DRUG STUDY AND INFORMATION FORM Generic Name: Procarbazine Trade Name: Matulane Drug Class: Miscellaneous Alkylating

Drugs (Methylhydrazines) Structure/Chemistry: Methylhydrazine derivative

Pharmacodynamics

Mechanism of Action: Methylates DNA. Activated procarbazine can produce chromosomal damage, including chromatid breaks and translocations, consistent with its mutagenic and carcinogenic actions.

Pharmacologic Effects: Genomic damage

Drug Resistance or Tolerance: Resistance develops when used as a single agent. Increased MGMT (repairs methylated guanine) expression.

Pharmacokinetics

Absorption: 100 mg/m2/day for 10-14 days in combination regimens, such as MOPP (nitrogen mustard, oncovin, procarbazine, and prednisone) for Hodgkins disease. This drug is rarely still used, however. Distribution:

Elimination: t1/2 of 10 mins

Metabolism: Extensively metabolized to highly reactive alkylating agents (azo, methylazoxy, and benzylazoxy intermediates) by CYP-mediated hepatic oxidative metabolism

Adverse Side Effects/Toxicity: Thrombocytopenia and leukopenia (begins during second week, disappears 2 weeks after treatment cessation). Also, GI disturbances such as mild nausea, vomiting, diarrhea, and rash. Behavioral disturbances have also been reported. Highly carcinogenic, mutagenic, and teratogenic, especially to those receiving radiation therapy. Causes infertility. Drug Interactions: Augments activities of sedatives. Do not use CNS depressants concomitantly. Avoid alcohol intake.

Therapeutic uses: Formerly used for Hodgkins disease but now used as a second-line therapy in malignant brain tumors

Miscellaneous: