Cough syrups: silent killer of Gambian children

The WHO issued a health warning on October 5 over four items ‘ that fail to ful ﬁ ll either their quality criteria or speci ﬁ cations. ’ This included Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup, and Magrip N Cold Syrup, all of which had Maiden Pharmaceuticals Limited, Haryana, India, listed as their manufacturer [1] . The advisory continued by stating that the low-quality items indicated were dangerous and that their usage, especially by children, may ‘ end in serious harm or death. ’ As per the company ’ s website, the company also exports its medicines to countries in Southeast Asia, such as Laos, Vietnam, Thailand, Cambodia, the Philippines, Malaysia

issued a warning detailing the potentially fatal consequences of the two substances, including discomfort, vomiting, diarrhea, difficulty passing urine, headache, a changed mental state, and severe renal damage (Fig. 1).
Earlier in the year 2011, this company was blacklisted from Vietnam due to nongood manufacturing practices violations. According to the report, the Bihar government blacklisted Maiden Pharmaceuticals in 2011 for supplying substandard drugs. Methylergometrine tablets, which were taken from a hospital in Munger, were discovered to be counterfeit. Another batch of drugs, erythromycin sterate syrup 125 mg/5 mL, was found to be of unsatisfactory quality. According to the extended licensing, laboratory, and legal node (XLN) database maintained by the Government of India, the Kerala, and Gujarat state governments have repeatedly issued warnings against the company's illegal practices. A Kerala drug inspector even filed a case in 2005, after which the company was fined in 2017. In another case, a central government drug inspector prosecuted the company in Sonipat for quality violations under the Drugs and Cosmetics Act. The company was charged with offenses related to adulteration.
This was the fourth case of mass glycol poisoning in India. In 1973, there was a similar incident at the Children's Hospital, Egmore, in Chennai that caused the deaths of 14 children. A similar poisoning at Mumbai's J.J. Hospital in 1986 killed 14 patients who were otherwise on the mend. In 1998, 33 children died in two hospitals located in New Delhi due to similar poisoning.
Experts in the medical field have warned that due to the compounds' solubility, DEG and ethylene glycol may be accidentally contaminated when they are substituted by less expensive commercial-grade versions of the same solvents that also include DEG and ethylene glycol.
Solvents such as DEG and ethylene glycol, both of which are banned in the USA, are sometimes used to illegally adulterate liquid medications. The United States National Center for Biotechnology Information reports that glycerin (also known as glycerol) and propylene glycol are frequently used as solvents in cough syrups because they provide a liquid base for the nonwatersoluble paracetamol or acetaminophen.

HIGHLIGHTS
• Hundreds of child deaths from acute kidney damage were linked to the use of paracetamol syrup. • Methylergometrine tablets were discovered to be counterfeit. • Experts in the medical field have warned that due to the compounds' solubility. Learning from this kind of case, the Indonesian Government, on October 19, 2022, laid a temporary ban on all liquid medicines in the country over a reported spike in children's deaths linked to medical syrups. On October 18th, news came out from Indonesia that 99 out of 206 young people with acute renal failure in 20 different regions had passed away. As the health ministry continues its investigations into unlicensed medicinal syrups supplied in the country, that number is projected to grow further, having already reached 133.
Apart from this sequence, the major question is why this happened. What led to this incident? When the product is released in the market, it is accompanied by a certificate of analysis that shows the tests done on the product as per the specifications or pharmacopeia to which it has been subjected. That certificate is signed by an FDA-approved person (a quality control chemist) only. And for the registration of a product in a certain country, a dossier needed to be sent mentioning all the sources of raw material and packing material and their roles in formulation. Apart from this, the dossier contains another necessary document. These documents are sent to regulatory agencies for product approval. Now discussing these documents, which were missed during the approval and export of the product, If the regulatory agency had gone through these documents properly, these kinds of things could have been avoided. Based on documents, the company supplying the raw material containing the DEG should also be investigated; may be they have a higher content of DEG in their product itself.
As a precaution, the regulatory agencies should go for audit checks regularly and ask the manufacturers for proper documentation. Also, the regulatory agencies of the importing country should establish satellite testing laboratories for testing the product from each consignment getting shipped. Though it will increase the time taken to get the product exported, surely it will save lives.

Ethical approval
Not applicable.

Sources of funding
None.

Conflicts of interest disclosure
The authors declare that they have no financial conflict of interest with regard to the content of this report.

Provenance and peer review
Not commissioned, internally peer-reviewed.

Data statement
No specific data collected for the above manuscript. The data in this correspondence article is not sensitive in nature and is accessible in the public domain. The data is therefore available and not of a confidential nature.