India’s apex drug regulatory authority has asked drug companies to justify 19 cocktails of medicines, or fixed dose combinations (FDCs), which its own expert panel had three years ago deemed risky for humans and unfit for sale.

The Central Drugs Standard Control Organisation has in a notice issued on Monday asked “concerned stakeholders” to submit information on “the rationality, safety and efficacy” of the 19 FDCs that companies have produced in India since before 1988.

The FDCs include combinations of two or more medicines sold as single formulation products such as paracetamol plus nimesulide, paracetamol plus phenylephrine plus caffeine, or amoxycillin plus bromhexine, among others.

Drug companies have promoted the nimesulide-paracetamol formulation for relief from pain and fever, the paracetamol-phenylephrine-caffeine formulation for relief from symptoms of common cold or influenza, and the amoxycillin-bromhexine cocktail for relief from asthma or bronchitis. Among the 19, there is also a five-drug FDC promoted for relief from cold, allergies and headache.

“The move to get these FDCs examined is right,” said Sourirajan Srinivasan with the All India Drug Action Network (AIDAN), a consortium of doctors and patients’ rights advocates who have been urging the Centre to ban irrational FDCs since 2015.

“But the CDSCO had already had them examined by an expert committee which scrutinised these FDCs from a technical, pharmacological viewpoint,” Srinivasan told The Telegraph. “What is the need for going through this exercise again?”

The CDSCO’s Monday notice underlines that the Supreme Court had in December 2017 passed an order saying the Centre may “de novo” (afresh) carry out an inquiry whether FDCs licensed prior to 1988 should be examined.

The notice said an expert committee led by M.S. Bhatia, professor of psychiatry at the University College of Medical Sciences, New Delhi, tasked with examining these FDCs, had sought data on rationality, safety and efficacy by August 25.

But an earlier expert panel under the CDSCO’s drug technical advisory board had in July 2018 recommended a ban on more than 300 FDCs that it had examined after a process during which it heard arguments from FDC manufacturers.

The earlier panel, chaired by Neelima Kshirsagar, former head of pharmacology at the King Edward Memorial Hospital, Mumbai, had also examined the rationality of pre-1988 FDCs and labelled many as unjustified.

A query sent to the CDSCO by The Telegraph asking about the need for a fresh expert review of the FDCs already deemed unfit for sale by the Kshirsagar panel did not evoke a response.

But Srinivasan said some drug companies had approached the courts arguing that the Kshirsagar panel should not have examined pre-1988 FDCs.

The Kshirsagar panel had, for instance, underlined concerns that both paracetamol and nimesulide had the potential to harm the liver and that there was “no convincing scientific or clinical evidence” to justify this FDC.

It had said the paracetamol-phenylephrine-caffeine formulation might expose some patients to medicines they did not need and underlined that the caffeine content in some formulations was not adequate to justify the claim of “analgesic” effects.

“There could be several reasons for the irrationality of certain FDCs,” Kshirsagar said.

Some FDCs might contain drugs that, when combined into a single formulation, carry the risk of enhanced side-effects or lead to dose mismatching. For instance, a drug that needs to be taken twice a day when combined with a drug to be taken four times a day can, when consumed as an FDC, expose the patient to either a lower dose or an extra dose of one of the two.

The Kshirsagar panel had in its comments on the five-drug FDC expressed concern that it contained some medications that worked against each other — the antihistamine called chlorpheniramine dried up secretions, while bromhexine and guaifenesin both increased secretions by thinning the mucus in the airways. All three are part of the five-drug FDC.

The AIDAN consortium had nearly six years ago submitted a plea to the Centre seeking a ban on what it considered irrational FDCs that it said were exposing patients to potential harm and unnecessary medications.