What are combination drugs; why have 156 of them been banned?

In its notification issued last week, the central government termed these FDCs irrational, and said they do not have any therapeutic benefit.

What are FDCs; whom do they help?

FDCs are medicines that have more than one active ingredient — chemical compounds in medicines that have an effect on the body — in a single pill, capsule, or shot. FDCs are meant for patients with conditions such as tuberculosis and diabetes for which they need to take multiple medicines regularly. FDCs reduce the number of pills the patient needs to take each day, and help improve adherence to the treatment.

Sometimes, however, an FDC could mean that a patient ends up taking a drug that they may not need. Cheston Cold, for instance, contains paracetamol for fever, cetirizine for allergy relief, and phenylephrine for nasal decongestion. So while this drug will help people who have these symptoms because of allergies, it is not really required for a bacterial infection.

Which FDCs have been banned?

Among the banned drugs are:

*Several combinations of enzymes used for treatment of gastrointestinal problems;

*Combinations of anti-allergic medicines such as levocetirizine with nasal decongestant, syrups that break down mucus, and paracetamol;

*Combinations used for the treatment of skin conditions, including menthol with aloe vera; aloe vera with vitamin E in the form of medicated soap; silver sulfadiazine (used for burns) with an antiseptic agent, aloe extract and vitamin; calamine lotion with aloe and a natural substance (for skin irritation);

*Combination of a migraine medicine with one to prevent nausea;

*Combination of the drug mefenamic acid — usually used for menstrual cramps — with anti-fibrotic medicine tranexamic acid;

*Combination of sildenafil, the active ingredient in the erectile dysfunction drug Viagra, with a drug that relaxes blood vessels and muscles.

Are these drugs still available?

Manufacturers have been told to immediately stop producing, stocking, and selling these drugs, says the government notification. However, they are likely to remain available in the market for some time. “We have seen that the companies usually go to court after such an order, and the courts allow them to sell the stock that is already in the market,” a senior Health Ministry official told The Indian Express.

So what can happen if you consume one of these banned FDCs?

These medicines may have been in the market for years, and thousands of people may have consumed them already. Having one now is unlikely to cause any harm.
What was the need to ban them, then?

These “irrational” combinations have been banned because they contain ingredients that either do not work well together or have ingredients that are not needed by patients to be taken together.

A major reason is to take combinations of antibiotics out of circulation, because the unnecessary consumption of antibiotics can lead to increase in antibiotic resistance — which means increasingly higher doses or stronger antibiotics are needed for the treatment of even simple infections.

Despite the earlier bans, a 2023 study found that FDCs as a proportion of total antibiotics sold in India had actually increased from 32.9% in 2008 to 37.3% in 2020.

The study noted that India has among the highest number of FDCs in the market anywhere in the world, many of which were potentially inappropriate. “In India, of the 4.5 billion standard units of antibiotic FDCs sold in 2020, 41.5% were attributed to combinations listed as ‘not recommended’ by WHO,” the study said.

Another reason for the ban is the pricing control on essential medicines. The government decides ceiling prices for these medicines based on average market prices. Companies are known to create FDCs to escape the pricing control mechanism.

Why has the government acted now?

The action is in line with the government’s effort to weed out irrational medicine combinations that have entered the market over the years. These banned drugs were initially approved by various state licensing authorities without any trials for combinations because the ingredients were individually approved, the senior ministry official said.

“The new drugs and clinical trial rules of 2019 make it clear that fixed dose combinations are to be considered as new drugs, and as such have to be approved by the central drug regulator. This has helped in bringing down the number of these irrational combinations available in the market,” the official said.

In 2012, a parliamentary panel first highlighted the problem of irrational drug combinations receiving such approvals. The government set up a committee in 2014 to examine 3,450 FDCs approved for manufacture and sale in the country after 1988. The committee found 963 drugs to be irrational, and suggested an immediate ban. It also identified a set of FDCs which needed to be studied further. Of these, 499 have been banned so far.