Eur J Clin Pharmacol (2003) 59: 177 DOI 10.1007/s00228-003-0604-4
L E T T ER TO TH E E D I T O R S
Nader Abdelrahman Æ Yosef Kleinman Æ Deborah Rund Nael Da` as
Hyponatremia associated with the initiation of reboxetine therapy
Received: 15 November 2002 / Accepted: 31 March 2003 / Published online: 7 May 2003 Ó Springer-Verlag 2003
Keywords Reboxetine Æ Hyponatremia To the editor. Hyponatremia and the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) have been associated with tricyclic antidepressants (TCA) and serotonergic drugs [1, 2, 3, 4]. This association was reported only once with reboxetine, a new selective norepinephrine-reuptake inhibitor [5]. We describe another case of hyponatremia associated with initiation of reboxetine therapy. The patient was an 80year-old woman who was hospitalized for symptomatic hyponatremia, confusion and agitation. Her medical history included longstanding hypertension, hyperlipidemia, chronic ischemic heart disease and varicose veins. The patient was followed in our outpatient clinic for a number of years, and had always normal serum sodium levels (141–143 mmol/l). During the last 2 weeks prior to hospitalization she had been receiving reboxetine 2 mg/day for depression. For the past 2 years she had also been taking the following medications on a regular basis: losartan potassium 50 mg/day, diltiazem 60 mg/day, furosemide 40 mg/day, spironolactone 25 mg/day and pantoprazole 40 mg/day. On admission, the serum sodium was 127 mmol/l, and osmolality 280 mOsm/kg. The urine sodium was 40 mmol/l, and osmolality was 534 mOsm/kg. No other electrolyte abnormalities were noted. None of the other possible causes of hyponatremia, including tumors or acute respiratory or central nervous system disease, were present. Reboxetine therapy was discontinued; all other medications were continued unchanged and the patient was closely
N. Abdelrahman Æ Y. Kleinman Æ N. Da` as (&) Department of Internal Medicine, Bikur Cholim Hospital, PO Box 492, 91004 Jerusalem, Israel E-mail:
[email protected] Tel.: +972-2-6464208 Fax: +972-2-6464193 D. Rund Department of Hematology, Hadassah University Hospital, Jerusalem, Israel
monitored. During the next 4 days, the symptoms disappeared and her serum sodium concentration gradually returned to normal and remained so thereafter during a 6-month follow-up. We believe that the patient’s SIADH and hyponatremia was caused by reboxetine, as that was the only medicine recently administered and because the sodium values returned to normal after its discontinuation [3]. As in the previously reported case [5], our patient was an elderly woman with several illnesses and she was on more than one medication. However, she was also receiving diuretics that could potentially cause electrolyte imbalance but, as stated, none of her medicines was changed, including the diuretics, during the reboxetine treatment or after its discontinuation; thus reboxetine seems to be the only offending drug. The exact relationship between reboxetine and the syndrome is still unknown, but, in the records of Pharmacia & Upjohn (the manufacturer of reboxetine), there are three additional cases of patients who may have had this syndrome; thus additional data is needed. Meanwhile, we suggest that serum sodium levels be monitored closely during the initiation of reboxetine in order to prevent this serious and potentially fatal side effect of the drug.
References 1. Pilans PI, Coulter DM (1994) Fluoxetine and hyponatremia—a potential hazard in the elderly. N Z Med J 107:85–86 2. Strachan J, Sepherd J (1998) Hyponatremia associated with the of selected serotonin reuptake inhibitors. Aust N Z J Psychiatry 32:295–298 3. Boumann WP, Pinner G, Johnson H (1998) Incidence of selective serotonin reuptake inhibitor induced hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion in elderly. Int J Geriatr Psychiatry 13:12–15 4. Jackson C, Carson W, Markowitz J, Mintzer J (1995) SIADH associated with fluoxetine and sertraline therapy. Am J Psychiatry 152:809–810 5. Ranieri P, Franzone S, Trabuchi M (2000) Reboxetine and hyponatremia: a letter to the editor. NEJM 342:215–216
