Fixed-dose combination antibiotics in India: global perspectives.

Abstract

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 minimising 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. The government's decision was influenced by reports expressing concern about the safety and efficacy of FDCs manufactured in India.1McGettigan P Roderick P Mahajan R Kadam A Pollock AM Use of fixed dose combination (FDC) drugs in India: central regulatory approval and sales of FDCs containing non-steroidal anti-inflammatory drugs (NSAIDs), metformin, or psychotropic drugs.PLoS Med. 2015; 12: e1001826Crossref PubMed Scopus (35) Google Scholar, 2Harris G Medicines made in India set off safety worries. New York Times (New York).http://www.nytimes.com/2014/02/15/world/asia/medicines-made-in-india-set-off-safety-worries.htmlDate: April 14, 2014Google Scholar In view of the substantial financial loss to industry, some pharmaceutical companies have taken legal action to exempt their FDCs from the ban. However, we believe the government's action was necessary to safeguard public health. 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.3Shafiq N Kumar G Gautam V Ray P Malhotra S Fixed-dose combinations of antimicrobials: a need for special attention.Indian J Med Microbiol. 2016; 34: 208Crossref Scopus (5) Google Scholar Despite repeated investigations into the shortcomings of some FDCs, such drugs are still being manufactured and promoted on the Indian drug market. 118 antibiotic FDCs are available on the Indian market, 80 (68%) of which are not registered with the Central Drugs Standard Control Organisation.1McGettigan P Roderick P Mahajan R Kadam A Pollock AM Use of fixed dose combination (FDC) drugs in India: central regulatory approval and sales of FDCs containing non-steroidal anti-inflammatory drugs (NSAIDs), metformin, or psychotropic drugs.PLoS Med. 2015; 12: e1001826Crossref PubMed Scopus (35) Google Scholar The regulation of FDCs of antimicrobials in India is important from a global perspective. The growth of worldwide trade and travel has allowed resistant microorganisms to spread rapidly to distant countries and continents. New Delhi metallo-β-lactamase, an enzyme that causes bacteria to be resistant to antibiotics, was first reported in India in 2008 and is now found worldwide.4Nordmann P Naas T Poirel L Global spread of Carbapenemase-producing Enterobacteriaceae.Emerg Infect Dis. 2011; 17: 1791-1798Crossref PubMed Scopus (1695) Google Scholar Moreover, FDCs that have been banned in India have been reported to be exported to other African and Asian countries.5Garari K Drugs banned in India to go abroad. Deccan Chronicle (Hyderabad).http://deccanchronicle.com/nation/current-affairs/170316/drugs-banned-in-india-to-go-abroad.htmlDate: March 17, 2016Google Scholar Such exports are a setback for the individuals or organisations trying to implement antimicrobial stewardship initiatives in these settings. Inadequate knowledge of physicians about FDCs is also an exacerbating factor in antibiotic resistance. The Indian Government has taken a much-needed step to restrict antibiotic resistance by banning irrational FDCs. Since implementation of the ban is still pending, we urge the international community to support the Indian Government's initiative to ensure full implementation of the ban on irrational FDCs, because controlling antibiotic resistance in India is key for controlling antibiotic resistance worldwide. We declare no competing interests.