The government may ban nearly 400 fixed-dose combination medicines made by 1,500 manufacturers in the next six months due to harmful side-effects as part of an ongoing attempt at cleaning up the sector where lax regulation has led to proliferation of harmful drugs.
The move comes days after the ministry banned 344 fixed-dose combination medicines – including popular brands such as Vicks Action 500, Benadryl and Phensedyl -- over fears that they cause anti-microbial resistance and might even cause organ-failure because of high toxicity.
India is one of the world’s largest markets for fixed dose combination drugs that make up almost half the market share but medical experts say most of them are irrational, that is they haven’t been approved by the national regulator. Many aren’t approved for sale in countries with more stringent regulation.
“I would say 90% are irrational and we have no business letting our people consume all sorts of funny combinations that are no longer in use globally,” said Dr CM Gulhati, editor, Monthly Index of Medical Specialities (MIMS).
But the crackdown may invite a lengthy legal battle. Global giant Pfizer has already obtained a stay on the ban of its drug Corex while American pharmaceutical major Abott indicated it will move court over its Phensedyl combination.
This is a repeat of 2007 when drug firms obtained a stay on a similar ban on 300 combinations.
Fixed-dose combination drugs, or FDCs, combine two or more drugs in a single pill and are widely used to improve patient compliance as it is easier to get someone to take one drug than several.
Many of them slip through India’s labyrinthine regulation process with agencies at the central and state level, which often don’t coordinate.
This, combined with inconsistent enforcement of drug laws, has led hundreds of such drugs entering the market based on state approval without a nod from the Centre.
The central government blames the manufacture, sale and distribution of harmful fixed dose combination medicines on the lax attitude of state governments.
“The products were approved at the state level despite our issuing warnings to states’ drug licensing authorities, but to no avail,” said a health ministry official.
Doctors say the misuse of these combinations may be contributing to antibiotic resistance and causing the rise of some superbugs, strains of bacteria that have become resistant to antibiotics.
The sale of such medicines is illegal because a combination drug needs to be cleared by the national regulator even if the individual constituents are pre-approved.
“Before 1988, combinations of old drugs were not legally termed as new drugs, but under the new law, the combination is a new drug and needs to follow the adequate approval process that includes also having undergone clinical trials,” said Dr Gulhati
“It’s not right to follow the logic that since A, B and C are independently approved drugs, so A+B+C will automatically is approved.”
The health ministry issued a public notice in 2013, asking drug manufacturers to declare fixed dose combination medicines.
“A large chunk ignored our notice, and only 6,600 responded out of about 15,000 pharma units that are active in India, thinking probably we may not take action.
Now that we have taken action they are rushing to courts for respite,” said the health ministry official.
A fresh list is being scrutinised by the committee experts. “We have been working on it for years and there’s absolutely no therapeutic justification for most of these fixed dose combinations. We had issued show cause notices also as a warning, but didn’t get any response,” said the official.
The medicines were broadly divided into four categories. Two of them --rational (approved) and irrational (not approved) use were significant. The medicines under the irrational category were taken up for immediate scrutiny.
“It has been a comprehensive exercise that took into account entire literature on fixed dose combination medicines available in Indian markets. It’s an on-going process and some combinations may even require clinical trials,” said the official.
What is the solution?
“We must check the efficient drug regulators in western countries, namely US and UK to see what is safe and what’s not. It may not be an ideal solution as Indians are a different race but some reference point to begin with,” Dr Gulhati said.