Int J Curr Pharm Res, Vol 9, Issue 5, 64-66Original Article


STUDY TO EVALUATE USE OF IRRATIONAL FIXED DRUG COMBINATIONS

SUDHAKAR K., C. DEEPA LATHA, DEEPIKA BALOJU, A. R. MALAHAT, G. VIJAYALAKSHMI

1,2,3,5Department of Pharmacology Bhaskar Medical College Moinabad, 4Pharmacovigilance Associate, ADR Monitoring Centre Bhaskar Medical College, Moinabad
Email: docsudhakar@gmail.com

Received: 22 May 2017, Revised and Accepted: 22 Jul 2017

ABSTRACT

Objective: To identify fixed drug combinations causing the adverse drug reactions both rational and irrational.

Methods: A prospective observational study was carried out over a period of 6 mo (between June 2016 to December 2016) to evaluate adverse drug reactions related to fixed drug combinations in a tertiary care teaching hospital using suspected adverse drug reaction reporting form.

Results: A total number of 64 adverse drug reactions were reported during this period. Of the total adverse drug reactions reported, 27 (42%) were due to fixed drug combinations. 6 (28.5%) were serious and 21(71.5%) were non-serious. Causality was certain in 4 (14.8%) cases and probably in remaining 23 (85.2%) cases. 19(70%) irrational fixed drug combinations were reported.

Conclusion: The above results show that irrational fixed drug combinations contribute major extent to adverse drug reactions. Hence, awareness programs should be conducted for all the health care workers to improve the rationality of prescription and to decrease adverse drug reactions.

Keywords: Fixed Drug Combinations (FDC), Adverse Drug Reactions, Rationality, Pharmacovigilance, National list of essential medicines (NLEM)

© 2017 The Authors. Published Published Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijcpr.2017v9i5.22140

INTRODUCTION

The World Health Organization (WHO) defines fixed Dose Combinations (FDCs) as combination of two or more active ingredients in a fixed ratio of doses [1]. Polypharmacy is the commonest mode of prescription for single or multiple ailments. Irrational FDC are a part of polypharmacy, which need to be curbed. It is need of the hour to adopt essential medical list and preferred drugs to improve rational therapeutics. The estimated number of FDCs in India is over 6000 and financial turnover associated with it is Rs 7000 crores. Whereas only 24 FDCs out of 376 entities in the National List of Essential Medicines of India (NLEM) 2015 [2] are considered to be rational. Recently health ministry banned 344 fixed-dose combination drugs [3] in March due to questionable efficacy, safety, and rationality. But pharma companies obtained a judicial stay on the order. So the present study was conducted to evaluate irrational fixed dose combinations.

MATERIALS AND METHODS

The present study is carried out at Bhaskar General HospitalAdverse drug reactionsmonitoring centre after obtaining permission from Pharmacovigilance committee members and ethicscommittee. No financial implications are seen. The study is done for a period of 6 mo, it is aprospective observational study wherein adverse drug reactions were collected through notification form (yellow form) and CDSCO form (red form), and further evaluated for irrational prescriptions. Hartwig and Seigelscale do severity assessment of the adverse drug reaction. Causality assessment is done by WHO-UMC causality assessment scale. Rationality was assessed using National List of Essential Medicines of India (NLEM) 2015[2].

Inclusion criteria: Suspected adverse drug reaction reported in Bhaskar Medical College and General Hospital, for 6 mo.

Exclusion criteria: ADR due medication error, over dosage, non-compliance, natural products, alternate medicinesand unidentified drugs were excluded.

Statistical methods

Data entry and analysis was done using Microsoft Excel 2010 version. Data was presented in percentages and proportions. Bars diagrams and pie charts were used to depict percentages.

RESULTS

A total of 64 adverse drug reactions were reported during this period out of which 27 were due to fixed dose combinations.

Pie Chart 1: Sex distribution

Table 1: ADR s due to fixed dose combination and single drugs

Fixed dose combinations Single drugs
27 (42%) 37 (58%)

Table 2: Age distribution table

Age group No of patients
Paediatric (0-19yrs) 1
Adult (22-64yrs) 22
Geriatric (>65yrs) 4

Most of the patients were in adult age group and mean age of patients is 43.2 y.

