Do Keppra (Levetiracetam) or Xcopri (Cenobamate) cause thrombocytopenia?

Keppra (Levetiracetam) Can Cause Thrombocytopenia, While Xcopri (Cenobamate) Has No Reported Association

Levetiracetam (Keppra) can cause thrombocytopenia as a rare but documented adverse effect, while there is no evidence that cenobamate (Xcopri) causes low platelet counts.

Levetiracetam and Thrombocytopenia

Evidence from Drug Label

• The FDA-approved drug label for levetiracetam explicitly lists thrombocytopenia as a post-marketing adverse event 1
• The label states: "thrombocytopenia, pancytopenia (with bone marrow suppression identified in some of these cases)" have been reported in patients receiving levetiracetam worldwide 1

Case Reports and Studies

• Multiple case reports have documented levetiracetam-induced thrombocytopenia:
  • A 6.5-year-old boy developed thrombocytopenia requiring platelet transfusion 5 weeks after starting levetiracetam; platelet counts normalized after drug discontinuation 2
  • A patient with glioblastoma multiforme and partial epilepsy developed thrombocytopenia attributed to levetiracetam after ruling out other causes 3
  • A 64-year-old patient with symptomatic epilepsy developed thrombocytopenia that resolved rapidly after levetiracetam discontinuation 4

Incidence and Recognition

• A retrospective study of 758 hospitalized patients on levetiracetam found only 1 clear case of levetiracetam-induced thrombocytopenia, suggesting it is a rare adverse effect 5
• The study concluded that "LEV-induced thrombocytopenia is a rare but reversible complication of LEV therapy" 5

Cenobamate (Xcopri) and Thrombocytopenia

• There is no evidence in the provided materials suggesting that cenobamate causes thrombocytopenia
• None of the guidelines or drug information provided mentions thrombocytopenia as an adverse effect of cenobamate

Clinical Implications

Monitoring Recommendations

• For patients on levetiracetam:
  • Monitor platelet counts, particularly in the first few months of therapy
  • Be vigilant for signs of thrombocytopenia: easy bruising, petechiae, bleeding from gums or nose, blood in urine or stool 6
  • The risk appears highest within the first few weeks to months of therapy based on case reports 2, 4

Management of Thrombocytopenia

• If thrombocytopenia develops while on levetiracetam:
  1. Consider discontinuation of levetiracetam if platelet counts drop significantly
  2. Monitor platelet counts until normalization
  3. Consider alternative antiepileptic medication (potentially cenobamate)
  4. Case reports suggest platelet counts typically normalize rapidly after discontinuation 4

Risk Assessment

• A platelet count nadir of 125 × 10^9/L has been identified as a threshold below which bleeding risk increases linearly 6
• Thrombocytopenia in patients on medications is associated with significantly increased risk of thrombotic events, MI, major bleeding, and in-hospital mortality 6

Conclusion

For patients requiring antiepileptic therapy who have a history of or are at risk for thrombocytopenia, cenobamate may be preferable to levetiracetam based on the available evidence regarding hematologic adverse effects. When prescribing levetiracetam, clinicians should be aware of the rare but documented risk of thrombocytopenia and monitor platelet counts accordingly.