Assessment of non-steroidal anti-inflammatory drugs use and its complications among pediatric patients at a private tertiary care hospital in Malaysia

Abstract

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to pediatric patients, but inappropriate use can lead to adverse health outcomes. Therefore, a study was conducted to analyse the prescribing patterns and drug-related problems (DRPs) associated with NSAIDs among pediatric patients at a private tertiary care hospital in Malaysia.

Methods

This single-centre, ambidirectional cohort study was conducted at a private tertiary care hospital in Kuala Lumpur, Malaysia, from January 2024 to March 2025. Pediatric patients under 18 years old who were prescribed NSAIDs were included in the study. Data was collected from the patient’s prescriptions and clinical progress notes.

Results

A total of 1958 pediatric prescriptions were analysed. The mean age of patients prescribed NSAIDs was 8.26 ± 5.08 years (Median: 8 years, IQR: 8.75). Of the 1958 patient visits, 882 (45.05%) were to pediatricians, and 803 (41.01%) were to the emergency department. A total of 2072 NSAIDs were prescribed, with the majority (94.48%; p < 0.001) of prescriptions containing only one NSAID. The most common reason for prescribing NSAIDs was pain (63.18%). Ibuprofen was the most commonly prescribed NSAID for both male and female patients (n = 1216, 58.94%), followed by Diclofenac (n = 270, 12.75%) and Celecoxib (n = 218, 10.57%). Age was significantly associated with the type of NSAID prescribed (p < 0.001). A total of 405 potential DRPs were identified. Ibuprofen had the highest number of potential DRPs (n = 193, p < 0.001) due to its high usage, followed by Diclofenac (n = 142) and Celecoxib (n = 16).

Conclusion

Ibuprofen was the most commonly prescribed NSAID for pediatric patients, primarily for painful inflammatory conditions, leading to an increase in drug-related complications. While the prescribing pattern of NSAIDs appears appropriate, there is a rising trend in drug-related complications. Structured educational intervention programmes are needed to improve the prescribing pattern of NSAIDs in healthcare settings and ensure the safety of pediatric patients.

Introduction

The pediatric population exhibits different physiological and developmental characteristics [1–3], necessitating tailored healthcare and treatment as children grow from infancy to adulthood. Due to safety issues, most medicines undergo pre-marketing clinical trials in adults, not in the pediatric population. This leads to a lack of pediatric-friendly formulations and increased unlicensed use of medicines in this population [4, 5]. The inappropriate use of these drugs brings adverse health outcomes to this vulnerable population, making it a global threat.

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) work by inhibiting Cyclooxygenase (COX) enzymes, reducing the synthesis of prostaglandins (PGs) responsible for pain and inflammation [6, 7]. This makes NSAIDs safe and effective in managing conditions such as febrile illness, pain, and inflammation, as evidenced by their recommendation as first-line treatment options alongside paracetamol in the World Health Organisation’s (WHO) analgesic ladder [8–10]. Besides being effective for acute nociceptive pain [11–13], NSAIDs are also recommended in pediatric inflammatory rheumatic diseases (PiRDs) as first-line therapy to reduce pain and inflammation [14–16], thus decreasing the need for corticosteroids [17–19].

While a large-scale randomized clinical trial has proven the safety profile of Ibuprofen in pediatrics, this cannot be generalized to all NSAIDs that can be prescribed to the pediatric population [20, 21]. By inhibiting PG synthesis, NSAIDs also compromise the homeostatic functions of PG [22–24], leading to gastrointestinal or renal side effects [25–27]. Long-term NSAID use may negatively affect cardiovascular health due to the imbalance between thromboxane A2 (TXA2) and prostacyclins [28]. The imbalance may increase the risk of bleeding and heighten the potential for cardiovascular events such as stroke and myocardial infarction [22].

Drug-related problems (DRPs) are more prevalent in the pediatric population compared to adults [29, 30], often involving the inappropriate use of medicines in treatment [31, 32]. The four most common errors among the pediatric population are incorrect dosage, incorrect frequency, incorrect route of administration, and duplication of treatment [33].

