Severe hyponatraemia associated with omeprazole

A 43-year-old woman presented with epigastric pain and tenderness nine days after completing her second cycle of chemotherapy for a temporoparietal lymphoma. She was prescribed omeprazole 20 mg twice a day.

Two days later, after three doses of omeprazole, the patient complained of nausea, weakness and feeling twitchy. Physical examination was unremarkable, but her serum sodium concentration had fallen from its pre-treatment value of 138 to 117 mmol/L. Her serum urate was 0.12 mmol/L, urine sodium was 35 mmol/L and urine osmolality 615 mmol/L. Plasma glucose and tests of thyroid, adrenal and renal function were normal. This is consistent with the syndrome of inappropriate antidiuretic hormone secretion.

The patient was given one litre of hypertonic saline over 24 hours and was placed on fluid restrictions. The omeprazole was ceased. Within three days her sodium concentration had returned to normal and has remained so over the ensuing eight months without fluid restrictions.

In 2003-04, omeprazole was the fourth most commonly prescribed drug on the Pharmaceutical Benefits Scheme.¹ Seven previous cases of hyponatraemia have been associated with proton pump inhibitors. With the exception of one case ascribed to lansoprazole, all these cases followed exposure to omeprazole.^{2,3,4,5,6,7,8} Consistent features were the:

• rapid onset of hyponatraemia with the majority of cases presenting within 11 days of starting treatment
• severity of hyponatraemia
• rapid recovery after cessation of the drug.

The Adverse Drug Reactions Advisory Committee has received 18 reports of hyponatraemia associated with omeprazole, including six where it, or esomeprazole, was the sole suspected drug.

Hyponatraemia has a variety of causes including renal salt wasting and inappropriate antidiuretic hormone secretion^.9 Our patient probably had drug-induced inappropriate secretion of antidiuretic hormone.

Although we used hypertonic saline, it is important to remember not to correct the patient's sodium concentration too quickly. Rapid replacement of sodium can induce the osmotic demyelination syndrome which is potentially fatal.

This is a rare adverse drug reaction, but it is included in the product information of omeprazole. As our patient developed hyponatraemia after three doses, this adverse reaction needs to be considered whenever there is clinical deterioration even after brief exposure to a proton pump inhibitor.