Why are adverse reactions to drugs not reported in India? Here is the surprising answer!

‘We call the sales representatives’

“The first of the complications any patient experiences after any medication is an allergic reaction, such as itching or redness of the skin. When they come back to us, we ask them to not take the medicine anymore, and give them some anti-allergy tablets,” said a paediatrician from a Hyderabad hospital on condition of anonymity.

“In a case where two or more patients come with complications arising due to the medication, we immediately talk to the sales representatives of the pharma company, and then along with the sales representatives we speak to the sales manager, who then takes the issue to the director of the company, who gives the order to take the medicine off the shelf,” he explained.

“We rarely go to the State Drug Regulatory Authorities (SDRAs). It may not even come to notice of the authorities,” added the paediatrician.

The doctors added that the process of filing a formal complaint in such cases was too long, and they don’t want to entangle themselves in the legal process either.

“Complaining to the SDRAs means a whole lot of paperwork. Besides, we will also be asked why we recommended certain drugs. We believed in the composition of the medicine, and that’s why we recommended them, but that was not our fault. It was the pharmaceutical company’s fault, but the first finger would be pointed at us. However, we have to report adverse cases to the SRDAs,” said an immunologist from Hyderabad.

The pharmacist also said that sometimes company representatives come and ask them to remove a certain medicine from the shelf.

“In one case, patients were getting hiccups due to a cough syrup. We heard this from a few patients first. After 10-15 days, a sales representative came and asked us not to prescribe this cough syrup,” Hyderabad-based pharmacist K Anjaiah told South First.

He added that the cough syrup of that company was pulled from the market, but another cough syrup of the same company came into the market within a few months.

“For them, it’s a trial-and-error situation. They get approval for their medication by some means, and then try it out in the market. If there are no complaints, it’s business as usual. Otherwise, they pull their medication from the market. The business of any drug company is to make money, and most of the time you can see that some products remain in the market for a few years, and vanish after that,” added Anjaiah.

The process of drug approval

Dr Narahari, a professor of paediatrics at the Nagarkurnool Medical College in Telangana, said that in India, the drug regulatory responsibilities are distributed between the Central Drugs Standard Control Organisation (CDSCO) — the national regulatory body for pharmaceuticals and medical devices — under the Central government and the SDRAs under the respective state governments.

This means each Indian state can provide market approval even without CDSCO approval.

Although most SDRAs have limited technical capacity, it varies widely, thereby diminishing regulatory effectiveness.

An analysis of the Indian drug market in 2007-12 showed that a considerable proportion of antibiotics are unapproved by the CDSCO.

However, South First did not find studies that used the AWaRe classification to assess the sales and consumption of antibiotics against approval.

The Gambia case

The WHO said that laboratory analysis of the samples of each of the four cough syrups in question confirmed that they contained unacceptable amounts of diethylene glycol and ethylene glycol as contaminants.

The four products are Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup, and Magrip N Cold Syrup.

The manufacturer of these products is Maiden Pharmaceuticals Limited. Until the WHO ban, the manufacturer has not provided guarantees to WHO on the safety and quality of these products.

“The combination of medicine in these syrups is not controversial. CDSCO and DCGI have allowed these combinations of drugs. The issue here is the contamination which is dangerous. The contamination happened during the process of manufacturing, due to which this situation has arisen,” said a Hyderabad-based paediatrician.

Government reaction

The Union Ministry of Health and Family Welfares (MoHFW) and the Haryana State Drug Controller had given licences to Maiden Pharmaceuticals Limited only for the export of these four drugs.

“All these four drugs were manufactured only for exports, and are not licensed for sale in India. In effect, none of these four drugs is sold domestically in India,” said the MoHFW.

Meanwhile, Kerala has banned the supply and sale of all drugs manufactured by MAiden Pharmaceuticals.

Adverse events related to diethylene glycol

Diethylene glycol (DEG) — one of the contaminants found in the cough syrups — is a colourless, syrupy (viscous) liquid at room temperature. It is often coloured fluorescent yellow-green when used in automotive antifreeze.

It is a useful industrial compound found in many consumer products, like hydraulic brake fluids, some stamp-pad inks, ballpoint pens, solvents, paints, plastics, films, and cosmetics.

DEG is a preservative chemical to prolong the shelf life of medication. It also prevents decomposition in adverse temperate conditions, besides dissolving the components in cough syrups.

The first reported case of DEG poisoning dates back to 1937, when it killed 105 people in the United States.

According to Dinesh Thakur, a public health activist, the first DEG poisoning incident reported in India was in 1972 in modern-day Chennai — erstwhile Madras.

At least 14 people died in Mumbai in 1986 when they were given glycerin contaminated with DEG.

In 1998, at least 33 children are known to have died in Gurgaon in Haryana after ingesting diethylene glycol.

In recent times, nine children died due to DEG poisoning in Chandigarh in 2020.