Procarbazine

Procarbazine

Procarbazine hydrochloride, a methylhydrazine derivative with monoamine oxidase inhibitor (MAOI) properties, is used to treat Hodgkin’s disease and primary and metastatic brain tumors.

Pharmacokinetics

After oral administration, procarbazine is well absorbed. It readily crosses the blood-brain barrier and is well distributed into CSF.

Metabolism and excretion

Procarbazine is metabolized rapidly in the liver and must be activated metabolically by microsomal enzymes. It’s excreted in urine, primarily as metabolites. Respiratory excretion of the drug occurs as methane and carbon dioxide gas.

Pharmacodynamics

An inert drug, procarbazine must be activated metabolically in the liver before it can produce various cell changes. It can cause chromosomal damage, suppress mitosis, and inhibit DNA, RNA, and protein synthesis. Cancer cells can quickly develop resistance to procarbazine.

Pharmacotherapeutics

Procarbazine is used in the treatment of Hodgkin’s disease, lymphoma, and brain cancer.

Drug interactions

Interactions with procarbazine can be significant.

• It produces an additive effect when administered with CNS depressants.
• Taken with meperidine, it may result in severe hypotension and death.

Warning!

Adverse reactions to procarbazine

Late-onset bone marrow suppression is the most common dose-limiting toxicity associated with procarbazine. Interstitial pneumonitis (lung inflammation) and pulmonary fibrosis (scarring) may also occur.

A bad start

Initial procarbazine therapy may induce flulike symptoms, including fever, chills, sweating, lethargy, and muscle pain.

Gut reactions

GI reactions include nausea, vomiting, stomatitis, and diarrhea.

Mirroring MAO

Because of procarbazine’s MAOI properties, hypertensive reactions may occur when it’s administered concurrently with sympathomimetics, antidepressants, and tyramine-rich foods.