Brivaracetam Found Safe in Combination with Other Epilepsy Drugs

In a poster presented at the 69th Annual Meeting of the American Academy of Neurology, researchers from the University of Cincinnati studied brivaracetam (Briviact) for drug-drug interactions (DDI) using data from a wealth of previous phase 2 and phase 3 studies. Brivaracetam is an antiepileptic drug that was approved for use by the FDA in 2016.

The drug was approved because it was shown effective in reducing seizure frequency when combined with other agents. Upon approval, Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said he was “pleased that patients with epilepsy have a new treatment option,” citing the wide range of responses people with epilepsy have to various drugs designed for it.

The drug is a racetam, and it’s approved as an add-on treatment for those aged 16 or older who have partial, or focal, seizures. Given its status as an add-on, any DDIs it may have are important to know. Though its exact working mechanism is unknown, it has a selective affinity for protein 2A (SV2A) in the brain, potentially contributing to its anticonvulsant effect. It’s typically taken twice daily in doses ranging between 50 and 200mg.

In the study, the drugs impact on enzyme-inducing antiepileptic drugs (AEDs) including carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PBI) was assessed in 5 different phase 2 and 3 trials, and its impact on CYP3A was investigated in healthy controls using midazolam as a probe.

“In patients with epilepsy, brivaracetam did not alter the concentrations of AEDs lamotrigine, levetiracetam, oxcarbazepine, topiramate, valproate, carbamazepine, lacosamide, phenobarbital, pregabalin, phenytoin or zonisamide, in a clinically-relevant manner,” in any manner, the team led by Brian Moseley, MD, concluded. A “modest increase” in PHT exposure was, however, observed when combined with a “supra-therapeutic” 400mg daily dose of brivaracetam.

The drug did significantly increase CBZ epoxide concentration in a dose-related manner, but that increase was not observed to indicate symptoms of toxicity. It did not significantly inhibit nor induce CYP3A. The authors also found it had no clinically significant effects on oral contraceptives.

The only notable exception in terms of DDIs was rifampin, which the study calls a “potent, enzyme-inducing antibiotic.” Brivaracetam exposure was nearly halved by the product, requiring an increased dose “of up to 100% in patients on concomitant rifampin.” It was the only counteraction that brought a recommendation of dose adjustment.

The findings of the meta-analysis led the authors to conclude that brivaracetam “is unlikely to have clinically relevant interactions with any commonly prescribed AEDs,” and that dosage adjustments would not be required when co-administered with CBZ, PB, PHT or contraceptives, though monitoring of PHT levels was recommended.

The study was sponsored by UCB Pharma, who make Briviact.