INTRODUCTION:

The basic aim of drug therapy is treatingailments with good quality drugs which is safe and effective.¹ Irrational drug therapy can lead to a decrease in quality of drug therapy, it can also bring about increased risk of side effects and drug resistance.² Fixed dose combinations (FDCs) is a combination product of two or more active pharmacological ingredients (APIs) in a single dosage form. FDCs enhance the efficacy of individual drugs, improve patient compliance, decrease the chance of drug resistance and decrease the pill burden on the patients.³

Presently, there is lot of debate over rationality and irrationality of FDCs. As, there are two sides of each coin FDCs do also have advantages and disadvantages. It is up to the stakeholder to misuse it or use it judiciously by maintaining the balance. Considering, the present scenario it is observed that the balance is tilting towards misuse of the concept of FDC. The reasons for misuse are: most commercial approach of industry, casual approach of all the stakeholders of health care regarding the rational drug therapy.⁴

For any educational intervention to be successful and for the changes to bear effect, the target group should change their knowledge, attitudes and practices (KAP).⁵The knowledge about prescribing fixed dose combinations is becoming increasingly important as many FDCs are manufactured every year. Tertiary care teaching hospitals have a dual role to play in terms of educating medical students and providing health care facilities to the patients.⁶ Resident doctors are primarily involved in patient management at tertiary care teaching hospitals, so their awareness about prescribing medicines is of prime importance for the treatment of patients.⁶Thus, the present study is conducted to evaluate the knowledge, attitude and practices about prescribing fixed dose combinations among resident doctors from different departments at a tertiary care teaching hospital.

OBJECTIVE OF THE STUDY

To evaluate knowledge, attitude and practices regarding FDC’s among resident doctors at a tertiary care teaching hospital.

MATERIALS AND METHODS:

After Institutional Ethics Committee (IEC) approval, a questionnaire based study was carried out with interns, first, second and third year postgraduate students working in medicine, surgery, paediatrics, obstetrics and gynaecology, skin and venereal diseases , psychiatry and orthopaedics department of Rajarajeswari Medical College and Hospital, a tertiary care teaching hospital, Bangalore. A prevalidated questionnaire, with details such as the resident's information about their respective department, year of study and questions regarding knowledge, attitude and prescribing practices of fixed dose combinations was used as a tool, which was administrated to all the resident doctors and the collected data was analyzed. Written informed consent from resident doctors was taken before administering the questionnaire.

RESULTS:

A total of 200 resident doctors of which 120 were postgraduate students and 80 were interns. Analysis of their knowledge revealed that 95% of the postgraduates and 87.5% were aware about FDCs. Improved patient compliance and synergistic drug effect were the major advantages while difficulty in dosage adjustments and increased adverse drug reactions were the common disadvantage of prescribing FDCs mentioned by the study population [Table 1]. 72 % of resident doctors were aware of availability of Essential Medicine List (EML) but none prescribed according to EML. Among them 53.3 % of postgraduates, 18.7% of interns were aware of a single banned FDC in WHO EML and 46.7% postgraduate students , 16.2 % of interns were able to mention a single banned FDC in India [Fig 1].

Antimicrobials (Amoxicillin + Clavulanic acid) were the most commonly prescribed FDCs (34%) followed by analgesics (Paracetamol + Aceclofenac) (27%) [Table 2]. The most common conditions for prescribing FDCs were infections in Medicine (55%), Orthopaedics (62.4%), Paediatrics (61.2%), OBG (47.8%), Surgery (69.7%), Skin and VD (60%) and depression (50%) in psychiatry. The detailed results about most commonly prescribed FDCs and the conditions in various departments are mentioned in Table 3 and 4.

88 % of resident doctors opined that FDCs should be allowed to be marketed. Textbooks (27.9 %), Senior doctors, colleagues and peers (25.3 %) and Medical representatives (MRs) (18.3 %) were the most common sources of information of FDCs for the postgraduate students whereas Senior doctors, colleagues and peers (46.9 %) , Medical representatives (MRs) (18.3 %) and internet (12.8 %) were the most common sources of information of FDCs for the interns [Fig-2].

