Can a patient with seizures secondary to cerebral metastases, who is intolerant to phenytoin, be switched to lamotrigine?

Yes, Switch from Phenytoin to Lamotrigine Immediately

You should discontinue phenytoin and initiate lamotrigine in this patient with cerebral metastases, as phenytoin is explicitly contraindicated in brain tumor patients according to EANO-ESMO guidelines, and lamotrigine is a recommended first-line alternative. 1, 2

Why Phenytoin Must Be Stopped

• Phenytoin is explicitly contraindicated in brain tumor patients per EANO-ESMO guidelines (Level III, Grade D recommendation) due to its enzyme-inducing properties that cause significant drug interactions with chemotherapy agents and corticosteroids. 1

• Phenytoin has critical interactions with dexamethasone, which is frequently used to manage cerebral edema in metastatic brain disease. 1

• Phenytoin toxicity is particularly problematic in cancer patients due to its narrow therapeutic window, non-linear kinetics, and high protein binding—small dose increases can rapidly cause confusion, nystagmus, agitation, abnormal gait, and hallucinations. 3

Lamotrigine as the Appropriate Alternative

• Lamotrigine is explicitly recommended as a first-line option by EANO-ESMO guidelines alongside levetiracetam for brain tumor-related seizures due to its lack of enzyme-inducing properties. 4, 1

• The non-enzyme-inducing profile of lamotrigine avoids drug interactions with chemotherapy, targeted therapies, and steroids (EANO: III, B; ESMO: III, D). 4, 1

• Lamotrigine demonstrates efficacy against partial and secondarily generalized tonic-clonic seizures, with good tolerability profiles in long-term use. 5

Practical Switching Strategy

• Initiate lamotrigine using a slow titration schedule to minimize the risk of rash (occurs in ~10% of patients), which is the most common cause of treatment withdrawal. 5

• Consider bridging with levetiracetam 1,000-3,000 mg/day for immediate seizure control while titrating lamotrigine, as lamotrigine requires several weeks to reach therapeutic levels. 1, 2

• Taper phenytoin gradually while initiating lamotrigine to avoid withdrawal seizures, though the urgency of discontinuing phenytoin due to drug interactions may warrant more rapid transition with levetiracetam bridge therapy. 1

Critical Monitoring Points

• Watch for maculopapular or erythematous rash during lamotrigine initiation—this risk is minimized through low, slow dosage titration. 5

• Continue anticonvulsants until local tumor control is achieved through surgery, radiation, or radiosurgery, then consider tapering within weeks if near-gross total resection was accomplished. 1, 2

• Obtain repeat MRI if seizures worsen during the transition, as this often indicates tumor progression rather than medication failure. 1, 2

Common Pitfall to Avoid

• Do not continue phenytoin "just because it's working"—the drug interaction risks with cancer therapies and steroids outweigh any perceived benefit of maintaining the current regimen. 1, 2