About Demser®
Demser® (metyrosine) is indicated in the treatment of patients with pheochromocytoma for preoperative preparation of patients for surgery, management of patients when surgery is contraindicated, and as chronic treatment of patients with malignant pheochromocytoma. When used preoperatively, it can be given alone or in combination with an alpha-adrenergic blocking agent (phenoxybenzamine).1
Clinical pharmacology
Demser® inhibits tyrosine hydroxylase, which catalyzes the first transformation in catecholamine biosynthesis. Because the first step is also the rate-limiting step, blockade of tyrosine hydroxylase activity results in decreased endogenous levels of catecholamines, usually measured as decreased urinary excretion of catecholamines and their metabolites.1
Summary of clinical benefits
In patients with pheochromocytoma who produce excessive amounts of norepinephrine and epinephrine, administration of one to four grams of Demser® per day has reduced catecholamine biosynthesis from about 35 to 80% as measured by the total excretion of catecholamines and their metabolites (metanephrine and vanillylmandelic acid).
Most patients with pheochromocytoma treated with Demser® experience decreased frequency and severity of hypertensive attacks with their associated headache, nausea, sweating, and tachycardia. In patients who respond, blood pressure decreases progressively during the first two days of therapy with Demser®. After withdrawal, blood pressure usually increases gradually to pretreatment values within two to three days.1
Dosing considerations
The recommended initial dosage of Demser® 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 daily to a maximum of 4 grams per day in divided doses. When used for preoperative preparation, the optimally effective dosage – usually between 2 and 3 grams per day – should be given for at least five to seven days.1
How to obtain Demser®
Within the United States, to order product or for customer service please call 1-877-ATON-549 (1-877-286-6549).
Outside of the United States, click here for information regarding product availability.
Important Safety Information
DEMSER® (Metyrosine) inhibits tyrosine hydroxylase which catalyses the first transformation in catecholamine biosynthesis, i.e., the conversion of tyrosine to dihydroxyphenylalanine (DOPA). When DEMSER is used preoperatively, adequate intravascular volume must be maintained intraoperatively (especially after tumor removal) and postoperatively to avoid hypotension and decreased perfusion of vital organs. Life threatening arrhythmias may occur during anesthesia and surgery. DEMSER does not eliminate the danger of hypertensive crises or arrhythmias during manipulation of the tumor. DEMSER may add to the sedative effects of alcohol and other CNS depressants. Metyrosine crystalluria has been observed in a few patients. Patients should be urged to maintain water intake sufficient to achieve a daily urine volume of 2000mL or more. If crystalluria persists, the dosage should be reduced or the drug discontinued. DEMSER should be used with caution in patients with impaired hepatic or renal function, and in patients receiving phenothiazines or haloperidol. Safety of use in pregnancy has not been established and caution should be exercised when DEMSER is administered to a nursing woman. Safety and efficacy in pediatric patients under the age of 12 has not been established. The most common adverse reaction to DEMSER is moderate to severe sedation, which has been observed in almost all patients. Extrapyramidal signs such as drooling, speech difficulty and tremor have been reported in 10 percent of the patients, occasionally accompanied by trismus and frank Parkinsonism. Anxiety and psychic disturbances may occur. Diarrhea occurs in about 10 percent of patients and may be severe. Other adverse reactions have been reported.
PLEASE SEE FULL PRESCRIBING INFORMATION.
Reference: 1. Demser package insert. Lawrenceville, NJ: Aton Pharma; 2007.
