Summary safety review - Proglycem (diazoxide) - Assessing the Potential Risk of Pericardial Effusion

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2023-03-24

Product

Proglycem (diazoxide)

Potential Safety Issue

Pericardial effusion, an accumulation of fluid in the space around the heart

Key Messages

  • Proglycem (diazoxide) is authorized for sale in Canada to manage low blood sugar (hypoglycaemia) in infants, children and adults caused by a higher-than-normal amount of insulin in the blood (hyperinsulinism) associated with specific tumors, surgeries, maternal or fetal medical conditions, delivery-related complications or genetic conditions, when other medical therapy or surgical management has been unsuccessful or is not feasible.

  • Health Canada reviewed the potential risk of pericardial effusion with the use of Proglycem. The safety review was triggered by published cases in the scientific literature.

  • A very small number of international cases, including cases occurring in infants and children, have been observed.

  • Health Canada’s review of the available information found a possible link between the use of Proglycem and the risk of pericardial effusion.

  • Health Canada is working with the manufacturer to update the product safety information in the Canadian product monograph (CPM) for Proglycem with a warning about cases of pericardial effusion having been observed, including in infants and children. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Overview

Health Canada reviewed the potential risk of pericardial effusion with the use of Proglycem. This safety review was triggered by published cases in the scientific literature.

Pericardial effusion is the accumulation of fluid in the space around the heart. It can evolve into cardiac tamponade, a life-threatening condition, if there is too much fluid or if it accumulates too quickly. In this event, the fluid compresses the heart and could cause it to stop functioning properly.

Use in Canada

  • Proglycem is a prescription drug authorized for sale in Canada to manage low blood sugar (hypoglycaemia) in infants, children and adults caused by a higher-than-normal amount of insulin in the blood (hyperinsulinism) associated with specific tumors, surgeries, maternal or fetal medical conditions, delivery-related complications or genetic conditions, when other medical therapy or surgical management has been unsuccessful or is not feasible. Proglycem works by preventing the release of insulin from the pancreas.

  • Diazoxide has been marketed in Canada for over 35 years. It is currently available as 100 mg capsules, under the brand name Proglycem.

  • The estimated yearly number of Proglycem capsules dispensed by Canadian retail pharmacies and used in hospitals increased from approximately 75,000 capsules in 2017 to approximately 130,000 capsules in 2021.

Safety Review Findings

  • Health Canada reviewed information provided by the manufacturer, and from searches of the Canada Vigilance databasea and the published literature.

  • At the time of the review, Health Canada had not received any Canadian reports of pericardial effusion related to the use of Proglycem.

  • Health Canada reviewed 8 international cases of pericardial effusion in patients taking Proglycem from the Canada Vigilance database. Of the 8 cases assessed, 6 were in infants and children.

  • Of the 8 cases, 2 (both published in the scientific literature1,2) were found to be probably linked to the use of Proglycem, 4 were found to be possibly linked and 2 were unlikely to be linked.

Conclusions and actions

  • Health Canada’s review of the available information concluded that there is a possible link between the use of Proglycem and the risk of pericardial effusion.

  • Health Canada is working with the manufacturer to update the CPM for Proglycem with a warning about cases of pericardial effusion having been observed, including in infants and children.

  • Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Proglycem and other health products to the Canada Vigilance Program.

  • Health Canada will continue to monitor safety information involving Proglycem, 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.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, international information, and what is known about the use of Proglycem both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Avatapalle B, Banerjee I, Malaiya N, Padidela R. Echocardiography monitoring for diazoxide induced pericardial effusion. BMJ Case Rep. 2012

  2. Maffre I, Vincenti M, Dalla Vale F, Amouroux C, Werner O, Meilhac A, de Barry G, Amedro P. Diazoxide Causality Assessment of a Pericardial Effusion in a Child with Kabuki Syndrome. J Clin Res Pediatr Endocrinol. 2019 May 28;11(2):218-219.

Footnotes

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

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