DrugindexOnline^{2nd edition}

Pronouncation: (pro-CAR-buh-ZEEN)
Class: Methylhydrazine derivative

Trade Names:
Matulane
- Capsules 50 mg

Mechanism of Action

Pharmacology

The mode of cytotoxic action is not clear; procarbazine may inhibit protein, RNA, and DNA synthesis.

Pharmacokinetics

Absorption

Rapidly and completely absorbed from the GI tract. T _max is 60 min (oral).

Distribution

Quickly equilibrates between plasma and CSF.

Metabolism

Metabolized in the liver and kidneys to cytotoxic products.

Elimination

Urine (mostly as N-isopropylterephthalamic acid, less than 5% as unchanged). Plasma t _½ approximately 10 min (IV).

Indications and Usage

Adult and Pediatric

Advanced Hodgkin disease (stage III and IV) as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.

Unlabeled Uses

Non-Hodgkin lymphoma, brain tumors, small cell lung cancer (adult use).

Contraindications

Hypersensitivity to procarbazine. Inadequate marrow reserve demonstrated by bone marrow aspiration.

Dosage and Administration

Base dosages on patient's actual weight. The following doses are for administration of procarbazine as a single agent. When used in combination with other anticancer drugs, appropriately reduce procarbazine dosage. In the MOPP regimen, the dose is 100 mg/m ² daily for 14 days.

Hodgkin Disease
Adults

PO To minimize nausea and vomiting, give single or divided doses of 2 to 4 mg/kg/day for the first wk. Maintain daily dosage at 4 to 6 mg/kg/day until the WBC falls below 4000/mm ³ or the platelets fall below 100,000/mm ³ , or until max response is obtained. Upon evidence of hematologic toxicity, discontinue the drug until there has been satisfactory recovery. Resume treatment at 1 to 2 mg/kg/day. When max response is obtained, maintain the dose at 1 to 2 mg/kg/day.

Pediatric

PO Individualize dosage. The dosage schedule is a guideline only: 50 mg/m ² /day for the first week. Maintain daily dosage at 100 mg/m ² until leukopenia or thrombocytopenia occurs or max response is obtained. When max response is attained, maintain the dose at 50 mg/m ² /day. Upon evidence of hematologic or other toxicity, discontinue drug until there has been satisfactory recovery.

General Advice

• Administer without regard to meals. Administer with food if GI upset occurs.
• Follow procedures for proper handling and disposal of anticancer drugs.

Storage/Stability

Store capsules at controlled room temperature (59° to 86°F).

Drug Interactions

Alcohol

Alcohol consumption may cause a disulfiram-like reaction in patients on procarbazine.

CNS depressants (eg, narcotics, analgesics, alcohol, antiemetics, benzodiazepines, sedatives, and tranquilizers)

Concurrent use may potentiate CNS effects.

Digitalis glycosides

May result in a decrease in digoxin plasma levels, even several days after stopping chemotherapy.

High-tyramine foods (eg, wine, yogurt, ripe cheese, bananas), OTC antihistamines, and sympathomimetics

Avoid known high-tyramine foods, OTC antihistamines, and sympathomimetics. Procarbazine is a weak MAO inhibitor.

Levodopa

Flushing and a significant rise in BP may result within 1 hr of levodopa administration.

Methotrexate

May increase methotrexate-induced nephrotoxicity.

Radiation or other chemotherapy

May depress bone marrow activity.

Sympathomimetics (indirect-acting)

May cause an abrupt increase in BP, resulting in a potentially fatal hypertensive crisis.

Tricyclic antidepressants

Severe toxic and fatal reactions including excitability, fluctuations in BP, convulsions, and coma may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension; tachycardia; syncope.

CNS

Coma; neuropathy; nystagmus; diminished reflexes; falling; foot drop; headache; unsteadiness; paresthesias; dizziness; depression; insomnia; hallucinations; ataxia; seizures; apprehension; nervousness; confusion; nightmares.

Dermatologic

Dermatitis; pruritus; urticaria; alopecia; flushing; herpes; hyperpigmentation; rash; flushing.

GI

Hepatic dysfunction; jaundice; stomatitis; hematemesis; melena; nausea; vomiting; anorexia; dry mouth; dysphagia; abdominal pain; diarrhea; constipation.

Genitourinary

Amenorrhea; azoospermia; hematuria; urinary frequency; nocturia.

