Procarbazine

A to Z Drug Facts

Actions The mode of cytotoxic action is not clear; procarbazine may inhibit protein, RNA, and DNA synthesis. Procarbazine is rapidly and completely absorbed from the GI tract and quickly equilibrates between plasma and CSF. Peak CSF levels occur in 30 to 90 min. Following PO administration, max peak plasma concentrations occur within 60 min. Procarbazine is metabolized in the liver and kidneys to cytotoxic products.

 Indications

Adult and Pediatric

Advanced Hodgkin's disease (stage III and IV).

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

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

 Route/Dosage Base dosages on the 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.

Hodgkin's Disease

ADULTS: PO To minimize nausea and vomiting, give single or divided doses of 2 to 4 mg/kg/day for the first week. Maintain daily dosage at 4 to 6 mg/kg/day until the WBC falls < 4000/mm³ or the platelets fall < 100,000/mm³, or until maximum 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 maximum 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/m² daily for the first week. Maintain daily dosage at 100 mg/m² until leukopenia or thrombocytopenia occurs or maximum response is obtained. Upon evidence of hematologic or other toxicity, discontinue drug until there has been satisfactory response. When maximum response is attained, maintain the dose at 50 mg/m²/day.

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 monoamine oxidase 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.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Paresthesias; dizziness; depression; insomnia; hallucinations; ataxia; psychosis; mania; delirium; seizures. DERMATOLOGIC: Dermatitis; pruritius; urticaria; alopecia. GI: Nausea; vomiting; anorexia; dry mouth; dysphagia; abdominal pain; mucositis; diarrhea; constipation. GU: Amenorrhea, azoospermia. HEMATOLOGIC: Bone marrow suppression; nadir at » 4 wk. OPHTHALMIC: Retinal hemorrhage; photophobia; diplopia; papilledema. RESPIRATORY: Acute interstitial pneumonitis. OTHER: Acute myelocytic leukemia; myelosclerosis; fever.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Not recommended. Children: Close clinical monitoring is mandatory. Toxicity, evidenced by tremors, convulsions, and coma, has occurred. 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 < 4000/mm³); thrombocytopenia (platelets < 100,000/mm³); 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. Renal/Hepatic function impairment: Undue toxicity may occur if used in patients with known impairment of renal or hepatic function. Carcinogenesis: Carcinogenesis in mice, rats, and monkeys has been reported. Mutagenesis: Procarbazine is mutagenic in a variety of bacterial and mammalian test systems. Fertility impairment: Azoospermia and antifertility effects associated with procarbazine coadministered with other antineoplastics for treating Hodgkin's disease have been reported.

 Administration/Storage

• Store capsules in light-resistant containers at room temperature.
• Administer PO. Give with or after meals.

 Assessment/Interventions

• Interrupt therapy for WBC < 4000/mm³ or platelet count < 100,000/mm³.
• Obtain baseline laboratory data prior to initiation of therapy. Monitor hemoglobin, hematocrit, WBC, differential, reticulocytes, and platelets ³ q 3 or 4 days after the start of infection. Bone marrow depression often occurs 2 to 8 wk after the start of infection.
• Evaluate hepatic and renal function prior to initiation of therapy.
• Repeat urinalysis, transaminases, alkaline phosphatase, and BUN at least weekly.

 Patient/Family Education

• Patients should restrict tyramine-containing foods. Instruct patients to avoid the following during procarbazine therapy: sympathomimetics (including nasal drops and cough medicines), local anesthetics, tricyclic antidepressants (eg, amitriptyline, imipramine), serotonin reuptake inhibitors, meperidine, dextromethorphan, and levodopa.
• May produce drowsiness and dizziness; patients should observe caution while driving or performing other tasks requiring alertness.
• Consumption of alcoholic beverages while taking procarbazine may cause a disulfiram-like reaction.
• Notify health care provider if cough, shortness of breath, thickened bronchial secretions, fever, chills, sore throat, unusual bleeding or bruising, black tarry stools, or vomiting of blood occurs.
• Medications may cause muscle or joint pain, nausea, vomiting, sweating, tiredness, weakness, constipation, headache, difficulty swallowing, loss of appetite, loss of hair, and mental depression; notify health care provider if these become pronounced.
• Avoid prolonged exposure to sunlight; photosensitivity may occur. Wear protective clothing and use sunscreens until tolerance is determined.
• Contraceptive measures are recommended during therapy for men and women.

Books@Ovid
Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts