How to manage subtherapeutic Dilantin (Phenytoin) levels in an ESRD patient on dialysis with seizures?

Management of Subtherapeutic Phenytoin Levels in ESRD Patient on Dialysis

For this 85-year-old female with ESRD on dialysis, Wegener granulomatosis, and seizures with a subtherapeutic Dilantin level <2.5, I recommend increasing the phenytoin dose to 400 mg every 8 hours orally, with close monitoring of serum levels and clinical response.

Assessment of Current Situation

The patient is currently receiving Dilantin (phenytoin) 100 mg every 8 hours, but has a significantly subtherapeutic level (<2.5 μg/mL), well below the therapeutic range of 10-20 μg/mL 1. This places her at high risk for breakthrough seizures and potentially status epilepticus.

Dosing Considerations in ESRD

Several important factors must be considered when managing phenytoin in this patient:

• ESRD and dialysis: Patients with ESRD may have altered phenytoin pharmacokinetics
• Age: At 85 years old, she may have decreased drug metabolism
• Comorbidities: Wegener granulomatosis and ESRD can affect drug metabolism and protein binding
• Current dose: 100 mg every 8 hours (300 mg/day) is inadequate based on the very low level

Management Algorithm

Step 1: Loading Dose

• Administer an oral loading dose of phenytoin to rapidly achieve therapeutic levels
• For adults, the recommended loading dose is 1 gram divided into three doses (400 mg, 300 mg, 300 mg) administered at two-hour intervals 1
• This loading approach should be done in a monitored setting with frequent serum level determinations 1

Step 2: Maintenance Dose Adjustment

• After loading, increase maintenance dose to 400 mg every 8 hours (1200 mg/day)
• The satisfactory maintenance dosage for most adults is one 100 mg capsule three to four times daily, but an increase up to two capsules (200 mg) three times daily may be necessary 1
• Given the severely subtherapeutic level, the higher end of dosing is warranted

Step 3: Monitoring

• Check phenytoin level 24 hours after loading dose
• Monitor for signs of toxicity including nystagmus, ataxia, slurred speech, and confusion
• Adjust dose based on clinical response and serum levels
• Target therapeutic range: 10-20 μg/mL 1

Special Considerations for ESRD Patients

1. Protein binding: Phenytoin is highly protein-bound (90-95%) 2, and ESRD patients often have hypoalbuminemia, which can affect interpretation of total phenytoin levels

2. Monitoring: More frequent monitoring of free (unbound) phenytoin levels is preferred over total levels in ESRD patients

3. Dialyzability: Phenytoin is minimally dialyzable, so no specific post-dialysis supplementation is typically required

4. Risk of hyperphosphatemia: Avoid using fosphenytoin (IV phenytoin prodrug) in this patient as it can cause acute hyperphosphatemia in ESRD patients 3

Alternative Considerations

If the patient continues to have subtherapeutic levels or breakthrough seizures despite dose optimization:

1. Evaluate for medication interactions: Check for drugs that might increase phenytoin metabolism

2. Consider alternative agents: Levetiracetam may be a better option for ESRD patients as it has minimal protein binding and predictable clearance with dialysis 4

3. Assess compliance: Ensure the patient is taking medication as prescribed

Evidence-Based Rationale

Research has shown that some patients require higher than standard doses to achieve seizure control 5. A study by Leppik et al. demonstrated that patients with subtherapeutic levels who were seizure-free did not benefit from dose increases, but this patient is clearly not well-controlled at the current dose 6.

The 2014 clinical policy from the Annals of Emergency Medicine supports individualized dosing of phenytoin with careful monitoring of serum levels to achieve optimal seizure control 4.

Monitoring for Adverse Effects

• Cardiovascular: Monitor for hypotension and cardiac arrhythmias
• Neurological: Watch for signs of cerebellar dysfunction, nystagmus, and cognitive impairment
• Hematological: Monitor complete blood count periodically
• Dermatological: Watch for rash or hypersensitivity reactions

By following this approach, you should be able to safely optimize this patient's phenytoin therapy while minimizing the risk of breakthrough seizures and adverse effects.