Table 3: Drug classes used in FDCs contributing to adverse effects

Drug class Rational % Irrational %
Antimicrobials 10 37 6 22.2
NSAID 0 0 3 11.1
Oral Hypoglycemics 0 0 2 7.4
Proton Pump Inhibitor With Prokinetic 0 0 2 7.4
Antihistamine With NSAID 0 0 2 7.4
Multivitamin 1 3.7 1 3.7

Table 4: Pattern of ADRs reported with the use of irrational FDCs

ADR reported with FDC Irrational
Edema 5
Nausea And Vomiting 5
Rash 2
Itching 2
Syncope 1
Gastric Irritation 2
Tightness Of Chest 1
Fixed Drug Eruption 1
Angioedema 1
Eruption 1

Pie Chart 2: Percent of severe cases reported due to FDC according to hartwig and siegel scale

Bar Diagram 1: Percent of cases reported to be possible, probable, certain

Bar Diagram 2: Rational Vs irrational FDC

DISCUSSION

Spontaneously reported adverse drug reactions were evaluated for a period of 6 mo in this study. Of the total adverse drug reactions reported, 27 (42%) were due to fixed drug combinations. This shows that FDCs contribute significantly to adverse drug reactions, which is supported by a study conducted by Vijay Khjauria et al. [4], who reported that FDC was responsible for 26.67% of the total adverse drug reactions reported. Adverse drug reaction reported by irrational and rational FDC were 19(70%) and 8 (30%) respectively. Balat JD et al. [5] in relation to study conduct this where irrational FDC contributed to 90%. Antimicrobial class has the highest incidence (59.2%) of adverse drug reactions, which is consistent with a study done by Radhika MS et al., [6] who reported that antimicrobials cause 65.52% Adverse drug reactions. Manu Gangadhar et al.[7]evaluated knowledge, attitude and practices about prescribing fixed dose combinations among postgraduate’s and suggested in accordance with our study that concepts of rational drug use should be implemented in undergraduate curriculum vigorously.

CONCLUSION

The above results show that irrational fixed drug combinations contribute major extent to adverse drug reactions. Hence, awareness programs should be conducted for all the health care workers to improve the rationality of prescription and decrease the adverse drug reactions. Improvisation can be done by -

1. Conducting training sessions at every step of healthcare by higher authorities.

2. Educating Health Care professional from undergraduate level regarding fixed dose combination.

3. Promoting prescription audit every six months to see that strict adherence to rationality is followed.

Further studies are needed to delineate the cause for irrational FDC prescriptions.

CONFLICT OF INTERESTS

Declare none

REFERENCES

  1. WHO Expert Committee on Specifications for Pharmaceutical Preparations: thirty-ninth report. (WHO technical report series); 2005. p. 929.

  2. National List of Essential Medicines (NLEM); 2015.

  3. Health ministry bans 344 fixed dose combination drugs-times of India; 2016.

  4. Vijay Khjauria, Vishal R Tandon, Neelam Rani, Roshi, Sanjeev Gupta, S Habnam Choudhary, et al. Profile of adverse drug reactions with fixed drug combinations: how big is the problem? JK Sci 2015;17:33-7.

  5. Balat JD, Gandhi AM, Patel PP, Dikshit RK. A study of the use of fixed dose combinations in Ahmedabad, India. Indian J Pharmacol 2014;46:503-9.

  6. Radhika MS, Mayur SS, Priyadarshini Kop. The pattern of cutaneous adverse drug reactions due to the use of fixed dose drug combinations. Int J Basic Clin Pharmacol 2013;2:558.

  7. Manu Gangadhar, Narasimhamurthy Kalenahally Muthahanumai, Padmanabha Thiruganahalli Shivaraju. An evaluation of knowledge, attitude and practices about prescribing fixed dose combinations among postgraduates of a rural tertiary health care teaching hospital. Int J Basic Clin Pharmacol 2016;5:2480.

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