Drug use evaluations (DUEs) examine the medication prescribing patterns across healthcare settings, identifying deviations or areas for improvement in the safe and effective use of medicines [34–36]. Although NSAID-associated DUEs have been conducted in several countries, most studies have not thoroughly examined NSAID use and its specific indication [27, 35, 37]. In Malaysia, no studies have been conducted or published analyzing prescribing patterns, and the appropriateness of NSAID use among the pediatric population. As a result, there remains a gap in understanding the actual prescribing practices and DRPs associated with NSAIDs among Malaysian pediatric patients [38]. Therefore, this study analyzed the NSAID prescribing pattern and DRPs associated with NSAIDs use among the pediatric patients of a tertiary care hospital.

Methods

Study design, setting, and population

This ambidirectional cohort study was conducted at a tertiary care hospital in Selangor, Malaysia. The inclusion criteria were all pediatric patients under 18 years of age at the time of their visit to the hospital who were prescribed at least one NSAID for treatment in the outpatient setting. Patients above the age of 18, admitted as inpatients, with incomplete prescriptions or prescriptions beyond the study period were excluded.

The study reviewed prescriptions over 12 months, from January to December 2024. This included retrospective data from January to June 2024 and prospective data from July to December 2024. Due to the ambidirectional nature of the study, all pediatric patients’ prescriptions who were prescribed at least one NSAID during the study period were included. A total of 1586 retrospective prescriptions and 372 prospective prescriptions were collected, totaling 1958 prescriptions for final analysis.

Study instrument

A structured data collection form was used to gather patient information and prescription data from the hospital information system (HIS), MedicaCloudCare. Patients’ demographic data such as age, gender, weight, allergy status, past and current medical conditions, details of NSAIDs use and dosage, and concomitant medicines prescribed were also recorded.

The appropriateness of NSAIDs prescribed to patients was compared with hospital guidelines for NSAID use, the British National Formulary, Micromedex, the Frank Shann dosing guide, and product leaflets. DRPs associated with NSAIDs prescribed and concomitant medications were also analyzed with appropriate established guidelines. Potential DRPs were categorized according to the Pharmaceutical Care Network Europe (PCNE) Classification for Drug-Related Problems, version 9.1, namely drug, dose, formulation, and duration [39].

Data analysis

Descriptive statistics, such as mean and median, were performed. For categorical variables, a Chi-squared (χ2) test of independence was conducted. This test compared the distribution of various types of NSAIDs prescribed across different age groups and medical specialties. Additionally, the chi-squared test investigated the incidence of potential DRPs across different patient demographics.

Ethics approval

This study was an ambidirectional study that consisted of retrospective and prospective data. Ethical approval was obtained from the research and ethics committee of the institution (approval number: MPP 1-2024(04)) and the management of the clinical research center of the hospital (approval number: 030/2024/IND/ER). For the retrospective data, there was no direct involvement of patients, whereas for the prospective data, informed consent to participate in the study was obtained from the parents or legal guardians of any participant under the age of 18. All patients’ data were kept anonymous and confidential.

Results

Demographic characteristics of the study population

The mean age of pediatric patients prescribed NSAIDs was 8.26 ± 5.08 years (Median: 8 years, IQR: 8.75). The largest age group consisted of children aged 3 to 11 years old (n = 1067; 54.5%), classified as early and middle childhood stages by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [40]. There is a statistically significant association between weight and gender (p < 0.001). There were more male patients in the 10–20 kg and > 50 kg weight categories, and the majority did not have any allergies or pre-existing medical conditions. The details are presented in Table 1.

Table 1.

Demographic characteristics of the pediatric patients (n = 1958)

Socio-demographic Characteristics	Male	%	Female	%	Total	%	P-value
Gender	1076	54.95	882	45.05	1958	100	0.95
Ethnicity
Chinese	661	33.76	538	27.48	1199	61.24	0.40
Malay	199	10.16	146	7.46	345	17.62
Indian	90	4.60	90	4.60	180	9.19
Others	126	6.44	108	5.52	234	11.95
Age (in years)
< 1	32	1.63	19	0.97	51	2.60	0.13
1–2	142	7.25	121	6.18	263	13.43
3–5	231	11.80	154	7.87	385	19.66
6–11	369	18.85	313	15.99	682	34.83
12–18	302	15.42	275	14.04	577	29.47
Weight (in Kilogram)
< 10	57	2.91	46	2.35	103	5.26	0.000*
10–20	322	16.45	243	12.41	565	28.86
20–30	164	8.38	147	7.51	311	15.88
30–40	70	3.58	73	3.73	143	7.30
40–50	48	2.45	79	4.03	127	6.49
> 50	120	6.13	68	3.47	188	9.60
Unknown Weight	295	15.07	226	11.54	521	26.61
Allergy Status
Yes	69	57.50	51	42.50	120	6.13	0.56
No	1007	54.79	831	45.21	1838	93.87
Concomitant Medical Condition
Yes	244	57.14	183	42.86	427	21.81	0.30
No	832	54.34	699	45.66	1531	78.19

