the conversion of 11-desoxycortisol and 11-desoxycorticosterone to cortisol and corticosterone, respectively. Secondary to inhibition of 11-beta-hydroxylase, plasma levels of cortisol (a suppressor of ACTH release) decrease while levels of 11-desoxycortisol and 11-desoxycorticosterone increase. Both 11-desoxycortisol and 11-desoxycorticosterone weakly suppress the release of ACTH; thus, ACTH levels increase following the administration of metyrapone. There is also an increase in the urinary excretion of 17-hydroxycorticosteroids and 17-ketogenic steroids, metabolites of 11-desoxycortisol and 11-desoxycorticosterone. Following administration of metyrapone, plasma levels of 11-desoxycortisol and ACTH or urinary concentrations of 17-hydroxycorticosteroids are measured to evaluate the hypothalamic-pituitary ACTH function. Metyrapone is also believed to cause mild natriuresis through the inhibition of the synthesis of aldosterone.

    PHARMACOKINETICS

    Metyrapone is administered orally. It is metabolized to metyrapol, an active alcohol metabolite. Both metyrapone and metyrapol undergo conjugation with glucuronide. The elimination half-life of metyrapone is 1.9 +/- 0.7 hours while metyrapol takes twice as long to be eliminated. Within 72 hours after the administration of the first 4.5 g dose, administered as 750 mg every 4 hours, an average of 5.3% is excreted in the urine as metyrapone (9.2% as free drug and 90.8% as glucuronide) and 38.5% as metyrapol (8.1% as free metyrapol and 91.9% as glucuronide).
     
    Affected cytochrome P450 isoenzymes and drug transporters: Unknown

    Oral Route

    Metyrapone has a rapid onset with peak plasma concentrations reached 1 hour after oral administration. The peak plasma concentration is 3.7 mcg/ml and 7.3 mcg/ml following administration of 750 mg and 2000 mg of metyrapone, respectively. The plasma ratio of metyrapone to metyrapol is 1:15 at 8 hours after oral administration.