Drug makers continue to sell banned or unapproved cocktails of two antibiotics packed as single pills or tablets under “weak, convoluted and inefficient” regulatory enforcement by India’s drug control authorities, health researchers have cautioned.

The researchers, who analysed regulatory initiatives to curb sales of such formulations or fixed-dose combinations (FDCs) of drugs, have found that 278 (70 per cent) of the 395 FDCs of antibiotics marketed across India in 2020 had been banned earlier or had never been approved.

The Central Drugs Standard Control Organisation (CDSCO), the apex drug regulatory authority, has taken multiple initiatives over the past decade to curb sales of FDCs amid concerns among doctors and expert panels that many FDCs are irrational, unjustified and may carry potential health risks to patients.

Irrational FDCs may expose patients to drugs, including antibiotics, that they do not really require and drive up medical bills.

“This is a longstanding issue of huge public health importance — but we find weak regulatory enforcement and no evidence for surveillance needed to understand what’s being sold in the market,” Aashna Mehta, a health economist and assistant professor at the Public Health Foundation of India, New Delhi, a research and training institution, told The Telegraph.

Mehta and her collaborators in academic institutions in the UK and Qatar analysed pharmaceutical sales of FDCs in India between 2008 and 2020 alongside a series of initiatives by the CDSCO and its technical expert panels in 2007, 2013, 2016, 2018 and 2019 to curb the sales of irrational FDCs.

Their analysis, published this week in the Journal of Pharmaceutical Policy and Practice, has found that under those initiatives the total number of FDCs fell from 574 in 2008 to 395 in 2020. But among those 395 FDCs, 39 formulations had been banned between 2016 and 2018 or 2019, and 239 had never been approved.

“The slow and limited progress is the result of weak, convoluted, badly targeted and inefficient regulatory enforcement,” the researchers have said in their study.

Allyson Pollock, clinical professor of public health at Newcastle University in the UK and a study collaborator, said there was no clinical basis for such combinations. “The risk is that irrational combinations of medicines whose safety and efficacy has not been determined will cause harm to patients and fuel antimicrobial resistance,” she told this newspaper.

There should be regular surveillance of the market and regular reviews of all top-selling FDCs, Pollock said.

A query sent by this newspaper to Rajeev Raghuvanshi, the Drugs Controller General of India and head of the CDSCO, on Wednesday seeking his responses to the study has not evoked a reply.

Examples of such FDCs banned in 2016 and 2018 or never approved but still marketed in 2020 include azithromycin and ofloxacin, azithromycin and levofloxacin, cefixime and ofloxacin, norfloxacin and tinidazole, ofloxacin and metronidazole.

Several such FDCs — such as ofloxacin and ornidazole or norfloxacin and tinidazole — continue to be marketed in November 2023, according to information available from retail chemists and online pharmacy websites.

“Some FDCs such as azithromycin with cefixime or azithromycin with ofloxacin don’t make sense because azithromycin needs to be taken once in 24 hours, but cefixime or ofloxacin need to be taken twice in 24 hours,” said Yogiraj Ray, associate professor of infectious disease at the Institute of Postgraduate Medical Education and Research, Calcutta.

Such FDCs will overdose patients with azithromycin if taken twice a day and will underdose patients with cefixime or ofloxacin if taken once a day, Ray said.

The Centre had in March 2016 notified a ban on over 300 FDCs, including antibiotic combinations, after an expert panel set up by the CDSCO said the FDCs were not supported by evidence and could pose a risk to patients. But sections of the drug industry challenged the ban in courts. Following fresh reviews, the Centre issued another ban in 2018 and 2019.

Many experts have been worried that irrational FDCs of antibiotics could fuel the emergence of antimicrobial resistance.