metyrosine

Adult Dosing

Treatment of pheochromocytoma

250 mg PO qid; may increase the dose by 250 mg to 500 mg everyday to a max of 4000 mg/day in divided doses

Notes:

Administer the dose for at least 5-7 days when used for preoperative preparation
Optimally effective dosages range between 2000 and 3000 mg/day; titrate the dose individually by monitoring clinical symptoms and catecholamine excretion
In hypertensive patients, dosage should be titrated to achieve normalization of blood pressure and control of clinical symptoms
In normotensive patients, dosage should be titrated to reduce urinary metanephrines and/or vanillylmandelic acid by 50% or more
If adequate control of symptoms is not achieved, add an alpha-adrenergic blocking agent to the regimen

Pediatric Dosing

Treatment of pheochromocytoma

Below 12 yrs

Safety and effectiveness in pediatric patients <12 yrs have not been established

Above 12 yrs

250 mg PO qid; may increase the dose by 250 mg to 500 mg everyday to a maximum of 4000 mg/day in divided doses

Notes:

Administer the dose for at least 5-7 days when used for preoperative preparation
Optimally effective dosages range between 2000 and 3000 mg/day; titrate the dose individually by monitoring clinical symptoms and catecholamine excretion
In hypertensive patients, dosage should be titrated to achieve normalization of blood pressure and control of clinical symptoms
In normotensive patients, dosage should be titrated to reduce urinary metanephrines and/or vanillylmandelic acid by 50% or more
If adequate control of symptoms is not achieved, add an alpha-adrenergic blocking agent to the regimen

Indications ⬆ ⬇

Treatment of patients with pheochromocytoma for:

Preoperative preparation of patients for surgery
Management of patients when surgery is contraindicated
Chronic treatment of patients with malignant pheochromocytoma

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredients of the product
Essential hypertension

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Renal impairment: Dose adjustments not defined. Caution advised

Hepatic Dose Adjustment

Hepatic impairment: Dose adjustments not defined. Caution advised

Warnings/Precautions ⬆ ⬇

See Supplemental Patient Information

When metyrosine is used pre-operatively, maintain adequate intravascular volume during and after surgery to avoid the risk of hypotension and reduced perfusion of vital organs due to vasodilatation and expanded volume capacity
Blood pressure and electrocardiogram should be monitored continuously during surgery
Large amounts of plasma may be needed to maintain blood pressure and central venous pressure within normal range after tumor removal
Life-threatening arrhythmias may occur during anesthesia and surgery, which may require treatment with a beta-blocker or lidocaine
The risk of hypertensive crises or arrhythmias during manipulation of the tumor is not eliminated by metyrosine; use of alpha-adrenergic blocking agent (phentolamine) may be indicated
Metyrosine may potentiate the sedative effects of alcohol and other CNS depressants such as sedatives, hypnotics, and tranquilizers
Crystalluria has been reported in certain patients treated with metyrosine. Maintain adequate water intake sufficient to achieve a daily urine volume of 2 liters or more, especially when doses of metyrosine >2000 mg/day are given
If crystalluria persists even after increasing the fluid intake, consider reducing the dose or discontinuing therapy
Suitable laboratory evaluations should be performed periodically in patients treated with metyrosine for prolonged periods
Because metyrosine may cause sedation, patients should be cautioned to avoid performing hazardous tasks that require mental alertness and motor coordination such as driving or operating machinery

Cautions: Use cautiously in

Renal impairment
Hepatic impairment
Elderly patients

Supplemental Patient Information

Advice patients to refrain from performing tasks that require mental alertness and motor coordination such as driving or operating machinery
Instruct patients to maintain a liberal fluid intake

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:C

Breastfeeding: Safety unknown. As many drugs are excreted in human milk, manufacturer advises caution while administering to nursing mothers.

Adverse Reactions ⬆ ⬇

CNS: Moderate to severe sedation, headache; extrapyramidal symptoms such as drooling, speech difficulty, tremor, trismus, frank parkinsonism
PSYCHIATRY: Anxiety, depression, hallucinations, disorientation, confusion
GI: Diarrhea, decreased salivation, dry mouth, nausea, vomiting, abdominal pain
GU: Crystalluria, transient dysuria, hematuria
EENT: Nasal stuffiness
HEMA: Eosinophilia, anemia, thrombocytopenia, thrombocytosis
REPRODUCTIVE: Mild swelling of the breast, galactorrhea, impotence, failure of ejaculation
HYPERSENSITIVITY: Urticaria, pharyngeal edema
MISC: Peripheral edema

Clinical Pharmacology ⬆ ⬇

Tyrosine hydroxylase inhibitor; blocks the enzyme tyrosine hydroxylase, essential for conversion of tyrosine to dihydroxyphenylalanine (DOPA), resulting in reduced endogenous levels of catecholamines and their synthesis
Metabolized in the liver
Excreted in the urine (53-88% unchanged)
Half-life: 3-3.7 hrs

Brands and Availability ⬆ ⬇

US Trade Name(s)

Demser

US Availability

Demser

CAPS: 250 mg

Canadian Trade Name(s)

Canadian Availability

UK Trade Name(s)

UK Availability

Australian Trade Name(s)

Australian Availability

Classification ⬆ ⬇

Endocrine/Metabolic

Catecholamine Synthesis Inhibitors
Tyrosine Hydroxylase Enzyme Inhibitors

Cardiovascular

Catecholamine Synthesis Inhibitors
Tyrosine Hydroxylase Enzyme Inhibitors

Pill ⬆

Drug Name: Demser 250 MG Oral Capsule

Ingredient(s): Metyrosine

Imprint: MSD;690;Demser

Color(s): Blue

Shape: Capsule

Size (mm): 22.00

Score: 1

Inactive Ingredient(s): colloidal silicon dioxide / gelatin / hydroxypropyl cellulose / magnesium stearate / titanium dioxide / fd&c blue 2

Drug Label Author:
Aton Pharma, Inc.

DEA Schedule:
Non-Scheduled