Demser

DEMSER (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 to four grams of DEMSER (metyrosine) per day has reduced catecholamine biosynthesis from about 35 to 80 percent 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 pretreatment levels within three to four days after DEMSER (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 DEMSER (metyrosine) for periods of one to 10 years.

Most patients with pheochromocytoma treated with DEMSER (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 DEMSER (metyrosine) ; after withdrawal, blood pressure usually increases gradually to pretreatment values within two to three days.

Metyrosine is well absorbed from the gastrointestinal tract. From 53 to 88 percent (mean 69 percent) was recovered in the urine as unchanged drug following maintenance oral doses of 600 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 3-3.7 hours in three patients.

For further information, refer to: Sjoerdsma, A.; Engelman, K.; Waldman, T.A.; Cooperman, L.H.; Hammond, W.G.: Pheochromocytoma: Current concepts of diagnosis and treatment, Ann. Intern. Med. 65: 1302-1326, Dec. 1966.

Metyrosine is used to treat pheochromocytoma (tumor of the adrenal gland).

Metyrosine is given before surgery to control pheochromocytoma, and is also given when surgery is not possible.

Metyrosine may also be used for other purposes not listed in this medication guide.

Metyrosine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol. It can increase some of the side effects of metyrosine.

Call your doctor at once if you have confusion, trouble speaking, tremors, drooling, diarrhea, or painful urination.

Drink plenty of fluid every day--at least six to eight full glasses (8 ounces)--to prevent metyrosine crystals from forming in your urine.

• Tell all of your health care providers that you take Demser. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
• Have your urine checked as you have been told by your doctor.
• Have your blood work checked if you are on Demser for a long time. Talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• In most people who get sleepy when taking Demser, changes in sleep pattern happen after stopping this medicine. People who do not get sleepy when taking Demser may also have changes in sleep pattern after stopping this medicine. Changes like not being able to sleep may last for 2 to 3 days. Talk with your doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Demser while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Demser, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Demser (metyrosine). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Demser.

Review Date: October 4, 2017

Demser1 (Metyrosine) is (–)-α-methyl-L-tyrosine or (α-MPT). It has the following structural formula:

Metyrosine is a white, crystalline compound of molecular weight 195. It is very slightly soluble in water, acetone, and methanol, and insoluble in chloroform and benzene. It is soluble in acidic aqueous solutions. It is also soluble in alkaline aqueous solutions, but is subject to oxidative degradation under these conditions.

Demser is supplied as capsules, for oral administration. Each capsule contains 250 mg metyrosine. Inactive ingredients are colloidal silicon dioxide, gelatin, hydroxypropyl cellulose, magnesium stearate, titanium dioxide, and FD&C Blue 2.

Demser is contraindicated in persons known to be hypersensitive to this compound.

Capsules Demser, 250 mg, are opaque, two-toned blue capsules coded Aton 305 on one side and Demser on the other. They are supplied as follows:

NDC 25010-305-15 bottles of 100

Manufactured for:

Aton Pharma, Inc., a division of Valeant

Pharmaceuticals North America LLC

Bridgewater, NJ 08807 USA

Manufactured by:
Pharmaceutics International, Inc.
10819 Gilroy Road
Hunt Valley, MD 21031 USA

9643-C68

Rev. 11/2015

9493900

Demser® 250 mg

(Metyrosine)

NDC 25010-305-15

Distributed by:

ATON PHARMA, INC.

LAWRENCEVILLE, NJ 08648, USA

Rx only

USUAL ADULT DOSAGE:

See accompanying circular.

This is a bulk package and not intended

for dispensing.

Package not child resistant.

Dispense in a well-closed container.

100 Capsules