No

Antineoplastic Agent, Alkylating Agent

Treatment of Hodgkin's disease, non-Hodgkin's lymphoma, brain tumor, bronchogenic carcinoma

D

Hypersensitivity to procarbazine or any component, or pre-existing bone marrow aplasia, alcohol ingestion

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered; use with caution in patients with pre-existing renal or hepatic impairment; modify dosage in patients with renal or hepatic impairment, or marrow disorders; reduce dosage with serum creatinine >2 mg/dL or total bilirubin >3 mg/dL; procarbazine possesses MAO inhibitor activity. Procarbazine is a carcinogen which may cause acute leukemia; procarbazine may cause infertility.

>10%:

Central nervous system: Mental depression, manic reactions, hallucinations, dizziness, headache, nervousness, insomnia, nightmares, ataxia, disorientation, confusion, seizure, CNS stimulation

Gastrointestinal: Severe nausea and vomiting occur frequently and may be dose-limiting; anorexia, abdominal pain, stomatitis, dysphagia, diarrhea, and constipation; use a nonphenothiazine antiemetic, when possible

Emetic potential: Moderately high (60% to 90%)

Time course of nausea/vomiting: Onset: 24-27 hours; Duration: variable

Hematologic: Thrombocytopenia, hemolytic anemia

Myelosuppressive: May be dose-limiting toxicity; procarbazine should be discontinued if leukocyte count is <4000/mm³ or platelet count <100,000/mm³

WBC: Moderate

Platelets: Moderate

Onset (days): 14

Nadir (days): 21

Recovery (days): 28

Neuromuscular & skeletal: Weakness, paresthesia, neuropathies, decreased reflexes, foot drop, tremors

Ocular: Nystagmus

Respiratory: Pleural effusion, cough

1% to 10%:

Dermatologic: Hyperpigmentation

Hepatic: Hepatotoxicity

Neuromuscular & skeletal: Peripheral neuropathy

<1%: Orthostatic hypotension, hypertensive crisis, irritability, somnolence, dermatitis, alopecia, pruritus, hypersensitivity rash, disulfiram-like reaction, cessation of menses, jaundice, arthralgia, myalgia, diplopia, photophobia, pneumonitis, hoarseness, secondary malignancy, allergic reactions, flu-like syndrome

Symptoms of overdose include arthralgia, alopecia, paresthesia, bone marrow suppression, hallucinations, nausea, vomiting, diarrhea, seizures, coma

Treatment is supportive, adverse effects such as marrow toxicity may begin as late as 2 weeks after exposure

Increased toxicity:

Sympathomimetic amines (epinephrine and amphetamines) and antidepressants (tricyclics) should be used cautiously with procarbazine.

Barbiturates, narcotics, phenothiazines, and other CNS depressants can cause somnolence, ataxia, and other symptoms of CNS depression

Alcohol has caused a disulfiram-like reaction with procarbazine; may result in headache, respiratory difficulties, nausea, vomiting, sweating, thirst, hypotension, and flushing

Protect from light

Mechanism of action is not clear, methylating of nucleic acids; inhibits DNA, RNA, and protein synthesis; may damage DNA directly and suppresses mitosis; metabolic activation required by host

Absorption: Oral: Rapid and complete

Distribution: Crosses the blood-brain barrier and distributes into CSF

Metabolism: In the liver and kidney

Half-life: 1 hour

Elimination: In urine and through respiratory tract (<5% as unchanged drug) and 70% as metabolites

Refer to individual protocols. Dose based on patient's ideal weight if the patient is obese or has abnormal fluid retention. Oral:

BMT aplastic anemia conditioning regimen: 12.5 mg/kg/dose every other day for 4 doses

Hodgkin's disease: MOPP/IC-MOPP regimens: 100 mg/m²/day for 14 days and repeated every 4 weeks

Neuroblastoma and medulloblastoma: Doses as high as 100-200 mg/m²/day once daily have been used

Adults: Initial: 2-4 mg/kg/day in single or divided doses for 7 days then increase dose to 4-6 mg/kg/day until response is obtained or leukocyte count decreased <4000/mm³ or the platelet count decreased <100,000/mm³; maintenance: 1-2 mg/kg/day

In MOPP, 100 mg/m²/day on days 1-14 of a 28-day cycle

Dosing in renal/hepatic impairment: Use with caution, may result in increased toxicity

Alcohol: Avoid use, including alcohol-containing products

Food: Avoid foods with high tyramine content

CBC with differential, platelet and reticulocyte count, urinalysis, liver function test, renal function test.

Dizziness, nervousness, insomnia, confusion, mania, depression, and hallucinations are common

May cause myelosuppression; use caution with clozapine and carbamazepine; procarbazine possesses MAOI activity; avoid with antidepressants, narcotics, phenothiazines, and foods containing tyramine

No information available to require special precautions

No effects or complications reported

Take as directed. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Avoid aspirin and aspirin-containing substances. Avoid alcohol; may cause acute disulfiram reaction - flushing, headache, acute vomiting, chest and/or abdominal pain. Avoid tyramine-containing foods (aged cheese, chocolate, pickles, aged meat, wine, etc). You may experience mental depression, nervousness, insomnia, nightmares, dizziness, confusion, or lethargy (use caution when driving or engaging in tasks that require alertness until response to drug is known); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). You may experience rash or hair loss (reversible), loss of libido, increased sensitivity to infection (avoid crowds and infected persons). Report persistent fever, chills, sore throat; unusual bleeding; blood in urine, stool (black stool), or vomitus; unresolved depression; mania; hallucinations; nightmares; disorientation; seizures; chest pain or palpitations; or difficulty breathing. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects. Breast-feeding is not recommended.

Capsule, as hydrochloride: 50 mg

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Longo DL, Young RC, Wesley M, et al, "Twenty Years of MOPP Therapy for Hodgkin's Disease," J Clin Oncol, 1986, 4(9):1295-306.

Rodriguez LA, Prados M, Silver P, et al, "Re-evaluation of Procarbazine for the Treatment of Recurrent Malignant Central Nervous System Tumors," Cancer, 1989, 64(12):2420-3.

Spivack SD, "Procarbazine," Ann Intern Med, 1974, 81:795-800.