What are the considerations for using Phenytoin (antiepileptic medication) in elderly patients?

Phenytoin Use in Elderly Patients: Critical Considerations

Phenytoin should generally be avoided or used with extreme caution in elderly patients due to increased toxicity risk, drug-drug interactions, and availability of safer alternatives like levetiracetam or valproate. 1

Key Age-Related Concerns

Altered Pharmacokinetics in the Elderly

• Elderly patients show early signs of toxicity due to impaired liver function and slower drug metabolism, requiring lower initial doses than younger adults 2, 3
• The half-life of phenytoin is prolonged in elderly patients, increasing accumulation risk 4
• Free (unbound) phenytoin levels can be dangerously elevated even when total serum levels appear therapeutic, particularly in elderly patients with hypoalbuminemia 5
• Elderly patients require more frequent monitoring of both total and free phenytoin levels, with dose adjustments based on individual Vmax and Km values 3

Heightened Risk of Serious Adverse Effects

• Phenytoin encephalopathy manifesting as cognitive impairment and cerebellar syndrome is particularly concerning in elderly patients already susceptible to balance disturbances and cognitive dysfunction 4
• Cardiovascular adverse effects including hypotension (12% risk) and arrhythmias are more dangerous in elderly patients, especially those over 75 years with cardiovascular comorbidities 1, 6
• Infusion rates must be slower than 50 mg/min in elderly patients with continuous ECG and blood pressure monitoring required 7, 6

Problematic Drug-Drug Interactions

• The 2019 AGS Beers Criteria specifically warns about trimethoprim-sulfamethoxazole (TMP-SMX) combined with phenytoin increasing risk of phenytoin toxicity 1
• Phenytoin induces CYP450 enzymes, creating numerous drug interactions particularly problematic in elderly patients on polypharmacy 1, 2
• Macrolide antibiotics (excluding azithromycin) and ciprofloxacin interactions are specifically highlighted as concerns in older adults 1

Safer Alternative Anticonvulsants for Elderly Patients

First-Line Alternatives

• Levetiracetam 30 mg/kg IV offers 68-73% efficacy with minimal cardiovascular effects and no cardiac monitoring requirements, making it ideal for elderly patients 8, 9
• Valproate 20-30 mg/kg IV demonstrates 88% efficacy with 0% hypotension risk compared to phenytoin's 12% risk 8, 7
• Both alternatives avoid the enzyme-inducing properties that create problematic drug interactions in elderly patients on multiple medications 1

When Phenytoin Must Be Used

• Start with lower doses than standard adult dosing and monitor closely for early toxicity signs 2, 3
• Measure both total and free phenytoin levels, using the Sheiner-Tozer equation to calculate free levels when albumin is low 5
• Infusion rate should not exceed 25-50 mg/min with continuous cardiac monitoring 6
• Watch specifically for confusional states, ataxia, and cerebellar signs requiring immediate dose reduction or discontinuation 2, 4

Critical Monitoring Parameters

• Serum albumin levels must be checked to interpret total phenytoin levels accurately in elderly patients 5
• Monitor for vitamin D deficiency, osteoporosis risk, and bone fractures with chronic use 2
• Assess for hyperglycemia in diabetic elderly patients, as phenytoin inhibits insulin release 2
• Regular evaluation for gingival hyperplasia, cognitive decline, and cerebellar dysfunction 4, 10

Common Pitfalls to Avoid

• Never rely solely on total serum phenytoin levels in elderly patients with low albumin—calculate or measure free levels 5
• Do not use phenytoin as seizure prophylaxis in asymptomatic elderly patients, as this practice is ineffective and exposes them to unnecessary risks 1
• Avoid rapid IV infusion rates (>50 mg/min) which significantly increase mortality risk in elderly patients 6
• Do not continue phenytoin long-term in elderly patients with marked cognitive impairment, balance problems, or cerebellar signs—switch to alternatives 4