Adult: In combination with other chemotherapeutic drugs, such as part of MOPP regimen (nitrogen mustard, vincristine, prednisone): 100 mg/m2 daily for 10-14 days of each 4- to 6-week cycle. As monotherapy: Initially, 50 mg daily, increased gradually by 50 mg daily up to 250-300 mg daily in divided doses. Continue doses until max possible response is achieved or unacceptable toxicity occurs. Maintenance: 50-150 mg daily, continued until a total dose of at least 6,000 mg is reached. Alternatively, initial dose of 2-4 mg/kg daily for the 1st week is recommended, then increased to 4-6 mg/kg daily until max response is obtained or unacceptable toxicity. Maintenance: 1-2 mg/kg daily. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline). Dosage and chemotherapeutic regimens may vary among individual products and between countries (refer to local treatment protocols). Child: Dosage must be individualised. In combination with other chemotherapeutic drugs: Same as adult dose. As monotherapy: Initially, 50 mg/m2 daily for the 1st week, then increased to 100 mg/m2 until max possible response is achieved or unacceptable toxicity occurs. Maintenance: 50 mg/m2 daily. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline). Dosage and chemotherapeutic regimens may vary among individual products and between countries (refer to local treatment protocols).
Renal Impairment
Severe: Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Contraindications
Pre-existing severe leucopenia or thrombocytopenia, inadequate bone marrow reserve. Severe renal and hepatic impairment. Pregnancy and lactation.
Special Precautions
Patient with CV or cerebrovascular disease, phaeochromocytoma or epilepsy. Not indicated for use in the management of non-malignant disease. Avoid live vaccines during or within at least 6 months of therapy. Mild to moderate renal and hepatic impairment. Children.
Adverse Reactions
Significant: Bone marrow suppression (e.g. leucopenia, thrombocytopenia, neutropenia), haemorrhage or bleeding tendencies; CNS effects (e.g. paraesthesias, neuropathies, confusion), CNS depression, gastrointestinal toxicities (e.g. nausea, vomiting, diarrhoea, stomatitis); haemolysis and/or presence of Heinz inclusion bodies in erythrocytes; secondary malignancies (e.g. acute myeloid leukaemia, lung cancer); hypersensitivity reactions. General disorders and administration site conditions: Fever. Infections and infestations: Infection. Hepatobiliary disorders: Jaundice, hepatic dysfunction. Investigations: Abnormal LFTs. Metabolism and nutrition disorders: Loss of appetite. Musculoskeletal and connective tissue disorders: Myalgia. Psychiatric disorders: Lethargy. Renal and urinary disorders: Haematuria, urinary frequency. Reproductive system and breast disorders: Azoospermia, ovarian failure, decreased fertility. Respiratory, thoracic and mediastinal disorders: Pneumonitis. Skin and subcutaneous tissue disorders: Dermatitis, pruritus, hyperpigmentation, rash.
Monitor haematologic status (e.g. CBC with differential, platelet and reticulocyte count) at least every 3 or 4 days; urinalysis. Evaluate renal and hepatic function prior to and during therapy. Assess for signs and symptoms of infection, CNS and gastrointestinal toxicities.
Overdosage
Symptoms: Severe nausea, vomiting, dizziness, hallucinations, depression, convulsion, hypotension or tachycardia. Management: General supportive treatment. May administer activated charcoal in patients presenting within 1 hour of ingestion. Give prophylaxis against possible infection; monitor blood counts weekly for at least 3 weeks or more frequently depending on symptoms.
Drug Interactions
May diminish the effects of live vaccines. May potentiate the effects of barbiturates, narcotic analgesics (particularly pethidine), agents with anticholinergic effect (e.g. phenothiazine derivatives, TCAs), other CNS depressants (e.g. anaesthetic agents), and anti-hypertensive drugs. May increase risk of agranulocytosis with clozapine. May decrease the absorption of phenytoin and cardiac glycosides. May increase risk of hypersensitivity reactions with enzyme-inducing antiepileptics.
Food Interaction
Increased risk of disulfiram-like reaction with alcohol. May rarely cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome) with tyramine-containing foods (e.g. aged cheese, pickled or cured meats, fava beans, soy sauce, wines).
Action
Description: Procarbazine is a methylhydrazine derivative cytostatic agent with weak MAOI activity. Its exact mechanism is not clearly defined; however, it is known to inhibit transmethylation of methionine into transfer ribonucleic acid (RNA) thus suppressing deoxyribonucleic acid (DNA), RNA and protein synthesis. Additionally, it may directly damage DNA by alkylation. Pharmacokinetics: Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 0.5-1 hour. Distribution: Crosses the blood-brain barrier and distributed into the CSF. Metabolism: Rapidly metabolised primarily in the liver via oxidation into methylazoxy-procarbazine and benzylazoxy-procarbazine (active metabolites), then undergoes further metabolism in the kidneys into inactive metabolites. Excretion: Via urine (Approx 70% as N-isopropylterepththalamic acid [major urinary inactive metabolite], approx 5% as unchanged drug). Elimination half-life: Approx 1 hour.
Chemical Structure
Procarbazine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4915, Procarbazine. https://pubchem.ncbi.nlm.nih.gov/compound/Procarbazine. Accessed Mar. 25, 2021.
Storage
Store below 25°C. Protect from light. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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