Pheochromocytoma: Oral: Initial: 250 mg 4 times/day, increased by 250 to 500 mg/day up to 4 g/day in 4 divided doses; titrate hypertensive patients to achieve normal blood pressure and symptom control and titrate normotensive patients to reduce catecholamines by ≥50%. Usual maintenance: 2 to 3 g/day in 4 divided doses; for preoperative preparation, administer optimum effective dosage for 5 to 7 days. Note: May be given in conjunction with an alpha-adrenergic antagonist (eg, phenoxybenzamine) to increase intraoperative hemodynamic stability; however, consider limiting dose of metyrosine to 2 g/day due to greater potential for intraoperative hemodynamic instability with higher doses (Butz 2017; Thanapaalasingham 2015; Wachtel 2015).
No dosage adjustment provided in manufacturer’s labeling.
No dosage adjustment provided in manufacturer’s labeling.
Children ≥12 years: Refer to adult dosing.
There are no dosage adjustments provided in manufacturer’s labeling.
There are no dosage adjustments provided in manufacturer’s labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Demser: 250 mg [contains fd&c blue #2 (indigotine)]
Generic: 250 mg
Yes
Administer without regard to meals.
Oral: Administer without regard to meals.
Pheochromocytoma: Short-term management of pheochromocytoma before surgery; long-term management of pheochromocytoma when surgery is contraindicated or when chronic malignant pheochromocytoma exists
Note: In general, metyrosine is reserved for patients who cannot be treated with combined alpha- and beta-adrenergic blockade due to intolerance or cardiopulmonary reasons (Butz 2017).
MetyroSINE may be confused with metyraPONE
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Extrapyramidal reaction (10%)
Gastrointestinal: Diarrhea (10%)
Frequency not defined:
Cardiovascular: Peripheral edema
Central nervous system: Anxiety, confusion, depression, disorientation, hallucination, headache, overstimulation (after withdrawal), Parkinson’s disease, sedation
Dermatologic: Urticaria
Endocrine & metabolic: Galactorrhea
Gastrointestinal: Abdominal pain, nausea, vomiting, xerostomia
Genitourinary: Breast swelling, crystalluria, dysuria, ejaculatory disorder, hematuria, impotence
Hematologic & oncologic: Anemia, eosinophilia, thrombocythemia, thrombocytopenia
Hepatic: Increased serum AST
Hypersensitivity: Hypersensitivity reaction
Respiratory: Nasal congestion, pharyngeal edema
Hypersensitivity to metyrosine or any component of the formulation
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Crystalluria: May cause crystalluria; to minimize risk, maintain adequate hydration to achieve urine output ≥2L especially with doses >2 g/day. Reduce dose or discontinue use if crystalluria occurs.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Other warnings/precautions:
• Appropriate use: Maintain fluid volume during and after surgery to avoid hypotension and maintain adequate perfusion. Metyrosine does not eliminate the danger of hypertensive crises or arrhythmias during surgery; blood pressure and electrocardiogram should be continuously monitored.
• Long-term use: Safety of long-term use is not established; periodic evaluation of patient is recommended.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Antipsychotic Agents: MetyroSINE may enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Bromopride: MetyroSINE may enhance the adverse/toxic effect of Bromopride. Risk X: Avoid combination
CNS Depressants: May enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Droperidol: MetyroSINE may enhance the adverse/toxic effect of Droperidol. Risk C: Monitor therapy
Metoclopramide: MetyroSINE may enhance the adverse/toxic effect of Metoclopramide. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with metyrosine for development of extrapyramidal symptoms. Risk D: Consider therapy modification
Promethazine: MetyroSINE may enhance the adverse/toxic effect of Promethazine. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: MetyroSINE may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Tetrabenazine: MetyroSINE may enhance the adverse/toxic effect of Tetrabenazine. Risk C: Monitor therapy
Tricyclic Antidepressants: MetyroSINE may enhance the adverse/toxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Animal reproduction studies have not been conducted.
It is not known if metyrosine is excreted in breast milk. The manufacturer recommends that caution be exercised when administering metyrosine to nursing women.
Monitor blood pressure and electrocardiogram during surgery; routine urinalysis (urine output ≥2000 mL recommended especially with doses >2 g/day)
Blocks the rate-limiting step in the biosynthetic pathway of catecholamines. It is a tyrosine hydroxylase inhibitor, blocking the conversion of tyrosine to dihydroxyphenylalanine. This inhibition results in decreased levels of endogenous catecholamines. Catecholamine biosynthesis is reduced by 35% to 80% in patients treated with metyrosine at recommended doses.
Absorption: Well absorbed
Half-life elimination: ~3-4 hours
Excretion: Primarily urine (53% to 88% as unchanged drug)
Capsules (Demser Oral)
250 mg (per each): $505.73
Capsules (metyroSINE Oral)
250 mg (per each): $437.57
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