Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Behavioral Abnormalities and Psychotic Symptoms
- KEPPRA may cause behavioral abnormalities and psychotic symptoms. Patients treated with KEPPRA should be monitored for psychiatric signs and symptoms.
Somnolence and Fatigue
- KEPPRA may cause somnolence and fatigue. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on KEPPRA to gauge whether it adversely affects their ability to drive or operate machinery.
- Somnolence and asthenia occurred most frequently within the first 4 weeks of treatment. In general, the incidences of somnolence and fatigue in the pediatric partial onset seizure studies, and in pediatric and adult myoclonic and primary generalized tonic-clonic seizure studies were comparable to those of the adult partial onset seizure studies.
- KEPPRA can cause hematologic abnormalities. Hematologic abnormalities occurred in clinical trials and included decreases in red blood cell (RBC) counts, hemoglobin, and hematocrit, and increases in eosinophil counts. Decreased white blood cell (WBC) and neutrophil counts also occurred in clinical trials. Cases of agranulocytosis have been reported in the postmarketing setting.
Increase in Blood Pressure
- Monitor patients 1 month to <4 years of age for increases in diastolic blood pressure.
- added...drug rash with eosinophilia and systemic symptoms (DRESS)
WARNINGS AND PRECAUTIONS
- A total of 13.3% of adult KEPPRA-treated patients and 37.6% of pediatric KEPPRA-treated patients (4 to 16 years of age) compared to 6.2% and 18.6% of adult and pediatric placebo patients respectively, experienced nonpsychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder...
Serious Dermatological Reactions
- Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults treated with levetiracetam. The median time of onset is reported to be 14 to 17 days, but cases have been reported at least four months after initiation of treatment…
- Partial Onset Seizures: In the controlled cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the KEPPRA-treated group had high eosinophil count values that were possibly clinically significant (≥10% or ≥0.7X109/L).
Blood Pressure Increases
- In a randomized, placebo-controlled study in patients aged 1 month to <4 years of age, a significantly higher risk of at least one measured increase in diastolic blood pressure was observed in the KEPPRA-treated patients (17%) compared to the placebo-treated patients (2%)...
Seizure Control During Pregnancy
- Physiological changes may gradually decrease plasma levels of levetiracetam throughout pregnancy. This decrease is more pronounced during the third trimester. It is recommended that patients be monitored carefully during pregnancy. Close monitoring should continue through the postpartum period especially if the dose was changed during pregnancy.