Matulane

Procarbazine is used in combination with other medications to treat certain types of Hodgkins disease (types of cancer that begin in a type of white blood cells that normally fights infection). Procarbazine is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in your body.

You will need to avoid eating foods that contain very high amounts of tyramine, such as certain cheeses, yogurt, and bananas during your treatment with procarbazine. Talk to your doctor or dietitian about which foods you should avoid during your treatment or if you do not feel well after eating or drinking certain foods while taking procarbazine.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Dosage Forms & Strengths

capsule

• 50mg

Hodgkin's Disease

Part of COPP, BEACOPP & MOPP regimens

2-4 mg/kg/day in single or divided doses for 7 days; increase dose by 4-6 mg/kg/day until maximum response obtained or WBC<4,000 cells/mm³ or plateletes<100,000 cells/mm³; reduce dosage to 1-2 mg/kg/day after maximum effect obtained 

Alternatively, 100 mg/m² PO qDay for 7-14 days of each 28 day cycle in combo with other antineoplastics 

Monitor: CBC

Glioma (Orphan)

Treatment of malignant glioma

Orphan indication sponsor

• Sigma-Tau Pharmaceuticals, Inc; 9841 Washingtonian Blvd, Suite 500; Gaithersburg, MD 20878

Renal Impairment

Use caution; may result in increased toxicity if BUN above 40 mg/dL

Hepatic Impairment

Use caution; may result in increased toxicity if AST or ALT >1.6 ULN

Dosage Forms & Strengths

capsule

• 50mg

Hodgkin's Disease

50 mg/m² PO qDay for 7 days; increase to 100 mg/m²/day until maximum response obtained or leukopenia or thrombocytopenia observed 

Monitor: CBC

Hodgkin's Disease

Adjust for renal impairment if necessary

Part of COPP, BEACOPP & MOPP regimens

2-4 mg/kg/day in single or divided doses for 7 days; increase dose by 4-6 mg/kg/day until maximum response obtained or WBC<4,000 cells/mm³ or plateletes<100,000 cells/mm³; reduce dosage to 1-2 mg/kg/day after maximum effect obtained 

Alternatively, 100 mg/m² PO qDay for 7-14 days of each 28 day cycle in combo with other antineoplasticsMonitor: CBC 

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:

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 antidepressant 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

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.

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, Impairment Of Fertility

The carcinogenicity of procarbazine hydrochloride in mice, rats and monkeys has been reported in a considerable number of studies. Instances of a second nonlymphoid malignancy, including lung cancer and acute myelocytic leukemia, 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. The International Agency for Research on Cancer (IARC) considers that there is “sufficient evidence” for the human carcinogenicity of procarbazine hydrochloride 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.

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

Azoospermia and antifertility effects associated with procarbazine hydrochloride administration in combination with other chemotherapeutic 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.

Matulane is a prescription medication used to treat certain types of Hodgkins disease. Matulane belongs to a group of drugs called alkylating agents. These work by slowing or stopping the growth of cancer cells in your body.

Matulane comes as a capsule to take by mouth. It is usually taken one or more times a day, with or without food.

Common side effects include nausea, vomiting, and low blood counts.

Common side effects include the following:

• nausea
• vomiting
• loss of appetite
• constipation
• stomach pain
• dryness of mouth
• changes in skin color
• hair loss
• difficulty falling asleep or staying asleep
• headache
• bone, joint, or muscle pain
• increased urination

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

It is recommended that Matulane be given only by or under the supervision of a physician experienced in the use of potent antineoplastic drugs. Adequate clinical and laboratory facilities should be available to patients for proper monitoring of treatment.

You should not take procarbazine if you have bone marrow suppression.

Procarbazine can lower blood cells that help your body fight infections and help your blood to clot. You may get an infection or bleed more easily. Call your doctor if you have unusual bruising or bleeding, or signs of infection (fever, chills, body aches).

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Taking procarbazine with other drugs that make you sleepy or slow your breathing can increase these effects. Ask your doctor before taking procarbazine with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with procarbazine, especially:

• blood pressure medication;

• an antidepressant--amitriptyline, doxepin, imipramine, nortriptyline, and others;

• a barbiturate--butabarbital, secobarbital, pentobarbital, phenobarbital;

• diet pills, stimulants, or ADHD medication such as Adderall or Ritalin; or

• phenothiazines--chlorpromazine, fluphenazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine.

This list is not complete. Other drugs may interact with procarbazine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

• Risk of bone marrow suppression, nausea, vomiting, and secondary malignancies.100

• Importance of close medical supervision during therapy.100

• Importance of avoiding alcoholic beverages and tobacco during therapy.100

• Importance of avoiding foods with known high tyramine content such as wine, yogurt, ripe cheese, and bananas.100

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and to advise pregnant women of risk to the fetus.100

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs (e.g., antihistamines) and dietary or herbal supplements, as well as any concomitant illnesses.100

• Importance of advising patients of other important precautionary information.100 (See Cautions.)

Procarbazine belongs to the group of medicines known as alkylating agents. It is used to treat some kinds of cancer.

Procarbazine is thought to interfere with the growth of cancer cells which are eventually destroyed. It also blocks the action of a chemical substance in the central nervous system called monoamine oxidase (MAO), but this is probably not related to its effect against cancer. Since the growth of normal body cells may also be affected by procarbazine, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with procarbazine, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Procarbazine is available only with your doctor's prescription.