Low blood sodium is seen in 20-30% of people taking oxcarbazepine and 8-12% of those experience severe hyponatremia. Some side effects, such as headaches, are more pronounced shortly after a dose is taken and tend to fade with time (60 to 90 minutes). Other side effects include stomach pain, tremor, rash, diarrhea, constipation, decreased appetite and dry mouth. Photosensitivity is a potential side-effect and people could experience severe sunburns as a result of sun exposure.Oxcarbazepine may lead to hypothyroxinemia. The well-known reduction in free and total thyroxine concentration may be due to both peripheral and central mechanisms. Interactions
Oxcarbazepine, licarbazepine and many other common drugs influence each other through interaction with the Cytochrome P450 family of enzymes. This leads to a cluster of dozens of common drugs interacting with one another to varying degrees, some of which are especially noteworthy:
Oxcarbazepine and licarbazepine are potent inhibitors of CYP2C19 and thus have the potential to increase plasma concentration of drugs, which are metabolized through this pathway. Other antiepileptics, which are CYP2C19 substrates and thus may be metabolised at a reduced rate when combined with oxcarbazepine include diazepam, hexobarbital, mephenytoin, methylphenobarbital, nordazepam, phenobarbital, phenytoin, primidone. However, many classes of drugs are ligands to CYP2C19. In addition, oxcarbazepine and licarbazepine are CYP3A4 and CYP3A5 inducers and thus have the potential to decrease the plasma concentration of CYP3A4 and CYP3A5 substrates. Drugs which are CYP3A4 or CYP3A5 substrates and therefore may have reduced efficacy include calcium channel antagonists against high blood pressure and oral contraceptives.
However, whether the extent of CYP3A4/5 induction at therapeutic doses reaches clinical significance is unclear. Furthermore, for example phenytoin and phenobarbital are known to reduce plasma levels of licarbazepine through induction of Cytochrome P450 enzymes. Pharmacology
Oxcarbazepine is a prodrug, which is largely metabolized to its pharmacologically active 10-monohydroxy derivative licarbazepine (sometimes abbreviated MHD). Oxcarbazepine and MHD exert their action by blocking voltage-sensitive sodium channels, thus leading to the stabilization of hyper-excited neural membranes, suppression of repetitive neuronal firing and diminishment propagation of synaptic impulses. Furthermore, anticonvulsant effects of these compounds could be attributed to enhanced potassium conductance and modulation of high-voltage activated calcium channels. Pharmacokinetics
Oxcarbazepine has high bioavailability upon oral administration. In a study in humans, only 2% of oxcarbazepine remained unchanged, 70% were reduced to licarbazepine; the rest were minor metabolites. The half-life of oxcarbazepine is considered to be about 2 hours, whereas licarbazepine has a half-life of nine hours. Through its chemical difference to carbamazepine metabolic epoxidation is avoided, reducing hepatic risks. Licarbazepine is metabolised by conjugation with Glucuronic acid. Approximately 4% are oxidised to the inactive 10,11-dihydroxy derivative. Elimination is almost completely renal, with faeces accounting to less than 4%. 80% of the excreted substances are to be attributed to licarbazepine or its glucuronides. Pharmacodynamics
Both oxcarbazepine and licarbazepine were found to show anticonvulsant properties in seizure models done on animals. These compounds had protective functions whenever tonic extension seizures were induced electrically, but such protection was less apparent whenever seizures were induced chemically.