|Year : 2016 | Volume
| Issue : 1 | Page : 3-6
Comparative efficacy, safety, and tolerability of diclofenac and aceclofenac in musculoskeletal pain management: A systematic review
Faizal Vohra, Asawari Raut
Department of Clinical Pharmacy, Bharati Vidyapeeth University, Poona College of Pharmacy, Pune, Maharashtra, India
|Date of Web Publication||7-Jan-2016|
Assistant Professor, Department of Clinical Pharmacy, Bharati Vidyapeeth University, Poona College of Pharmacy, Pune - 411 038, Maharashtra
Source of Support: None, Conflict of Interest: None
Diclofenac and aceclofenac are nonsteroidal antiinflammatory drugs (NSAIDs). Diclofenac is advocated for the treatment of painful and inflammatory rheumatic and certain nonrheumatic conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, and bursitis, and in other inflammatory or painful conditions such as strains and sprains, dysmenorrhea, back pain, sciatica, and postoperative pain. Aceclofenac provides symptomatic relief in a variety of painful conditions such as joint inflammation, and reduces pain intensity and the duration of morning stiffness in the patients with rheumatoid arthritis, improves spinal mobility in the patients with ankylosing spondylitis. Gastrointestinal (GI) problems are the most frequent effects, which are caused by diclofenac and include dyspepsia and abdominal pain. Aceclofenac also has similar adverse effect but they are mild compared to diclofenac. We have reviewed 9 prospective studies that compared efficacy and safety of diclofenac with those of aceclofenac, 5 studies on osteoarthritis patients, 1 study on rheumatoid arthritis patients, 1 study on overall musculoskeletal disorders, 1 study on lower back pain, and 1 study on postextraction dental pain. Western Ontario and McMaster (WOMAC) universities scores, visual analogue scale (VAS), the Ritchie index, Lequesne OA severity index (OSI) were used in assessing the pain intensity and measuring the efficacy of the drug that proved beneficial in assessing the pain intensity and measuring the efficacy of both the drugs. All the studies came to the conclusion that aceclofenac is a better choice of drug in managing pain in case of all the above conditions with better efficacy and tolerability, patients experienced more number of adverse events (AEs) with diclofenac when compared with aceclofenac.
Keywords: Aceclofenac, diclofenac, efficacy, safety, tolerability, visual analogue scale (VAS), Western Ontario and McMaster (WOMAC) scores
|How to cite this article:|
Vohra F, Raut A. Comparative efficacy, safety, and tolerability of diclofenac and aceclofenac in musculoskeletal pain management: A systematic review. Indian J Pain 2016;30:3-6
|How to cite this URL:|
Vohra F, Raut A. Comparative efficacy, safety, and tolerability of diclofenac and aceclofenac in musculoskeletal pain management: A systematic review. Indian J Pain [serial online] 2016 [cited 2019 Oct 23];30:3-6. Available from: http://www.indianjpain.org/text.asp?2016/30/1/3/173431
| Introduction|| |
Diclofenac and aceclofenac both fall in the category of nonsteroidal antiinflammatory drugs (NSAIDs). Diclofenac is advocated for in the treatment of painful and inflammatory rheumatic and certain nonrheumatic conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, and bursitis, and in other inflammatory or painful conditions such as strains and sprains, dysmenorrhea, back pain, sciatica, and postoperative pain. It is available in a number of administration forms that can be given orally, rectally, or intramuscularly. Diclofenac is considered as one of the few NSAIDs of "first choice" in the treatment of acute and chronic painful and inflammatory conditions. The anti-inflammatory activity of diclofenac, and most of its other pharmacological effects, is generally thought to be related to its inhibition of prostaglandin synthesis. Diclofenac is a potent inhibitor of cyclooxygenase in vitro and in vivo, thereby decreasing the synthesis of prostaglandins, prostacyclin, and thromboxane products. Whereas aceclofenac is an orally administered phenyl acetic acid derivative with effects on a variety of inflammatory mediators. Aceclofenac provides symptomatic relief in a variety of painful conditions such as joint inflammation and reduces pain intensity and the duration of morning stiffness in patients with rheumatoid arthritis, it also improves spinal mobility in the patients with ankylosing spondylitis.
