What should you pay attention to when combining brivaracetam/brivaracetam with other anti-epileptic drugs?

Brivaracetam/Brivaracetam is a new anti-epileptic drug that acts as a highly selective synaptic vesicle protein 2A (SV2A) ligand, which stabilizes neuronal activity by regulating neurotransmitter release. Due to its rapid onset of action, relatively single metabolic pathway, and low central side effects, brivaracetam is widely used in the adjuvant treatment of refractory partial seizures. However, in clinical practice, this drug often needs to be used in combination with other antiepileptic drugs (AEDs) to achieve a synergistic effect or control intractable epileptic seizures. At this time, the issue of drug interactions is of particular concern.

Brivaracetam is mainly metabolized in the liver by CYP2C19, but its pharmacokinetics are relatively stable and not easily affected by mild CYP enzyme inhibitors. However, if combined with potent enzyme inducers such as carbamazepine, phenytoin, etc., their metabolic clearance may be accelerated, resulting in a decrease in blood concentration and affecting the efficacy. Appropriate dosage adjustments may be necessary at this time based on clinical response. In addition, although the combined use with Levetiracetam is similar in mechanism, no clear advantages have been found, and both drugs belong to the SV2A regulatory category. Combined use may aggravate neuropsychiatric side effects such as fatigue and mood swings.

In terms of psychiatric symptoms, although brivaracetam has better emotional tolerance than levetiracetam, when combined with other drugs with central nervous system depressant effects such as benzodiazepines (such as lorazepam) or gabapentin, it may still increase the risk of sedation, drowsiness and cognitive impairment, especially in elderly patients or those with reduced liver and kidney function, which requires more careful evaluation. Although some drugs such as lamotrigine or sodium valproate do not significantly change the pharmacokinetics of brivaracetam, if they are used in combination, attention should be paid to whether the drug effects will be superimposed or cancel each other out.

Reference materials:https://www.briviact.com/