Hyponatremia due to an additive effect of carbamazepine and clarithromycin.

To the Editor: Both carbamazepine (CBZ) and clarithromycin are commonly prescribed drugs. CBZ is a first-line antiepileptic drug and has multiple other off-label uses. CBZ-induced hyponatremia has been described in the literature. (1,2) However, to our knowledge, a possible interaction between CBZ and clarithromycin for hyponatremia has not been described.

We report a 30-year-old woman with a 25-year history of epilepsy treated with CBZ 200 mg b.i.d., in whom a new onset of acute sinusitis developed and 500 mg b.i.d. of clarithromycin was prescribed. Within 4 days of the initiation of clarithromycin, the patient developed lethargy, dizziness, and imbalance. Her sodium had decreased from a baseline of 137 mEq/L to 126 mEq/L. Her renal, liver, and thyroid functions, glucose, potassium and chloride levels were all normal. We continued CBZ and converted clarithromycin to levofloxacin. Five days later, her sodium had corrected to 136 mEq/L, and her neurologic symptoms had resolved. The patient had a normal sodium level with CBZ treatment, had hyponatremia after the addition of clarithromycin, and had resolution of her symptoms after discontinuation of the clarithromycin.

The mechanisms whereby CBZ causes hyponatremia are not entirely clear. The possible mechanism of CBZ-induced hyponatremia is through the induction of excessive water reabsorption in the collecting tubule. Whether this is due to a central effect by increasing ADH secretion from the pituitary gland, or due to increased sensitivity of ADH receptors in the kidney, is debated. (3) Interaction between these two drugs might result in higher blood levels of CBZ. To our knowledge, there are no reports of clarithromycin-induced hyponatremia in the literature, and there is only one report of hyponatremia after combination therapy with clarithromycin and CBZ. (4) The Naranjo probability scale revealed a probable adverse reaction of hyponatremia associated with CBZ and clarithromycin therapy. (5)

This case suggests a potential additive effect between CBZ and clarithromycin to reduce serum sodium levels. This potential effect should be kept in mind when prescribing clarithromycin to patients receiving CBZ. Any change in physical or cognitive function after introducing a new drug should prompt a review for adverse events, and an evaluation of the necessity for continuing the medication.

Mehmet Kanbay, MD

Department of Nephrology 

Mehmet Alkis, MD

Department of Emergency Medicine

Faruk Turgut, MD

Ebru Uz, MD

Nuket Bavbek, MD

Ali Akcay, Assoc Prof

Department of Nephrology

Fatih University School of Medicine

Ankara, Turkey

References

1. Dong X, Leppik IE, White J, et al. Hyponatremia from oxcarbazepine and carbamazepine. Neurology 2005;65:1976-1978.

2. Kuz GM, Manssourian A. Carbamazepine-induced hyponatremia: assessment of risk factors. Ann Pharmacother 2005;39:1943-1946.

3. Ranta A, Wooten GF. Hyponatremia due to an additive effect of carbamazepine and thiazide diuretics. Epilepsia 2004;45:879.

4. Alegre Herrera S, Araujo Sanabria J, Rubio Rubio JM. Clarithromycin-carbamazepine interaction: neurological symptoms and hyponatremia. Ann Med Interna 1998;15:48-49.

5. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-245.Letters to the Editor

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