Rational drug therapy means the use of right medicine in the right manner (dose, route and frequency of administration, duration of therapy etc.) in right patient at a right cost. Rational drug therapy also means using the drug when necessary. Hence, the drug chosen for a patient should be effective, safe and acceptable quality and cost. The World Health Organizations (WHO) had initiated efforts to promote rational drug use in 1977 with the introduction of the concept of essential drugs. Subsequently, the International Network for Rational Use of Drugs (INRUD) was established in 1989 to promote the rational use of pharmaceuticals. In India, the Delhi Society for Promotion of Rational Use of Drugs (DSPRUD) was formed in 1996 to promote the rational use of drugs within the country.
World Health Organizations (WHO) statistics indicate that 80,000 to 1,00,000 formulations are available in India. But the total number of essential drugs listed in 13th essential medicine list of WHO are only 316 whereas the national list of essential medicine has 354. Out of these, only 19 Fixed Dose Combinations (FDCs) are found in WHO list of essential medicine and 14 in national list of essential medicine. But the number of FDCs in Indian market is quite large.
FDCs in Indian market
There are many FDCs, which are highly popular in the Indian pharmaceutical market and are particularly flourishing in the last few years. Medical experts world over have been expressing serious concern over the marketing of increasing number of drug combinations by pharmaceutical companies particularly in the developing countries. Even though some combinations may not be considered as rational, yet they are heavily promoted, widely prescribed, and consumed. Irrational FDCs can impose unnecessary financial burden, increased adverse effects as well as hospitalization, and decreased quality of life of consumers.
Over the past years, the Indian drug control authority has issued notifications banning many FDCs. The principal notification Under Section 26-A of the Drugs and Cosmetics Act, 1940 prohibiting manufacture, sale and distribution of certain FDCs which do not have any therapeutic justification or are likely to involve risk to human beings in the year 1983 to 2001. FDCs of vitamins with anti-inflammatory agents and tranquilizers, of anti-histamines with anti-diarrhoeals etc are a few examples.
The Drugs Controller General of India (DCGI) has given marketing approvals for 40 fixed dose combinations in January 2002. It is an accepted fact that a fixed dose combination be treated as a new drug because combining two or more drugs together the safety, efficacy, and bioavailability of the individual Active Pharmaceutical Ingredient (API) may change. As per Drugs and Cosmetic Act, 1940 any new combination of drugs is a new drug and the marketing permission is to be given by the DCGI. The same criteria hold good for USA markets, too. The World Health Organization has made the following observations regarding the FDCs. "New fixed ratio combination products are regarded as new drugs in their own right. They are acceptable only when (a) the dosage of each ingredient meets the requirements of a defined population group, and (b) the combination has a proven advantage over single compounds administered separately in terms of therapeutic effects, safety, or compliance. They should not be considered as generic versions of single component products". The WHO Model List of Essential Drugs also provides examples of some rational FDCs such as: Sulfamethoxazole + Trimethoprim, Rifampicin + Isoniazid, Isoniazid + Ethambutol, Levodopa + Carbidopa etc. It is therefore very clear that the rationality of an FDC needs to be established before marketing. There are several issues one comes across either as a newspaper report or an editorial about the irrationality of the FDCs. One editorial report in a well read pharma magazine reported that there are as many as 130 combinations of Nimesulide. Another similar report published elsewhere, "Irrational combinations, Rajasthan Drug Controller seeks DCGI response" showed a list of 100 FDCs as being irrational. This list was prepared by a leading medical journal. But the basis behind this irrationality has not been clearly mentioned. Many experts have expressed their views regarding the individual combinations (safety of Nimesulide combinations). Some experts also addressed certain aspects of combinations like pharmacokinetic parameters, efficacy issue, cost effectiveness, improved patient compliance etc.
Rationality of FDCs
Although various opinions have been expressed regarding rationality of FDCs no research work has been carried out to prove so. One study carried out in M. L. N. Medical College, Allahabad, has elucidated the rationality of FDCs prescribed by doctors by using WHO list of essential medicine. Unfortunately, there seems to be no uniform worldwide acceptable criteria to define irrational FDCs and hence, it became a debated issue in today's scenario. In the recent past there has been substantial effort to improve the usage of medicines by the patients. Several institutions and agencies have prepared user-friendly patient education material. Such material is being used and it will have an impact in the years to come. The issue of using an FDC (which might be banned in another country) will haunt the minds of the patients/their caregivers. With the media coming up on one sensational issue every three months, the fears in the mind of the user(s) need to be allayed. This requires that the FDCs need to be evaluated on a set of criteria which is uniform throughout the country and therefore, acceptable to all the stakeholders.
Unfortunately, such a criteria has been not available and therefore, the users get a contradictory opinion on the same formulation. The need of the hour, therefore, is that researchers, clinicians and policy makers come together and devise a set of parameters on which the evaluation of a fixed dose combination vis-à-vis its rationality. Such criteria will not only help the researchers and clinicians but also aid to allay the fears in the minds of the users.
(Dr P. Tiwari is Associate Professor, Department of Pharmacy Practice,
National Institute of Pharmaceutical Education and Research (NIPER). Jayanti Panda is M. Pharm student).