Matulane (procarbazine hydrochloride), a hydrazine derivative antineoplastic agent, is available as capsules containing the equivalent of 50 mg procarbazine as the hydrochloride. Each capsule also contains cornstarch, mannitol and talc. Gelatin capsule shells contain parabens (methyl and propyl), potassium sorbate, titanium dioxide, FD&C Yellow No. 6 and D&C Yellow No. 10.

Chemically, procarbazine hydrochloride is N-isopropyl-α-(2-methylhydrazino)-p-toluamide monohydrochloride. It is a white to pale yellow crystalline powder which is soluble but unstable in water or aqueous solutions. The molecular weight of procarbazine hydrochloride is 257.76 and the structural formula is:

Last updated on RxList: 12/29/2008

Matulane is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. Matulane is used as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.

The following doses are for administration of the drug as a single agent. When used in combination with other anticancer drugs, the Matulane dose should be appropriately reduced, eg, in the MOPP regimen, the Matulane dose is 100 mg/m² daily for 14 days. All dosages are based on the patient's actual weight. However, the estimated lean body mass (dry weight) is used if the patient is obese or if there has been a spurious weight gain due to edema, ascites or other forms of abnormal fluid retention.

Adults: To minimize the nausea and vomiting experienced by a high percentage of patients beginning Matulane therapy, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until the white blood count falls below 4000/cmm or the platelets fall below 100,000/cmm. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity (see PRECAUTIONS section), the drug should be discontinued until there has been satisfactory recovery. After toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day.

Pediatric Patients: Very close clinical monitoring is mandatory. Undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. Dosage, therefore, should be individualized. The following dosage schedule is provided as a guideline only.

Fifty (50) mg per square meter of body surface per day is recommended for the first week. Dosage should then be maintained at 100 mg per square meter of body surface per day until maximum response is obtained or until leukopenia or thrombocytopenia occurs. When maximum response is attained, the dose may be maintained at 50 mg per square meter of body surface per day. Upon evidence of hematologic or other toxicity (see PRECAUTIONS section), the drug should be discontinued until there has been satisfactory recovery, based on clinical evaluation and appropriate laboratory tests. After toxic side effects have subsided, therapy may then be resumed.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.^1-6 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Capsules, ivory, containing the equivalent of 50 mg procarbazine as the hydrochloride; bottles of 100 (NDC 54482-053-01). Imprint on capsules: MATULANE σ sigma-tau.

REFERENCES:

1. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: U.S. Government Printing Office NIH Publication No. 832621.

2. AMA Council Report. Guidelines for handling parenteral antineoplastics. JAMA. Mar 15, 1985; 253:1590-1592.

3. National Study Commission on Cytotoxic Exposure: Recommendations for handling cytotoxic agents. Available from Louis P. Jeffrey, ScD, Director of Pharmacy Services, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02902.

4. Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. Apr 30,1983; 1:426428.

5. Jones RB, Frank R, Mass T: Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA. Sept-Oct 1983; 33:258263.

6. ASHP technical assistance bulletin on handling cytotoxic drugs in hospitals. Am J Hosp Pharm. Jan 1985; 42:131-137.

Manufactured by: AAI Development Services, An aaiPharma Company, 1726 North 23rd St. Wilmington, NC 28405 for: sigma-tau Pharmaceuticals, Inc., Gaithersburg, MD 20877. Revised: February 2004

Last updated on RxList: 12/29/2008

Leukopenia, anemia and thrombopenia occur frequently. Nausea and vomiting are the most commonly reported side effects.

Other adverse reactions are:

Hematologic: Pancytopenia; eosinophilia; hemolytic anemia; bleeding tendencies such as petechiae, purpura, epistaxis and hemoptysis.

Gastrointestinal: Hepatic dysfunction, jaundice, stomatitis, hematemesis, mele-na, diarrhea, dysphagia, anorexia, abdominal pain, constipation, dry mouth.

Neurologic: Coma, convulsions, neuropathy, ataxia, paresthesia, nystagmus, diminished reflexes, falling, foot drop, headache, dizziness, unsteadiness.

Cardiovascular: Hypotension, tachycardia, syncope.

Ophthalmic: Retinal hemorrhage, papilledema, photophobia, diplopia, inability to focus.

