Carbamazepine hyponatremia with

Carbamazepine Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug discontinue if platelets are less than 100,000/mm3, if white blood cell (WBC) count is less than 3,000/mm3 or if there is evidence of bone marrow suppression or liver dysfunction. Serum electrolyte levels should be monitored in the elderly or those at risk for hyponatremia. Carbamazepine interferes with some pregnancy tests. 

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. 

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... 

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. 

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... 

Hyponatremia Hyponatremia has been reported in association with carbamazepine use, either alone or in combination with other drugs. 

The syndrome of inappropriate antidiuretic hormone secretion, with resultant hyponatremia, may be induced by carbamazepine treatment. Alcoholic patients may be at greater risk for hyponatremia. 

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. 

Carbamazepine increases the release of endogenous antidiuretic hormone and can therefore potentiate the antidiuretic effect of desmopressin. Of 103 children with cranial diabetes insipidus included in a retrospective analysis, 10% became hyponatrcmic (76). The risk of hyponatremia was three-fold higher when desmopressin and carbamazepine were given in combination. 

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

Kelly BD, HUlery J. Hyponatremia during carbamazepine therapy in patients with intellectual disability. J Intellect Disabil Res 2001 45(Pt 2) 152-6. 

In two children with cranial diabetes insipidus, desmopressin requirements fell while they were taking lamotrigine (34). Lamotrigine may act at voltage-sensitive sodium channels and reduce calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatremia secondary to inappropriate secretion of antidiuretic hormone. 

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. 

The most common cause of hyponatremia in hospital patients is SIADH. However, other disorders can cause dilutional hyponatremia and must be differentiated from SIADH. These conditions include (1) congestive heart failure, (2) renal insufficiency, (3) nephrotic syndrome, (4) liver cirrhosis, and (5) hypothyroidism. Excessive administration of hypotonic fluids and treatment with drugs that stimulate AVP (e.g., chlorpropamide, vincristine, clofibrate, carbamazepine, nicotine, phenothiazines, and cyclophosphamide) can cause dilutional hyponatremia as well. Hyponatremia may also occur from renal or extrarenal sodium losses (depietional hyponatremia) as a result of vomiting, diarrhea, excessive sweating, diuretic abuse, saltlosing nephropathy, or mineralocorticoid deficiency. 

Kamiyama T, Iseki K, Kawazoe N, et al. Carbamazepine-induced hyponatremia in a patient with partial central diabetes insipidus. Nephron 1993 64 142-145. 

The use of diuretics which promote heavy potassium loss (e.g., loop diuretics and thiazide diuretics) with carbamazepine therapy may precipitate a marked hyponatremia. 

Carbamazepine and tricyclic antidepressants, as well as phenothiazines, opiates, and barbiturates can cause hyponatremia, which would be additive with that produced by demeclocycline. 

Carbamazepine and lithium can elevate each other s serum levels (the mechanism is unknown). Toxicity is possible while blood levels are within the normal range, and is partially associated with pre-existing brain abnormalities. The diuretic effect of lithium outweighs the antidiuretic effect of carbamazepine. Carbamazepine does not protect against lithium-induced diabetes insipidus. Lithium can enhance carbamazepine-induced hyponatremia. 

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). 

C. Chronic use has been associated with bone marrow depression, hepatitis, renal disease, cardiomyopathy, hyponatremia, and exfoliative dermatitis. Carbamazepine has also been implicated in rigidity-hyperthermia syndromes (eg, neuroleptic malignant syndrome and serotonin syndrome) in combination with other drugs. 

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