Musculoskeletal disorders (MSDs) constitute one of the leading causes of disability worldwide, affecting an estimated 1.71 billion people according to the Global Burden of Disease Study (1). These conditions encompass a wide range of disorders involving muscles, bones, joints, joints, tendons, ligaments, and associated structures, including conditions such as low back pain, osteoarthritis, rheumatoid arthritis, neck pain, and various soft tissue injuries. MSDs are a major contributor to chronic pain, functional limitations, and reduced mobility, often leading to long-term disability and diminished quality of life (2). Beyond their direct impact on individual health, MSDs place a substantial burden on healthcare systems due to increased healthcare utilization, long-term treatment requirements, and rehabilitation needs. Additionally, they significantly affect workforce productivity through absenteeism, presenteeism, and early retirement, thereby contributing to considerable socioeconomic costs (3). As populations age and lifestyles become increasingly sedentary, the prevalence and impact of MSDs are expected to rise further, highlighting the need for effective preventive strategies, timely diagnosis, and optimized management approaches to reduce their overall burden.

Epidemiology in India: In India, MSDs affect over 190 million adults, with osteoarthritis (OA) rising from 23.46 million cases in 1990 to 62.35 million in 2019, yielding an age-standardized prevalence of 5,313 per 100,000. Knee OA alone prevails in 47% (95% CI: 38.4%-55.8%) of elderly ≥60 years, higher in urban (49.3%) and female (50.7%) populations; community surveys like COPCORD underscore MSK pain's massive burden, necessitating national control programs (4-6).

Pain Management Challenges: Orthopedic pain—inflammatory from synovitis, nociceptive from bone/joint stress, and edematous post-trauma—demands multimodal therapy to expedite recovery amid challenges like NSAID-induced GI ulcers (15-30% risk), paracetamol's limited anti-inflammatory action, and opioid misuse in India's escalating crisis (7).

Evolution of Pharmacological Options: Therapies progressed from monotherapy NSAIDs (diclofenac, ibuprofen) and enzymes (trypsin-chymotrypsin) to FDCs, which synergize mechanisms, boost adherence (by 40%), and cut adverse events via lower doses; diclofenac-acetaminophen FDCs prove safe/effective postoperatively. Combinations of NSAIDs, paracetamol, and proteolytic enzymes such as serratiopeptidase and trypsin are commonly used for the effective management of painful conditions, particularly those associated with inflammation and swelling (7, 8). Aceclofenac (preferential COX-2 inhibitor, 97% selectivity vs. 46% COX-1) offers aceclofenac's rapid onset (30-60 min), superior analgesia, and 2-4x lower GI risks than diclofenac; paracetamol complements centrally; serratiopeptidase reduces edema (20-50%), pain (VAS drop), and cytokines superiorly in sprains/OA (9-11).

The combination of aceclofenac, paracetamol, and serratiopeptidase is widely used in orthopedic practice for the management of painful musculoskeletal conditions associated with inflammation and swelling, such as post-traumatic injuries, postoperative pain, and soft tissue inflammation. The multimodal mechanism of action of this combination is considered beneficial in providing effective pain relief while also aiding in the reduction of inflammatory edema. Given its frequent use in routine orthopedic practice, it is important to understand the real-world prescribing patterns and clinical perspectives associated with this therapy. Therefore, the present study was undertaken to evaluate the prescribing preferences, utilization patterns, and clinical experiences of orthopedic surgeons regarding the use of the aceclofenac–paracetamol–serratiopeptidase combination in the management of musculoskeletal pain and inflammation.

MATERIALS AND METHODS

This study was designed as a descriptive, questionnaire-based cross-sectional survey conducted among orthopedic surgeons attending IOACON-2025, 70th Annual National Conference of the Indian Orthopedic Association held in Guwahati, Assam, who were willing to participate and provided informed consent were included in the survey. A total of 138 orthopedic surgeons completed the questionnaire, and their responses were considered for final analysis.

The survey tool comprised nine structured, multiple-choice questions. The questionnaire was converted into a Google Forms format and disseminated to participants during the conference. Responses were collected electronically and subsequently exported to Microsoft Excel for data compilation and management. Data analysis was performed using descriptive statistical methods, with results expressed as frequencies and percentages to summarize the distribution of responses.

