A combination drug is a fixed dose combination (FDC) that includes two or more active pharmaceutical ingredients combined in a single dosage form, which is manufactured and distributed in fixed doses.

Advantages of fixed dose combinations:

Improved medication compliance by reducing the pill burden of patients .Note that pill burden is not only the number of pills needing to be taken, but also the associated burdens such as keeping track of several medications, understanding their various instructions

Disadvantages of fixed dose combinations:

If an adverse drug reaction occurs from using an FDC, it may be difficult to identify the active ingredient responsible for causing the reaction. This problem might be alleviated by starting the medications individually and monitoring for reactions, and then switching to an FDC when no problems have been observed

Why are FDCs banned in India?

1. Patient may not actually need those many drugs, thus he is subjected to additional side
2. Some drug doses have to be individualized based on patient's You cannot do that if you're using FDCs.
3. Some companies have been selling FDCs in India under this pretext without consulting the central government, like the cefixime-azithromycin combination, which has already been banned in the
4. These non-essential FDCs thus do more harm than good by encouraging irrational and indiscriminate prescribing of more drugs than

How were the drugs banned?

1. On March 10, 2016, the Indian Government banned around 330 “irrational” fixed-dose combination drugs (FDCs) with immediate effect. FDCs are products that contain two or more active drugs in a fixed-dose ratio, and are

useful for minimizing pill burden and lowering cost. However, FDCs should ideally contain constituents that act via different mechanisms and do not cause additive toxic effects. An FDC is described as irrational if these conditions are not met

2.63 (19%) of the 330 banned FDCs are antibiotics. Antibiotic resistance is of increasing concern worldwide, but initiatives to curtail inappropriate use have had little success. Studies of several antibiotic combinations, such as meropenem and sulbactam, have reported no additional advantage over their individual constituents, and have been reported to cause toxic reactions and promote resistance. 118 antibiotic FDCs are available in the Indian market, 80 (68%) of which are not registered with the Central Drugs Standard Control Organization.

Why was the ban wrong?

Justice Rajiv Sahai Endlaw allowed 454 petitions moved by various pharma and healthcare majors such as Pfizer, Glenmark, Procter and Gamble and Cipla, who challenged the government's ban on FDCs, saying the decision was taken by the Centre without following procedure prescribed in the Drugs and Cosmetics Act. The bench noted that the government had not consulted the Drugs Technical Advisory Board or the Drugs Consultative Committee but had acted on the advice of a 'technical committee', which, they said, violated the provisions of the Drugs and Cosmetics Act.

Companies against the ban:

In its argument, Pfizer said that its Corex syrup had been granted approval by the Drug Controller in 1995, which implied that there was “therapeutic justification” for the ingredients, and said that a non-statutory committee could not have withdrawn the approval without even conducting tests. The pharma companies also argued that the ban order was passed without considering clinical data and was termed as “absurd”. The government claimed that it took the decision to ban FDCs on the ground that safer alternatives were available.

Government defense:

The government said that the lack of approval for FDCs were a secondary issue and the primary focus was that they “lacked safety and efficacy” and thus, “ban was the only answer”. It also argued that these FDC medicines are “new drugs” and require licenses from the Drugs Controller General of India (DCGI), not the state drugs licensing authorities.

Past references:

Independent studies across the world have pointed out that many of these combinations do not have any advantage over the individual drugs. A study in the Indian Journal of Pharmacology in 2010 found that the “nimesulide and paracetamol combination offers no advantage over nimesulide alone or paracetamol alone, either in terms of degree of analgesia or onset of action.” There was also a parliamentary Standing Committee report that called for a “clear, transparent policy” for approving FDCs.

What happens now?

The quashing of the notification does not imply that the drugs will now be available in the market. The Centre may challenge the judgment in the Supreme Court or take the steps prescribed under the Drugs Act. Also, the Supreme Court is in the process of hearing a plea filed by the Central government to transfer all cases challenging the March 10 notification before itself — pharma companies had challenged the ban before the Delhi, Chennai and Bangalore high courts.

Examples (Banned fixed dose combination)-

• fixed dose combination of Aceclofenac + Paracetamol + Rabeprazole
• fixed dose combination of Nimesulide + Diclofenac
• fixed dose combination of Nimesulide + Cetirizine + Caffeine

Sahjesh Soni

F. Y. B. Pharm

Tags: MET Institute of Pharmacy