Hematologic

Leukopenia; anemia; thrombopenia; pancytopenia; eosinophilia; hemolytic anemia; petechiae; purpura; epistaxis; hemoptysis; bone marrow suppression; nadir at approximately 4 wk.

Ophthalmic

Retinal hemorrhage; photophobia; diplopia; papilledema; inability to focus.

Respiratory

Pneumonitis; pleural effusion; cough.

Miscellaneous

Acute myelocytic leukemia; malignant myelosclerosis; lung cancer; fever; generalized allergic reactions; gynecomastia in prepubertal and early pubertal boys; intercurrent infections; hearing loss; pyrexia; diaphoresis; lethargy; weakness; fatigue; edema; chills; slurred speech; hoarseness; drowsiness.

Precautions

Warnings Recommend procarbazine 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 made available to patients for proper monitoring of treatment.

Monitor Baseline tests Assess urinalysis, BUN, creatinine, transaminases, and alkaline phosphatase before starting and q wk during treatment. Reticulocyte count/CBC Asses reticulocyte count and CBC with differential and platelet count before starting and q 3 to 4 days during treatment.

Pregnancy

Category D .

Lactation

Undetermined. Not recommended.

Children

Close clinical monitoring is mandatory. Toxicity, evidenced by tremors, convulsions, and coma, has occurred.

Renal Function

Undue toxicity may occur.

Hepatic Function

Undue toxicity may occur.

Carcinogenesis

Tobacco use during procarbazine therapy increases risk of developing secondary lung cancer. Advise patients not to use tobacco.

Fertility

Azoospermia and antifertility effects associated with procarbazine coadministered with other antineoplastics for treating Hodgkin disease have been reported.

Bone-marrow suppression

If radiation or a chemotherapeutic agent known to have marrow-depressant activity has been used, wait at least 1 mo before starting procarbazine.

Toxicity

Toxicity includes hemolysis and the appearance of Heinz-Ehrlich inclusion bodies in erythrocytes.

Discontinue

Discontinue if any of the following occurs: CNS signs or symptoms; leukopenia (WBC less than 4000/mm ³ ); thrombocytopenia (platelets less than 100,000/mm ³ ); hypersensitivity reaction; stomatitis (the first small ulceration or persistent spot soreness); diarrhea; hemorrhage or bleeding tendencies. Resume therapy after side effects clear; adjust to a lower dosage schedule.

Overdosage

Symptoms

Nausea, vomiting, enteritis, diarrhea, hypotension, tremors, convulsions, coma.

Patient Information

• Explain name, action, and potential side effects of drug.
• Advise patient or caregiver that medication may usually be used in combination with other chemotherapy agents to achieve max benefit possible.
• Review dosing schedule with patient or caregiver.
• Advise patient to take prescribed dose without regard to meals but to take with food if GI upset occurs.
• Advise patient or caregiver that if a dose is missed not to take the missed dose and not to double the next dose. Take the next dose at the regularly scheduled time.
• Instruct patient to avoid foods with high tyramine content. Review common foods known to have high tyramine content (eg, aged cheeses, soy sauce, fermented or air-dried meats, sauerkraut, tap beers, red wines).
• Advise patient to discontinue therapy and immediately notify health care provider if any of the following occur: diarrhea; fever, chills or other signs of infection; bleeding; abnormal skin sensations; confusion; allergic reaction; pain, burning, or numbness of feet, legs, or hands.
• Advise patient that medication may cause muscle or joint pain, nausea, vomiting, tiredness, weakness, constipation, headache, difficulty swallowing, loss of appetite, loss of hair, and mental depression and to notify health care provider if any develop and are intolerable.
• Caution patient to avoid alcohol, other CNS depressants (eg, antihistamines), and decongestants (eg, pseudoephedrine) while taking procarbazine.
• Advise patient who smokes that a second malignancy, including lung cancer, can develop following treatment and that tobacco use increases the risk. Advise patient who smokes to discontinue smoking to reduce the risk of developing a secondary lung cancer.
• Caution patient that medication may cause drowsiness and dizziness and to use caution while driving or performing hazardous tasks until tolerance is determined.
• Caution women of childbearing potential to avoid becoming pregnant while being treated.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Instruct patient not to take any prescription or OTC medications or dietary supplements unless advised by health care provider.
• Advise patient that frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.