Oxcarbazepine serum concentrations

Concurrent use of oxcarbazepine with ethinyl estradiol and levonoi estrel-containing contraceptives may render these agents less effective. Qxcar-bazepine may increase serum concentrations of phenytoin and decrease serum concentrations of lamotrigine (induction of uridine diphosphate glucuronosyltransferase). 

In a placebo-controlled study in healthy women, oxcarbazepine 900 mg/day reduced the serum concentrations of ethinylestradiol and levonorgestrel by about 50% (23). This confirms that oxcarbazepine may reduce the efficacy of the contraceptive pill, as does carbamazepine. Women taking oxcarbazepine should be given a contraceptive that contains 50 pg of ethinylestradiol and they should be monitored for signs of insufficient contraceptive cover, such as breakthrough bleeding. 

Hospitalization optimize dose and/or serum concentrations of lithium or valproate, then lithium or valproate atypical antipsychotic Alternative carbamazepine or oxcarbazepine atypical antipsychotic ... 

Gastric upset from CBZ may be diminished by taking the drug after meals. Common toxicities include blurred vision, dizziness, drowsiness, and ataxia. Tremor, depression, hyponatremia, and cardiac disturbances are seen at high serum concentrations. Idiosyncratic rashes are common rarer severe idiosyncratic effects include aplastic anemia, agranulocytosis, thrombocytopenia, and jaundice. Therefore, patients receiving CBZ should have periodic blood count determinations and liver function tests. Both CBZ and oxcarbazepine can reduce plasma 25-hydroxy vitamin D levels (45). CBZ increases levels of phenytoin and decreases levels of... 

In a second study, the effect of oxcarbazepine monotherapy for 18 months on bone turnover was longitudinally explored in 34 newly diagnosed prepubertal and pubertal children [227 ]. The serum concentrations of 25-hydroxycolecalciferol were significantly reduced by oxcarbazepine, while osteocalcin and gamma-glutamyl transferase activity were significantly increased compared with baseline values. Phosphorus, parathyroid hormone, and calcitonin concentrations and alkaline phosphatase activity increased non-significantly. In three patients who had... 

An investigation of the effects of various AEDs on serum concentrations of olanzapine was performed in 226 patients taking olanzapine in addition to VPA, lamotrigine plus VPA, CBZ, oxcarbazepine, gabapentin, levetiracetam, or topiramate [50 ]. Significantly lower serum concentrations of olanzapine were found in patients comedicated with VPA, VPA plus lamotrigine, and CBZ compared with controls. 

Oxcarbazepine Hyponatremia (serum sodium concentrations less than 125 mEq/L) has been reported and occurs more frequently during the first 3 months of therapy serum sodium concentrations should be monitored in patients receiving drugs that lower serum sodium concentrations (e.g., diuretics or drugs that cause inappropriate antidiuretic hormone secretion) or in patients with symptoms of hyponatremia (e.g., confusion, headache, lethargy, and malaise). Hypersensitivity reactions have occurred in approximately 25-30% of patients with a history of carbamazepine hypersensitivity and requires immediate discontinuation. 

Phenytoin increases high-density lipoprotein (HDL) cholesterol (118), and may also increase total cholesterol and serum triglyceride concentrations (SED-13,143) (119). In a 5-year prospective study with carbamazepine, there was a persistent rise in total cholesterol and HDL cholesterol, whereas triglycerides and low-density lipoprotein (LDL) cholesterol increased only transiently (120). In a more recent study, total cholesterol fell when 12 patients were switched from carbamazepine to oxcarbazepine, but HDL cholesterol and triglycerides were unchanged (121). In a comparison of 101 epileptic patients with matched controls, valproate was associated with lower total and LDL cholesterol, whereas carbamazepine was associated with higher HDL cholesterol and apolipoprotein A concentrations and phenobarbital with higher concentrations of total and HDL cholesterol and apolipoproteins A and B. The ratio of total to HDL cholesterol was reduced with valproate and carbamazepine but not with phenobarbital (122). 

In one series in which there were low serum sodium concentrations in patients taking oxcarbazepine, 25% had concentrations below 135 mmol/1 and 3% had concentrations below 125 mmol/1 (12). In most patients, the... 

A possible interaction of oxcarbazepine with ciclosporin has been reported after renal transplantation in a 32-year-old man (19). The ciclosporin trough semm concentration and serum sodium concentration fell after oxcarbazepine was added. 

Oxcarbazepine reduces serum felodipine concentrations, although less than carbamazepine does (20). 

In human liver microsomes with cDNA-expressed CYP2C19, oxcarbazepine and its 10-monohydroxy metabolite inhibited CYP2C19-mediated phenytoin metabolism at therapeutic concentrations (22). Thus, coadministration of oxcarbazepine with phenytoin could significantly increase serum phenytoin concentrations. 

Patients with hypersensitivity reactions to carbamazepine can be expected to show cross-sensitivity (e.g., rash) or related problems to oxcarbazepine. The improved toxicity profile for oxcarbazepine when compared to CBZ may result from absence of the epoxide or CBZ-iminoquinone metabolites (47). The most common side effects are headache, dizziness, nystagmus, blurred vision, somnolence, nausea, ataxia, and fatigue. The Incidence of adverse effects has been related to elevated serum MHD concentrations (52). Adverse effects on cognitive status, hyponatremia, and serious dermatological reactions have been reported, as has hyponatremia (53). 

Striano S, Striano P, DiNocera P, et ai. Relationship between serum mono-hydroxy-carbazepine concentrations and adverse effects in patients with epilepsy on high-dose oxcarbazepine therapy. Epilepsy Res 2006 69 170-176. 

Electrolyte balance In a prospective study in 73 patients with epilepsy and older than 17 years taking oxcarbazepine who had repeated measurements of serum sodium concentrations, those who had hyponatremia before oxcarbazepine therapy and those who took it for non-epileptic disorders were excluded [220 ]. TTie frequency of hyponatremia (serum sodimn <134mmol/l) was 25% ( = 18), and 8.2%... 

Drug formulations Extended-release oxcarbazepine should cause fewer adverse effects because of the less marked peak serum oxcarbazepine concentration before metabolism to its active monohydroxy derivate. In an open study, 27 patients with difiicult-to-treat localization-related epilepsies who had been taking immediate-release oxcarbazepine were abruptly switched to extended-release oxcarbazepine in identical dosages and the concentrations of oxcarbazepine and its active metabolite were measured before and after the switch [229. The new formulation was associated with significantly fewer adverse effects and better quality of life, and this was explained by lower peak oxcarbazepine concentrations. 

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