Regarding the Medicinal Mishap ‘Chronic lithium toxicity’, I wonder if the role that empagliflozin played in the patient’s cascade of symptoms was considered.1 Acidosis can occur in the setting of reduced oral intake or hypovolaemia. Interestingly, a case report2 suggests that lithium concentrations may be reduced in patients taking empagliflozin, although there is no mention of this in the product information for empagliflozin. 

Vicki Dyson
Pharmacist, Shepparton, Vic


Authors' response

Ian Whyte and Frank Reimann, the authors of the article, comment:

Thank you for your question about the role empagliflozin may have played in our patient’s cascade of symptoms. 

While the patient’s diarrhoea and neurological findings could not be related to empagliflozin, the biochemical abnormalities were consistent with euglycaemic ketoacidosis.1 Empagliflozin can produce this complication in the presence of physiological stress.3 However, the patient’s blood ketone concentrations were only mildly raised, and the large anion gap was better explained by renal failure. Further, the abnormalities had normalised by 48 hours without administration of insulin or glucose solutions. 

The case report highlights a potential role of empagliflozin in facilitating lithium excretion.2 Although sodium-glucose co-transporter 2 (SGLT2) inhibitors can acutely increase lithium renal clearance by decreasing proximal sodium reabsorption, the effect is transient and, within a month, compensated for by a rise in plasma renin activity and aldosterone.4 This makes it unlikely that the patient's long-term empagliflozin was affecting his lithium clearance. Additionally, for SGLT2 inhibitors to exert an effect on the renal tubule, sufficient kidney function would have been required. 

In the context of acute illness and severe kidney injury, most of the patient’s regular medicines could have caused mishaps and required sick-day plans.


The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by any responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Vicki Dyson

Pharmacist, Shepparton, Vic

Ian Whyte

Clinical pharmacologist, Calvary Mater Hospital, Newcastle, NSW

Clinical pharmacologist, University of Newcastle, NSW

Frank Reimann

Clinical pharmacology trainee, Calvary Mater Hospital, Newcastle, NSW