Hyponatremia oxcarbazepine

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. 

Drug overdose Of 16 796 toxic exposures to antiepileptic drugs (phenytoin, valproic acid, and carbamazepine) in the USA in 2006, 12 resulted in death, as reported by the US Toxic Surveillance System [67 ]. Some specific problems determined by overdose of some old and new antiepileptic drugs have been briefly reviewed. For example, topiramate can cause a significant metabolic acidosis, lamotrigine Stevens-Johnson syndrome, oxcarbazepine hyponatremia, and levetiracetam psychosis. Possible adoption of guidelines for critical care management of overdose are discussed. 

Oxcarbazepine Modulate sodium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 600-1200 mg/day. Start at 300 mg twice daily and titrate upward as indicated by response Half-life Not established Parent drug 2 hours 1 0-monohydroxy metabolite 9 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding 40% Primary elimination route Hepatic Diplopia, dizziness, somnolence Hyponatremia, 25-30% cross sensitivity in patients with hypersensitivity to carbamazepine... 

Adverse Effects Adverse effects due to oxcarbazepine include drowsiness, dizziness, gastrointestinal upset, and hyponatremia, the latter two of which may be more likely than with carbamazepine. It is less likely than carbamazepine to cause hematologic abnormalities.34... 

Oxcarbazepine Sedation Dizziness Ataxia Nausea Rash Hyponatremia... 

Neurosensory side effects (e.g., diplopia, blurred vision, nystagmus, ataxia, dizziness, and headache) are the most common, occurring in 35% to 50% of patients initially. It may induce hyponatremia, and the incidence may increase with age. Hyponatremia occurs less frequently than with oxcarbazepine. 

The most frequently reported side effects are dizziness, nausea, headache, diarrhea, vomiting, upper respiratory tract infections, constipation, dyspepsia, ataxia, and nervousness. It generally has fewer side effects than pheny-toin, valproic add, or carbamazepine. Hyponatremia has been reported in up to 25% ofpatients and is more likely in the elderly. About 25% to 30% of patients who have had a rash with carbamazepine will have a cross-reaction with oxcarbazepine. 

Hyponatremia Clinically significant hyponatremia generally occurred during the first 3 months of treatment with oxcarbazepine, although there were patients who first developed a serum sodium less than 125 mmol/L greater than 1 year after initiation of therapy. Most patients who developed hyponatremia were asymptomatic, but patients in the clinical trials were frequently monitored and some had their oxcarbazepine dose reduced or discontinued or had their fluid intake restricted for hyponatremia. When oxcarbazepine was discontinued, normalization of serum sodium generally occurred within a few days without additional treatment. 

Oxcarbazepine is typically started at a dosage of 150 mg twice a day and titrated by 300 mg/day at weekly intervals. Therapeutic dosages are in the range of 450 mg twice a day to 1,200 mg twice a day. The conversion from carbamazepine to oxcarbazepine is approximately 1 to 1.5. Oxcarbazepine has a higher risk of hyponatremia than does carbamazepine. Serum sodium should be monitored in patients at risk for hyponatremia, such as the elderly or patients who are also taking diuretics. Stevens-Johnson syndrome and toxic epidermal necrolysis may occur between 3 and 10 times more frequently in oxcarbazepine-treated patients than in the general population. Median time from starting treatment to the development of these serious reactions is 19 days. 

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. 

A 49-year-old woman, who was taking oxcarbazepine for bipolar disorder, developed hyponatremia after also taking bupropion (25). 

Oxcarbazepine can also cause hyponatremia, but in this case the hyponatremia appeared to correlate with the prescription of bupropion rather than oxcarbazepine and was also reproduced by amfebutamone re-challenge. This case suggests that amfebutamone can also cause hyponatremia, although it is possible that the presence of oxcarbazepine was necessary for the adverse effect to occur. 

Most significant risk of oxcarbazepine may be clinically significant hyponatremia (sodium level <125 m mol/L), most likely occurring within the first 3 months of treatment, and occurring in 2-3% of patients... 

Van Amelsvoort T, Bakshi R, Devaux CB, Schwabe S. Hyponatremia associated with carbamazepine oxcarbazepine therapy a review. Epilepsia 1994 35(l) 181-8. 

Oxcarbazepine has not been associated with hepatotoxi-city or hematological toxicity. It is less likely than carbamazepine to cause hypersensitivity reactions, but may be more often associated with hyponatremia. It is less likely than carbamazepine to induce CYP450 isozymes, but it may significantly increase the clearance of oral contraceptives and significantly induce CYP450 at higher doses. 

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 is a new, relatively safe anticonvulsant however, crosshypersensitivity was noted in patients previously hypersensitive to carbamazepine (25-30%). Asymptomatic hyponatremia has occurred in clinical trials during the first 3 months of therapy. Clinicians are advised to monitor serum sodium levels for patients during maintenance treatment. 

I Adverse Effects. Oxcarbazepine has dose-related adverse effects of dizziness, sedation, headache, ataxia, fatigue, vertigo, abnormal vision, diplopia, nausea, vomiting, and abdominal pain. Hyponatremia has been reported in up to 3% of patients. 

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... 

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). 

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%... 

Lin CH, Lu CH, Wang FJ, Tsai MH, Chang WN, Tsai NW, Lai SL, Tseng YL, Chuang YC. Risk factors of oxcarbazepine-induced hyponatremia in patients with epilepsy. Clin Neuropharmacol 2010 33(6) 293-6. 

Hematologic Reversible leukopenia and hyponatremia have been attributed to high-dose oxcarbazepine [222 ]. 

Observational studies In a prospective study of 30 patients with autism spectrum disorder, of the patients treated with oxcarbazepine for symptoms of irritability or agitation, seven discontinued treatment due to adverse events attributed to the medication [109 ]. This included four instances of worsening irritability, one case of hyponatremia, and one case of patient developing allergies that were not further elaborated upon. The seventh patient developed new-onset generalized seizures it is not clear why this was thought to be a medication effect. 

Electrolyte balance A review of the incidence of hyponatremia associated with medications administered to psychiatric inpatients in Europe found that the most common causative agent was oxcarbazepine, which accounted for 1.29% of all hyponatremia cases [Ill ll. 

Pregnancy Ababy boy was bom at 35 weeks gestation to a mother being treated with oxcarbazepine 1400 mg/day. The baby developed hyponatremia by day of life four, and a withdrawal syndrome by day seven. He was additionally found to have severe left hydronephrosis and bilateral hyperechogenic renal parenchyma compatible with renal dysplasia on kidney ultrasoxmd, as well as mild aortic stenosis, a bicuspid aortic valve, patent foramen ovale, and patent ductus arteriosus on echocardiogram [112 ]. 

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