Summary

The combination of procarbazine and phenelzine represents a potentially life-threatening drug interaction due to both medications having monoamine oxidase inhibitor (MAOI) properties. This interaction can lead to severe hypertensive crisis, serotonin syndrome, and other serious cardiovascular complications.

Introduction

Procarbazine is an alkylating chemotherapy agent primarily used in the treatment of Hodgkin's lymphoma, often as part of the MOPP or BEACOPP regimens. It belongs to the class of antineoplastic agents and possesses weak monoamine oxidase inhibitor activity. Phenelzine is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) antidepressant used to treat major depressive disorder, particularly atypical depression and treatment-resistant cases. Both medications affect monoamine oxidase enzymes, which metabolize neurotransmitters like serotonin, norepinephrine, and dopamine.

Mechanism of Interaction

The interaction between procarbazine and phenelzine occurs through their combined inhibition of monoamine oxidase enzymes (MAO-A and MAO-B). Procarbazine, while primarily an anticancer agent, has weak but clinically significant MAOI activity. When combined with phenelzine, a potent MAOI, there is an additive effect on monoamine oxidase inhibition. This leads to excessive accumulation of neurotransmitters including serotonin, norepinephrine, and dopamine. The result is potentially dangerous increases in sympathetic nervous system activity, leading to severe hypertension, hyperthermia, and possible serotonin syndrome.

Risks and Symptoms

The primary risks of combining procarbazine and phenelzine include hypertensive crisis with potentially fatal blood pressure elevations, serotonin syndrome characterized by altered mental status, neuromuscular abnormalities, and autonomic instability. Patients may experience severe headaches, chest pain, cardiac arrhythmias, stroke, and hyperthermia. Additional risks include excessive CNS stimulation, agitation, confusion, and cardiovascular collapse. The interaction is considered contraindicated due to the high risk of serious adverse events and potential fatality.

Management and Precautions

The combination of procarbazine and phenelzine should be avoided entirely. If a patient requires treatment with procarbazine and has been taking phenelzine, the MAOI should be discontinued at least 14 days before starting chemotherapy to allow for enzyme regeneration. Conversely, phenelzine should not be initiated until at least 14 days after completing procarbazine therapy. Healthcare providers should carefully review all medications before prescribing either drug. If inadvertent co-administration occurs, immediate medical attention is required with continuous monitoring of vital signs, blood pressure management with appropriate antihypertensive agents, and supportive care for any complications that arise.

Phenelzine interactions with food and lifestyle

Phenelzine requires strict dietary restrictions due to its mechanism as a monoamine oxidase inhibitor (MAOI). Patients must avoid foods high in tyramine, including aged cheeses, cured meats, fermented foods, aged or smoked fish, certain alcoholic beverages (especially red wine, beer, and aged spirits), overripe fruits, and yeast extracts. Consuming tyramine-rich foods while taking phenelzine can cause a dangerous hypertensive crisis with symptoms including severe headache, chest pain, rapid heartbeat, and potentially life-threatening blood pressure elevation. Alcohol consumption should be avoided or strictly limited as it can interact with phenelzine to cause unpredictable blood pressure changes and enhanced sedation. Patients should also avoid dietary supplements containing tyramine or tyrosine. These dietary restrictions must continue for at least 2 weeks after discontinuing phenelzine due to the drug's irreversible enzyme inhibition. All patients taking phenelzine should receive comprehensive dietary counseling and a detailed list of foods to avoid from their healthcare provider.