Most of the postgraduates (91.7%) and interns (93.7%) believed that regular Continuous Medical Education (CMEs) stressing upon rational use of medicine could sensitize them to the rational FDCs [Table 5]. Only 44.1% postgraduates and 23.75 % were aware of concept of P-drugs.

Table-1: KNOWLEDGE OF ADVANTAGES AND DISADVANTAGES OF FDC’S (n=200)

	% of POSTGRADUATES	% of INTERNS
ADVANTAGES
Better patient compliance	99.1	93.7
Synergistic drug effect	91.6	55
Prevent drug resistance	93.3	37.5
Decreased chances of adverse drug reactions	33.4	23.3
Less cost	29.1	12.5
DISADVANTAGES
Difficulty in dose adjustment	86.7	85
Increased adverse drug reactions	85.8	80
Increased financial burden on patient	66.7	62.7
Timing of different components of FDC cannot be adjusted	65.8	51.2

Fig-1:ANALYSIS OF KNOWLEDGE ABOUT FDCS INCLUDED IN WHO ESSENTIAL MEDICINES LIST (EML) AND BANNED FDCS

Table-2: COMMONLY PRESCRIBED FDC’s BY RESIDENT DOCTORS

FDC’s	No. of Resident Doctors (n=200)
Amoxicillin +Clavulanic acid	68
Paracetamol+ Aceclofenac	54
Pantaprazole + Domperidone	20
Aspirin + Clopidogrel	20
Paracetamol + Diclofenac	18
Glimipiride + Metformin	12
Multiviamins	12
Ambroxol + Salbutamol	10
Diclofenac + Serratiopeptidase	8
Ipratropium bromide + Salbutamol	7
Ofloxacin + Ornidazole	6
Losartan + Hydrochlorthiazide	6
Paracetamol + Chlorpheniramine maleate + Phenyl propanolamine	5
Pipercillin + Tazobactum	5
Escitalopram + Clonazepam	4
Olanzepine + Fluoxetine	3
Ethinylestradiol + norethisterone	2
Trimethoprim + sulfamethaxozole	2
Clobetasol + Betamethasone	1

TABLE-3: COMMON CONDITIONS FOR PRESCRIBING FDC’s IN VARIOUS DEPARTMENTS (n=200)

DEPARTMENTS	MEDICINE	ORTHOPEDICS	PAEDIATRICS	OBG	SURGERY	PSYCHIATRY	SKIN AND VD
Common Conditions	Infections (55%)	Infections (62.4%)	Infections (61.2%)	Infections (47.8 %)	Wound infections, Ulcers (69.7%)	Depression (50%)	Infections (60%)
	Hypertension (20%)	Pain relief (37.6%)	Fever and Common cold (29.7%)	Pain relief (28.5 %)	Pain relief (30.4%)	Schizophrenia (50%)	Acne vulgaris (40%)
	Diabetes Mellitus (15%)		Wheezing (9.2%)	Multivitamins (14.4 %)
	Fever and Body pains(10 %)		Wheezing (9.2%)	Contraception (9.3 %)

TABLE-4: COMMONLY PRESCRIBED FDC’s IN VARIOUS DEPARTMENTS (n=200)

DEPT

MEDICINE (%)

ORTHOPEDICS (%)

PAEDIATRICS (%)

OBG (%)

SURGERY (%)

PSYCHIATRY

(%)

SKIN AND VD (%)

Common FDC’s Prescribed

Amoxicillin + Clavulanic acid ( 19.7)

Diclofenac + Serratiopeptidase

( 34.5)

Paracetamol + Chlorpheniramine maleate + Phenyl propanolamine (27.6)

Amoxicillin +Clavulanic acid

(18.6)

Amoxicillin + Clavulanic acid (43.7)

Escitalopram + Clonazepam

(49.4)

Trimethoprim + sulfamethaxozole

(38.7)

Pantoprazole + Domperidone

(15.8)

Pipercillin + Tazobactum

(29.8)

Amoxicillin + Clavulanic acid

(25.8)

Pantoprazole + Domperidone

(15.4)