Diclofenac is rapidly and efficiently absorbed after conventional oral, rectal, or intramuscular administration. After intramuscular administration peak plasma concentrations are attained after 10-30 min. With the enteric-coated formulation peak concentrations are reached after 1.5-2.5 h, and this is delayed by food to 2.5-12 h. After a single 50 mg dose of these formulations, mean peak plasma concentrations of unchanged diclofenac are 0.7-1.5 mg, in comparison with aceclofenac that is also rapidly and completely absorbed after oral administration, with peak plasma concentrations (Cmax) being reached 1.25-3 h after ingestion. The volume of distribution (Vd) is approximately 25 L, and the drug is highly protein-bound (>99%) in plasma. The tolerability profile of diclofenac is well established. About 12% of patients experience side effects, which are usually mild and transient, and 1.5-2% have the drug withdrawn, gastrointestinal (GI) problems are the most frequent effects, followed by minor central nervous system (CNS) symptoms and allergic or local reactions; however, adverse events (AEs) reported with aceclofenac are mild and reversible and primarily involve the GI system. Most common events include dyspepsia and abdominal pain (≥5% incidence). Dizziness, vertigo, pruritus, rash, and dermatitis have been reported with aceclofenac, but the incidence of these events is low (<5%). The initial dosage of conventional or enteric-coated tablets of diclofenac is 150 mg daily in two or three divided doses with meals, and in most patients therapeutic control can be maintained on 100 mg daily. The recommended dosage of aceclofenac is 100 mg twice daily [bis in die (b.i.d.)]. Although a dosage reduction is generally not needed in elderly patients or in those with mild renal impairment, monitoring is recommended in such cases. A dosage reduction to 100 mg daily is suggested in patients with hepatic impairment. Aceclofenac should be given with caution to elderly patients with renal, hepatic, or cardiovascular impairment, and to those receiving other medication. Aceclofenac should not be administered to patients with peptic ulcers or GI bleeding, moderate or severe renal impairment, sensitivity to aceclofenac or other NSAIDs, or a history of aspirin (acetylsalicylic acid)- or NSAID-related allergic or anaphylactic reactions. ,
| Methodology|| |
Nine prospective studies comparing the safety, efficacy, and tolerability of diclofenac and aceclofenac were reviewed. Literature mainly included prospective studies on musculoskeletal disorders that included osteoarthritis, rheumatoid arthritis, acute low back pain, postextraction dental pain.
| Result|| |
Out of 9 prospective studies that compared efficacy and safety of diclofenac with aceclofenac, 5 were on osteoarthritis patients, 1 was on rheumatoid arthritis patients, 1 was on overall musculoskeletal disorders, 1 was on lower back pain, and 1 study on postextraction dental pain. A study conducted by Anand R Kanaki et al. with osteoarthritis patients included the patients from the age group of 40-60 years of which 57 were males and 70 were females. One group received aceclofenac in a dose of 100 mg b.i.d. and other group received diclofenac in a dose of 75 mg b.i.d. after food. Clinical assessment was done after 1-month, 2-month, 3-month period by using Western Ontario and McMaster (WOMAC) universities scores, time taken to walk 100 feet, visual analogue scale for pain, investigator's assessment on a Likert scale and joint tenderness. Tolerability assessment was based on adverse effects. After the third month of assessment high efficacy and tolerability was observed with aceclofenac compared to diclofenac.  Another prospective study done by Ward et al. where 200 patients received 100 mg of aceclofenac b.i.d. and 197 patients received 50 mg of diclofenac thrice daily [ter in die (t.i.d.)] in osteoarthritis of knee result 71% of patients in the aceclofenac group reported improvement in pain intensity as compared to 59% treated with diclofenac. Greater improvement in complete knee movement and reduced pain on movement was observed with aceclofenac. Tolerability to aceclofenac was high compared to diclofenac that showed GI AEs incidence of treatment related diarrhea was more in diclofenac group (6.6%) compared to the aceclofenac group where the incidence of diarrhea was only 1%.  