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Research Article Journal of Exercise, Sports & Orthopedics Open Access

Comparative Efficacy and Safety Evaluation of

Tramadol plus Diclofenac versus Tramadol plus
Paracetamol in a Subgroup of Indian Patients
with Moderate to Severe Acute Musculoskeletal
Pain: A Phase III, 5 Day Open Label Study
Gauri Billa1*, Ajay S Chandanwale2, Subramanian Sundar3, Kaliaperumal Latchoumibady4, Swati Biswas5   
1
Medical Advisor, Abbott Healthcare Pvt Ltd, 1st floor, D Mart Bldg, Mulund-Goregaon Link Road, Mumbai.
2
Department of Orthopedics& Traumatology, ByramjeeJeejeebhoy Medical College and. Sassoon General Hospital, Pune.
3
Consultant orthopedic surgeon, Vasantha Subramanian Hospital, Chennai, Tamil Nadu.
4
Consultant orthopedic surgeon, Vijay Hospital, Pondicherry.
5
Chief Medical Advisor, Abbott Healthcare Pvt Ltd, 1st floor, D Mart Bldg, Mulund-Goregaon Link Road, Mumbai.

Received: May 30, 2016; Accepted: October 5, 2016; Published: January 6, 2017

*Corresponding author: Gauri Billa, Medical Advisor, Abbott Healthcare Pvt Ltd, 1st floor, D Mart Bldg, Mulund-Goregaon Link Road, Mumbai
400080, India, E-mail: [email protected]

Abstract Introduction
Objective: To evaluate safety and efficacy of Fixed Pain either alone or associated with other conditions is one
Dose Combination (FDC) of tramadol+diclofenac vs. FDC of of the main reasons for consultations in general practice [1].
tramadol+paracetamol in patients with Acute Musculo Skeletal Pain represents a global health problem with estimated about
Pain (AMSP). 20% adults suffering from pain [2]. Musculoskeletal conditions,
Methods: This was a randomized, open label, comparative, one of the causes of pain are also a significant health problem
parallel group, and multicentric trial. 52 patients with AMSP worldwide. Patients of all age with acute musculoskeletal pain are
were randomized to receive either of the two treatments: frequently seen in clinical practice which needs to be successfully
Tramadol hydrochloride 50 mg immediate release/diclofenac treated to avoid progression into chronic conditions [3]. Different
sodium 75 mg sustained release (one tablet twice daily-Group A) analgesic agents from opioid and non-opioid group are available
or tramadol hydrochloride 37.5 mg/paracetamol 325 mg (two
for the treatment of pain. Tramadol hydrochloride is a centrally
tablets every 4-6 hours upto a maximum of 8 tablets daily-Group
B) for 5 days. The primary efficacy endpoint was reduction in pain acting analgesic which acts as a weak atypical opioid agonist and
intensity from baseline at day 3 and day 5 as assessed by Visual monoamine neurotransmitter reuptake inhibitor [4,5]. Thus, the
Analogue Scale (VAS) score. Secondary endpoints were reduction analgesia provided by tramadol is a result of both opioid and
in swelling and inflammation from baseline. Global assessment of nonopioid mechanisms [6] which appear to act synergistically
tolerability by patients was done on day 5. [7]. Paracetamol is rapidly acting non-opioid analgesic [8]
Results: Fifty one patients completed the study. At day routinely used in clinical practice. It is effective for the treatment
five, reduction in VAS (p=0.002), pain at rest ( p<0.0001), pain of moderate pain [9]. Single analgesic agent can not treat all types
on movement (p=0.003) and mean score of inflammation of pain [10], hence the analgesics are often selected based on the
(p=0.001) was significantly better in group A compared to group difference in pain severity and duration of pain [1]. Combination of
B. Reduction in swelling and total score of inflammation was analgesic agents with complementary mechanisms may provide
superior in group 1 at day three and five. Global assessment of
tolerability by patients was good in 92.31% and 24% patients in
higher efficacy because of the action on multiple pain-inhibiting
group A and B respectively (p<0.0001). No serious adverse event pathways [10] and a better safety compared to individual agents
was reported. [10, 11]. Fixed Dose oral Combination (FDC) of tramadol 37.5
mg plus paracetamol 325 mg is indicated for the symptomatic
Conclusion: FDC of tramadol/diclofenac showed significantly
greater reduction in pain intensity and was well tolerated as treatment of moderate to severe pain [5]. The combination has
compared to tramadol/paracetamol in patients suffering from been shown to provide supra-additive analgesic effects [12] and
AMSP. well studied in acute moderate to severe pain.
Keywords: Acute musculoskeletal pain; Combination Non-Steroidal Anti-Inflammatory agent (NSAID) can also
analgesics, Tramadol plus diclofenac combination be combined with an opioid for the management of moderate

