procarbazine (Matulane, Natulan, ibenzmethyzin)

Indications

• brain tumors (astrocytoma)
• Hodgkin's disease (MOPP) & non-Hodgkins lymphoma
• lung cancer (bronchogenic carcinoma)
• multiple myeloma
• polycythemia vera

Contraindications

• bone marrow aplasia

pregnancy category = d

Dosage

• oral: 50-200 mg/m2/day for 10-20 days every 3-4 weeks
• MOPP: 100 mg/m2/day for 14 days every 4 weeks

Capsule: 50 mg.

Pharmacokinetics

• well absorbed orally
• CNS levels approximately equal to serum levels
• metabolized by the liver
• eliminated in the urine
• 1/2life 1 hour

elimination via kidney

1/2life = 8-12 hours

Monitor

complete blood count (CBC)

Adverse effects

• 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
• less common (1-10%)
  • alopecia, hepatotoxicity, hyperpigmentation
• 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
• 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 adverse effects of alkylating agents

Drug interactions

• tricyclic antidepressants, benzodiazepines in combination lead to increased CNS toxicity
• tyramine-rich foods lead to MAO reactions, hypertension
• CNS-active agents
• meperidine
• dextromethorphan
• local anesthetics

Test interactions

increases serum K+

Mechanism of action

• alkylating agent, methylhydrazine derivative
• interferes with DNA & RNA synthesis
• S phase & G2 cell cycle-specific
• MAO inhibitor properties

More general terms

• benzamide
• alkylating agent

Component of

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

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4915
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9703
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=441273