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Phenytoin-induced methadone withdrawal

T G Tong, S M Pond, M J Kreek

Annals of Internal Medicine

|March 1, 1981

Summary

Phenytoin use in patients on methadone maintenance therapy can trigger moderate opiate withdrawal symptoms by accelerating methadone metabolism. Dosage adjustments are crucial when starting or stopping phenytoin.

Area of Science:

Pharmacology
Clinical Pharmacy
Addiction Medicine

Background:

Opioid use disorder treatment often involves methadone maintenance therapy (MMT).
Drug interactions can affect MMT efficacy and patient safety.

Purpose of the Study:

To investigate the effect of phenytoin on methadone pharmacokinetics and withdrawal symptoms in MMT patients.

Main Methods:

Assessed opiate withdrawal symptoms in methadone-maintained volunteers.
Measured methadone plasma concentrations and urinary metabolite excretion.
Analyzed the impact of therapeutic phenytoin doses.

Main Results:

Phenytoin initiation led to moderately severe opiate withdrawal within 3-4 days.

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A significant decrease in the area under the methadone plasma concentration-time curve was observed.

An increased ratio of pyrrolidine-to-metabolite excretion indicated accelerated methadone metabolism.

Conclusions:

Phenytoin significantly accelerates methadone metabolism.
Clinicians must anticipate methadone dosage adjustments when initiating or discontinuing phenytoin in MMT patients.
This interaction poses a risk for precipitated withdrawal symptoms.