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. Demser is not recommended for the control of essential hypertension. If patients are not adequately controlled by the use of Demser®, an alpha-adrenergic blocking agent (phenoxybenzamine) should be added.1
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 (normetanephrine, 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
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.
See Demser® full Prescribing Information for additional Warnings and Precautions.
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
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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 chronic treatment of patients with malignant pheochromocytoma. Demser is not recommended for the control of essential hypertension.
IMPORTANT SAFETY INFORMATION
- Demser is contraindicated in persons known to be hypersensitive to this compound.
- Maintain adequate intravascular volume intraoperatively (especially after tumor removal) and postoperatively to avoid hypotension and decreased perfusion of vital organs resulting from vasodilatation and expanded volume capacity.
- Life-threatening arrhythmias may occur during anesthesia and surgery. Monitor blood pressure and electrocardiogram continuously during surgery.
- 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.
- DEMSER may add to the sedative effects of alcohol and other CNS depressants, e.g., hypnotics, sedatives, and tranquilizers.
- 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. If metyrosine crystalluria occurs, fluid intake should be increased further. If crystalluria persists, the dosage should be reduced or the drug discontinued.
- Observe caution in patients with impaired hepatic or renal function.
- Warn patients about engaging in activities requiring mental alertness and motor coordination, such as driving a motor vehicle or operating machinery.
- Advise patients to maintain liberal fluid intake.
- Use caution 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.
- The most common adverse reaction to DEMSER is moderate to severe sedation. Other commonly reported adverse reactions are extrapyramidal signs such as drooling, speech difficulty and tremor in approximately 10 percent of patients, occasionally accompanied by trismus and frank Parkinsonism. Anxiety and psychic disturbances such as depression, hallucinations, disorientation, and confusion may occur. Diarrhea occurs in about 10 percent of patients and may be severe.
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Reference: 1. Demser [package insert]. Bridgewater, NJ: Aton Pharma Inc; 2015.