Carbamazepine oxcarbazepine similarities

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

Oxcarbazepine Similar to carbamazepine shorter half-life but active metabolite with longer duration and fewer interactions reported ... 

Doses of oxcarbazepine need to be about one-third higher than those of carbamazepine for similar results... 

Oxcarbazepine (Trileptal) (10,ll-dihydro-10-oxocar-bamazepine) is a keto analog of carbamazepine. Oxcarbazepine functions as a prodrug, in that it is almost immediately converted to its main active metabolite, a 10-monohydroxy derivative, which is inactivated by glucuronide conjugation and eliminated by renal excretion. Its mechanism of action is similar to that of carbamazepine. Oxcarbazepine is a less potent enzyme inducer than is carbamazepine, and substitution of oxcarbazepine for carbamazepine is associated with increased levels of phenytoin and valproic acid, presumably because of reduced induction of hepatic enzymes. Oxcarbazepine does not induce the hepatic enzymes involved in its own degradation. Although oxcarbazepine does not appear to... 

One chronic adverse effect that is of concern is osteoporosis.32,33 Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, and valproate have all been shown to decrease bone mineral density, even after only 6 months of treatment. Data on the relationship between other AEDs and osteoporosis are not currently available. Multiple studies have shown the risk of osteoporosis due to chronic AED use to be similar to the risk with chronic use of corticosteroids. Patients taking carbamazepine, phenytoin, phenobarbital, or valproate for longer than 6 months should take supplemental calcium and vitamin D. Additionally routine monitoring for osteoporosis should be performed every 2 years, and patients should be instructed on ways to protect themselves from fractures. 

Oxcarbazepine has mood-stabilizing effects similar to those of carbamaz-epine, but with milder side effects, no autoinduction of metabolizing enzymes, and potentially fewer drug interactions. There are fewer data supporting its efficacy than there are for carbamazepine s efficacy. 

Oxcarbazepine is a derivative of carbamazepine and although its precise mechanism of action is unknown it has similar properties as carbamazepine and is also used for the treatment of primary generalized tonic-clonic seizures and partial seizures. Also the adverse effects are similar to those of carbamazepine. However the drug interaction profile is different as oxcarbazepine has hardly any enzyme-inducing capacity. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

Oxcarbazepine is closely related to carbamazepine and is useful in the same seizure types, but it may have an improved toxicity profile. Oxcarbazepine has a half-life of only 1-2 hours. Its activity, therefore, resides almost exclusively in the 10-hydroxy metabolite, to which it is rapidly converted and which has a half-life similar to that of carbamazepine, ie, 8-12 hours. The drug is mostly excreted as the glucuronide of the... 

Oxcarbazepine is less potent than carbamazepine, both in animal models of epilepsy and in epileptic patients clinical doses of oxcarbazepine may need to be 50% higher than those of carbamazepine to obtain equivalent seizure control. Some studies report fewer hypersensitivity reactions to oxcarbazepine, and cross-reactivity with carbamazepine does not always occur. Furthermore, the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interactions. Although hyponatremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine. 

Iminostilbenes Carbamazepine (Tegretol) Oxcarbazepine (Trileptal) Similar to hydantoins... 

Oxcarbazepine is structurally similar to carbamazepine, A/hich is thought to be teratogenic in humans... 

Two doses of oxcarbazepine have been compared in a double-blind, parallel-group, randomized trial in patients with uncontrolled partial-onset epilepsy who had previously taken carbamazepine monotherapy (10). After two open phases in 143 patients, 96 were randomized to oxcarbazepine 300 or 2400 mg/day for 126 days. The time to meet an exit criterion was significantly in favor of oxcarbazepine 2400 mg/day. In aU, 24 of the 47 non-rando-mized patients withdrew because of an adverse event, most commonly dizziness, ataxia, headache, nansea, vomiting, or fatigne. Three withdrew becanse of laboratory abnormalities, one each with leukopenia, hjrponatre-mia, and hjrperglycemia. Headache, dizziness, and nansea were the only adverse events that occurred in more than 10% in either gronp. Similar adverse events were reported in the randomized patients, but none withdrew. 

