A Study of Prescribing Pattern of Non-Steroidal Anti-Inflammatory Drugsin the Department of Orthopaedics, KIMS Hospital and Research Centre,Bangalore

Introduction

The current International Association for the Study of Pain (IASP) defines pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”¹ Pain often is so subjective; however many clinicians define pain as whatever the patient explains it to be.²

Pain, as well as inflammation, is treated primarily with Non-steroidal Anti-inflammatory Drugs (NSAIDs). They are the most widely prescribed drugs with good efficacy as an analgesic, antipyretic and anti-inflammatory agents and are also available over-the-counter.^3,4 These FDAapproved drugs are useful for the treatment of muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, migraines,⁵ rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), etc.⁶ NSAIDs are frequently involved in drug-drug interactions, leading to increased hospitalization and health care cost.⁷ NSAIDs have well- known adverse effects affecting the gastric mucosa, renal system, cardiovascular system, hepatic system, and hematologic system.⁵ NSAID guidelines have been established to increase physician awareness of the complications associated with their use. However, some physicians either do not recognize or do not adhere to such guidelines. A recent survey of physicians identified six major barriers that affected their use of established NSAID guidelines. The barriers mentioned were: Unfamiliar guidelines along with an overwhelming number of published medical guidelines and difficulties in keeping up to date with new recommendations; perceived limited validity of the guidelines; and limited applicability of the guidelines to specific patient populations, clinical inertia, anecdotal experiences, and clinical heuristics. A research backing this identified more than 20 different guidelines that mention NSAIDs and the elderly in addition to other highly acclaimed medication risk factor guidelines or tools.⁷ Although NSAIDs are one of the most widely used, they are also extensively misused; hence prescribing pattern studies and drug utilization studies are essential in evaluating the usage of NSAIDs and their rationality.⁸ A study of a prescription pattern is an important tool to determine rational drug therapy, maximize utilization of resources, and to reduce prescription errors. In 2008, the WHO reported that more than 50% of all medicines are prescribed, dispensed, or sold inappropriately and that 50% of all patients fail to take them correctly.⁹

The WHO defined rational drug prescribing as patients receiving “medications appropriate to their clinical needs, in doses that meet their requirements for an adequate period, and the lowest cost to them and their community.” Irrational drug prescribing is a threat globally to the healthcare system, especially in developing countries. According to the WHO, more than 50% of the patients receive inappropriate prescriptions.¹⁰ Some of the reckless practices are polypharmacy, irrational prescribing of drugs, abuse of injectable medicines, non-adherence to clinical guidelines, etc.¹¹ In developing countries like India, where there are limited financial resources and a low economy, implementing rational use of medicines (RUM) becomes essential. Drug utilization studies play an important role in the in-patient and outpatient settings and are great tools to evaluate prescribing behaviours, efficacy, and cost-effectiveness of hospital formularies.¹² Gaining insight into physician’s patterns to identify a prescribing problem is the fundamental step in improving the quality of prescription and patient care in the orthopaedic department.⁹ Few studies showed irrational and inappropriate prescribing in their hospitals and were not following the current guidelines.^13-17 The aim of our study was to determine the prescribing pattern of NSAIDs in the orthopaedic department, to report and document the potential drug-drug interactions associated with NSAID and to report and document the adverse drug reactions associated with NSAID’s usage.

Materials and Methods

A prospective cross-sectional study was conducted for a period of six months (6/2/2021 – 30/8/2021). A total of 200 patients from both inpatient and outpatient of Orthopaedic Department at Kempegowda Institute of Medical Sciences Hospital & Research Centre, Karnataka, Bangalore, India, who satisfied the study criteria were included. After obtaining the ethical clearance from the KIMS institutional ethical committee (Ref No: KIMS/IEC/D133/P/2021), the study participants were recruited based on the study criteria, and the details were collected only after obtaining the consent of the patient through an informed consent form. The patient details included socio-demographic details like age, gender, presenting complaints, details of the diagnosis made, and information on the drugs prescribed like brand and/or generic name, dose, dosing frequency, formulation, route of administration, duration of treatment. The procedure was as follows:

• Method of data collection

• Statistical analysis (using SPSS version 27)

The data collected during the study were:

• Prescribing pattern of NSAID’S

• The drug-drug interactions (severity was checked using Medscape and Lexicomp interaction checker)

• The adverse drug reactions (using Naranjo scale for assessment of causality)

Study criteria

• Inclusion criteria:

i. Both the genders, aged above 12 years ii. Both inpatients and outpatients of the Orthopaedic Department for whom NSAID’s were prescribed

• Exclusion criteria:

i. Pregnant and breastfeeding women

Results

Demographic details

Two hundred subjects were enrolled in the present study and 45 (22.5%) subjects who were frequently prescribed NSAIDs were from the age group of 30 – 39 years, and the majority were males. 124 (62%) subjects were inpatients.