Respiratory: Pneumonitis, pleural effusion, cough.

Dermatologic: Herpes, dermatitis, pruritus, alopecia, hyperpigmentation, rash, urticaria, flushing.

Allergic: Generalized allergic reactions.

Genitourinary: Hematuria, urinary frequency, nocturia.

Musculoskeletal: Pain, including myalgia and arthralgia; tremors.

Psychiatric: Hallucinations, depression, apprehension, nervousness, confusion, nightmares.

Endocrine: Gynecomastia in prepubertal and early pubertal boys.

Miscellaneous: Intercurrent infections, hearing loss, pyrexia, diaphoresis, lethargy, weakness, fatigue, edema, chills, insomnia, slurred speech, hoarseness, drowsiness.

Second nonlymphoid malignancies, (including lung cancer, acute myelocytic leukemia and malignant myelosclerosis), and azoospermia have been reported in patients with Hodgkin's disease treated with procarbazine in combination with other chemotherapy and/or radiation. The risks of secondary lung cancer from treatment appear to be multiplied by tobacco use.

See WARNINGS section.

No cross-resistance with other chemotherapeutic agents, radiotherapy or steroids has been demonstrated.

Last updated on RxList: 12/29/2008

To minimize CNS depression and possible potentiation, barbiturates, antihistamines, narcotics, hypotensive agents or phenothiazines should be used with caution. Ethyl alcohol should not be used since there may be an Antabuse (disulfiram)-like reaction. Because Matulane exhibits some monoamine oxidase inhibitory activity, sympathomimetic drugs, tricyclic antide-pressant drugs (eg, amitriptyline HCI, imipramine HCI) and other drugs and foods with known high tyramine content, such as wine, yogurt, ripe cheese and bananas, should be avoided. A further phenomenon of toxicity common to many hydrazine derivatives is hemolysis and the appearance of Heinz-Ehrlich inclusion bodies in erythrocytes.

Pregnancy

Teratogenic Effects: Pregnancy Category D. Procarbazine hydrochloride can cause fetal harm when administered to a pregnant woman. While there are no adequate and well-controlled studies with procarbazine hydrochloride in pregnant women, there are case reports of malformations in the offspring of women who were exposed to procarbazine hydrochloride in combination with other antineoplastic agents during pregnancy. Matulane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Procarbazine hydrochloride is teratogenic in the rat when given at doses approximately 4 to 13 times the maximum recommended human therapeutic dose of 6 mg/kg/day.

Nonteratogenic Effects: Procarbazine hydrochloride has not been adequately studied in animals for its effects on peri- and postnatal development. However, neurogenic tumors were noted in the offspring of rats given intravenous injections of 125 mg/kg of procarbazine hydrochloride on day 22 of gestation. Compounds which inhibit DNA, RNA and protein synthesis might be expected to have adverse effects on peri- and postnatal development.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Carcinogenesis

The carcinogenicity of procarbazine hydrochloride in mice, rats and monkeys has been reported in a considerable number of studies. Instances of a second non-lymphoid malignancy, including lung cancer and acute myelocytic leukemia, have been reported in patients with Hodgkin's disease treated with procar-bazine in combination with other chemotherapy and/or radiation. The risks of secondary lung cancer from treatment appear to be multiplied by tobacco use. The International Agency for Research on Cancer (IARC) considers that there is "sufficient evidence" for the human carcinogenicity of procarbazine hydrochlo-ride when it is given in intensive regimens which include other antineoplastic agents but that there is inadequate evidence of carcinogenicity in humans given procarbazine hydrochloride alone.

Mutagenesis

Procarbazine hydrochloride has been shown to be mutagenic in a variety of bacterial and mammalian test systems.

Impairment of Fertility

Azoospermia and antifertility effects associated with pro-carbazine hydrochloride administration in combination with other chemothera-peutic agents for treating Hodgkin's disease have been reported in human clinical studies. Since these patients received multicombination therapy, it is difficult to determine to what extent procarbazine hydrochloride alone was involved in the male germ-cell damage. The usual Segment I fertility/reproduction studies in laboratory animals have not been carried out with procarbazine hydrochloride. However, compounds which inhibit DNA, RNA and/or protein synthesis might be expected to have adverse effects on gametogenesis. Unscheduled DNA synthesis in the testis of rabbits and decreased fertility in male mice treated with procarbazine hydrochloride have been reported.

