Brands, Medical Use, Clinical Data
- Tablet (150 mg, 300 mg and 600 mg film coated)
Brands / Synonyms
Oxaprozin; Oxaprozine; Oxcarbamazepine; Oxcarbazepine (Subject to patent free); Trileptal; Trileptal
For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy.
Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat the same conditions.
Mechanism of Action
The exact mechanism by which oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of oxcarbazepine occurs primarily through its 10-monohydroxy metabolite (MHD). In vitro studies indicate an MHD-induced blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neuronal membranes, inhibition of repetitive neuronal discharges, and diminution of propagation of synaptic impulses.
Completely absorbed following oral administration. Food has no effect on the rate and extent of absorption of oxcarbazepine.
Isolated cases of overdose with oxcarbazepine have been reported. The maximum dose taken was approximately 24,000 mg. All patients recovered with symptomatic treatment.
Biotrnasformation / Drug Metabolism
Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). MHD is metabolized further by conjugation with glucuronic acid.
Oxcarbazepine should not be used in patients with a known hypersensitivity to oxcarbazepine or to any of its components.
Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially
important effects on plasma concentrations of other drugs. In addition,
several AEDís that are cytochrome P450 inducers can decrease plasma concentrations
of oxcarbazepine and MHD.
Oxcarbazepine was evaluated in human liver microsomes to determine its
capacity to inhibit the major cytochrome P450 enzymes responsible for
the metabolism of other drugs. Results demonstrate that oxcarbazepine
and its pharmacologically active 10-monohydroxy metabolite (MHD) have
little or no capacity to function as inhibitors for most of the human
cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1,
CYP4A9 and CYP4A11) with the exception of CYP2C19 and CYP3A4/5. Although
inhibition of CYP 3A4/5 by OXC and MHD did occur at high concentrations,
it is not likely to be of clinical significance. The inhibition of CYP-2C19
by OXC and MHD, however, is clinically relevant.
In vitro, the UDP-glucuronyl transferase level was increased, indicating
induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine
were observed. As MHD, the predominant plasma substrate, is only a weak
inducer of UDP-glucuronyl transferase, it is unlikely to have an effect
on drugs that are mainly eliminated by conjugation through UDP-glucuronyl
transferase (e.g., valproic acid, lamotrigine).
In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome
P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine
calcium antagonists and oral contraceptives, resulting in a lower plasma
concentration of these drugs.
As binding of MHD to plasma proteins is low (40%), clinically significant
interactions with other drugs through competition for protein binding
sites are unlikely.
Potential interactions between Trileptal and other AEDs were assessed
in clinical studies. The effect of these interactions on mean AUCs and
Cmin are summarized in Table 2:
Table 2: Summary of AED interactions with Trileptal
Dose of AED (mg/day)
Trileptal dose (mg/day)
Influence of Trileptal on AED Concentration (Mean
change, 90% Confidence Interval)
Influence of AED On MHD Concentration (Mean change,
90% Confidence Interval)
|| 40% decrease [CI: 17% decrease, 57% decrease]
| 14% increase [CI: 2% increase, 24% increase]
||25% decrease [CI: 12% decrease, 51% decrease]
||30% decrease [CI: 3% decrease, 48 % decrease]
||up to 40% increase3 [CI: 12% increase, 60 % increase]
||18% decrease [CI: 13% decrease, 40 % decrease]
1- nc denotes a mean change of less than 10%
3- Mean increase in adults at high Trileptal doses
In vivo, the plasma levels of phenytoin increased by up to 40%,
when Trileptal was given at doses above 1200 mg/day. Therefore, when using
doses of Trileptal greater than 1200 mg/day during adjunctive therapy,
a decrease in the dose of phenytoin may be required. The increase of phenobarbital
level, however, is small (15%) when given with Trileptal.
Strong inducers of cytochrome P450 enzymes (i.e. carbamazepine, phenytoin
and phenobarbital) have been shown to decrease the plasma levels of MHD
No autoinduction has been observed with Trileptal.
Co-administration of Trileptal with an oral contraceptive has been shown
to influence the plasma concentrations of the two hormonal components,
ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of
EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI:
38-52] in another study [1,2]. The mean AUC values of LNG were decreased
by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another
study. Therefore, concurrent use of Trileptal with hormonal contraceptives
may render these contraceptives less effective. Studies with other oral or implant contraceptives have not been
After repeated co-administration of Trileptal, the AUC of felodipine
was lowered by 28% [90% CI: 20-33].
Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels
Other drug interactions
Cimetidine, erythromycin and dextropropoxyphene had no effect on the
pharmacokinetics of MHD. Results with warfarin wshow no evidence of interaction
with either single or repeated doses of Trileptal.