Medical speciality visited

Of the total 1958 patient visits, 882 (45.05%) were to pediatricians, while 803 (41.01%) were to the emergency department, making up 86.06% of outpatient visits. A significant association was found between speciality visits and gender (p = 0.003). Males were more likely to visit the emergency department (59.78%), orthopedics (54.61%), and Hands and Micro (73.33%).

Pediatric rheumatology was the most visited subspeciality (15.73%), reflecting the clinical profile of PiRD patients. Other notable subspecialities included pediatric cardiology (4.90%) and pediatric orthopedics (4.55%), highlighting the prevalence of musculoskeletal conditions and Kawasaki disease. The details are presented in Table 2.

Table 2.

Distribution of the pediatric patients according to the speciality department visited (n = 1958)

Speciality Department Visited	Male	%	Female	%	Total	%
Cardiology	1	50.00	1	50.00	2	0.10
Dentistry	3	30.00	7	70.00	10	0.51
Dermatology	7	53.85	6	46.15	13	0.66
Emergency	480	59.78	323	40.22	803	41.01
Endocrinology	0	0.00	1	100.00	1	0.05
Ear, nose, and throat	22	51.16	21	48.84	43	2.20
Hematology	0	0.00	2	100.00	2	0.10
Hands and Micro	11	73.33	4	26.67	15	0.77
Neurology	3	60.00	2	40.00	5	0.26
Obstetrics & Gynecology	0	0.00	6	100.00	6	0.31
Ophthalmology	0	0.00	2	100.00	2	0.10
Orthopedics	77	54.61	64	45.39	141	7.20
Rheumatology	3	75.00	1	25.00	4	0.20
Surgery	8	36.36	14	63.64	22	1.12
Urology	0	0.00	3	100.00	3	0.15
Plastic & Reconstructive Surgery	2	50.00	2	50.00	4	0.20
Pediatrics departments (All)	459	52.04	423	47.96	882	45.05
Unit of Pediatric Department
General Pediatrics	54	52.43	49	47.57	103	5.26
Pediatrics Cardiology	50	52.08	46	47.92	96	4.90
Pediatrics Dermatology	5	50.00	5	50.00	10	0.51
Pediatrics Endocrinology	14	51.85	13	48.15	27	1.38
Pediatrics Ear, Nose, and Throat	14	41.18	20	58.82	34	1.74
Pediatrics Gastroenterology	32	72.73	12	27.27	44	2.25
Pediatrics Infection Diseases	6	42.86	8	57.14	14	0.72
Pediatrics Intensivist	12	57.14	9	42.86	21	1.07
Pediatrics Nephrology	14	58.33	10	41.67	24	1.23
Pediatrics Neurology	30	48.39	32	51.61	62	3.17
Pediatrics Orthopedics	52	58.43	37	41.57	89	4.55
Pediatrics Respiratory	5	83.33	1	16.67	6	0.31
Pediatrics Rheumatology	145	47.08	163	52.92	308	15.73
Pediatrics Surgery	24	57.14	18	42.86	42	2.15
Pediatrics Hemato-oncology	1	100.00	0	0.00	1	0.05
Pediatrics Urology	1	100.00	0	0.00	1	0.05

Clinical indication for NSAIDs use

Among the common presenting illnesses and diagnoses for the use of NSAIDs, the majority were prescribed NSAIDs for pain (63.18%), which included musculoskeletal pain (n = 462, 23.60%) and other painful conditions. The second most frequent indication was fever (22.52%). The dual indications of pain and inflammation (4.65%) highlight the use of NSAIDs in managing inflammatory conditions, which are common in Juvenile Idiopathic Arthritis (JIA), Kawasaki disease, and SLE. The details are presented in Table 3.

Table 3.