Diagnosis

Table 1 shows that maximum subjects [56(28%)] were diagnosed with a fracture of the lower limb, followed by fracture of the upper limb [30 (15%)], and with lower backache without deficits [24 (12%)].

Prescribing pattern

The analysis of monotherapy shows that out of 200 subjects, 64 (32%) were prescribed paracetamol, followed by 17 (9%) who were prescribed diclofenac. The analysis of the fixed-dose combination of NSAIDs showed a majority of subjects 69 (34.5%) were prescribed a combination of aceclofenac+paracetamol, 27 (13.5%) with aceclofenac+serratiopeptidase, 14 (7%) with aceclofenac+thiocolchicoside. 177 (88.5%) prescriptions with preferential COX-2 inhibitors like aceclofenac and diclofenac were the most chosen drugs for the treatment. 8 (4%) were prescribed non-selective COX-2 inhibitors while 10 (5%) were prescribed selective COX-2 inhibitors. However, among other classes of drugs prescribed (excluding NSAIDs), 178 (89%) were prescribed with gastro-protective agents. The preferred route of administration in the department was oral form 196 (53%) followed by parenteral form 83 (41.5%). More than half of the subjects 125 (62.5%) 50±6.48 were prescribed two NSAIDs. Figure 1 shows the distribution based on monotherapy of NSAID’s

Drug interaction

Figure 2 shows the distribution of drug-drug interactions. Majority of subjects’ prescriptions 117 (59%) did not have any interactions with NSAIDs, whereas 62 (31%) subject prescriptions were found to have interactions with aceclofenac + bromelain together.

Figure 3 shows the evaluation of drug-drug interactions based on the severity. 72 (36%) subject prescriptions were found to have moderate interactions, 6 (3%) with minor interactions and 3 (2%) had major severity of interactions.

Discussion

Out of 200 subjects, 106 (53%) subjects who were frequently prescribed with NSAIDs were males. A similar study was done in a teaching hospital in Uttar Pradesh also showed a higher number of male subjects.¹⁸ Large numbers of subjects were diagnosed with lower body fractures whereas the study conducted by Kholoud

Z Qoul et al., reported many osteoarthritis patients.¹⁹ In the case of monotherapy with NSAIDs, 64 (32%) were prescribed paracetamol while the study carried out by Saldanha LV et al., revealed that diclofenac was more prescribed as monotherapy.²⁰ The majority of subjects 69 (34.5%) were prescribed a combination of aceclofenac + paracetamol while the study conducted by Farheen H et al., showed that mostly tramadol + paracetamol was given in combination.²¹ Among other classes of drugs prescribed, 178 (89%) were prescribed with gastro-protective agents. However, Saldanha LV et al., revealed that 90% of the prescriptions were coprescribed with NSAIDs and gastroprotective agents.²⁰ The preferred route of administration in the department was oral form 196 (53%) followed by parenteral form 83 (41.5%), whereas the study conducted by Zeinali M and co-authors concluded that oral route NSAIDs were more prescribed.¹² More than half of the subjects 125 (62.5%) were prescribed two NSAIDs; this was less compared to the study conducted by Alshakka MA et al.,²² but the study was conducted by M Rangapriya et al., showed common prescription of one NSAID in patients.²³ Most subjectsubjects’ prescriptions 117 (59%) did not have any interactions with NSAIDs, and 62 (31%) subjects’ prescriptions were found to have interactions with aceclofenac + bromelain together. This was contrasting with the study conducted by Bahreini A et al., which showed major interaction between tramadol and dexamethasone.¹⁷ Up to 72 (36%) subject’s prescriptions were found to have moderate interactions and even the study conducted by Bahreini A et al., reported the majority of moderate interactions.¹⁷

Conclusion

NSAID use is mostly accompanied by gastrointestinal complications. In the present study, gastro-protective agents were widely prescribed along with NSAIDs for the prevention of NSAIDs associated ulcers or any other potential gastrointestinal complications. The prescribing pattern in our department seems to be rational. All NSAIDs were prescribed according to the National list of essential medicines (NLEM), except selective COX2 inhibitors. Proper awareness is required among prescribers for encouraging prescriptions in generic names. Generic prescribing sessions, discussion with prescribers, and awareness within the general public concerning the utilization of Over the counter (OTC) NSAIDs may help in reducing the undesirable effects of the drug on its users. Drug interaction combinations must be avoided to bypass their adverse effects on the therapy provided and to improve better patient care.

Acknowledgment

The authors would like to acknowledge KIMS Hospital and Research Centre and the faculty of the orthopedics department along with the faculty of VIPS college for support throughout the study.

Conflicts of interest

None