Pipercillin + Tazobactum

(25.8)

Olanzepine + Fluoxetine

(51.7)

Clobetasol + Betamethasone

(26.9)

Aceclofenac + Paracetamol

(14.6)

Amoxicillin + Clavulanic acid

(16.7)

Ambroxol +Salbutamol

(18.9)

Aceclofenac + Paracetamol

(14.7)

Diclofenac + Paracetamol(12.5)

Aspirin + Clopidogrel

(12.9)

Aceclofenac + Paracetamol

(15.9)

Ipratropium bromide + Salbutamol

(15.2)

Ethinylestradiol + norethisterone

(25.9)

Ofloxacin + Ornidazole

(10.8)

Losaratan + Hydrochlorthiazide (10.4)

Diclofenac + Paracetamol (14.6)

Diclofenac + Paracetamol

(14.9)

Diclofenac + Paracetamol

(13.7)

Ambroxol +Salbutamol ( 10.5)

Ipratropium bromide + Salbutamol 10.5)

Glimipiride + Metformin(9.7)

Multivitamins(8.3)

Fig-2: SOURCES OF INFORMATION ABOUT FDC’s

TABLE-5: VARIOUS INTERVENTIONS TO REDUCE IRRATIONAL FDC’S

Interventions to reduce Irrational FDC’s	Postgraduate students (%)	Interns (%)
Regular CME’s stressing upon rational use of medicines	91.7	93.7
Prescribing drugs from Indian National Formulary and WHO Model Formulary	54.2	40
Regular updating of National Formulary	47.5	30
Hospital based Formulary based on concept of essential medicine	40.8	21.2
Guidelines for production, sale, distribution and import export of irrational FDC’s products	76.6	82.5

DISCUSSION:

The knowledge , attitude and practice refers to understanding of the subject , preconceived ideas and feelings towards the subject and the ways in which these are demonstrated through actions.⁶ The triad of knowledge, attitude and practice is a more efficient process of understanding the present situation and the reasons for it. It can also be useful for finding the areas where deficiencies are present. The trend of prescribing fixed dose combinations (FDCs) is increasing in clinical practice.^{7, 8}The most imperative concern with irrational FDCs is that they expose patients to unnecessary risk of drug reactions, antibiotic FDCs are responsible for increasing the chances of resistance.⁹In tertiary care hospitals, the interns and the post graduate students are mostly involved in prescribing medicines hence the present study was carried out to evaluate knowledge, attitude and practice about prescribing FDCs among them.

In the present study it was observed that improved patient compliance and synergistic drug effect were the most common advantages, while difficulty in dosage adjustment and increased adverse drug reactions were the common disadvantage of FDCs mentioned by resident doctors. According to World Health Organization (WHO) guidelines there are a number of other advantages like decreased chances of adverse drug reactions, simplified management and handling of drug convenience of prescribing. Incompatible pharmacokinetics, drug interactions, potential quality problems are the other disadvantages of using FDCs.^{6, 9}

WHO introduced the concept essential drug list in 1977 and updates the model list every year. The government of India, under the Ministry of Health and Family Welfare has recommended the list of essential medicines in India. Knowledge about Essential Medicines List and its updates helps the prescribers to select the drugs and use them rationally for better treatment outcome.⁶Knowledge about the availability of the WHO Essential Medicine List was lacking in interns and postgraduates in our study and twenty eight percent of them were unaware about the existence of EML.The lack of knowledge about EML may be due to lack of sensitization of the interns and postgraduates during their MBBS curriculum and may be one of the important causal factors for prescribing errors.

India has banned a total of 69 drugs and their combinations with other drugs for manufacturing and marketing in India.¹⁰ Knowledge about the banned drugs/FDCs is very important as lack of this knowledge and prescribing of these agents may lead to serious, adverse drug reactions. In our study only 46.7% postgraduates and 16.2 % interns could recall a single banned FDC in India.

