Metirosine

Animal reproduction studies have not been conducted with metirosine. It is also not known whether metirosine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Metirosine should be given to a pregnant woman only if clearly needed.

It is not known whether metirosine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when metirosine is administered to a nursing woman.

Long-term carcinogenic studies in animals and studies on mutagenesis and impairment of fertility have not been performed with metyrosine.

When receiving metirosine, patients should be warned about engaging in activities requiring mental alertness and motor coordination, such as driving a motor vehicle or operating machinery. Metirosine may have additive sedative effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, and tranquilizers.

Central Nervous System

Sedation

The most common adverse reaction to metirosine 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 metirosine 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 metirosine 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 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.