Symbiosis Group *Corresponding author email: [email protected]

 Comparative Efficacy and Safety Evaluation of Tramadol plus Diclofenac versus Copyright:
Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to © 2017 Billa et al.
Severe Acute Musculoskeletal Pain: A Phase III, 5 Day Open Label Study
to severe acute pain because of their different mechanisms of on movement). Pain relief was measured at the end of five day
action [13]. Similar to paracetamol [9], NSAIDs also have opioid treatment. The global assessment of efficacy and tolerability was
sparing action [14]. Diclofenac is a well studied and commonly done at the end of study while laboratory investigations were
used NSAID having analgesic, anti-inflammatory, and antipyretic performed at screening, baseline and day five.
properties. Multiple mechanisms of action including inhibition
Adverse events reported during the study period,
of thromboxane-prostanoid receptor, arachidonic acid release
abnormalities during physical examination, vital signs and
and uptake, lipoxygenase enzymes, and activation of the nitric
laboratory analysis (haematological and biochemistry) were
oxide-cGMP antinociceptive pathway by diclofenac suggests
considered for safety analysis. Tolerability was assessed on
better profile compared to other NSAIDs [15]. A fixed dose
a three point scale (good-side effects mild or not observed;
combination of immediate release tramadol plus sustained
moderate-side effects of moderate intensity; poor-severe side
release diclofenac has been developed with the rationale of
effects or discontinuation) and efficacy on a five point scale
providing better analgesia in moderate to severe pain due to
(poor, satisfactory, good, very good and excellent) at the end of
different and complimentary mechanisms of action and also to
the therapy.
provide immediate as well as sustained pain relief.
The study protocol and informed consent form were
The objective of this study was to evaluate the efficacy and
approved by respective hospital’s ethics committee. The study
safety of tramadol -diclofenac versus tramadol-paracetamol FDC
was conducted in accordance with the Declaration of Helsinki
in Indian patients with acute musculoskeletal pain.
(1964). The patients reviewed and voluntarily signed the
Methods informed consent form before enrolment in the study.