Ethical Considerations

The study protocol was reviewed by an Independent Ethics Committee, and the study was granted an ethics committee waiver, as the survey was non-interventional, anonymized, and involved no patient data. Participation was entirely voluntary, and electronic informed consent was obtained from all respondents prior to survey initiation. Confidentiality and anonymity of participants were strictly maintained throughout the study.

RESULTS

The survey responses were analyzed to understand the demographic profile of participating orthopedic surgeons and their prescribing practices related to the aceclofenac–paracetamol–serratiopeptidase combination in routine clinical practice. The results provide insights into the frequency of prescription, common clinical indications, preferred duration of therapy, perceived effectiveness in pain relief and swelling reduction, tolerability, observed adverse events, impact on patient compliance, and the likelihood of recommending this combination for the management of acute musculoskeletal pain associated with inflammation.

Demographic detail:

A total of 138 orthopedic surgeons participated in the survey. The majority of respondents were male (132), while 6 were female. The mean age of the participants was 46.41 ± 12.58 years, indicating that the respondents represented a group of experienced clinicians actively involved in orthopedic practice (Table 1).

Table 1: Demographic details of the participants

Regarding the prescribing frequency of the aceclofenac–paracetamol–serratiopeptidase combination, the majority of orthopedic surgeons reported using this combination regularly in their clinical practice. A large proportion of respondents indicated that they prescribe it very frequently (71) or often (54), suggesting widespread utilization of this combination in routine orthopedic care. A smaller number of surgeons reported prescribing it occasionally (11), while only two respondents indicated that they do not prescribe this combination in their practice. These findings highlight the common use of this combination for the management of painful musculoskeletal conditions. (Figure 1)

Figure 1: Frequency of Prescription of Aceclofenac–Paracetamol–Serratiopeptidase Combination in Clinical Practice

When asked about the clinical conditions in which the aceclofenac–paracetamol–serratiopeptidase combination is most commonly prescribed, the majority of orthopedic surgeons reported using it for post-traumatic pain and swelling (103) and post-operative pain and inflammation (85). The combination was also prescribed for soft tissue or sports injuries (48), osteoarthritis or degenerative joint diseases (38), and low back pain (32). Only two respondents reported that they do not prescribe this combination in their clinical practice. These findings indicate that the combination is primarily utilized for managing acute painful conditions associated with inflammation and swelling in orthopedic settings (Figure 2).

Figure 2: Common Clinical Indications for Prescribing Aceclofenac–Paracetamol–Serratiopeptidase Combination

Regarding the preferred duration of prescribing the aceclofenac–paracetamol–serratiopeptidase combination for acute pain and swelling, most orthopedic surgeons preferred a treatment duration of 6–10 days (79). A considerable number of respondents indicated prescribing the combination for ≤5 days (54). Only a small proportion reported extended use for more than 10 days (3), while two respondents indicated that they do not prescribe this combination. These findings suggest that the combination is predominantly prescribed for short-term management of acute painful inflammatory conditions (Figure 3).

Figure 3: Preferred Duration of Therapy with Aceclofenac–Paracetamol–Serratiopeptidase for Acute Pain and Swelling

Orthopedic surgeons were asked to rate the effectiveness of adding serratiopeptidase to aceclofenac–paracetamol for the reduction of swelling. The majority of respondents perceived the addition of serratiopeptidase to be more effective, with 90 rating it as much better and 42 as somewhat better compared with aceclofenac–paracetamol alone. Only 4 respondents considered it less effective, while 2 reported no opinion. Overall, these findings indicate a strong perception among orthopedic surgeons that the inclusion of serratiopeptidase enhances swelling reduction in painful inflammatory conditions (Figure 4).

Figure 4: Orthopedic Surgeons’ Perception of Swelling Reduction with Addition of Serratiopeptidase

Most orthopedic surgeons reported high satisfaction with the pain relief provided by this combination. A majority of respondents were very satisfied (67) or satisfied (61), while 6 expressed a neutral opinion and 4 reported dissatisfactions. (Figure 5)

Figure 5: Satisfaction with Pain Relief Provided with the Combination

Regarding patient tolerability, most orthopedic surgeons reported that this combination was similarly tolerated (80) or better tolerated (52) compared with other NSAID combinations. Only 4 respondents perceived it to be poorly tolerated, while 2 were unsure. (Figure 6)

Figure 6: Patient Tolerability of the Combination Compared with Other NSAID Combinations

When asked about adverse events associated with this combination, the most frequently reported were gastric irritation/dyspepsia (69), followed by nausea/vomiting (31). A smaller number of respondents reported allergic reactions (7) and edema (4). Additionally, 39 orthopedic surgeons reported that they had not observed any adverse events with this combination in their patients. (Figure 7)