Clinical indication for NSAIDs use among pediatric patients

Indication	Frequency (n)	Percentage (%)
Pain	1237	63.18
Fever	441	22.52
Pain + Inflammation	91	4.65
Fever + pain	50	2.55
Kawasaki disease	43	2.20
Pain + swelling	34	1.74
Systemic Lupus Erythematosus (SLE)	33	1.69
Unknown	10	0.51
Inflammation	9	0.46
Antiphospholipid syndrome	4	0.20
Fever + pain + inflammation	2	0.10
Pain + JIA	2	0.10
Fever + swelling	1	0.05
Heart disease	1	0.05
TOTAL	1958	100.00

Prescribing pattern of NSAIDs

A total of 2072 NSAIDs were prescribed, with the majority (94.48%) of prescriptions containing only one NSAID, while only 0.31% of prescriptions (n = 6) had three NSAIDs. Oral administration was the most common route for NSAIDs (90.20%), with liquid formulations preferred over solids. External formulations accounted for 5.79%, while parental use was minimal (0.72%).

Ibuprofen was the most commonly prescribed NSAID for both male and female patients (n = 1216, 58.94%), followed by Diclofenac (n = 270, 12.75%) and Celecoxib (n = 218, 10.57%). Meloxicam, Flurbiprofen, and Parecoxib were the least frequently prescribed NSAIDs for both genders.

There is a statistically significant association between age and type of NSAIDs (p < 0.001). Ibuprofen was the most prescribed NSAID (58.94%), peaking in children aged 6 to 11 years old before declining in adolescence. COX-2 inhibitors, specifically Celecoxib (10.08%), were primarily prescribed to adolescents aged 12 years and above. The details are presented in Table 4.

Table 4.

Distribution of NSAIDs according to the patient’s age group

NSAIDs/age group	< 1 Yr	1 to 2	3 to 5	6 to 11	12 to 18	Total
Aspirin	9	28	26	10	10	83
Celecoxib	0	0	0	10	208	218
Diclofenac	10	50	61	75	74	270
Esflurbiprofen	0	0	0	1	14	15
Etoricoxib	0	0	0	3	54	57
Flurbiprofen	0	0	0	1	8	9
Ibuprofen	31	189	315	564	117	1216
Ketoprofen	0	0	1	11	52	64
Mefenamic Acid	0	0	0	3	48	51
Meloxicam	0	0	0	4	8	12
Naproxen	0	0	0	30	39	69
Parecoxib	0	0	0	0	8	8
Total	50	267	403	712	640	2072

NSAID combinations involve different routes of administration to enhance efficacy while reducing systemic exposure. The most common combination was Diclofenac and Ibuprofen (1.74%), followed by Celecoxib and Ketoprofen (0.87%) and Ibuprofen and Ketoprofen (0.46%). The NSAIDs combination and dosage form/route of administration are presented in Table 5.

Table 5.

Top 10 common combinations of NSAIDs prescribed and their route of administration

NSAID combinations	Frequency	Percentage (%)
Diclofenac + Ibuprofen	34	1.74
PO Diclofenac + PO Ibuprofen	5	0.26
PR Diclofenac + PO Diclofenac + PO Ibuprofen	1	0.05
PR Diclofenac + PO Ibuprofen	25	1.28
Top Diclofenac + PO Ibuprofen	3	0.15
Celecoxib + Ketoprofen	17	0.87
PO Celecoxib + Top Ketoprofen	17	0.87
Ibuprofen + Ketoprofen	9	0.46
PO Ibuprofen + Top Ketoprofen	9	0.46
Celecoxib + Diclofenac	7	0.36
PO Celecoxib + Inj Diclofenac	2	0.10
PO Celecoxib + PO Diclofenac	1	0.05
PO Celecoxib + Top Diclofenac	4	0.20
Celecoxib + Flurbiprofen	4	0.20
PO Celecoxib + Top Flurbiprofen	4	0.20
Celecoxib + Esflurbiprofen	2	0.10
PO Celecoxib + Top Esflurbiprofen	2	0.10
Flurbiprofen + Mefenamic Acid	2	0.10
Top Flurbiprofen + PO Mefenamic Acid	2	0.10
Ketoprofen + Mefenamic Acid	2	0.10
Top Ketoprofen + PO Mefenamic Acid	2	0.10
Aspirin + Ibuprofen	1	0.05
PR Aspirin + PO Ibuprofen	1	0.05
Celecoxib + Diclofenac + Esflurbiprofen	1	0.05
PO Celecoxib + Top Diclofenac + Top Esflurbiprofen	1	0.05

PO - by mouth or orally, PR - by rectum, Top – Topical, Inj - Injection. Bolded items represents the common NSAIDs combinations prescribed

Prescribing pattern of non-NSAIDs

Out of 3099 non-NSAID items, 68.38% were administered orally, with liquid formulations (41.01%) being the most common. External preparations accounted for 13.13%, while ear routes were least prescribed (1.16%). Analgesics (21.91%) were the most frequently dispensed across all routes of administration, with Paracetamol being the most common medication (36.49%). Antibiotics (13.91%), antihistamines (8.87%), and cough and cold preparations (4.94%) were also commonly prescribed, highlighting the prevalence of fever, pain, and acute respiratory infections in pediatric patients.

