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procarbazine (Matulane, Natulan, ibenzmethyzin)

Indications: - brain tumors (astrocytoma) - Hodgkin's disease (MOPP) & non-Hodgkins lymphoma - lung cancer (bronchogenic carcinoma) - multiple myeloma - polycythemia vera [4] Contraindications: - bone marrow aplasia Dosage: 1) oral: 50-200 mg/m2/day for 10-20 days every 3-4 weeks 2) MOPP: 100 mg/m2/day for 14 days every 4 weeks Capsule: 50 mg. Pharmacokinetics: 1) well absorbed orally 2) CNS levels approximately equal to serum levels 3) metabolized by the liver 4) eliminated in the urine 5) 1/2life 1 hour Monitor: complete blood count (CBC) Adverse effects: 1) common (> 10%) - pleural effusion, cough, amenorrhea, paresthesia, neuropathy, depression, manic reactions, hallucinations, dizziness, headache, nervousness, insomnia, nightmares, nystagmus, ataxia, disorientation, foot drop, decreased reflexes, tremors, confusion, seizures nausea/vomiting*, anorexia, abdominal pain, stomatitis, dysphagia, diarrhea, constipation, myelosuppression 2) less common (1-10%) - alopecia, hepatotoxicity, hyperpigmentation 3) uncommon (< 1%) - orthostatic hypotension, hypertensive crisis, nervousness, irritability, dermatitis, hypersensitivity rash, arthralgia, myalgia, nystagmus, diplopia, photophobia, flu-like syndrome, jaundice, hoarseness, somnolence, disulfiram-like reaction with alcohol, cessation of menses 4) other - prolonged myelosuppression - WBC & platelets moderate - onset 14 days - nadir 21 days - recovery 28 days - urinary frequency * severe nausea/vomiting occur frequently & may be dose- limiting; use non-phenothiazine anti-emetic when possible emetic potential 60-90% Drug interactions: 1) tricyclic antidepressants, benzodiazepines in combination lead to increased CNS toxicity 2) tyramine-rich foods lead to MAO reactions, hypertension 3) CNS-active agents 4) meperidine 5) dextromethorphan 6) local anesthetics Test interactions: increases serum K+ Mechanism of action: 1) alkylating agent, methylhydrazine derivative 2) interferes with DNA & RNA synthesis 3) S phase & G2 cell cycle-specific 4) MAO inhibitor properties

Interactions

drug adverse effects of alkylating agents

General

alkylating agent benzamide

Properties

MISC-INFO: elimination route KIDNEY 1/2life 8-12 HOURS pregnancy-category D

Database Correlations

PUBCHEM correlations

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
  4. Deprecated Reference

Component-of

cyclophosphamide/vincristine (Oncovin)/prednisone/procarbazine (C-MOPP) lomustine/procarbazine/vincristine (PCV) nitrogen mustard/vincristine (Oncovin)/prednisone/ procarbazine (MOPP)