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Many fixed-dose drug combinations in India lack central regulatory approval


Fixed-dose drug combinations (FDCs) that have not received central regulatory approval are sold in substantial numbers in India, despite concerns over the safety and efficacy of these combinations, according to new research published this week in PLOS Medicine.

A committee of the Parliament of India reported in 2012 that "a very large number" of FDCs had been licensed by state drug authorities without approval by CDSCO (the Indian central drug licensing agency) and raised the concern that FDCs being sold without proper testing could put patients at risk. In the current study, Patricia McGettigan, of Barts and The London School of Medicine and Dentistry in the UK, and colleagues provide specific evidence in support of the 2012 report.

Using information from CDSCO on FDC formulations approved between 1961 and 2013, and FDC sales data between 2007 and 2012 from PharmaTrac, a database of drug sales in India, the researchers analyzed approval status and sales volumes of FDCs in each of 4 therapeutic areas: formulations containing a non-steroidal anti-inflammatory drug (NSAID, for pain relief); formulations containing metformin (for diabetes); formulations containing an anti-depressant or a benzodiazepine or both (for depression/anxiety); and formulations containing an anti-psychotic drug.

Of 175 FDC formulations marketed in India between 2011-2012 in the therapeutic areas studied, the researchers found CDSCO approval for only 60 (34%). Across these 4 areas, formulations with and without record of CDSCO approval contributed varying proportions of FDC sales volumes: almost all metformin FDC sales were from CDSCO-approved formulations, but formulations without record of CDSCO approval accounted for over two-thirds of anti-depressant/benzodiazepine FDC sales (69%), almost half of anti-psychotic FDC sales (43%), and more than a quarter of NSAID FDC sales (28%). Multiple formulations included drugs restricted, banned, or never approved in other countries because of associations with serious adverse events.

Limitations of the study include reliance on publicly available records for central approvals and on commercial sales records, which were not compiled for the purpose of supporting research.

The authors conclude that India should implement "an immediate ban on sales and manufacturing of FDCs not approved by the CDSCO." They note further that "Withdrawal from the market should be staged, prioritising FDCs that include drugs banned or unapproved internationally and potentially most likely to harm patients," and that prescribers should "review the needs of patients taking these FDCs, taper off the drugs, and substitute appropriate alternatives... with monitoring of benefit/need."


Research Article

Funding: Funding: EU FP7 Health-2009-4.3.2-2 (Grant 242262). This paper results from research funded by the European Union Seventh Framework Programme Theme: Health-2009-4.3.2-2 (Grant no. 242262) under the title 'Access to Medicines in Africa and South Asia [AMASA]'. The project team includes partners at the University of Edinburgh (UK), Foundation for Research in Community Health (India), University of Ghent (Belgium), Mbarara University of Science and Technology (Uganda), Makerere University (Uganda), Queen Mary University of London (UK), Swiss Tropical and Public Health Institute at the University of Basel (Switzerland) and the University of the Western Cape (South Africa). Details are located at: and at The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: McGettigan P, Roderick P, Mahajan R, Kadam A, Pollock AM (2015) 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 12(5): e1001826. doi:10.1371/journal.pmed.1001826

Author Affiliations:

William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom

Global Health, Policy and Innovation Unit, Queen Mary University of London, London, United Kingdom

Foundation for Research in Community Health, Mumbai, India



Dr. Patricia McGettigan

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