Paracetamol was the most common concomitant medication prescribed along with NSAIDs. A total of 122 (9.08%) patients received Paracetamol with at least one NSAID, followed by 41 (3.05%) patients who received Amoxicillin-Clavulanate along with NSAIDs.

Drug-related problems (DRPs)

A total of 405 potential DRPs were identified based on product licensing and reference standards. Age was significantly associated with potential DRPs (p < 0.001), with the highest number of cases in children aged 6 to 11 years old, followed by those aged 12 to 18 years. Weight was also a significant factor (p < 0.001), with a high number of cases recorded among children weighing between 10 and 20 kg. The type of NSAID also significantly influenced the occurrence of potential DRPs (p < 0.001). Ibuprofen had the highest number of potential DRPs (n = 193) due to its high usage, followed by Diclofenac (n = 142) and Celecoxib (n = 16). In terms of Celecoxib, inappropriate drug selection (n = 7) was the major DRP as the patients were allergic to this medication, followed by inappropriate dosing (n = 5), wrong indication (n = 2), wrong duration (n = 1), and wrong frequency.

The most common potential DRP was dose-related, where NSAID doses were either higher or lower than the recommended dose ranges based on the patient’s weight. This was most frequent with Ibuprofen (n = 169) and Diclofenac (n = 57). Solid Ibuprofen formulations sometimes exceed the recommended 5–10 mg/kg for convenience, whereas Diclofenac liquid formulations are under-dosed as it is served in drops rather than milliliters.

Indication-related potential DRPs were the second most common, relating to unlicensed indications or use in younger patients. Rectal Diclofenac is used by many prescribers for its rapid antipyretic effect, even though it is not approved for fever. Parecoxib was not recommended for use in patients under 18 years old, while Aspirin lacked documented clinical indications in four cases. Drug-related potential DRPs included potential allergy risks and therapy duplication. However, no patients were prescribed an NSAID they were allergic to. The details are presented in Table 6.

Table 6.

NSAIDs and the types of potential DRPs

Active Ingredient	Potential DRPs (related to)							Total
	Dose	Drug	Duration	Frequency	Indication	More than 1 DRP	Others
Aspirin	1	0	0	1	4	0	0	6
Celecoxib	5	7	1	1	2	0	0	16
Diclofenac	57	0	3	16	40	26	0	142
Esflurbiprofen	0	0	0	4	8	0	0	12
Etoricoxib	0	0	3	0	0	0	0	3
Flurbiprofen	0	0	0	0	8	0	0	8
Ibuprofen	169	4	0	4	14	1	1	193
Ketoprofen	0	1	0	0	1	0	0	2
Mefenamic Acid	2	1	0	0	0	0	0	3
Meloxicam	0	0	0	7	0	0	0	7
Naproxen	2	1	0	0	2	0	0	5
Parecoxib	0	0	0	0	8	0	0	8
Grand Total	236	14	7	33	87	27	1	405

A total of 27 cases had more than one potential DRP. Out of 1958 prescriptions, four patients (0.20%) returned to the hospital within a one-week timeframe to consult a healthcare provider due to adverse drug reactions (ADRs) or hypersensitivity. Two patients had Diclofenac 1.5% oral drops-induced rashes and swelling. One patient experienced hypersensitivity (0.05%) after taking prescribed Celebrex 200 mg capsules, while the other suffered from severe nausea and vomiting after taking Ibuprofen 100 mg/5 ml syrup (0.05%). All patients were advised to discontinue their medications and were provided with symptomatic treatment.