Pareek et al. performed comparative, randomized, and double-blind study to compare efficacy and safety of diclofenac with aceclofenac in Indian patients. Their study included 247 patients (82 males and 165 females, 40-82 years), suffering from osteoarthritis. Patients were randomized to receive either aceclofenac (100 mg b.i.d.) or diclofenac (75 mg b.i.d.). Clinical assessment was done at 2 weeks, 4 weeks, and 8 weeks of treatment similar to Anand R Kanaki et al. they also did clinical assessment by calculating Western Ontario and McMaster (WOMAC) universities scores, time taken to walk 100 feet, visual analogue scores for pain, investigator's assessment on a Likert scale, and joint tenderness. The result showed aceclofenac to be statistically superior to diclofenac in efficacy parameters of WOMAC scores, investigator's assessment, and joint tenderness, epigastric discomfort, dyspepsia, and abdominal pain was higher in diclofenac group comparing to aceclofenac group. The overall response of the patients toward aceclofenac was found to be superior to diclofenac by both physician and patient.  Pareek et al. performed another study in 591 patients to identify and compare GI tolerability and efficacy of aceclofenac with diclofenac in patients with knee osteoarthritis. In this randomized, double-blind study, patients were randomly allocated to receive either aceclofenac (100 mg b.i.d.) or diclofenac 50 mg t.i.d., and the follow-up was taken for next 6 weeks, out of 591 patients, aceclofenac group consisted of 297 patients whereas diclofenac group consisted 294 patients. The GI tolerability was evaluated based on the incidence and severity of predefined GI AEs, number of gastroprotective agents (GPAs) consumed by patients, and discontinuation from the study due to GI AEs. The secondary outcome included was similar to his previous study that was done through assessment of pain intensity using a visual analogue scale (VAS), Western Ontario and McMaster (WOMAC) universities score, pain relief score, and investigators' and patients' overall assessments of response to study drugs. The incidence of GI AEs for dyspepsia was 28.1% in acelofenac group versus 37.9% in diclofenac group, abdominal pain was 19% in acelofenac group versus 26.3% in diclofenac group, overall incidence of predefined GI AEs was 57.3% in acelofenac group versus 73.6% in diclofenac group, and number of patients reporting GI AEs was 28.9% in acelofenac group versus 36.5% in diclofenac group. This study concluded that aceclofenac was better tolerated in terms of incidence and severity of GI AEs and was as efficacious as diclofenac.  A study published in "European Journal of Rheumatology and Inflammation" by Diaz et al. which compared efficacy and tolerability of aceclofenac versus diclofenac in the treatment of knee osteoarthritis. It was a 6 months prospective study that included 355 patients who were randomly allocated to two groups, one group which included 170 patients who received aceclofenac 100 mg b.i.d., whereas the other group consisting 165 patients who received diclofenac 50 mg t.i.d., the assessment was done using Lequesne OA severity index (OSI) and pain on a VAS. Secondary measures used were knee flexion and extension and evaluation of knee function. All parameters were evaluated at baseline, after 15 days and monthly throughout the study, the result from this study showed that there was no statistically significant difference in efficacy between the two groups. However, in assessing the tolerability treatment withdrawals due to AEs (mainly GI) were 14 in the acelofenac group patients and 27 in the diclofenac group patients. This indicated that though acelofenac and diclofenac have similar efficacy, acelofenac is better tolerated.  