Summary Safety Review – Proglycem (diazoxide) - Assessing the Potential Risk of Necrotizing Enterocolitis in Newborns and Infants

Proglycem (diazoxide)

Necrotizing enterocolitis, the inflammation and death of tissue in the small or large intestine of a newborn or infant

• 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 necrotizing enterocolitis in newborns and infants with the use of Proglycem. The safety review was triggered by published cases in the scientific literature.

• Health Canada’s review of the available information found a possible link between the use of Proglycem and the risk of necrotizing enterocolitis in newborns and infants.

• Health Canada is working with the manufacturer to update the product safety information in the Canadian product monograph (CPM) for Proglycem to include the risk of necrotizing enterocolitis. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Health Canada reviewed the potential risk of necrotizing enterocolitis in newborns and infants with the use of Proglycem. This safety review was triggered by published cases in the scientific literature.

Necrotizing enterocolitis is a serious gastrointestinal problem that mostly affects premature babies. This potentially life-threatening condition involves the inflammation and death of tissue in the small or large intestine of a newborn or infant. Several factors, including pregnancy- and delivery-related complications, as well as premature birth, can cause necrotizing enterocolitis in newborns and infants. 

• 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.

• Health Canada reviewed information from searches of the Canada Vigilance database^a and the published literature.

• Health Canada reviewed 21 cases (1 Canadian and 20 international) of necrotizing enterocolitis in newborns and infants who were administered Proglycem. Of the 21 cases, 15 (all international) met the criteria for further assessment to determine if there was a link between the use of Proglycem and necrotizing enterocolitis.

• All 15 cases assessed were reported in infants 2 months of age or younger, with 13 of the 15 cases occurring within the first 28 days of life.

• Of the 15 cases, 2 were found to be probably linked to the use of Proglycem, 11 were found to be possibly linked, 1 was unlikely to be linked and 1 could not be assessed. Of the 11 cases found to be possibly linked, 3 deaths were reported.

• Health Canada also reviewed 4 articles published in the scientific literature on the use of Proglycem in neonatal intensive care units. Two studies, including one Canadian¹, found a higher risk of neonatal necrotizing enterocolitis with the use of Proglycem. A third study reported occurrences of neonatal necrotizing enterocolitis with the use of Proglycem but had limitations in its design. Another large study did not support a link between neonatal necrotizing enterocolitis and the use of Proglycem.

• Health Canada’s review of the available information found a possible link between the use of Proglycem and the risk of necrotizing enterocolitis in newborns and infants.

• Health Canada is working with the manufacturer to update the CPM for Proglycem to include the risk of necrotizing enterocolitis.

• 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.

The analysis that contributed to this safety review included scientific and medical literature, Canadian and 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.

1. Prado, Laura A., et al. "Necrotising enterocolitis in newborns receiving diazoxide." Archives of Disease in Childhood-Fetal and Neonatal Edition 106.3 (2021): 306-310.

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