A randomized, open label, comparative, parallel group, Statistical analysis

multi-centre trial was conducted to evaluate the efficacy and
Two treatment groups were evaluated for comparing
safety of the immediate release tramadol 50 mg plus sustained
demographic data and baseline symptom scores. Efficacy
release diclofenac 75 mg FDC vs tramadol 37.5 mg plus
analysis was done with per-protocol population while safety
paracetamol 325 mg FDC in treatment of patients with moderate
analysis was done with intent-to-treat population. Quantitative
to severe pain due to Acute Musculoskeletal Pain (AMSP), acute
data was analyzed using student’s ‘t’ test &analysis of variance
flare of osteoarthritis, acute flare of rheumatoid arthritis, or
(ANOVA), and ranking/qualitative data was analyzed using
postoperative pain in Indian patients. The results of this study
Mann-Whitney ‘U’ test and the Kruskall-Wallis test. Proportions
are published in 2014[13]. In this paper, the subgroup analysis of
were compared using the Chi-square test. P values <0.05 were
comparative efficacy and safety of the two combinations in acute
considered statistically significant.
musculoskeletal conditions is presented. Adult subjects >18 years
and < 70 years with clinical diagnosis of acute musculoskeletal Results
pain (tendonitis, bursitis, synovitis) having VAS [16] score> 50 A total of 52 patients were enrolled out of whom 51 completed
mm during last five days prior to the baseline visit were enrolled. the study. One patient from tramadol-paracetamol group lost to
Pregnant women, nursing mothers and those hypersensitive to follow up. The baseline demographics are presented in table 1.
tramadol, diclofenac or paracetamol were excluded. Patients with No significant difference was seen in the gender between two
active peptic ulcer, gastrointestinal bleeding, having history of groups. Other baseline parameters i.e. pulse rate, systolic and
peptic ulcers, gastric irritations and NSAID intolerance, abnormal diastolic blood pressure were also comparable in both groups
renal and liver functions and on any other treatment medications (table 1).
such as NSAIDs, corticosteroids, and opioid analgesics or alternate
therapy (physiotherapy and acupuncture) were excluded from The reduction in the intensity of overall pain was assessed
the study. During the treatment period, unbearable pain was using VAS scale of 0-100 mm. The scores were compared between
treated with rescue medication diclofenac. two groups. No significant difference in the mean or percentage
change in the VAS score was observed between two groups at
The enrolled subjects were treated with immediate- day 3 (table 2 and figure 1; p=0.233). However the difference in
release tramadol hydrochloride 50 mg plus sustained-release mean and percentage change in the VAS score was significant
diclofenac sodium 75 mg one FDC tablet, twice daily or tramadol at day five (table 2 and figure 1; p=0.002) favouring tramadol-
hydrochloride 37.5 mg and paracetamol 325 mg two FDC tablets diclofenac over tramadol- paracetamol combination.
every 4–6 hours, up to a maximum of eight tablets daily. The
duration of treatment was five days. Randomization was done The mean and percentage change in the VAS score for pain
based on a PC based program Rando Version 2.0 ®. at rest was not significantly different between two groups at day
three (table 2 and figure 2; p=0.11). At day five, combination
The patients were assessed at baseline, on day 3 and day 5 of of tramadol- diclofenac resulted in significant improvement
treat­ment, on the following parameters: pain intensity, swelling, compared to tramadol-paracetamol combination (table 2 and
inflammation, and use of rescue medications. The primary figure 2; p<0.0001).
efficacy parameter was reduction in pain intensity from baseline
to day three and day five. The pain intensity was measured with Similarly, for pain on movement, the mean or percentage
a 0–100 mm VAS scale (for overall pain, pain at rest, and pain difference in VAS score was not significant between two groups