Figure 7: Notable adverse events with the combination

With respect to patient compliance, most orthopedic surgeons believed that this combination improves adherence compared with multi-drug regimens. A majority reported that it significantly improves compliance (103), while 26 respondents felt it improves compliance to some extent. Nine respondents were unsure, and none reported any difference. (Figure 8)

Figure 8: Perceived Impact of the Combination on Patient Compliance

Regarding recommendation in routine practice, the majority of orthopedic surgeons indicated that they would recommend this combination for the management of acute musculoskeletal pain with swelling. Most respondents reported definitely recommending it (98) or likely recommending it (34), while 2 remained neutral and 4 indicated they were unlikely to recommend it. (Figure 9)

Figure 9: Recommendation of the Combination for Acute Musculoskeletal Pain with Swelling

Overall, the survey findings indicate that the aceclofenac–paracetamol–serratiopeptidase combination is widely utilized in orthopedic practice, with most surgeons reporting frequent prescribing for acute painful conditions associated with inflammation and swelling. The combination was perceived to provide effective pain relief, better swelling reduction, acceptable tolerability, and improved patient compliance, with a majority of respondents expressing satisfaction with its clinical performance and recommending its use in routine practice. These results reflect a favorable clinical perception and widespread acceptance of this combination among orthopedic surgeons.

DISCUSSION

The findings of the present survey highlight the widespread use and favorable clinical perception of the aceclofenac–paracetamol–serratiopeptidase combination among orthopedic surgeons for the management of painful musculoskeletal conditions associated with inflammation and swelling.

Aceclofenac + paracetamol + serratiopeptidase is a commonly used fixed-dose combination indicated for the management of pain and inflammation associated with various acute and chronic conditions. Aceclofenac, a phenylacetic acid derivative NSAID, provides anti-inflammatory and analgesic effects through inhibition of cyclooxygenase-mediated prostaglandin synthesis, while paracetamol offers additional analgesic and antipyretic activity. Serratiopeptidase, a proteolytic enzyme, helps reduce inflammation and edema by facilitating the breakdown of inflammatory mediators and promoting tissue healing. Together, this combination provides multimodal pain relief with anti-inflammatory, analgesic, and anti-edematous effects, making it widely used in the management of musculoskeletal pain, postoperative inflammation, trauma, and dental conditions in routine clinical practice (12-13).

When benchmarked against similar clinician surveys and studies evaluating analgesic–anti-inflammatory combinations, our findings demonstrate strong concordance with established prescribing trends for the aceclofenac–paracetamol–serratiopeptidase combination in managing painful inflammatory conditions, particularly musculoskeletal disorders, trauma, and postoperative pain. The high levels of clinician-reported effectiveness and tolerability observed in our study further reinforce its continued preference in routine clinical practice. These observations likely reflect the multimodal mechanism of action of the combination, providing synergistic analgesic, anti-inflammatory, and anti-edematous effects, which supports its widespread use for rapid and sustained relief of pain and inflammation.

Regarding the prescribing frequency of the aceclofenac–paracetamol–serratiopeptidase combination, most orthopedic surgeons reported regular use of this combination in their clinical practice. A considerable proportion indicated prescribing it very frequently or often, reflecting its widespread utilization in routine orthopedic care. Overall, these findings demonstrate the high level of acceptance and frequent use of this combination for the management of painful musculoskeletal conditions in orthopedic settings. A parallel finding was observed in a study by Binu Mathew et, which states that, Aceclofenac + Paracetamol or Aceclofenac + Paracetamol + Serratiopeptidase are one of the most commonly prescribed analgesic (14).

In another study by Shikha Rai et al, it was observed that aceclofenac + paracetamol combination was prescribed in 34.5% of patients by orthopedic surgeon (15).

As per our study findings, the aceclofenac–paracetamol–serratiopeptidase combination was most commonly prescribed by orthopedic surgeons for the management of post-traumatic pain and swelling and post-operative pain and inflammation. The combination was also prescribed for soft tissue or sports injuries and osteoarthritis or other degenerative joint diseases. Similar kinds of findings were also seen in a study by Karthikeyan et al, where they state that 87% of the patients were prescribed with combination of Aceclofenac (100 mg), Paracetamol (325 mg), and Serratiopeptidase (15 mg) for the post-operative pain and swelling associated with dental implant surgery (16).

