Issues around Fixed Dose Combination (FDC) Drugs
Fixed-drug combinations (FDCs) refer to the combinations of two or more active drugs {called APIs or Active Pharmaceutical Ingredients} in a single dosage form. Such combination of drugs is used for treatment of wide range of ailments including HIV/AIDS, Malaria, Tuberculosis etc.
Advantages and Disadvantages
The single-most advantage of FDCs is that it gives a simple dose schedule which results in reduced “pill burden” and increased patient compliance. Such simple schedule is much better for elderly people or patients suffering from multiple disorders. Further, in multiple drugs, the doctors as well as patients might confuse on exact composition or dose of each APIs. Thus, the logic behind development of FDCs is to simplify the treatment regime.
However, there are several disadvantages. For example, if the doctors wish to alter the dosage of one drug in the combination, it would be impossible. The patient may not need one or few of the drugs in the FDCs but cannot be removed from dose schedule. Similarly, the cock-tail of drugs usually results in more adverse side-effects than individual drugs. Further, if one drug causes allergy or any other side-effect, the whole FDC cannot be prescribed for the patient.
Rational and Irrational FDCs
The general acceptance is that most drugs should be formulated as single compounds. However, as we discussed above, there are certain circumstances when FDCs are logical to be used. On the basis of few criteria, the WHO defines the FDCs as rational or irrational. A rational Fix ratio combination of drugs is when:
- The combination of ingredients meets the requirements of a defined population group
- Such combo has proved to be definitely advantageous over single compounds.
- The drug in the combination should act by different mechanisms and their mix should not result in supra-additive toxicity.
Some of the examples of rational FDCs include sulfamethoxazole + trimethoprim; rifampicin + isoniazid, isoniazid + ethambutol etc. (used in TB); levodopa + carbidopa (used in Parkinson’s disease) etc.
However, when the above given criteria are not met, the FDCs would be termed irrational.
One example of irrational FDCs is nimesulide + paracetamol formulations for children. Both Nimesulide and paracetamol reduce fever and are anti-inflammatory; and Nimesulide is in fact more effective than paracetamol. This irrational combination puts the children on risk and provides no additional benefits. Thus, it is the mushrooming of irrational FDCs which creates a problem. There are numerous examples which we come across every day of FDCs such as Ibuprofen+paracetamol, cefixime and azithromycin etc.
FDCs in India
FDCs are highly popular in the Indian pharmaceutical market and have been particularly flourishing in the last few years. Rampant introduction of irrational FDCs not only exposes the patients to unnecessary risk of adverse drug reactions but also creates health problem in larger groups of people. Most of these FDCs are available in India as over-the-counter products.
Despite of the fact that it is mandatory for the FDCs to get an approval from Central Drugs Standard Control Organisaton (CDSCO), there is a huge fraction of unapproved FDCs sold OTC in India.
Recent Ban on FDCs
On March 15, 2016, the Health Ministry banned 344 FDCs and that closed the immediate sale of some of the most popular OTC medicines. The ban was on the ground of risk to humans and that safer alternatives are available in the market. Immediately after this ban, many drug companies moved to court to get relief. The court admitted the case and issued a notice to health ministry to file a status report.
On December 2, 2016, Delhi High Court quashed ban imposed on 344 fixed dose combination (FDC) drugs by the Central Government over fears that they are potential health and safety hazards. The HC held that Centre had acted in a haphazard manner and did not take the advice of the statutory bodies under the Drugs and Cosmetics Act before issuing ban notification.
