INDONESIA — The Food and Drugs Supervisory Body (BPOM) announced that two pharmaceutical companies have been allegedly found to be using contaminants ethylene glycol (EG) and diethylene glycol (DEG) exceeding the tolerable daily intake in their medication products.
The finding came after the body announced a day earlier that 133 medicinal syrups are free from those chemical substances which have been allegedly linked to acute kidney failure.
The two contaminants have been suspected of causing a growing number of acute kidney problems. As of 24 October, 141 children have died from kidney failure with unknown causes, the official data showed.
The incident has spurred parents’ worry over the health of their children, finding substitutes for banned paracetamol syrups and voicing concerns over BPOM’s supervision of the country’s drug-manufacturing process.
“The most important thing is that we will take legal action against two pharmaceutical companies we identified,” BPOM Chief Penny Lukito said in the press briefing after a meeting at the Presidential Palace in Bogor, West Java, on 24 October, adding that the chemical substances found in the drugs were at a level that was toxic.
Mrs Penny did not specify the names of the two pharmaceutical companies but vowed to cooperate with the National Police’s Chief Detective (Bareskrim) to investigate the case.
“There is an indication that the levels of EG and DEG in their products are not only as contaminant concentration but very-very high. It is toxic and allegedly linked to acute kidney failure,” she continued.
Earlier on 21 October, BPOM banned five paracetamol syrup brands from sale as they were said to contain harmful compounds exceeding acceptable levels.
Subsequently, on Sunday (23 October), the agency released a list containing 133 paracetamol syrup brands that are safe from contaminants.
EG is one of the materials used for plastic manufacturing and HVAC (Heating, Ventilation, and Air-Conditioning). At the same time, DEG is commonly used as a solvent and a dehydrating agent in the natural gas industry.
Clinical pharmacology expert at the University of Gadjah Mada (UGM) Prof. Apt. Zullies Ikawati explained that EG and DEG are contaminants commonly found in solvent materials in medicinal syrups.
In paracetamol drugs and many other drugs that are difficult to dissolve in water, additional ingredients are needed for solubility; propylene glycol or glycerin is usually used in Indonesia. This raw material for propylene glycol or glycerin is likely to contain contaminants.
Indonesians have criticized BPOM for not ensuring the safety of drugs before they are sold on the market. One Twitter user urged the government to replace the BPOM chief and the Ministry of Health for their negligence that has cost hundreds of children’s lives.
“Sorry, Mr Jokowi. Not only free medication must be provided. But Health Minister and BPOM chief must be replaced due to negligence in monitoring the circulation of drugs containing a toxic substance,” said an account @AdvokatHmpan.
Speaking at an earlier press conference on 23 October, Mrs Penny insists that the agency had always conducted premarket and postmarket supervision of the pharmaceutical industry that adheres to international standards.
“In registering [medicines], there must not be any use of raw materials that contain EG and DEG – four solvents in Propylene Glycol, Polyethylene Glycol, Sorbitol, and/or Glycerin/Glycerol,” said Penny at the BPOM headquarters.
Physician-scientist at Harvard Medical School Jacob Wes Ulm, MD, PhD said in a Skype interview with TOC, suggests that supply chain problems may be the culprit behind the toxic drugs
“There have been supply-chain issues in many countries recently, and this may be causing errors with the medication components and chemical engineering, leading to contaminants causing this incident,” he stated.
Indonesia’s Ministry of Health, Mr Budi Sadikin, contacted Gambia’s Health Authority and the World Health Organization (WHO), as there was a similar case involving children with acute kidney failure seen in Gambia, a county in West Africa, with total fatalities of 70.
He stated that similar cases have also been found in India and Bangladesh.
WHO findings stated that four paracetamol syrups – made by an India-based pharmaceutical firm – in Gambia contained EG.
“The four products 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 (Haryana, India). To date, the stated manufacturer has not provided guarantees to WHO on the safety and quality of these products,” WHO medical product alert stated on 5 October.
However, Budi confirmed that those medications – as seen in Gambia – are not available in Indonesia’s markets.
The Ministry of Health has issued a circular that informs medical workers and pharmacists of 156 medicinal syrups that are safe from harmful chemical substances after it announced the earlier ban on syrups identified with contaminants.
The figure consists of 133 brands declared safe by BPOM, and 23 out of 102 products based on the ministry’s findings that do not contain propylene glycol, glycerin/glycol, polyethylene glycol, and sorbitol.
The temporary ban of medicinal syrup sales triggered panic among parents who usually prepare syrups at home in case of fever or cough as not all children can swallow tablets.
“I fully understand how stressful that must be for parents. And this does create a difficult situation. Since we generally don’t recommend crushing paracetamol tablets (we call it acetaminophen in the US), due to concerns about releasing too high a dose at once. However, we want to be careful about the extended-release paracetamol tablets (generally sold as Tylenol in the US) since they’re designed to have a large dose released slowly. We don’t want to crush or chew that form since it can lead to liver damage if the dose is too high,” stated Mr Jacob who has had experience in drug discovery, medical genetics, and genomics.
He suggested that parents can use chewable paracetamol tablets instead of syrups.
Mr Jacob also elaborated on the use of Ibuprofen for infants, saying that there are other pain-relieving and fever-reducing medications like NSAIDs (i.e. medications like IbuprofenIbuprofen) and aspirin, but paediatricians are generally more cautious about using those in kids.
“We generally don’t give Ibuprofen to infants younger than six months old, though it’s generally relatively safe after six months. However, we also recommend that parents talk to a doctor before giving Ibuprofen to kids younger than two years old since some kids (e.g. kidney or gastrointestinal issues) might have trouble with it.”
“If Ibuprofen is given, parents give it carefully in the doses prescribed on the package. Aspirin is also given for pain and fever; even for kids, it’s generally very safe with rare complications. However, aspirin can cause an infrequent complication called Reye’s syndrome in a tiny subset of kids, which can be dangerous (esp. in kids with genetic metabolic disorders). Hence, while it’s usually very safe, we prefer to give kids other pain relievers first,” said Mr Jacob.
