Metyrosine

Dosage Forms & Strengths

capsule

• 250mg

Chronic Pheochromocytoma

Indicated for treatment of patients with pheochromocytoma for: 1) preoperative preparation for surgery; 2) management when surgery is contraindicated; and 3) chronic treatment with malignant pheochromocytoma

Initial: 250 mg PO q6hr; may increase by 250-500 mg/day, not to exceed 4 g/day

Maintenance: Typically 2-3 g/day divided q6hr

Dosing Considerations

Not indicated for essential hypertension

When used for preoperative preparation, the optimally effective dose should be given for at least 5-7 days

Psychosis (Orphan)

Treatment of velocardiofacial syndrome associated psychosis

Orphan indication sponsor

• Aton Pharma, Inc; 3150 Brunswick Place; Lawrenceville, NJ 08648

Dosage Forms & Strengths

capsule

• 250mg

Chronic Pheochromocytoma

Indicated for treatment of patients with pheochromocytoma for: 1) preoperative preparation for surgery; 2) management when surgery is contraindicated; and 3) chronic treatment with malignant pheochromocytoma

<12 years: Safety and efficacy not established

≥12 years

• Initial: 250 mg PO q6hr; may increase by 250-500 mg/day, not to exceed 4 g/day
• Maintenance: Typically 2-3 g/day divided q6hr

Dosing Considerations

Not indicated for essential hypertension

When used for preoperative preparation, the optimally effective dose should be given for at least 5-7 days

Mechanism of Action

Inhibits synthesis of endogenous catecholamines by inhibiting tyrosine hydroxylase

Pharmacokinetics

Half-Life: 3-4 hr

Bioavailability: Well absorbed

Metabolism: liver

Metabolite: Catechol metabolites (inactive)

Excretion: urine 53-88%

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.

You should not use this medication if you are allergic to metyrosine.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:

• heart disease;
• kidney disease; or
• liver disease.

It is not known whether metyrosine is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether metyrosine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

Central Nervous System

Sedation: The most common adverse reaction to DEMSER (metyrosine) 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 (metyrosine) 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 percent 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 percent of patients and may be severe. Anti-diarrheal agents may be required if continuation of DEMSER (metyrosine) 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.

Read the entire FDA prescribing information for Demser (Metyrosine)

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.

Tell your doctor about all other medications you use, especially medicine to treat psychiatric disorders, such as:

• chlorpromazine (Thorazine);

• fluphenazine (Permitil, Prolixin);

• haloperidol (Haldol);

• mesoridazine (Serentil);

• perphenazine (Trilafon);

• thioridazine (Mellaril); or

• trifluoperazine (Stelazine).

This list is not complete and there may be other drugs that can interact with metyrosine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

• Tell all of your health care providers that you take metyrosine. 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 metyrosine 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 metyrosine, changes in sleep pattern happen after stopping this medicine. People who do not get sleepy when taking metyrosine 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 metyrosine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Feeling confused.
• Very loose stools (diarrhea).
• Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
• Drooling.
• Trouble passing urine.
• Pain when passing urine.
• Anxiety.
• Low mood (depression).
• Hallucinations (seeing or hearing things that are not there).

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.