A variety of NSAID combinations are available as over the counter products. In our study, some of the commonly prescribed FDCs were analgesics (Paracetamol + Diclofenac sodium, Paracetamol + Diclofenac, Diclofenac + Serratiopeptidae), antimicrobials (Amoxicillin + Clavulanic acid, Pipercillin + Tazobactum , Ofloxacin + Ornidazole), Multivitamins and Pantaprazole + Domperidone. Amoxicillin + Clavulanic acid was the most commonly (68%) prescribed FDC followed by Paracetamol + diclofenac (54%). Combining two NSAIDs or NSAID with analgesics like paracetamol does not improve the efficacy or potency of treatment and only adds to cost of therapy and risk of the adverse drug reactions.¹¹As per WHO guidelines, the combination of vitamins are part of nutrition, and vitamin combinations should not be used indiscriminately. The claim Serratiopeptidase, a proteolytic enzyme which relieves inflammation, is not based on controlled clinical trials and FDCs containing this compound with NSAIDs offer no additional anti-inflammatory advantage except higher cost to the patient.¹²H2 blockers and proton pump inhibitors are effective in peptic ulcer and it is irrational to combine these drugs with an antiemetic as peptic ulcer is not always associated with vomiting.⁵

Over 70 dangerous FDCs are being sold in India under more than 1000 brand names.¹³ In our country the pipeline of development of a new drug molecule is nearly dry. In addition, lack of profitability and strenuous effort, meticulous drug development factors have forced the pharmaceutical industry to create and manufacture so called novel products by just mixing two or more drugs. The cough mixtures contain expectorants, cough suppressants, antihistamines, sympathomimetics, alcohol and other CNS depressants without any rational basis.All the ingredients in the cough remedies may not be neededat the same time, they also contain certain drugs which have low therapeutic margin. Many FDCs which are not rational are still available in the market. Hence, the is need to educate resident doctors about the basis of rationality of each component of the FDCs is important.¹⁴

In FDCs of fever, cough and cold remedies such as cetirizine + phenylpropanolamine +paracetamol; phenylpropanolamine is a banned drug due to its potential to cause stroke. Phenylpropanolamine can also aggravate diabetes, glaucoma and prostate enlargement. The most common conditions for prescribing FDCs were infections in Medicine, Orthopaedics, Paediatrics, OBG, Surgery , Skin and VD and depression in psychiatry. Most of the infections are viral in origin and are self limiting so Injudicious use of antibiotic FDCs is giving rise to resistant strains of organisms which and the pipeline for new antimicrobials remains meager.⁵

Resident doctors were in favor of marketing of FDCs due to decreased pill burden of the patient and better patient compliance. In the present study, we observed that Textbooks (27.9 %), Senior doctors, colleagues and peers (25.3 %) and Medical representatives (MRs) (18.3 %) were the most common sources of information of FDCs for the postgraduate students whereas Senior doctors, colleagues and peers (46.9 %) , Medical representatives (MRs) (18.3 %) and internet (12.8 %) were the most common sources of information of FDCs for the interns. Lack of knowledge could be due to less use of EML, journals and CMEs.

Most of the postgraduates (91.7%) and interns (93.7%) believed that regular Continuous Medical Education (CMEs) stressing upon rational use of medicine could help them to the use of FDCs rationally.

In the present study, it was observed that the knowledge about FDCs was lacking in resident doctors which leads to irrational prescriptions. Most common cause of poor knowledge may be due to lack of utilization of authentic sources of drug information. Other factors such as increased patient load, lack of sensitization during undergraduate and postgraduate training and sparse number of CMEs stressing upon rational use of medicine are also responsible for the present situation. As patient’s health lies in the hands of healthcare professionals, the awareness about advantages and disadvantages of FDC’s and prescribing them rationally is essential, and it should be started from the undergraduate level of teaching. Sensitization towards authentic sources of information like EML, educational programme about FDCs and day to day updates regarding banned FDCs are necessary to promote rational use of drugs.¹⁵

CONFLICT OF INTEREST :

There is no conflict of interest

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Received on 22.03.2017 Modified on 21.05.2017

Res. J. Pharmacology & Pharmacodynamics.2017; 9(2): 70-76.

DOI: 10.5958/2321-5836.2017.00012.X