A total of 501 cases involving 95 Drug-Drug interactions were recorded, including 47 requiring monitoring (224 cases), 31 minor interactions (191 cases), and 17 serious drug interactions (86 cases). The most common drug-drug interactions identified were between Ibuprofen and Methotrexate (21 cases), which elevated the levels of Methotrexate by decreasing renal clearance and enhancing toxicity. This interaction was considered a serious drug-drug interaction. Following that, there were interactions between Azathioprine and Hydroxychloroquine, which were associated with immunosuppressive effects (16 cases), and Naproxen, which was associated with elevated Methotrexate levels (14 cases). In the moderate drug interactions category, combinations of Aspirin and Prednisolone (21 cases), as well as Ibuprofen and Prednisolone (21 cases), caused moderate to severe gastric ulceration among the study population.

Discussion

In the present study, NSAIDs were commonly used across different age groups of the pediatric population, with Ibuprofen being the most prescribed NSAID. This aligns with an earlier study that found that Ibuprofen was the most prescribed NSAID among pediatric patients [41]. Children above the age of 12 were more likely to receive COX-2 inhibitors or topical NSAIDs. The majority of NSAID prescriptions in both studies originated from the emergency and pediatric departments, reflecting their roles in managing acute and chronic conditions among the pediatric population.

Similar to a previous study [41], the present study recorded 1958 prescriptions with NSAIDs in a shorter timeframe, suggesting a possible preference for NSAIDs for fever and pain management in the study hospital. Access to progress notes allowed the identification of NSAID indications, including fever relief, inflammatory conditions, and Kawasaki disease.

The present study observed a similar dosing trend for Ibuprofen at 8–10 mg/kg, seen in 39.56% of prescriptions compared to an earlier study [35]. However, the present study noted challenges with weight documentation, leading prescribers to adhere to product recommendations instead of weight-based dosing. This practice, primarily noted for Ibuprofen in their study, likely applies to other NSAIDs included in the present study.

The current study did not examine NSAID prescriptions within the total pediatric prescription pool, as this would have required analysis of a significantly larger dataset. Nevertheless, the prescribing trends aligned with trends observed among Italian and Dutch pediatricians, who preferred Ibuprofen and Diclofenac, respectively [15, 20, 22].

Limited COX-2 inhibitor use was observed, similar to a previous study where it was prescribed almost exclusively to pediatric patients aged 12 years and above [36]. In particular, patients with PiRDs were managed by pediatric rheumatologists, who prescribe a larger range of NSAIDs such as Naproxen and Meloxicam aside from Ibuprofen, consistent with clinical guidelines recommending NSAIDs for managing chronic inflammatory conditions. ADRs in the present study were predominantly linked to traditional NSAIDs like Ibuprofen and Diclofenac, consistent with the broader prescribing pattern observed [42–44].

Previous studies have shown a preference for Ibuprofen in managing painful conditions, especially when Paracetamol is not effective in symptom management [27]. NSAIDs were commonly prescribed for both pain and fever, often in combination with other analgesics like Paracetamol or Tramadol. While dosage-related potential DRPs were the most common in the present study, they were not directly linked to any ADRs. Prolonged NSAID therapy, particularly for chronic inflammatory conditions like JIA, was more prevalent in this study.

Aspirin was primarily prescribed to children aged one to five years for Kawasaki disease, which aligns with epidemiological trends since Kawasaki disease mainly affects children under five and requires aspirin to reduce the risk of coronary artery aneurysms [44, 45]. During the acute febrile phase, patients are hospitalized and treated with intravenous immunoglobulins (IVIG) and Aspirin. Subsequently, low-dose aspirin (3–5 mg/kg) was prescribed during outpatient follow-up visits, leading to higher prescribing rates in these age groups.

The lack of weight documentation in this study was similar to other outpatient studies in tertiary hospitals [46, 47]. However, this study reported a lower proportion (26.61% vs. 72.8%), indicating better documentation efforts. Unlike the previous study, illegible and incomplete prescriptions were not observed due to the implementation of a computerized prescribing order system. The study also concluded that the potential DRPs identified were unlikely to have serious clinical consequences. Additionally, the current study did not classify the absence of weight documentation as a potential DRP but acknowledged its indirect impact on prescribing accuracy.

NSAID and Prednisolone interactions require monitoring due to an increased risk of gastrointestinal bleeding, which can be mitigated with the use of gastroprotection. Serious interactions include Ibuprofen or Naproxen with Methotrexate, which may elevate blood Methotrexate levels and lead to myelosuppression, hepatotoxicity, and kidney dysfunction. However, this combination is necessary for JIA patients [11]. Similarly, Hydroxychloroquine with Azathioprine or Mycophenolate mofetil (MMF) is a serious DDI but is recommended in Malaysia’s clinical practice guidelines for the management of systemic lupus erythematosus [48].

