DailyMed Label: metyrosine

DailyMed Label: metyrosine

2023

DailyMed Prescription

metyrosine

metyrosine

Amneal Pharmaceuticals NY LLC

NDC: 69238-1621

NDC: 69238-1621

Metyrosine is (–)-α-methyl-L-tyrosine or (α-MPT). It has the following structural formula: Metyrosine, USP is a white to off-white powder of molecular weight 195.22 g/mol and molecular formula C 10 H 13 NO 3 . It is very slightly soluble in methanol and insoluble in chloroform. Metyrosine, USP is supplied as capsules for oral administration. Each capsule contains 250 mg metyrosine, USP. Inactive ingredients are colloidal silicon dioxide, D & C yellow 10, FD & C blue 1, FD & C red 3, FD & C red 40, gelatin, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate, titanium dioxide and water. Each capsule is imprinted with black pharmaceutical ink which contains: butyl alcohol, dehydrated alcohol, ferrosoferric oxide, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac and strong ammonia solution. Meets USP Dissolution Test 2. QWERTY

Metyrosine capsules are 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 capsules are not recommended for the control of essential hypertension.

The recommended initial dosage of metyrosine capsules 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 capsules should be given for at least five to seven days. Optimally effective dosages of metyrosine capsules usually are between 2 g/day 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 capsules, an alpha-adrenergic blocking agent (phenoxybenzamine) should be added. Use of metyrosine capsules in children under 12 years of age has been limited and a dosage schedule for this age group cannot be given.

Metyrosine capsules are contraindicated in persons known to be hypersensitive to this compound.

Metyrosine Crystalluria Crystalluria and urolithias is have been found in dogs treated with 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 metyrosine and caution should be observed in patients with impaired hepatic or renal function. When receiving metyrosine, patients should be warned about engaging in activities requiring mental alertness and motor coordination, such as driving a motor vehicle or operating machinery. Metyrosine 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 ). Caution should be observed in administering metyrosine 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 metyrosine with alcohol or other CNS depressants can increase their sedative effects (see WARNINGS and PRECAUTIONS, Information for Patients ). Spurious increases in urinary catecholamines may be observed in patients receiving metyrosine due to the presence of metabolites of the drug. Long-term carcinogenic studies in animals and studies on mutagenesis and impairment of fertility have not been performed with metyrosine. Animal reproduction studies have not been conducted with metyrosine. It is also not known whether metyrosine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Metyrosine should be given to a pregnant woman only if clearly needed. It is not known whether metyrosine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when metyrosine is administered to a nursing woman. Safety and effectiveness in pediatric patients below the age of 12 years have not been established. Clinical studies of metyrosine 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.

Caution should be observed in administering metyrosine 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 metyrosine with alcohol or other CNS depressants can increase their sedative effects (see WARNINGS and PRECAUTIONS, Information for Patients ).

Metyrosine Capsules USP, 250 mg are supplied as size “0”, hard gelatin capsules with dark blue opaque cap imprinted with “AA” and light blue opaque body imprinted with “05A” with black ink. Each capsule is filled with white to off-white granular powder. They are available as follows: Bottles of 100:                                  NDC 69238-1621-1 Bottles of 30:                                    NDC 69238-1621-3 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Package is not child-resistant. Dispense in a tight, child-resistant container as defined in the USP. Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Oral Solid Dosage Unit Ahmedabad 382213, INDIA Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 11-2020-02

Metyrosine inhibits tyrosine hydroxylase, which catalyzes the first transformation in catecholamine biosynthesis, i.e. the conversion of tyrosine to dihydroxyphenylalanine (DOPA). 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. In patients with pheochromocytoma, who produce excessive amounts of norepinephrine and epinephrine, administration of one gram to four grams of metyrosine 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). The maximum biochemical effect usually occurs within two to three days, and the urinary concentration of catecholamines and their metabolites usually returns to pre-treatment levels within three to four days after metyrosine is discontinued. In some patients the total excretion of catecholamines and catecholamine metabolites may be lowered to normal or near normal levels (less than 10 mg/24 hours). In most patients the duration of treatment has been two to eight weeks, but several patients have received metyrosine for periods of 1 to 10 years. Most patients with pheochromocytoma treated with metyrosine 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 metyrosine; after withdrawal, blood pressure usually increases gradually to pre-treatment values within two to three days. Metyrosine is well absorbed from the gastrointestinal tract. From 53% to 88% (mean 69%) was recovered in the urine as unchanged drug following maintenance oral doses of 600 mg to 4000 mg/24 hours in patients with pheochromocytoma or essential hypertension. Less than 1% of the dose was recovered as catechol metabolites. These metabolites are probably not present in sufficient amounts to contribute to the biochemical effects of metyrosine. The quantities excreted, however, are sufficient to interfere with accurate determination of urinary catecholamines determined by routine techniques. Plasma half-life of metyrosine determined over an 8-hour period after single oral doses was 3 to 3.7 hours in three patients. For further information, refer to: Sjoerdsma A, Engelman K, Waldman TA, Cooperman LH, Hammond WG. Pheochromocytoma: Current Concepts of Diagnosis and Treatment: Combined Clinical Staff Conference at the National Institutes of Health. Ann Intern Med. 1966;65:1302-1326.

NDC 69238-1621-1 Metyrosine Capsules USP, 250 mg Rx Only 100 Capsules Amneal Pharmaceuticals LLC NDC 69238-1621-3 Metyrosine Capsules USP, 250 mg Rx Only 30 Capsules Amneal Pharmaceuticals LLC ad fgh