Fixed dose combination (FDC) drugs serve a limited purpose and are used for a few ailments only. FDCs are used to ensure patient compliance by reducing pill burden in the treatment of diseases like diabetes, tuberculosis and HIV/AIDS. In certain other ailments such as Parkinson's disease too, they work well. Take, for instance, the combination of levodopa and carbidopa, which is very effective in the treatment of Parkinson's. In diabetes too, there is a combination that blends a strong diuretic with a weak one, thereby helping in conserving potassium in the body. Loss of potassium is a side effect of a strong diuretic like lasix.
However, over the years, FDCs have become very popular for common ailments too, despite the fact that there is no justification or added benefit for the patient. Some combinations can be absurd and harm the patient, or they can just be irrational and display no distinct advantage. In such cases, the intention of the pharmaceutical companies is to rake in profits by increasing the cost of the drug. Taken in by the marketing hype, doctors also end up prescribing FDCs.
Take the case of a common drug called combiflam, a combination of paracetamol and ibuprofen. For pain, a simple paracetamol is enough, the second ingredient is not needed. But there is no harm as such and the drug works. It is still in use, despite the fact that there is no justification. Those in favour of FDCs argue that despite no theoretical justification, if a drug works, then there is no need to ban it.
Whenever a drug is combined with another, it is considered a new drug and must satisfy certain criteria. The drugs should display synergy, that is, if one drug gives a side effect, the second should negate that side effect. The pharmacokinetics of the drugs combined is also very important—that is, the movement of the drug within the body such as the absorption, distribution, metabolism and excretion. If one ingredient stays in the body for six hours and the other for 24 hours, then the combination is not right. The drug controller general of India has to look at all these criteria, and then give a no objection certificate. The drug then has to be licensed for manufacture by the state licensing authorities (SLA). But SLAs have been giving out licenses without prior no objection certificates from the Centre.
Several examples of problematic combinations are out there. For instance, a common combination of an antibiotic and an antipyretic. Antibiotics are meant to attack the infection. The infection is manifested by a fever and inflammation. They are also to be taken for a longer time than the antipyretic. So a combination of the two might mean that one is unnecessarily taking the antipyretic ingredient that may have its own side effects. It might also be dangerous since the antipyretic will work to mask the infection by containing the fever. Another marketing gimmick is to add lactobacillus to antibiotics. Some antibiotics are understood to disturb the gastric flora in some people. But to cater to those 10 per cent of the patients who might have this side effect, the rest are also given the combination.
In the case of a painkiller and muscle relaxant combination, usually given to patients suffering from injury, the muscle relaxant can become a problem. The patient will feel drowsy for a longer period—an effect of the muscle relaxant.
There are several anti-cough preparations in the market that include both cough suppressants and cough expectorants. These ingredients have actions that are diametrically opposite to each other. There are also antibiotics that are combined with vitamins. There might be no harm, but there is no benefit either, so why unnecessarily burden the patient with the cost? Hundreds of these irrational combinations have entered the market because they help pharmaceutical companies make money.
The process of granting no objection certificates and licences should be more rigorous so as to not let these drugs enter the market. A committee under my chairmanship is also working on additional guidelines for FDCs, and these will be released next month.
Gupta is professor and head, department of pharmacology, AIIMS, Delhi.