METYROSINE

Metyrosine is (–)-α-methyl- L -tyrosine or (α-MPT). It has the following structural formula: Metyrosine is a white to off-white, crystalline compound of molecular weight 195.22. It is very slightly soluble in water, acetone, and methanol, and insoluble in chloroform and benzene. It is soluble in acidic aqueous solutions. It is also soluble in alkaline aqueous solutions, but is subject to oxidative degradation under these conditions. Metyrosine is supplied as capsules for oral administration. Each capsule contains 250 mg metyrosine. Inactive ingredients are colloidal silicon dioxide, gelatin, hydroxypropyl cellulose, magnesium stearate, titanium dioxide, FD&C Blue 2 and edible black ink. image

Metyrosine is indicated in the treatment of patients with pheochromocytoma for: 1. Preoperative preparation of patients for surgery 2. Management of patients when surgery is contraindicated 3. Chronic treatment of patients with malignant pheochromocytoma Metyrosine is not recommended for the control of essential hypertension.

The recommended initial dosage of Metyrosine for adults and children 12 years of age and older is 250 mg orally four times daily. This may be increased by 250 mg to 500 mg every day to a maximum of 4 g/day in divided doses. When used for preoperative preparation, the optimally effective dosage of Metyrosine should be given for at least five to seven days. Optimally effective dosages of Metyrosine usually are between 2 and 3 g/day, and the dose should be titrated by monitoring clinical symptoms and catecholamine excretion. In patients who are hypertensive, dosage should be titrated to achieve normalization of blood pressure and control of clinical symptoms. In patients who are usually normotensive, dosage should be titrated to the amount that will reduce urinary metanephrines and/or vanillylmandelic acid by 50% or more. If patients are not adequately controlled by the use of Metyrosine, an alpha-adrenergic blocking agent (phenoxybenzamine) should be added. Use of Metyrosine in children under 12 years of age has been limited and a dosage schedule for this age group cannot be given.

Metyrosine is contraindicated in persons known to be hypersensitive to this compound.

Central Nervous System Sedation: The most common adverse reaction to Metyrosine is moderate to severe sedation, which has been observed in almost all patients. It occurs at both low and high dosages. Sedative effects begin within the first 24 hours of therapy, are maximal after two to three days, and tend to wane during the next few days. Sedation usually is not obvious after one week unless the dosage is increased, but at dosages greater than 2000 mg/day some degree of sedation or fatigue may persist. In most patients who experience sedation, temporary changes in sleep pattern occur following withdrawal of the drug. Changes consist of insomnia that may last for two or three days and feelings of increased alertness and ambition. Even patients who do not experience sedation while on Metyrosine may report symptoms of psychic stimulation when the drug is discontinued. Extrapyramidal Signs: Extrapyramidal signs such as drooling, speech difficulty, and tremor have been reported in approximately 10% of patients. These occasionally have been accompanied by trismus and frank parkinsonism. Anxiety and Psychic Disturbances: Anxiety and psychic disturbances such as depression, hallucinations, disorientation, and confusion may occur. These effects seem to be dose-dependent and may disappear with reduction of dosage. Diarrhea Diarrhea occurs in about 10% of patients and may be severe. Anti-diarrheal agents may be required if continuation of Metyrosine is necessary. Miscellaneous Infrequently, slight swelling of the breast, galactorrhea, nasal stuffiness, decreased salivation, dry mouth, headache, nausea, vomiting, abdominal pain, and impotence or failure of ejaculation may occur. Crystalluria (see PRECAUTIONS ) and transient dysuria and hematuria have been observed in a few patients. Hematologic disorders (including eosinophilia, anemia, thrombocytopenia, and thrombocytosis), increased SGOT levels, peripheral edema, and hypersensitivity reactions such as urticaria and pharyngeal edema have been reported rarely. To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.