Published: 2 March 2023

Publications

Starting empagliflozin or dapagliflozin in patients on lithium? Monitor lithium levels

Published: 2 March 2023
Prescriber Update 44(1): 6–8
March 2023

Key messages

  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin and dapagliflozin, may increase the renal excretion of lithium and lead to decreased serum lithium levels.
  • Monitor the patient’s serum lithium levels more frequently when a SGLT2 inhibitor is initiated or following dose changes. Adjust the lithium dose if necessary.


Medsafe has requested data sheet updates for sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin and dapagliflozin) and lithium products to include information on the drug-drug interaction between these medicines.

Inhibition of SGLT2 may enhance the renal excretion of lithium

The sodium-glucose co-transporter 2 is responsible for the reabsorption of glucose and sodium in the renal tubules.1,2

SGLT2 inhibitors are used in the treatment of type 2 diabetes mellitus to improve glycaemic control. They promote glucose excretion by reducing renal absorption of glucose into the blood stream.1,2

Lithium can substitute for sodium, presumably because it is atomically similar to sodium, and use sodium-transporting systems.3 Therefore, concomitant use of SGLT2 inhibitors and lithium may increase the renal excretion of lithium and lead to decreased serum lithium levels.1,2,4

Routine monitoring of serum lithium levels is important to ensure they are within therapeutic range

Lithium has a narrow therapeutic index. Routine and regular monitoring is required to ensure appropriate dosing.5

Many medicines can influence lithium clearance, by altering renal blood flow, glomerular filtration rate and sodium balance.3

Monitor the patient’s serum lithium levels more frequently when a SGLT2 inhibitor is initiated or following dose changes. Adjust the dose of lithium if necessary.1,2

New Zealand case reports

Up to 9 January 2023, the Centre for Adverse Reactions Monitoring (CARM) had not received any reports of an interaction between lithium and SGLT2 inhibitors (empagliflozin, dapagliflozin).

More information

Medsafe: Drug interactions with lithium and therapeutic drug monitoring

References

  1. AstraZeneca Limited. 2022. Forxiga New Zealand Data Sheet 18 July 2022. URL: medsafe.govt.nz/profs/Datasheet/f/forxigatab.pdf (accessed 12 January 2023).
  2. Boehringer Ingelheim (N.Z.) Limited. 2022. Jardiance New Zealand Data Sheet 29 August 2022. URL: medsafe.govt.nz/profs/Datasheet/j/jardiancetab.pdf (accessed 12 January 2023).
  3. Shnaider A and Azab AN. 2015. Lithium-induced nephrogenic diabetes insipidus – a case report and discussion on the pathophysiological mechanism. International Journal of Nephrology and Kidney Failure 1(3): 1–4. DOI: 10.16966/2380-5498.113 (accessed 12 January 2023).
  4. Armstrong GP. 2020. Empagliflozin-mediated lithium excretion: A case study and clinical applications. The American Journal of Case Reports 21: e923311. DOI: 10.12659/AJCR.923311 (accessed 12 January 2023).
  5. New Zealand Formulary (NZF). 2022. NZF v127: Lithium 1 Jan 2023. URL: nzf.org.nz/nzf_2216 (accessed 12 January 2023).
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