Consistent with a previous study [33], dose-related issues, such as underdosing and overdosing of NSAIDs, especially in patients with Ibuprofen and Celecoxib, were the most commonly observed potential DRPs in the present study. Conservative dose-per-weight calculations identified more potential DRPs due to strict reference ranges. However, real-world prescribing often involves dose rounding for ease of administration. Appropriate dosing, frequency, and duration, as well as selecting the right drug based on the indication, are crucial factors in determining treatment outcomes, especially for vulnerable populations such as pediatrics and infants.

The use of Diclofenac suppositories for fever relief was identified in the present study, despite recommendations against it by the National Pharmaceutical Regulatory Agency (NPRA) due to the risk of acute necrotizing encephalopathy of childhood (ANEC) [49]. Rectal formulations are perceived to be more effective, but a meta-analysis comparing oral and rectal Paracetamol showed that both formulations are comparable. This highlights an area where a more pediatric-friendly formulation is needed to effectively manage the younger patient population.

Contrary to other ADR studies, severe NSAID-associated ADRs, such as gastrointestinal ulcers or kidney injuries, were not reported, possibly due to differences in medication practices [25, 26]. The study only reported four ADRs associated with Celecoxib, Ibuprofen, and Diclofenac.

Hospitals facilitate seamless transitions from outpatient to inpatient care by prescribing single-dose medications for immediate symptom relief. This practice, while beneficial to the patient, may affect NSAID prescribing patterns in terms of dosing frequency and diclofenac’s unlicensed use for fever relief.

Contrary to recommendations for short-term NSAID use, one-fourth of the present study population was prescribed NSAIDs on a pro re nata (PRN) basis for fever or pain, giving parents flexibility in managing their child’s symptoms [50]. This approach helps prevent the overuse of NSAIDs and limits exposure to NSAID-associated DRPs. Caregivers were also given additional instructions on when to seek medical attention while managing the condition on a PRN basis.

This study investigated the use of NSAIDs among the pediatric population in Malaysia and identified rational prescribing practices of NSAIDs by pediatricians. Additionally, the study also explored complications or DRPs associated with the pediatric population and steps taken to alleviate them. The findings may assist healthcare providers in understanding the overview of NSAIDs practice in tertiary healthcare settings and in making necessary policies or regulations to standardize the use of NSAIDs across Malaysian healthcare settings. There were some limitations as the data collection process in the evolving electronic HIS background was challenging, as information was scattered across multiple reports. A key issue was that patients’ age was not recorded at the date of prescribing, requiring recalculations. Additionally, original prescriptions were not accessible after amendments, necessitating the use of prescription change and prescribing error reports. Lastly, this study was conducted as a single-center study, which may limit its generalisability to other private tertiary hospitals. Future research should include multiple centers to provide a more comprehensive understanding of NSAID use among healthcare providers.

Conclusion

Ibuprofen was the most commonly prescribed NSAID for pediatric patients due to its ease of dosing and safety profile. COX-2 inhibitors were primarily prescribed to teenagers, reflecting the clinical experience and practice of the prescribers. However, doses of Ibuprofen and Diclofenac were often prescribed outside of the recommended ranges, increasing the risk of complications. Overall, NSAID prescribing in the pediatric population was generally appropriate, but a significant number of potential drug-related problems were identified. Therefore, the study recommends greater caution when prescribing NSAIDs to pediatric patients due to their increased vulnerability to drug-associated complications.

Authors’ contributions

LJYC: concept and design, data collection, statistical analysis, research writing, preparing, and submission of final manuscript. PS: interpretation of results, preparing the final manuscript. PVI: revising, and approving the final manuscript. PM: concept and design of the study, revising, and approving the final manuscript.

Funding

This study was funded by the IMU University, Kuala Lumpur, Malaysia, and the grant approval number is MPP1-2024(04).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

Ethical approval was obtained from the Joint Committee on Research and Ethics of the IMU (IMU-JC) (approval number: MPP 1-2024(04)) and the management of the clinical research center of the hospital (approval number: 030/2024/IND/ER). For the retrospective data, there was no direct involvement of patients, whereas for the prospective data, informed consent to participate in the study was obtained from the parents or legal guardians of any participant under the age of 18. All patients’ data were kept anonymous and confidential. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki (2024).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.