General

Undue toxicity may occur if Matulane is used in patients with impairment of renal and/or hepatic function. When appropriate, hospitalization for the initial course of treatment should be considered.

If radiation or a chemotherapeutic agent known to have marrow-depressant activity has been used, an interval of one month or longer without such therapy is recommended before starting treatment with Matulane. The length of this interval may also be determined by evidence of bone marrow recovery based on successive bone marrow studies.

Prompt cessation of therapy is recommended if any one of the following occurs:

Central nervous system signs or symptoms such as paresthesias, neuropathies or confusion.
Leukopenia (white blood count under 4000).
Thrombocytopenia (platelets under 100,000).
Hypersensitivity reaction.
Stomatitis - The first small ulceration or persistent spot soreness around the oral cavity is a signal for cessation of therapy. Diarrhea - Frequent bowel movements or watery stools. Hemorrhage or bleeding tendencies.
Bone marrow depression often occurs 2 to 8 weeks after the start of treatment. If leukopenia occurs, hospitalization of the patient may be needed for appropriate treatment to prevent systemic infection.

Laboratory Tests

Baseline laboratory data should be obtained prior to initiation of therapy. The hematologic status as indicated by hemoglobin, hema-tocrit, white blood count (WBC), differential, reticulocytes and platelets should be monitored closely - at least every 3 or 4 days.

Hepatic and renal evaluation are indicated prior to beginning therapy. Urinalysis, transaminase, alkaline phosphatase and blood urea nitrogen tests should be repeated at least weekly.

Carcinogenesis, Mutagenesis and Impairment of Fertility

See WARNINGS section.

Pregnancy

Pregnancy Category D. See WARNINGS section.

Nursing Mothers

It is not known whether Matulane is excreted in human milk. Because of the potential for tumorigenicity shown for procarbazine hydrochloride in animal studies, mothers should not nurse while receiving this drug.

Pediatric Use

Undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. Dosage, therefore, should be individualized (See DOSAGE AND ADMINISTRATION). Very close clinical monitoring is mandatory.

Last updated on RxList: 12/29/2008

The major manifestations of overdosage with Matulane would be anticipated to be nausea, vomiting, enteritis, diarrhea, hypotension, tremors, convulsions and coma. Treatment should consist of either the administration of an emetic or gastric lavage. General supportive measures such as intravenous fluids are advised. Since the major toxicity of procarbazine hydrochloride is hematologic and hepatic, patients should have frequent complete blood counts and liver function tests throughout their period of recovery and for a minimum of two weeks thereafter. Should abnormalities appear in any of these determinations, appropriate measures for correction and stabilization should be immediately undertaken.

The estimated mean lethal dose of procarbazine hydrochloride in laboratory animals varied from approximately 150 mg/kg in rabbits to 1300 mg/kg in mice.

Matulane is contraindicated in patients with known hypersensitivity to the drug or inadequate marrow reserve as demonstrated by bone marrow aspiration. Due consideration of this possible state should be given to each patient who has leukopenia, thrombocytopenia or anemia.

Last updated on RxList: 12/29/2008

The precise mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA.

Procarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO₂ and CH₄ and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic acid, which is excreted in the urine.

Procarbazine is rapidly and completely absorbed. Following oral administration of 30 mg of ¹⁴C-labeled procarbazine, maximum peak plasma radioactive concentrations were reached within 60 minutes.

After intravenous injection, the plasma half-life of procarbazine is approximately 10 minutes. Approximately 70% of the radioactivity is excreted in the urine as N-isopropylterephthalamic acid within 24 hours following both oral and intravenous administration of ¹⁴C-labeled procarbazine.

Procarbazine crosses the blood-brain barrier and rapidly equilibrates between plasma and cerebrospinal fluid after oral administration.

Last updated on RxList: 12/29/2008

Patients should be warned not to drink alcoholic beverages while on Matulane therapy since there may be an Antabuse (disulfiram)-like reaction. They should also be cautioned to avoid foods with known high tyramine content such as wine, yogurt, ripe cheese and bananas. Over-the-counter drug preparations which contain antihistamines or sympathomimetic drugs should also be avoided. Patients taking Matulane should also be warned against the use of prescription drugs without the knowledge and consent of their physician. Patients should be advised to discontinue tobacco use.

