Procarbazine

Mechanism :

The mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA.

Indication :

• Hodgkin’s lymphoma
• Gliomas
• Medulloblastoma

Contraindications :

Contraindicated in patients with known hypersensitivity to the drug or inadequate marrow reserve as demonstrated by bone marrow aspiration. Due consideration of this possible state should be given to each patient who has leukopenia, thrombocytopenia or anemia. Full blood count should be satisfactory before commencing treatment.

Dosing :

Adverse Effect :

Myelosuppression, nausea, vomiting, diarrhea, CNS toxicity (paraesthesia, ataxia, dizziness, headaches, nightmares, depression and insomnia), and hallucinations are common. Rarely, pulmonary toxicity, possibly because of hypersensitivity reaction; nystagmus, diplopia, papilledema and photophobia.

Interaction :

No cross-resistance with other chemotherapeutic agents, radiotherapy or steroids has been demonstrated.
Procarbazine: May exacerbate respiratory depression, if taken in conjunction with CNS depressants.
Antidepressants and Sympathomimetics: Procarbazine has weak MAOI activity and may precipitate hypertensive crisis, agitation and tremors if taken in conjunction with some antidepressants and sympathomimetics. Avoid tyramine-containing foods e.g. cheese, marmite etc.
Alcohol: A disulfiram-type reaction may occur if taken with alcohol and CNS depression may be accentuated.

Renal Dose :

Hepatic Dose :