Patient on Briviact (brivaracetam) 100 mg has a recent plasma concentration < 0.05 µg/mL; what should be done?

Undetectable Brivaracetam Level: Immediate Assessment and Management

A brivaracetam plasma concentration <0.05 µg/mL indicates either non-adherence, malabsorption, or significant drug-drug interaction with enzyme inducers—you must immediately assess medication adherence, review concomitant medications (particularly carbamazepine, phenytoin, phenobarbital, or rifampin), and consider dose escalation if the patient is experiencing breakthrough seizures.

Initial Assessment Steps

Verify Adherence and Timing

• Confirm the patient is actually taking the medication as prescribed, as undetectable levels most commonly reflect non-adherence rather than pharmacokinetic issues 1
• Verify the timing of blood draw relative to last dose—the sample should have been drawn as a trough level (immediately before the next scheduled dose) to accurately reflect steady-state concentrations 2
• Ensure steady-state conditions were present at time of sampling (at least 5 half-lives after any dose changes, typically 2-3 days for brivaracetam given its short half-life) 2

Evaluate for Drug-Drug Interactions

• Review all concomitant medications for strong enzyme inducers, particularly:
  • Carbamazepine, phenytoin, and phenobarbital/primidone can moderately lower brivaracetam plasma concentrations by 20-30% 1
  • Rifampin is a more potent CYP inducer and can substantially reduce brivaracetam levels 1
  • St. John's wort is another strong enzyme inducer that significantly impacts brivaracetam metabolism 1

Management Algorithm

If Non-Adherence is Confirmed

• Address barriers to adherence through patient education about seizure risk and medication importance
• Consider simplifying the regimen if complexity is the issue (brivaracetam can be dosed twice daily at 50-100 mg per dose) 3
• Recheck levels in 2-3 days after confirming adherence to verify therapeutic concentrations are achieved

If Patient is Adherent Without Enzyme Inducers

• Investigate malabsorption issues (gastrointestinal disease, recent surgery, or other medications affecting absorption)
• Increase the brivaracetam dose incrementally—therapeutic doses range from 50-200 mg/day, with responder rates of 32.7-55.8% at 50 mg/day and 37.8% at 200 mg/day 3
• Recheck plasma levels after achieving steady state at the new dose (3-5 days) 2

If Strong Enzyme Inducers are Present

• Consider dose adjustment when brivaracetam is coadministered with rifampin or other potent inducers 1
• For carbamazepine, phenytoin, or phenobarbital, no routine dose adjustment is typically needed, but clinical response should guide management 1
• If adding or discontinuing St. John's wort, exercise caution and monitor levels closely 1
• Alternative strategy: Consider switching from the enzyme-inducing AED to a non-inducing agent if clinically appropriate, as brivaracetam has minimal drug-drug interactions with most other AEDs 1

Clinical Context and Seizure Control

Assess Current Seizure Activity

• If the patient is experiencing breakthrough seizures with undetectable levels, this strongly suggests inadequate drug exposure requiring immediate dose escalation 4
• For urgent seizure situations, intravenous brivaracetam can be administered with loading doses of at least 2 mg/kg (median bolus 163 mg) showing 77.6% response rates 4, 5
• Loading doses below 1.9 mg/kg are associated with poor response in status epilepticus, so minimum 2 mg/kg is advisable in acute settings 5

If Seizures are Well-Controlled Despite Low Levels

• Do not automatically increase the dose if the patient is seizure-free, as clinical response is the ultimate endpoint, not plasma concentration alone 2
• However, undetectable levels (<0.05 µg/mL) are well below any therapeutic threshold and suggest the patient is not receiving meaningful drug exposure, making breakthrough seizures highly likely 3

Common Pitfalls to Avoid

• Do not assume the level is accurate without verifying proper sample timing—random levels rather than trough levels can be misleadingly low 2
• Do not ignore concomitant enzyme inducers—even "moderate" inducers like carbamazepine can significantly impact brivaracetam exposure in individual patients 1
• Do not delay intervention if breakthrough seizures are occurring—undetectable levels with active seizures require immediate dose escalation or alternative therapy 4
• Do not routinely monitor brivaracetam levels—therapeutic drug monitoring should be reserved for specific situations like suspected non-adherence, breakthrough seizures, or concern about drug interactions 2

Follow-Up Strategy

• Recheck brivaracetam level in 3-5 days after addressing adherence or adjusting dose to confirm therapeutic concentrations are achieved 2
• Target therapeutic range is not well-established for brivaracetam, but clinical trials show efficacy with doses of 50-200 mg/day 3
• Monitor for adverse effects (somnolence, dizziness, fatigue) when escalating dose, though brivaracetam is generally well-tolerated 6, 3
• Consider switching to oral brivaracetam at discharge if IV formulation was used acutely, with 86% of patients successfully transitioned in real-world practice 4