Last updated on RxList: 12/29/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PROCARBAZINE - ORAL

(pro-KAR-buh-zeen)

COMMON BRAND NAME(S): Matulane

USES: Procarbazine is an alkylating chemotherapy drug used along with other chemotherapy drugs to treat Hodgkin's disease (also known as Hodgkin's lymphoma). It works by preventing cancer cells from growing and from creating new cancer cells. Because procarbazine also affects the growth of normal body cells, you will most likely experience side effects while using this drug.

Procarbazine also acts as a monoamine oxidase inhibitor. (See also Drug Interactions for cautions regarding use of procarbazine with other drugs and the need to limit the amount of tyramine in your diet.)

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat other cancers such as brain tumors.

HOW TO USE: This is a strong medication and is used in combination with other medicines. Use them exactly as directed by your doctor.

Dosage is based on your medical condition, weight, the other drugs used for cancer treatment, and response to treatment. In children, the dosage is based on body size instead of weight.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.

Do not stop taking this medication, even if you feel nauseated or experience vomiting. However, if you vomit shortly after a dose, contact your doctor immediately.

SIDE EFFECTS: Nausea, vomiting, loss of appetite, constipation, dry mouth, difficulty swallowing, drowsiness, dizziness, headache, trouble sleeping, muscle/joint pain, or darkening of the skin may occur. Nausea and vomiting can be severe. In some cases, drug treatment may be needed to prevent or relieve nausea and vomiting. Not eating before your treatment may help relieve vomiting. Changes in diet and lifestyle, such as eating several small meals and limiting activity, may help lessen some of these effects. If any of these effects continue or worsen, tell your doctor or pharmacist.

Temporary hair loss may occur. Normal hair growth should return several months after treatment has ended.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Some people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: black/bloody stools, bloody/pink urine, vomit that is bloody or looks like coffee grounds, stomach pain, yellowing eyes/skin, unsteadiness, fainting.

Seek immediate medical attention if any of these unlikely but very serious side effects occur: chest pain, vision problems, fast or slow heartbeat, severe headache, seizures, stiff/sore neck, increased sweating (with or without fever), cold/clammy skin, mental/mood changes, tingling/numbness of hands/feet, unusual bleeding/bruising, diarrhea, mouth/lip sores.

This medication can lower your body's ability to fight an infection. Tell your doctor if you develop any signs of an infection such as: fever, sore throat, chills, unusual tiredness, lower back or side pain, difficult urination, cough, breathing difficulty, thick mucus/phlegm.

Very rarely, people with cancer who are treated with this type of medication have developed other cancers (e.g., secondary leukemia). Your risk is greater if you have received certain types of chemotherapy or radiation therapy. Consult your doctor for more details.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking procarbazine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: history of alcohol use.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart/blood vessel problems, recent chickenpox, shingles (Herpes zoster), diabetes, seizures, liver disease, kidney disease, severe/frequent headaches, current infection, overactive thyroid (hyperthyroidism), current or past tobacco use, radiation therapy, blood diseases (e.g., bone marrow depression, low platelet counts).

Avoid alcoholic beverages or alcohol-containing products/foods (e.g., cough and cold syrups, mouthwash, aftershave, sauces, vinegars) while taking this medication. When procarbazine is combined with alcohol, a severe reaction (disulfiram/alcohol-like reaction) may occur, with symptoms such severe nausea, vomiting, flushing, blurred vision, headache, dizziness, severe tiredness, difficulty breathing, fast/pounding heartbeat, increased sweating, or seizures. Contact your doctor immediately if you drink alcohol or have any of the above symptoms while taking procarbazine.

Avoid smoking while using this medication. Smoking increases the risk of developing lung cancer while using this drug. Consult your doctor or pharmacist for more details.

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Before having surgery or emergency treatment, tell the doctor or dentist that you have been receiving this medication.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

To lower the chance of getting cut, bruised or injured, use caution with sharp objects like safety razors and nail cutters, and avoid activities such as contact sports.

Wash your hands well and often to prevent the spread of infections. Also, avoid touching your eyes or inside your nose without first washing your hands.

