Safety concerns flagged by the maker of the antihistamine prompted the ‘do not use’ age to rise to six years and under.
The TGA has raised the age contraindication for the antihistamine promethazine hydrochloride from two to six years over safety concerns.
The move comes after “further review by the sponsor of cumulative safety data in children two to five years of age demonstrated sufficient evidence of a causal association between promethazine and psychiatric and central nervous system adverse events in this age group”, a TGA spokesperson told Dermatology Republic.
They said the change was “a sponsor-initiated update prompted by advice from the TGA Advisory Committee on Medicines”.
“The TGA approved the updated Product Information, submitted by the sponsor for Phenergan, on 26 September 2024,” they said.
A spokesperson for the maker of Phenergan, Sanofi, told DR the company was in the process of finalising a direct healthcare professional communication letter with the TGA to provide the latest advice to healthcare professionals.
“Based on review of the Sanofi global pharmacovigilance database, worldwide scientific literature, and main reference textbooks as per below, the cumulative weight of evidence is sufficient and suggests a causal association between promethazine (and combination) and safety concerns pertaining to psychiatric and central nervous system events in children between two to five years of age,” said the spokesperson.
The issue was flagged by an ACM meeting statement published on the TGA website in July 2022. In this statement the ACM highlighted safety concerns of serious adverse outcomes and off-label use of first-generation sedating antihistamines in children.
It cited 226 cases to 24 May 2022 that involved adverse events from the use of the drugs in newborns, infants and children that were reported to the TGA. The reports included a range of adverse events, including hypersensitivity reactions, vomiting, hallucination, tremor and abnormal movement. Of the 226 cases, 20 related to off-label use, misuse or overdose in children aged four years and under.
The Sanofi spokesperson told DR that even though no specific safety concern in children had been identified during routine signal detection activities, it was decided to perform a targeted evaluation on the cumulative data in children between two and five years of age (both inclusive).
“The purpose of this safety evaluation report was therefore to provide a detailed analysis of safety data associated with promethazine and its use in children aged two to five years of age,” said the spokesperson.
A cumulative search up to 30 November 2022 of the Sanofi global pharmacovigilance database was performed, and a review of the cases “suggested a temporal association of the events with promethazine use with no confounders or alternate explanations”. An association of these events with promethazine could not be excluded, and it was noted that almost half of the cases involved accidental exposure.
While the official DCHP communications/letter was going through the relevant approvals with the TGA, the immediate advice for health professionals was to alert them to the updated safety advice and appropriately counsel patients who may plan to use Phenergan for a child.
“Caregivers and patients affected by the change should be directed to alternative products,” said the spokesperson.
“We expect there will be a time lag before all products with updated package labelling will be available in pharmacies [due to production lead timeline we are planning to implement the changes in 2025 in the market], however the updated advice not to use these products in children under the age of six years still applies to these products.”
