In fact, a substantial number of FDC formulations in the market are considered irrational by regulators in other countries. So these products have either never hit retailers shelves there or have been withdrawn after regulatory re-appraisals.
An FDC is a drug created by combining two or more existing drugs. Like in the West, the Indian regulatory system also treats any first-time FDC akin to a new drug that has to be approved by the Drugs Controller General of India (DCGI). Once the DCGI approves a new FDC, the states can issue licences for manufacturing and marketing of the drug.
When you combine two drugs for the first time, then under Indian law it becomes a new product. Because drug A is separate and drug B is separate, A+B is not AB, it makes C. Which means C is totally different from A+B and they have nothing in common, explained senior pharmacologist and editor of industry publication Monthly Issue of Medical Specialties CM Gulhati.
However, there is a long-held belief that certain combinations are irrational meaning one of the drugs used to make the new product may not necessarily cure the ailment it is meant for but may actually harm the patient.
There are also drugs available in the Indian market that have not been approved in any other country. For example, the DCGI approved a drug to treat diabetic neuropathy in August 2011 which, according to Gulhati, has not been approved by any other country.
On the FDC formulations approved in the last two years, he said: New combinations have been approved, which should not have been approved...and some FDCs they (DCGI) claim are less dangerous than the ones that are already available. For example, somebody applies for paracetamol to be combined with ibuprofen. But paracetamol-diclofenac FDC is already available in the market due to lax regulation even though this could be far less dangerous than the proposed one. They (DCGI), however, say the former (paracetamol-ibuprofen) is a less dangerous combination. So instead of banning the existing (irrational) drug it is introducing new such drugs in the market.
Last Mays issue of MIMS mentions nimesulide + diclofenac in its list of irrational combinations. Nimesulide is an anti-inflammatory drug used to treat acute pain and has been withdrawn from many countries because it can cause liver damage. The drug figures 13 times on the list of irrational combinations on the MIMS list.
Or take Pantoprazole 40mg + Cinitapride (ER) 3mg. Cinitapride can affect heart rhythm and can be fatal. There are also numerous examples of FDCs that contain drugs whose safety or efficacy is not a matter of dispute but where their combination could be bad for the patient.
On March 31, 2011, the health ministry formed the National Drug Advisory Committee (NDAC) comprising medical professionals to review applications for new drugs and clinical trials for 12 types of ailments. Head of the pharmacology department at Maulana Azad Medical College and Lok Nayak Jai Prakash Hospital and a member of the NDAC (pulmonary) Uma Tekur said: The committee can only give its suggestions to the DCGI on a drug. The DCGI only approves a drug based on our suggestions and the documents sent by the applicant.
It is very difficult to call a drug irrational. When we say irrational, we also have to look at irrationality in terms of prescriptions because over-the-counter sales are huge in India. Correcting that requires attitudinal change. Even the right drug in the wrong amount, duration and frequency to the wrong patient is irrational, she said.
In every situation, knowing that every drug has a side effect, we have to balance the risk-benefit ratio. Certain drugs are approved for specific conditions, but because they are freely available in the market, it is difficult to monitor their use. But we cant ban them because there are patients who require those drugs, she said.
The Indian Drug Manufacturers Association (IDMA) in an email reply said that FDCs are not just a domestic phenomenon but widely prescribed worldwide. It stressed that they have an enhanced effect on ailments and lighten the pill load on patients.
Chairman of IDMAs medical sub-committee RK Sanghavi clarified: We have strict laws that require us to evaluate the need for the FDC and establish its safety. Hence, every new FDC cleared by the DCGI office undergoes blood-level estimation to establish that the ingredients when combined do not interact, and also clinical studies are submitted to demonstrate that a particular FDC is better effective in managing a condition than a single ingredient monotherapy and/or the combination of drugs facilitate better patient acceptance.
Despite repeated attempts, newly appointed DCGI GN Singh was unavailable for comment.