Summary Safety Review - Colistin (colistimethate sodium) - Assessing the Potential Risk of Pseudo-Bartter Syndrome

Colistin (colistimethate sodium)-containing products

Pseudo-Bartter syndrome, a disorder involving acid-base and electrolyte imbalances

• Health Canada’s safety review found a link between the use of colistin (colistimethate sodium) and the risk of pseudo-Bartter syndrome.

• Health Canada reviewed the potential risk of pseudo-Bartter syndrome with the use of colistin (colistimethate sodium), a prescription antibiotic drug authorized for sale in Canada to treat acute or chronic infections, such as pneumonia, bloodstream infections and meningitis (infection of the protective membranes covering the brain and spinal cord). The safety review was triggered by published case reports in the scientific literature¹,²,³.

• Health Canada is working with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for colistin (colistimethate sodium)-containing products with a warning about reported cases of pseudo-Bartter syndrome.

Health Canada reviewed the potential risk of pseudo-Bartter syndrome with the use of colistin (colistimethate sodium). The safety review was triggered by published cases of pseudo-Bartter syndrome with the use of colistin (colistimethate sodium) in the scientific literature^1,2,3.

Pseudo-Bartter syndrome is an acquired condition (not passed on from a parent) primarily presenting as metabolic alkalosis (an acid-base disorder), hypokalemia (low blood potassium) and other electrolyte abnormalities.

• Colistin (colistimethate sodium) is a prescription antibiotic drug authorized for sale in Canada to treat acute or chronic infections, such as pneumonia, bloodstream infections and meningitis.

• Colistin (colistimethate sodium) has been marketed in Canada since 1974 under the brand name Coly-Mycin M. Various generic versions of colistin (colistimethate sodium) are also available. Colistin (colistimethate sodium) is available as an injection in specialized settings, such as hospitals.

• Health Canada reviewed the available information from searches of the Canada Vigilance database^a, international databases, and scientific literature.

• At the time of the review, Health Canada had not received any Canadian reports of pseudo-Bartter syndrome related to the use of colistin (colistimethate sodium).

• Health Canada reviewed 7 international cases of pseudo-Bartter syndrome in patients who were administered colistin (colistimethate sodium). All 7 cases were identified in the published literature.

• Of the 7 cases reviewed, 6 were found to be probably linked to the use of colistin (colistimethate sodium), and 1 was found to be possibly linked.

• In all 7 cases, hypokalemia (low blood potassium), metabolic alkalosis, and loss of potassium in the urine were reported. Some cases also involved hypomagnesemia (low blood magnesium) and hypocalcemia (low blood calcium).

• In all 7 cases, electrolyte abnormalities resolved or significantly improved following the discontinuation of colistin (colistimethate sodium).

• Following a review of the product safety information in other jurisdictions, such as Europe (EU), Health Canada determined that the action taken by the Department is consistent with what is taking place in the EU.

• Health Canada’s review of the available information found a link between the use of colistin (colistimethate sodium) and the risk of pseudo-Bartter syndrome.

• Health Canada is working with the manufacturers to update the CPM for colistin (colistimethate sodium)-containing products with a warning about reported cases of pseudo-Bartter syndrome.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of colistin (colistimethate sodium), and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving colistin (colistimethate sodium), as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

The analysis that contributed to this safety review included scientific and medical literature, and what is known about the use of colistin (colistimethate sodium) both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

1. Kamal Eldin T, Tosone G, Capuano A, Orlando R. Reversible Hypokalemia and Bartter-Like Syndrome during Prolonged Systemic Therapy with Colistimethate Sodium in an Adult Patient. Drug Saf Case Rep. 2017 Dec;4(1):10. doi: 10.1007/s40800-017-0052-1. 

2. Tabish M, Mahendran M, Ray A, Vikram NK. Colistin-induced acquired Bartter-like syndrome: an unusual cause of meltdown. BMJ Case Rep. 2020 Feb 5;13(2):e232630. doi: 10.1136/bcr-2019-232630. 

3. Yavas DP, Ekinci F, Horoz OO, Gundeslioglu OO, Atmis B, Yildizdas D. Acquired Bartter-like Syndrome Presenting with Polyuria and Reversible Hypokalemia Associated with Colistin Use in a Critically Ill Pediatric Patient. Indian J Crit Care Med. 2021 Jul;25(7):822-824. doi: 10.5005/jp-journals-10071-23898

1. Canadian reports can be accessed through the Canada Vigilance Online Database.