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Related Experiment Videos

Phenytoin intoxication induced by fluvoxamine.

K Mamiya1, K Kojima, E Yukawa

  • 1Hizen National Hospital, Saga, Japan.

Therapeutic Drug Monitoring
|February 24, 2001
PubMed
Summary

Fluvoxamine, a selective serotonin reuptake inhibitor, can cause dangerous phenytoin intoxication by significantly increasing its serum concentration. This drug interaction highlights the importance of monitoring phenytoin levels when coadministered with fluvoxamine.

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Area of Science:

  • Pharmacology
  • Clinical Toxicology
  • Drug Interactions

Background:

  • Phenytoin is an anticonvulsant medication with a narrow therapeutic index.
  • Selective serotonin reuptake inhibitors (SSRIs) like fluvoxamine are commonly prescribed for depression and anxiety.
  • CYP2C9 and CYP2C19 are key enzymes involved in phenytoin metabolism.

Observation:

  • A patient experienced phenytoin intoxication after initiating fluvoxamine therapy.
  • Phenytoin serum concentrations rose from 16.6 to 49.1 microg/mL without changes in phenytoin dosage.
  • Clinical signs of phenytoin toxicity, such as ataxia, were observed during coadministration.

Findings:

  • Fluvoxamine coadministration led to a dramatic increase in phenytoin serum levels.
  • The patient's CYP2C9 and CYP2C19 genotypes were wild-type (CYP2C9*1/*1 and 2C19*1/*1), suggesting genetic factors did not predispose to high phenytoin levels.

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  • The interaction is likely due to fluvoxamine's inhibition of CYP2C9 and CYP2C19, enzymes crucial for phenytoin clearance.

    • Implications:

    • Clinicians should exercise caution when prescribing fluvoxamine concurrently with phenytoin.
    • Therapeutic drug monitoring of phenytoin is essential in patients receiving fluvoxamine to prevent toxicity.
    • This case underscores the potential for significant drug-drug interactions involving SSRIs and narrow therapeutic index drugs.