Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs

Abstract

Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

Effects of cannabidiol on brivaracetam plasma levels

“…The major metabolic pathway involves non–CYP‐dependent hydrolysis, and the secondary pathway involves CYP2C19‐mediated oxidation . Previous studies suggest that brivaracetam has a low potential for clinically relevant interactions . However, BRV level is often not measured routinely and interactions could be missed.…”

Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy

“…BRV has a short half‐life and reaches a steady state after 2 days 1,2 . Previous studies reported a low potential for clinically relevant interactions with other AEDs 3 . In a population PK study, BRV exposure was reduced by 26%, 21%, and 19% with comedication with carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PB) or primidone (PRM), respectively, although this comedication did not have a significant effect on response 4 .…”

Interactions Between Anti-Epileptic Drugs and Contraceptives: A Review

“…2,9 Oxcarbazepine has a low enzyme induction potential, but unfortunately exerts a similar effect to carbamazepine on hormonal contraceptives. 9,14 Therefore, if oral contraception is indicated, use in combination with a barrier method such as condom or vaginal diaphragm is suggested. 15,16 These anticonvulsant drugs do not alter the efficacy of depot medroxyprogesterone acetate injection, copper intrauterine device or levonorgestrel release, therefore these may be another option.…”