Do not have immunizations/vaccinations without consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.

Caution is advised when using this drug in children because they may be more sensitive to its effects, especially the risk of shaking (tremors), loss of consciousness, or seizures.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. It is recommended that men and women use 2 effective forms of birth control (e.g., condoms and birth control pills) while being treated with this medication and for some time afterward. Consult your doctor for more details and to discuss reliable forms of birth control.

It is not known whether this drug passes into breast milk. Because this drug may harm a nursing infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious (possibly fatal) interactions may occur: antidepressants (e.g., TCAs such as amitriptyline/nortriptyline; mirtazapine; nefazodone; SSRIs such as citalopram/fluoxetine/paroxetine/venlafaxine), appetite suppressants (e.g., diethylpropion, sibutramine), drugs for attention deficit disorder-ADD (e.g., atomoxetine, methylphenidate), certain antihistamines (azatadine, carbetapentane, chlorpheniramine), bronchodilators (e.g., albuterol, salmeterol), bupropion, buspirone, carbamazepine, cyclobenzaprine, dextromethorphan, certain drugs for glaucoma (apraclonidine, brimonidine), herbal products (e.g., ephedra/ma huang), certain drugs for high blood pressure (guanethidine, methyldopa), other MAO inhibitors (furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine), certain narcotic medications (fentanyl, meperidine, morphine), certain drugs for Parkinson's (entacapone, levodopa, tolcapone), street drugs (e.g., MDMA/"ecstasy," LSD, mescaline), stimulants (e.g., amphetamines, cocaine, dopamine, epinephrine, phenylalanine), "triptan" migraine drugs (e.g., sumatriptan, rizatriptan), tramadol.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting procarbazine. Do not take these medications within the 2 weeks before, during or after treatment with procarbazine. If you have been taking fluoxetine, wait at least 5 weeks before starting procarbazine. Ask your doctor how much time to wait between starting or stopping any of these drugs and taking procarbazine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: bethanidine, drugs for diabetes (e.g., glyburide, insulin), digoxin, other drugs for high blood pressure (e.g., beta blockers such as atenolol, clonidine, rauwolfia alkaloids such as reserpine, "water pills"/diuretics such as hydrochlorothiazide), methotrexate, papaverine, tryptophan.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., phenytoin), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, lithium, risperidone, trazodone).

Check the labels on all your medicines (e.g., allergy, cough-and-cold products, decongestants, diet pills) because they may contain dextromethorphan, decongestants, stimulants, or drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

To prevent a very serious high blood pressure reaction, it is very important that you follow a special diet recommended by your doctor or dietician in order to limit your intake of tyramine while you are taking this medicine. Avoid foods and beverages that are high in tyramine, including: aged cheeses (e.g., bleu, cheddar, parmesan), dried/aged/fermented meats and sausages (e.g., salami, liverwurst), preserved fish (e.g., pickled herring), products containing large amounts of yeast (e.g., concentrated yeast extract, bouillon cubes, powdered soup/gravy, homemade or sourdough bread), fermented foods (e.g., sauerkraut, kim chee), most soybean products (e.g., soy sauce, tofu), broad/fava beans, red wine, sherry, tap beers, vermouth. Limit or avoid foods that are moderate in tyramine, including: avocados, bananas, eggplant, green beans, raisins, raspberries, red plums, spinach, tomatoes, chocolate, cultured dairy products (e.g., buttermilk, yogurt, sour cream), fish eggs, pate, peanuts, coffee, cola, alcohol-free beer, bottled beer, distilled spirits, port, white wine.

Consult your doctor or dietician for more details and a complete list of other tyramine-containing foods you should limit or avoid.

Seek immediate medical attention if you notice symptoms of very high blood pressure such as unusually fast/slow heartbeat, vomiting, unexplained sweating, headache, chest pain, sudden vision changes, weakness on one side of the body, slurred speech.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include nausea, vomiting, diarrhea, shakiness, severe dizziness, seizures, and loss of consciousness.

NOTES: Do not share this medication with others.

Keep all medical appointments. Laboratory and/or medical tests (e.g., complete blood counts, kidney function, liver function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Keep below 104 degrees F (40 degrees C). Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.