Published: November 2009

Safety signal - serious hyponatraemia

Prescriber Update 30(4): 23
November 2009

Ruth Savage, Medical Assessor, New Zealand Pharmacovigilance Centre

This article is a summary of a more detailed article to be published by NZPhvC

The New Zealand Centre for Adverse Reactions Monitoring (CARM) has examined recent reports of hyponatraemia in its database.

Hyponatraemia, defined as plasma sodium < 135mmol/L, is caused by a range of medicines and clinical conditions. Medicine-related hyponatraemia occurs most often in the elderly early in the course of treatment. The mechanism is most often syndrome of inappropriate antidiuretic hormone secretion (SIADH) or renal loss.

Medicines most often implicated in recent reports to CARM are selective serotonin or noradrenaline reuptake inhibitors (SSRIs/SNRIs) and thiazide diuretics. Other medicines reported more than once in 2007 and 2008 were anticancer agents, proton pump inhibitors, sodium valproate and ACE inhibitor/diuretic combinations. Carbamazepine has also been frequently implicated in the database.

Serious hyponatraemia (plasma sodium < 120mmol/L) can lead to confusion, convulsions and serious neurological damage. Examination of serious symptomatic reports to CARM revealed that in most cases more than one hyponatraemic medicine was implicated. Reports for three patients indicated that they each had persistent mild to moderately low plasma sodium levels (128 to 133mmol/L) while taking two hyponatraemic medicines. Following addition of a third hyponatraemic agent a much more profound fall ranging from 104 to 121mmol/L occurred.

The reports that CARM has received supports current advice that plasma sodium should be measured shortly after starting potentially hyponatraemic medicines, especially SSRIs or diuretics. Measurements should be repeated both before and after adding another hyponatraemic medicine. If there is mild persistent hyponatraemia the addition of further medicines or the development of clinical conditions that can decrease plasma sodium may lead to a more profound and symptomatic reaction.