A prospective open-labeled randomized interventional study was conducted at S.C.B. Medical College and Hospital, Cuttack, India by Patnaik et al., which was done to identify efficacy as well as cost-effective analysis of diclofenac, aceclofenac, and lornoxicam in musculoskeletal patients. This study included 150 patients divided into 3 groups of 50 patients in each group, group 1 received lornoxicam 4mg bd, group 2 received aceclofenac 100 mg bd, group 3 received diclofenac 50 mg bd; the duration of treatment varied from 2 weeks to 3 weeks. Comparative analgesic efficacy assessment between the three drugs were done by using visual analog scale (VAS) reading on day 0 and then weekly till 3 weeks, adverse drug reaction (ADR) information were collected by spontaneous reporting from patients. The cost of per day therapy with lornoxicam, aceclofenac, and diclofenac was calculated by finding the mean cost of per day therapy of individual drugs from three different well-known brands available; VAS revealed that mean basal VAS in lornoxicam, aceclofenac, and diclofenac treatment group were 4.16 ± 1.63, 4.34 ± 1.6, and 4.80 ± 1.5, respectively, without significant difference between them indicating equal analgesic potential of all the three drugs, study showed that the GI AE that is dyspepsia, abdominal pain, vomiting etc. were maximum that is 20% with diclofenac, whereas it was only 10% with lornoxicam and 8% with aceclofenac. The cost-effective analysis showed that the mean per day treatment cost with lornoxicam was 7.43, which was significantly higher than the per day cost of therapy with aceclofenac that is 4.7 and diclofenac 4.0 indicating that diclofenac was the cheapest option but aceclofenac was more tolerable.  Pasero et al. conducted a multicentric study in 343 patients with rheumatoid arthritis who were randomly assigned to aceclofenac group (170 patients), which received a dose of 100 mg b.i.d. and placebo once daily and diclofenac group (173 patients), which received a dose of 50 mg t.i.d. for a period of 6 months, improvement in all evaluations of pain and inflammation were assessed by a VAS and the Ritchie index and a progressive reduction in morning stiffness, there were no significant differences between the groups; however, a greater improvement in hand grip strength with aceclofenac was (22% improvement) than diclofenac (17% improvement). GI adverse effect with aceclofenac was 13% when compared to diclofenac which had 17% GI adverse effect than on diclofenac (17%).  Schattenkirchner et al. performed a similar comparative study on lower back pain that included 227 patients randomized to receive either aceclofenac 100 mg bd daily or diclofenac resinate 75 mg b.i.d for up to 10 days. Outcome was assessed using VAS and time to early cure (resolution of pain) and global assessment of tolerability. This study showed that acelofenac is as effective as diclofenac in managing pain and acelofenac is more tolerable than diclofenac total number of AEs reported was lower in patients receiving aceclofenac (22 versus 31 in the diclofenac resinate group).  Kudaravalli et al. carried out a similar study in postextraction dental pain. In their study out of 100 patients 51 were randomized to the diclofenac group receiving a dose of 50 mg t.i.d. and aceclofenc group receiving a dose of 100 mg b.i.d., and pain was assessed by using VAS. Results showed 27% reduction in pain in the diclofenac group compared to 40% pain reduction in the aceclofenac group within 8 h, and on the fifth day the pain reduction by diclofenac was 95% and by aceclofenac was 100% hence showing that acelofenac has rapid onset of action. 
| Conclusion|| |
All the nine studies included in this review indicate that aceclofenac is as effective diclofenac or even more effective than the latter. These studies performed also showed that aceclofenac was more tolerable compared to diclofenac with lower incidence of GI AEs including abdominal pain and dyspepsia. One study reported that diclofenac is cost-effective compared to aceclofenac; however, aceclofenac has a better efficacy and tolerability in the patients that makes aceclofenac the drug of choice. Use of assessment scales such as Western Ontario and McMaster (WOMAC) universities scores, VAS, the Ritchie Index, Lequesne OA severity index (OSI) all can be helpful in assessing the pain intensity and measuring the efficacy of the drug. This review concludes that aceclofenac is a better choice compared to diclofenac in reducing the pain in musculoskeletal disorders with lower incidence of AEs, providing better patient compliance and better tolerability.
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Conflicts of interest
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