AMR Crisis: Overuse, Misuse and Irrational Use of the FDCs Must Stop

Antimicrobial resistance (AMR) is a public health crisis that is likely to cause about 10 million deaths every year by 2050, unless strong health system-based actions are taken against it. Any antimicrobial use contributes to the development of resistance, but overuse, misuse and irrational use remain the biggest culprits, with or without prescription. The widespread availability, use and prescription of irrational fixed dose combinations (FDCs) of antimicrobials in India is one such contributor. The Ministry of Health and Family Welfare banned 344 FDCs in 2015, which was challenged by the drug companies and later the ban was quashed in the Delhi high court on the grounds that the government did not consult statutory authorities before enforcing the ban. Of these 344 FDCs, 63 contain antimicrobials. While an expert committee is reviewing the issue, clear regulatory loopholes are evident as People’s Health Movement and other public health organisations have pointed out—these formulations were never approved by Central Drug Standard Control Organization (CDSCO), but the drugs are available in the market by merely receiving manufacturing approvals from state drug authorities. Interestingly, state drug control authorities are not authorised to grant marketing approvals. Fortunately, as we write this article, there are reports that suggest the Drugs Technical Advisory Board (DTAB), to which Supreme Court had referred this matter, has recommended the prohibition of about 343 FDCs.

To promote a prudent use of antimicrobials, the WHO publishes a list of ‘Critically Important Antimicrobials for Human Medicines’ (WHO CIA List), classifying them into three categories: critically important, highly important and important. The critically important antimicrobials are further prioritised into highest priority and high priority drugs. Among the highest priority, CIAs that include Cephalosporins (3rd, 4thand 5thgenerations), Glycopeptides, Macrolides and Ketolides, Polymyxins and Quinolones; about 39 types of such FDCs are available, prescribed, and sold in India. Unfortunately, many of these are combinations of the two highest priority CIAs, for instance – Cephalosporins with Macrolides (like Cefixime and Azithromycin) and Quinolones (Cefixime and Levofloxacin). All the other categories also comprise of these FDCs with combinations of critical antibiotics like Linezolid and Cefixime, each of which is reserved for very serious infections! Apart from being unscientific, these FDCs unnecessarily increase the amount of antimicrobial use and may be hazardous in terms of unknown interactions with added risk of adverse effects. Most importantly, given the unregulated and privatised healthcare of the country, these broad spectrum cocktails are often misused at the cost of proper diagnosis and treatment, leading to increased selection of resistant microorganisms. To further strengthen the AMR agenda, the 2017 edition of the WHO Model list of Essential Medicines proposes three groups of antibiotics: i) the Access group which include empiric narrow spectrum, lower resistance potential drugs that should be widely available; ii) the Watch group which include first/second choice treatment drugs with higher resistance potential and should be used for a limited number of indications; and, iii) the Reserve group which are last-resort options tailored to highly specific patients and settings, when other alternatives are exhausted. Unfortunately, FDCs are abundant in the Access and Watch groups and are even available for the Reserve group of drugs like Linezolid.

Does mere availability mean that they are prescribed by the doctors despite the fact that they were never mentioned in any pharmacology or medicine textbooks? Unfortunately, and disturbingly, the answer is yes. For instance, in the summers, when diarrhoea is at its peak, thousands of patients are prescribed an FDC that include a quinolone with an antiprotozoal as a blanket therapy. Moreover, this does not include the tens of thousands that can be directly purchased over the counter (OTC) due to weak regulation of OTC sales. It is useful to reiterate that Quinolones are highest priority CIAs, and also belong to the Watch group. In a largely unregulated and privatised health sector, blanket combinations like that of a combikit of Fluconazole, Azithromycin and Ornidazole come in handy like a sort of ‘shotgun therapy’, first warned about in an NEJM article published in 1960. It is reported that in 2011-12 as compared to 2007-08, the sales of FDCs with Watch or Reserve group antibiotics rose by 73 per cent and 174 per cent respectively. Of the 118 FDC formulations, the study further reports, 64 per cent have no CDSCO approval and 46 per cent include Watch group antibiotics, some even including two of them like cefixime and azithromycin. 

In a country where most of the doctors and medical students, including the authors of this article, have seen antimicrobial resistance in their clinics and hospitals. Such widespread use of unscientific, irrational and hazardous FDCs is terrifying. While the complete weeding out of these FDCs requires stronger regulations and improved healthcare access to reduce non-prescription sales, weeding them out from our prescriptions should be our top priority in antimicrobial stewardship. While the pharma companies have exploited the regulatory loopholes to market these drugs, very few of us acknowledge the writing on the wall in this regard—that these FDCs should have no place in our prescriptions. There is little, if any, excuse for this unethical and irrational over treatment. Let us not continue to commit a mistake that might lead to a future where treatable infections become untreatable.

Nafis Faizi is an Assistant Professor of Community Medicine at JN Medical College, AMU, Aligarh, India, and an active member of the People’s Health Movement, which is a member of Antimicrobial Resistance Coalition.

Hazique Jameel is a Medical student at JN Medical College, AMU, Aligarh, India and an active member of the Public Health Research and Assistance Society (PHRASe) where he advocates for cleaner and rational medical prescriptions.

The views the authors express in this opinion pieces are entirely their own.