Regarding the preferred duration of prescribing the aceclofenac–paracetamol–serratiopeptidase combination for the management of acute pain and swelling, most orthopedic surgeons favored a treatment duration of 6–10 days (57%). A considerable proportion of respondents reported prescribing the combination for ≤5 days (39%), while only a small minority indicated extending the treatment duration to more than 10 days (2%). This finding was supported by Prem Luthra et al, who stated that 46.43% of the orthopedic surgeons prescribed this combination for 10 days, 37.14% of orthopedic surgeons prescribed it for 1 week, whereas for more than 10 days prescribed by 16.43% orthopedic surgeons (17).

In our study, more than 90% of orthopedic surgeons reported satisfaction with the effectiveness of the aceclofenac–paracetamol–serratiopeptidase combination. Similar observations were reported in a study by Prem Luthra et al., where 81.43% of healthcare professionals reported a high or moderate level of patient satisfaction with the fixed-dose combination (FDC) treatment. In that study, most respondents rated the FDC as good or excellent, and 96% indicated willingness to prescribe it again.

These findings are also consistent with the study by Pant et al, which demonstrated that a similar FDC (Parflex) resulted in significant reductions in pain scores, with excellent or good global efficacy assessments reported by 54% of patients and 59% of their treating healthcare professionals (12).

In our study, when orthopedic surgeons were asked about adverse events associated with the combination, the most frequently reported event was gastric irritation/dyspepsia (50%), followed by nausea/vomiting (22%) among the surveyed surgeons. A 2025 HCP survey (Int J Sci Res) of Indian clinicians using this combination for OA knee pain reported gastritis (62.14%) as the top AE, abdominal pain (9.29%), and nausea (5%), mirroring our dyspepsia (50%) and nausea/vomiting (22%) rankings, with GI events dominating due to aceclofenac's NSAID profile despite paracetamol's mitigating effect (17). Aceclofenac reviews (J Pain Res, PMID: 34876850) confirm dyspepsia (28%), abdominal pain (19%), and nausea (7%) as most common (>5%), with lower GI risk vs. diclofenac (dyspepsia 28% vs. 38%; p=0.014; abdominal pain 19% vs. 26%; p=0.037), supporting the combination's tolerability despite surgeon-reported frequencies (18). These patterns highlight GI risks as primary but manageable with gastroprotectants.

Additionally, it is well known that the combination of medicines decreases the pill burden on the patients which improves their compliance. Certainly, it has impact on the cost of the treatment. This was addressed by the orthopedic surgeon in our study. This finding was assured by another study as well (19). Ultimately compliance has direct impact on efficacy of the treatment.

Moreover, in our study, 96% of orthopedic surgeons indicated that they would definitely or likely recommend this combination in their clinical practice. This finding is consistent with results from a dental implant study, where 87% of clinicians (n = 200 cases) selected the aceclofenac–paracetamol–serratiopeptidase combination as the first-line postoperative therapy, markedly higher than paracetamol alone (10%) or other NSAIDs. These observations highlight the strong clinician preference for this combination in the management of acute pain and inflammatory conditions.

Limitation:

The present study has certain limitations. The survey included a limited number of orthopedic surgeons, which may not fully represent prescribing practices across all clinical settings. In addition, the findings are based on self-reported responses, which may introduce recall or response bias. The study also reflects clinicians’ perspectives rather than direct patient-level outcomes. Furthermore, the questionnaire-based design restricted responses to predefined options, which may have limited more detailed insights into clinical practice.

Overall, the findings of our study are consistent with existing literature and real-world prescribing patterns, suggesting that the aceclofenac–paracetamol–serratiopeptidase combination is widely utilized and well-perceived by orthopedic surgeons for the management of acute pain and inflammation in routine clinical practice.

CONCLUSION

In conclusion, the findings of our study highlight the widespread acceptance and frequent use of the aceclofenac–paracetamol–serratiopeptidase combination among orthopedic surgeons for the management of pain and inflammation, with most clinicians reporting high levels of effectiveness, satisfactory safety, and strong willingness to recommend the combination in routine clinical practice.

Conflict of Interest

All the authors (Dr. Ajitkumar Gondane, Dr. Dattatray Pawar, and Dr. Akhilesh Sharma) are full-time employees of Alkem Laboratories.

Author Contributions

All authors contributed substantially to the study conception, data analysis, manuscript drafting, and final approval of the submitted version.

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