Assessment of Rationality of Fixed Dose Combinations Approved in CDSCO List.

Abstract

Fixed Dose Combination (FDC) is highly popular in the Indian pharmaceutical market and has been particularly flourishing in the last few years. Though rationality status is not clear, the pharmaceutical industry has been manufacturing and marketing FDCs. To assess rationality of FDCs enlisted in CDSCO list and marketing in India according to pharmacokinetic (FD) and pharmacodynamic (FD) reasoning and WHO rationality criteria. In this study, 264 FDCs marketed in India from 2009 to 2014 from CDSCO list 2014 were included. Assessment was done on the basis of following parameters: 1) Year and system of FDC; 2) Dosage form; 3) Number of Active Pharmacological Ingredient (API); 4) Schedule of FDC; 5) The presence of the FDC and its ingredients in the WHO Essential Medicine List 2013 and National Essential Medicine List, India 2011; 6) FD and PK parameters of APIs of combination; 7) PK and PD interaction; 8) Safety parameters of ingredients in combination. Descriptive statistics in terms of frequency counts and percentages were used for variables. Out of total 264 FDCs selected, maximum number of combinations (112) were approved in 2010. System wise selection showed 51 (19.31%) FDCs were from cardiovascular system followed by 46 (17.42%) from pain/musculoskeletal system. Oral dosage form was found to be maximum with 200 (75.75%) combinations. According to schedules, 154 (58.33%) combinations were categorized under schedule H. There were 210 (79.54%) FDCs that had two API which was found to be maximum, whereas, only 3 (1.13%) combinations had 5 API. We could find possible PK and PD interactions in between API of 10 (3.78%) and 73 (27.65%) combinations respectively on basis of standard textbooks and references. Similarly dose reduction in API was seen in 58 (21.96%) FDCs. There were 123 (46.59%) FDCs had chances of increased ADRs due to its API. Out of 264 combinations, 52 combinations were rational (6-9), 75 combinations were semi-rational (3-<6) and 137 combinations were found to be irrational (0<3). We could reveal that majority of combinations approved in last six years were found to be semi-rational and irrational. It is important to carry out detailed study in this area to establish the fact and increase rationality of combinations.