Published: 5 September 2024

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Acid-base imbalances with medicines: hyperchloremic acidosis

Published: 5 September 2024
Prescriber Update 45(3): 57–58
September 2024

The Centre for Adverse Reactions Monitoring (CARM) and Medsafe recently received a report of hyperchloremic acidosis with topiramate. The person had been taking topiramate for a number of years before the reaction occurred (report ID 155109).

This article is a reminder about hyperchloremic acidosis with topiramate, plus other medicines that may cause this side effect.

Background

Metabolic acidosis occurs when either an increase in the production of acids or a loss of bicarbonate from the body overwhelms the mechanisms of acid-base homeostasis, or when renal acidification mechanisms are compromised.¹

Metabolic acidosis is further classified into two groups based on the presence of unmeasured anions (anion gap).¹

• High anion gap metabolic acidosis is associated with acid accumulation from increased acid production or acid ingestion. Causes include lactic acidosis, ketoacidosis and renal failure.¹
• Normal anion gap metabolic acidosis (also called hyperchloremic acidosis) is associated with bicarbonate loss from the gastrointestinal tract or impaired excretion of hydrogen ions or bicarbonate absorption from the kidneys (renal tubular acidosis). Causes include diarrhoea and adrenal insufficiency.¹

As well as physiological processes, medicines can impact the acid-base balance in the body and may contribute to metabolic acidosis by different mechanisms.¹

Topiramate lowers serum bicarbonate levels

Topiramate may cause a renal tubular, hyperchloremic acidosis in some individuals due to inhibition of carbonic anhydrase in the kidneys, affecting bicarbonate reabsorption.²

A decrease in serum bicarbonate level usually occurs early in treatment but may happen any time during treatment. Decreases are usually mild to moderate. However, decreases in serum bicarbonate to levels below 10 mmol/L have been reported² (the adult reference range³ is 22–29 mmol/L).

The topiramate data sheets recommend monitoring serum bicarbonate levels during topiramate treatment. Consider more frequent monitoring if people have underlying conditions that predispose them to metabolic acidosis (eg, diarrhoea, renal failure). If metabolic acidosis develops and persists, consider reducing the dose or discontinuing topiramate (using dose tapering).²

Chronic, untreated metabolic acidosis may increase the risk of nephrolithiasis (renal stone formation) or nephrocalcinosis (calcium deposits in the kidney) and reduce growth rates in children.²

Refer to the data sheets for further information.

Other medicines

Several other medicines have been reported to contribute to hyperchloremic acidosis due to direct or indirect effects on the reabsorption of bicarbonate or excretion of hydrogen in the kidneys.^1,4

Examples include:

• other carbonic anhydrase inhibitors, such as acetazolamide and zonisamide^1,2
• renin-angiotensin-aldosterone system inhibitors, such as angiotensin-converting enzyme inhibitors and aldosterone receptor blockers.⁴

References

1. Kraut JA, Madias NE. 2010. Metabolic acidosis: pathophysiology, diagnosis and management. Nature Reviews Nephrology 6(5): 274–85. DOI: 10.1038/nrneph.2010.33 (accessed 12 July 2024).
2. Janssen-Cilag (New Zealand) Ltd (2023). Topamax New Zealand Data Sheet 23 March 2023. URL: www.medsafe.govt.nz/profs/Datasheet/t/topamaxtabcap.pdf (acessed 24 July 2024).
3. Health New Zealand | Te Whatu Ora. 2023. Laboratory Test Reference Guide: Bicarbonate. URL: lab.waikatodhb.health.nz/test-guide/view/105/bicarbonate (accessed 26 July 2024).
4. Pham AQ, Xu LH, Moe OW. 2015. Drug-induced metabolic acidosis. F1000Research 4(F1000 Faculty Rev): 1460. DOI: 10.12688/f1000research.7006.1 (accessed 12 July 2024).