Pharmacokinetics, Safety, and Tolerability of Brivaracetam in Healthy Elderly Participants

Abstract

The pharmacokinetics, metabolism, safety, and tolerability of the antiseizure medication brivaracetam (BRV) were characterized in 16 healthy elderly participants (8 men/8 women) aged 65–78 years who received a single 200‐mg oral dose of BRV on day 1, followed by 200 mg twice daily from day 3 until day 12. BRV and three metabolites were determined in plasma and urine. Adverse events, vital signs, electrocardiograms, laboratory tests, general and neurological examinations, and psychometric rating scales were recorded at regular intervals. No clinically relevant changes or abnormalities were detected. The adverse events were similar to those observed in pivotal trials. Rating scales indicated transiently increased sedation and decreased alertness. BRV pharmacokinetics and metabolism were unchanged relative to younger populations. Based on our observations in this healthy elderly population receiving oral BRV 200 mg twice daily (twice the maximum recommended dose), dose reductions are not warranted relative to other, younger populations. Further investigations may be necessary in frail elderly populations aged >80 years.

New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

“…The medication activates GABAAR, causing increased neuronal excitability suppression, and exhibits neuroprotective effects [ 84 , 85 , 86 ]. GNX is administered for indications such as CDKL5 CDD [ 69 ]. The medication demonstrated a significant reduction in seizures in patients with CDD, cluster epilepsy, PCDH19, and treatment-resistant infantile spasms [ 73 , 80 , 81 , 82 ].…”

“…BRV is one of the substances that rapidly penetrates the blood–brain barrier, and its bioavailability is almost 100% [ 66 , 68 ]. The drug is metabolized in the liver with the involvement of CYP450, particularly CYP2C9 and CYP2C19 [ 69 , 70 ]. Patients using BRV have been noted to experience headaches, dizziness, drowsiness, back pain, fatigue, and irritability [ 71 ].…”

“…BRV is a drug approved in the European Union for adjunctive therapy in patients aged 2 years and older, while in the United States it is approved for monotherapy as well as adjunctive treatment in children aged 1 month and older [ 69 , 72 , 73 ]. The drug is used in patients with focal seizures, generalized seizures, drug-resistant epilepsy, and epileptic syndromes [ 72 , 74 , 75 , 76 ].…”

Narrative Review of Brivaracetam: Preclinical Profile and Clinical Benefits in the Treatment of Patients with Epilepsy

“…A phase I, open-label, repeated-dose study assessed the PK, metabolism, safety, and tolerability of BRV in 16 healthy elderly volunteers (65–78 years of age) [ 23 ]. Participants received a single dose of BRV (200 mg) on day 1, followed by 200 mg twice daily for 10 days (twice the maximum recommended dose [ 9 , 10 ]).…”

“…Safety and tolerability, adverse event profile, and PK and metabolism were similar to those observed in younger populations. No dose adjustments are therefore needed in the elderly (65–78 years of age), but it should be mentioned that there are no data for patients ≥ 80 years old [ 23 ].…”