Many fixed-dose drug combinations in India lack approval: Study

Such FDCs are not thoroughly tested and could put patients' lives at risk

Many fixed-dose drug combinations (FDCs) in India lack central regulatory approval despite concerns over the safety and efficacy of such combinations, say British researchers.

These FDCs are being sold in substantial numbers in India, said the study led by Queen Mary University of London. FDCs include two or more active pharmaceutical ingredients combined in a single dosage form.

They are used as effective treatments for many conditions, including Parkinson's disease, HIV, malaria and tuberculosis. In 2012, the Parliamentary Standing Committee on Health & Family Welfare reported that a very large number of FDCs had been licensed by state drug authorities without approval by the Central Drugs Standard Control Organisation (CDSCO).

It means these FDCs were not thoroughly tested and could put patients' lives at risk.

"India needs to ban the sale and manufacturing of fixed-dose drug combinations not approved by the CDSCO -- beginning with those which include drugs banned or unapproved internationally and, therefore, most likely to be harmful," explained Patricia McGettigan who led the study at Queen Mary University of London.

This study provides specific evidence in support of the 2012 committee 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 analysed approval status and sales volumes of FDCs in four therapeutic areas.

Among 175 FDC formulations marketed in India between 2011-2012, the researchers found CDSCO approval for only 60 (34 percent).

While almost all Metformin FDC sales were from CDSCO-approved formulations, products with no 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 which are restricted, banned or were never approved in other countries because of associations with serious adverse events including death.

The development of fixed-dose combination drugs is becoming increasingly important from a public health perspective and they are commonly used to manage some of the world's most infectious diseases.

"The well-being of patients is paramount. People taking these FDCs need to be reviewed and carefully switched to safe and appropriate alternatives," the authors noted.

In 2012, the Parliamentary Standing Committee on Health & Family Welfare has tabled before Parliament a unanimous 118-page report on the state of drug regulation in India and the manner in which it severely compromises the safety of Indian patients.

"Our research wholly supports the need for a complete overhaul of the new Drugs Bill and we urge the government of India to make this a priority," noted professor Allyson Pollock, global health expert and study co-author.

The paper was published in the journal PLOS Medicine.