Information Related to a WHO Risk Alert Regarding Children’s Cough and Cold Syrup
November 2, 2022
Dear International Colleague,
In the wake of international reports of children’s cough and cold syrup contaminated with diethylene glycol and ethylene glycol, the FDA is reminding manufacturers and foreign regulatory counterparts that it has a guidance that could help identify the presence of these contaminants. The FDA is working with the Centers for Disease Control and Prevention (CDC), our foreign regulatory counterparts, and the World Health Organization (WHO) to support investigation efforts to determine the root cause of the reported contamination. Even though the FDA currently has no indication that these products have entered the U.S. drug supply chain, the agency is investigating the potential impact and scope of this hazard on FDA-regulated products. The FDA is giving heightened scrutiny to formulations including syrups or suspensions made with glycerin, propylene glycol, or sorbitol.
On October 5, the WHO announced that contaminated children’s cough and cold syrup has been found in The Gambia, Africa, with unacceptable amounts of the contaminants diethylene glycol and ethylene glycol, which are toxic to humans when consumed and can be fatal. The products cited in the WHO alert are: Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup. The stated manufacturer of these products is Maiden Pharmaceuticals Limited in Haryana, India. According to the WHO, the products may have been distributed through informal markets to other countries or regions and have been potentially linked with acute kidney injuries and deaths among children. Again, the FDA does not have any indication the products are in the U.S. market.
The FDA is reminding manufacturers of drugs intended for the U.S. market, including over-the-counter monograph drug products, of their obligation to ensure their products meet Current Good Manufacturing Practice (CGMP) requirements and appropriate quality specifications. This includes testing of raw materials and finished product batches before release to ensure they meet appropriate specifications for identity, strength, quality, and purity. The identity of original manufacturers of ingredients, and any subsequent repackers, should receive heightened scrutiny to verify the supply chain. The FDA reminds companies that incoming raw material lots must undergo quality control acceptance testing as specified in the USP-NF monograph for glycerin, applicable CGMP regulations, and as further explained in the FDA’s guidance Testing of Glycerin for Diethylene Glycol. The FDA collaborated with the United States Pharmacopeial Convention to include specific tests for diethylene glycol and ethylene glycol that must be conducted for compliance with the USP-NF monographs for glycerin, propylene glycol, sorbitol solution as well as other related USP articles.
The guidance document, Testing of Glycerin for Diethylene Glycol, is intended to inform stakeholders, including pharmaceutical manufacturers, pharmacy compounders, repackers, and suppliers of the potential public health hazard of glycerin contaminated with diethylene glycol or ethylene glycol. Historically, the FDA has received reports about fatal diethylene glycol poisoning of consumers who ingested medicinal syrups, such as cough syrup or acetaminophen syrup, that were manufactured with diethylene-glycol–contaminated glycerin. The FDA guidance helps pharmaceutical manufacturers, repackers, and other suppliers of glycerin, as well as pharmacists who engage in drug compounding, to establish practices that prevent use of contaminated glycerin as it has been the cause of several past incidents of deadly diethylene glycol poisoning.
The CDC provides guidance for medical management of ethylene glycol including health effects, prehospital and emergency department management, antidotes, and other treatments. Fomepizole, a competitive inhibitor of alcohol dehydrogenase, is an FDA-approved antidote for ethylene glycol poisoning or for use in suspected ethylene glycol ingestion and is not listed in the FDA’s drug shortages database.
Additionally, the FDA notes that it does not recommend over-the-counter medications for cough and cold symptoms in certain very young children because they can cause serious and potentially life-threatening side effects. FDA-regulated manufacturers voluntarily label these cough and cold products to state: “Do not use in children under four years of age.”
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