In a 76‑year‑old bed‑bound female nursing‑home resident taking levetiracetam (Keppra) 500 mg twice daily with a serum level <5 µg/mL, how should her therapy be managed?

Management of Subtherapeutic Levetiracetam Level in a Bed-Bound Nursing Home Resident

Immediate Assessment and Decision Framework

In this 76-year-old bed-bound nursing home resident with a levetiracetam level <5 µg/mL, you should first determine whether she is actively seizing or has had recent breakthrough seizures, then assess whether deprescribing is more appropriate than dose escalation given her frail status and limited life expectancy. 1

Step 1: Evaluate Current Clinical Status

• Check for recent seizure activity by reviewing nursing documentation for the past 30 days and questioning staff about any witnessed events, as breakthrough seizures indicate true therapeutic failure requiring intervention 2
• Assess medication compliance by verifying administration records, as non-compliance is the most common cause of subtherapeutic levels in nursing home residents 2
• Review renal function with current creatinine clearance, as elderly patients have approximately 50% reduced levetiracetam clearance compared to younger adults, yet this patient's low level suggests either non-absorption, non-administration, or a dosing error 3, 4

Step 2: Consider Deprescribing vs. Optimization

For bed-bound nursing home residents with limited life expectancy, deprescribing levetiracetam should be strongly considered unless there is documented recent seizure activity. 1

• Deprescribing criteria that apply to this patient:

  • Bed-bound status indicates advanced frailty 1
  • Nursing home residence places her in a population where tools like STOPP-NH and NORGEP-NH recommend evaluating all preventive medications for appropriateness 1
  • Antiepileptic prophylaxis without recent seizures may represent low-value care in this population 1

• If she has NOT had seizures in the past 6–12 months: Consider tapering levetiracetam by 250–500 mg every 1–2 weeks while monitoring for breakthrough seizures, as the medication may no longer be necessary and contributes to polypharmacy burden 1

Step 3: If Continuing Therapy is Warranted

If she has had documented seizures within the past 6 months or has a high-risk seizure etiology (prior stroke, brain tumor, traumatic brain injury), optimize the current regimen rather than deprescribe. 1, 2

Dosing Optimization Strategy:

• Increase to levetiracetam 1000 mg twice daily (from current 500 mg twice daily), as this is the minimum dose shown to achieve therapeutic levels in elderly patients with normal renal function 5, 6
• Recheck level in 3–5 days after steady state is achieved (levetiracetam reaches steady state in 2 days with twice-daily dosing) 3
• Target trough level of 12–20 µg/mL for seizure control, though the therapeutic range is not rigidly defined and individual response varies 4

Renal Dosing Adjustments:

• If creatinine clearance 30–50 mL/min: Use 500–750 mg every 12 hours 2
• If creatinine clearance <30 mL/min: Use 250–500 mg every 12 hours 2
• Elderly patients typically require 30–40% lower doses than younger adults due to age-related decline in renal function 3, 4

Step 4: Monitor for Adverse Effects

Elderly patients are at significantly higher risk for levetiracetam-induced delirium, somnolence, and behavioral changes. 7

• Watch for new-onset confusion, agitation, or lethargy within 24–48 hours of dose increases, as delirium can occur even at standard doses in elderly patients 7
• Assess for excessive sedation that may worsen her bed-bound status and increase aspiration risk 4
• If neuropsychiatric symptoms develop: Discontinue levetiracetam immediately, as symptoms typically resolve within 24 hours of the last dose 7

Critical Pitfalls to Avoid

• Do not reflexively increase the dose without first confirming medication administration and compliance, as dosing errors are common in nursing homes and may explain the subtherapeutic level 4
• Do not add a second antiepileptic drug before optimizing levetiracetam monotherapy to maximum tolerated dose, as polypharmacy increases fall risk and drug interactions in frail elderly patients 2
• Do not ignore the opportunity to deprescribe in a bed-bound patient with no recent seizures, as quality of life should take priority over seizure prophylaxis in this population 1
• Avoid valproate as an alternative or add-on agent if the patient is female and any possibility of pregnancy exists, though this is unlikely at age 76 2

Alternative Considerations

• If levetiracetam is ineffective or poorly tolerated: Consider switching to lamotrigine or lacosamide as non-enzyme-inducing alternatives with favorable side-effect profiles in elderly patients 1
• Avoid phenytoin, carbamazepine, and phenobarbital due to significant drug interactions, cognitive impairment, and increased fall risk in elderly nursing home residents 1, 2