A 31-year-old man developed ocnlogjric crises after starting to take oxcarbazepine, and the freqnency of these episodes correlated with the dosage of the dmg (11). Similar episodes had occnrred in the past after exposure to carbamazepine. The implantation of a vagus nerve stimulator led to the disappearance of the oculogyric crises. 

Hyponatremia occurs in an appreciable proportion of patients taking oxcarbazepine (12), perhaps more often than with carbamazepine it is usually asymptomatic. Among 2166 oxcarbazepine-treated patients in the manufacturer s database, the incidence of sodium concentrations below 135 mmol/1 was 22% (13). There was marked hyponatremia (sodium concentrations below 125 mmol/1) in 2.7% overall and the risk increased with age 0% below 6 years, 0.5% 6-17 years, 3.4% at 18-64 years, and 7.3% above 65 years. The incidence of adverse events was similar in all sodium categories the absence of symptoms suggests that the fall in sodium concentrations was not precipitous. 

Oxcarbazepine. Oxcarbazepine (10,11-dihydro-10-oxo-5i -dibenz [6,/] azepine-5-car-boxamide or 10,ll,dihydro-10-oxo carbamazepine, 12) was designed to avoid the dose-dependent side effects noted in some patients (e.g., nausea, headache, dizziness, ataxia, diplopia) and to minimize enzyme induction and drug-drug interactions displayed by carbamazepine (195,196). As shown previously (Fig. 6.3), the change in structure results in a difference in metabolism. Although both carbamazepine and oxcarbazepine are ultimately converted to the inactive trans diol, oxcarbazepine does not form the active 10,11-epoxide intermediate, but does form the active 10-hydroxy metabolite MHD (197). The mechanism of action of oxcarbazepine is very similar... 

In non-psychotic patients, oxcarbazepine and valproate have been shown to exert similar efficacy in controlling mood symptoms in schizoaffective disorder. It is reasonable (although not tested) to use them in combination with SCAs in iller patients. Carbamazepine seems to be equipotent to lithium in controlling mood symptoms however, lithium is probably less effective than carbamazepine in improving depressive episodes as part of schizoaffective disorder. All in all, lithium and valproate are the first-line treatment of acute non-psychotic mania. Lithium is most effective in euphoric mania and valproate is probably more effective in mixed states. The time to onset of action of lithium may be somewhat slower than that of valproate, although data are not well established. 

The anticoagulant effects of warfarin can be markedly reduced by carbamazepine, and two case reports surest phenprocoumon is similarly affected. Oxcarbazepine appears not to interact significantly with warfarin. 

In a study in 12 healthy subjects citalopram 40 mg daily for 2 weeks caused no change in the pharmacokinetics of carbamazepine 400 mg once daily. An approximate 30% decrease in citalopram levels occurred in 6 patients taking citalopram 40 to 60 mg daily when they were given carbamazepine 200 to 400 mg daily for 4 weeks. Despite this decrease, the combination was considered clinically useful. Similarly, two patients with epilepsy, major depression, and panic disorder had increased citalopram levels (one had an improved antidepressant response, but the other patient experienced tremor and increased anxiety) when their treatment with carbamazepine was replaced by oxcarbazepine. ... 

The AUCs of oxcarbazepine and its active metabolite (monohydroxyoxcarbazepine) were reduced by phenobarbital, by 43% and 25%, respectively. There were no other significant effects on the pharmacokinetics of oxcarbazepine. Another study found that phenytoin caused a 29% reduction in the AUC of monohydroxyoxcarbazepine. Another study found that the serum levels of monohydroxyoxcarbazepine were not affected by phenobarbital or phenytoin but its further conversion to dihydroxyoxcarbazepine was increased. Since the conversion to dihydroxyoxcarbazepine is a minor step in the metabolism of monohydroxyoxcarbazepine, the overall antiepileptic action of oxcarbazepine is unlikely to be altered. Correspondingly, a study found that phenytoin 100 to 375 mg daily increased the clearance of the active metabolite, monohydroxyoxcarbazepine by almost 40%." The AUC of monohydroxyoxcarbazepine was also 40% lower in the presence of carbamazepine. Similarly, carbamazepine, phenobarbitaL and phenytoin were found to increase the apparent clearance of monohydroxyoxcarbazepine by 31 to 35% in a study in children. ... 

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