Demser metyrosine 250 mg Capsule, 100-count — NDC 25010-305-15 (Billing 25010-0305-15)

WARNINGS Maintain Fluid Volume During and After Surgery When DEMSER is used preoperatively, alone or especially in combination with alpha-adrenergic blocking drugs, adequate intravascular volume must be maintained intraoperatively (especially after tumor removal) and postoperatively to avoid hypotension and decreased perfusion of vital organs resulting from vasodilatation and expanded volume capacity. Following tumor removal, large volumes of plasma may be needed to maintain blood pressure and central venous pressure within the normal range.

In addition, life-threatening arrhythmias may occur during anesthesia and surgery, and may require treatment with a beta-blocker or lidocaine. During surgery, patients should have continuous monitoring of blood pressure and electrocardiogram. Intraoperative Effects While the preoperative use of DEMSER in patients with pheochromocytoma is thought to decrease intraoperative problems with blood pressure control, DEMSER does not eliminate the danger of hypertensive crises or arrhythmias during manipulation of the tumor, and the alpha-adrenergic blocking drug, phentolamine, may be needed.

Interaction with Alcohol DEMSER may add to the sedative effects of alcohol and other CNS depressants, e.g., hypnotics, sedatives, and tranquilizers. (See PRECAUTIONS, Information for Patients and Drug Interactions . )

ADVERSE REACTIONS Central Nervous System Sedation: The most common adverse reaction to DEMSER 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 DEMSER 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 DEMSER 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 Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

PRECAUTIONS General Metyrosine Crystalluria: Crystalluria and urolithiasis have been found in dogs treated with DEMSER (metyrosine) at doses similar to those used in humans, and crystalluria has also been observed in a few patients. To minimize the risk of crystalluria, patients should be urged to maintain water intake sufficient to achieve a daily urine volume of 2000 mL or more, particularly when doses greater than 2 g per day are given. Routine examination of the urine should be carried out.

Metyrosine will crystallize as needles or rods. If metyrosine crystalluria occurs, fluid intake should be increased further. If crystalluria persists, the dosage should be reduced or the drug discontinued.

Relatively Little Data Regarding Long-Term Use: The total human experience with the drug is quite limited and few patients have been studied long term. Chronic animal studies have not been carried out. Therefore, suitable laboratory tests should be carried out periodically in patients requiring prolonged use of DEMSER and caution should be observed in patients with impaired hepatic or renal function.

Information for Patients When receiving DEMSER, patients should be warned about engaging in activities requiring mental alertness and motor coordination, such as driving a motor vehicle or operating machinery. DEMSER may have additive sedative effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, and tranquilizers. Patients should be advised to maintain a liberal fluid intake.

(See PRECAUTIONS , General .) Drug Interactions Caution should be observed in administering DEMSER to patients receiving phenothiazines or haloperidol because the extrapyramidal effects of these drugs can be expected to be potentiated by inhibition of catecholamine synthesis. Concurrent use of DEMSER with alcohol or other CNS depressants can increase their sedative effects. (See WARNINGS and PRECAUTIONS , Information for Patients .) Laboratory Test Interference Spurious increases in urinary catecholamines may be observed in patients receiving DEMSER due to the presence of metabolites of the drug.

Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenic studies in animals and studies on mutagenesis and impairment of fertility have not been performed with metyrosine. Pregnancy Pregnancy: Animal reproduction studies have not been conducted with DEMSER. It is also not known whether DEMSER can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

DEMSER should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether DEMSER is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when DEMSER is administered to a nursing woman.

Pediatric Use Safety and effectiveness in pediatric patients below the age of 12 years have not been established. Geriatric Use Clinical studies of DEMSER did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.