Drug Index

Procarbazine

 
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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 :

Always consult the current treatment protocol for details of dosage and scheduling.

Hodgkin’s disease:

Oral 50 mg/sqm daily for 7 days; increase to 100 mg/sqm until maximum response is achieved or leukopenia/thrombocytopenia ensues.


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 :

Dose in Renal Impairment GFR (mL/min)
20-5050–100% of dose
10-2050–100% of dose. Use with caution
<1050–100% of dose. Use with caution

Dose in Patients undergoing Renal Replacement Therapies
CAPDUnknown dialysability. Dose as in GFR<10 mL/min
HDUnlikely to be dialysed. Dose as in GFR<10 mL/min
HDF/High fluxUnknown dialysability. Dose as in GFR<10 mL/min
CAV/VVHDUnknown dialysability. Dose as in GFR=10–20 mL/min

Hepatic Dose :

Pre-existing severe hepatic impairment:
Use is not recommended.

If hepatotoxicity develops during therapy and based on adult data:
If liver transaminases levels are between 1.6 and 6 times the upper limit of normal (ULN): Reduce dose by 1/4th.
If liver transaminases levels reach greater than 6 times the ULN: use with caution, apply clinical judgement.
If serum bilirubin is greater than 5 mg/dL and liver transaminases levels are greater than >3 times the ULN: use is not recommended.
05/25/2020 08:55:45 Procarbazine
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