Citation: Billa G, Chandanwale AS, Sundar S, Latchoumibady K, Biswas S(2017) Comparative Efficacy and Safety Evaluation Page 2 of 6
of Tramadol plus Diclofenac versus Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to Severe Acute
Musculoskeletal Pain: A Phase III, 5 Day Open Label Study. J Exerc Sports Orthop 4(1): 1-6.
 Comparative Efficacy and Safety Evaluation of Tramadol plus Diclofenac versus Copyright:
Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to © 2017 Billa et al.
Severe Acute Musculoskeletal Pain: A Phase III, 5 Day Open Label Study
at day three (table 2 and figure 3; p=0.388). At day five, tramadol- Table 2: Comparison of efficacy parameters between between
diclofenac combination was significantly better in reducing mean tramadol-diclofenac and tramadol-paracetamol
and percentage VAS score compared to tramadol-paracetamol Tramadol + Tramadol +
‘t’ test
combination (table 2 and figure 3; p=0.003). Diclofenac Paracetamol
P value
(n=26) (n=25)
The mean and percentage reduction of swelling was
Mean score for overall pain on 0-100 VAS scale
significantly superior with tramadol -diclofenac compared to
tramadol-paracetamol both at day three and five (table 2; day Baseline, mean (SEM) 70.38 (2.74) 68.20 (2.63) 0.568
three p=0.002; day 5 p=0.012) while improvement in the mean Day 3, mean change (% -31.54
-22.56 (-33.08%) 0.233
score of inflammation was significantly better with tramadol- change) (-44.81%)
diclofenac combination at day 5 (table 2; p=0.001). The Day 5, mean change (% -48.46
-30.44 (-44.63%) 0.002
change) (-68.85%)
improvement in the total score of inflammation was significantly
superior to tramadol-paracetamol combination at both visits Mean score for pain at rest on 0-100 VAS scale
(table 2; day three p=0.004; day five p < 0.0001). Baseline, mean (SEM) 56.92 (2.34) 56.80 (2.50) 0.971
Day 3, mean change (% -26.15
Overall, a total of 15.38% and 32% patients receiving -17.00 (-29.93%) 0.11
change) (-45.95%)
tramadol-diclofenac and tramadol-paracetamol respectively
Day 5, mean change (% -42.12
received concomitant medication. One day three and five there change) (-73.99%)
-24.48 (-43.80) <0.0001
was no difference for use of concomitant medication between
Mean score for pain on movement on 0-100 VAS scale
two groups.
Baseline, mean (SEM) 76.92 (2.06) 74.80 (2.17) 0.481
Global assessment of efficacy data evaluated by both Day 3, mean change (% -33.08
-26.36 (-35.24%) 0.388
change) (-43%)
Table 1: Baseline characteristics Day 5, mean change (% -50.19
-33.16 (-44.33%) 0.003
Tramadol + Tramadol + change) (-65.25%)
Diclofenac Paracetamol P value Mean score for swelling
(n=26) (n=25) Baseline, mean (SEM) 1.80 (0.21) 1.68 (0.18) 0.665
Age (Years)
44.23 (2.56) 46.32 (2.82) P=0.586 Day 3, mean change (%
mean (SEM) -0.92 (-51.11) -0.22 (-13.19 ) 0.002
change)
Sex Day 5, mean change (%
Male n (%) 16 (61.54%) 12 (48%) χ2, 0.943 -1.44 (-80%) -0.85 (-50.40) 0.012
change)
Female n (%) 10 (38.46%) 13 (52%) P=0.331 Mean score for Inflammation
Vital signs mean
Baseline, mean (SEM) 1.84 (0.19) 1.54 (0.21) 0.293
(SEM)
Pulse (per min.) Day 3, mean change (%
76.92 (1.38) 75.28 (1.08) P=0.355 -1.04 (-56.52) -0.50 (-32.43%) 0.232
Systolic BP (mm change)
120.46 (1.37) 121.12 (1.84) P=0.774
Hg) Day 5, mean change (% -1.60
77.38 (1.05) 76.16 (1.32) P=0.470 -0.79 (-51.35%) 0.001
Diastolic BP (mm change) (-86.96%)
Hg) Total score for Inflammation
BP: Blood Pressure: SEM: Standard Error of the Mean
Baseline, mean (SEM) 3.64 (0.32) 3.24 (0.30) 0.368
Day 3, mean change (% -1.96
-0.74 (-22.84%) 0.004
change) (-53.85%)
Day 5, mean change (% -3.04
-1.70 (-52.42%) <0.0001
change) (-83.52%)

physician and patient is shown in table 3. The results showed

that according to the global assessment of efficacy as evaluated
by physician 88% patients receiving tramadol-diclofenac had
very good to excellent efficacy while only 24% patients in the
tramadol-paracetamol had very good to excellent efficacy ( table
3; p<0.0001). About 96% of patients who received tramadol-
diclofenac had very good to excellent efficacy while 20% who
received tramadol-paracetamol had very good to excellent
efficacy ( table 3; p<0.0001).
Table 4 shows the global assessment of tolerability evaluated
by physicians and patients. According to the global assessment
Figure 1: Comparison of mean (SEM) VAS score for overall pain be-
tween tramadol-diclofenac and tramadol-paracetamol of tolerability evaluated by physician 88.46% patients who

Citation: Billa G, Chandanwale AS, Sundar S, Latchoumibady K, Biswas S(2017) Comparative Efficacy and Safety Evaluation Page 3 of 6
of Tramadol plus Diclofenac versus Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to Severe Acute
Musculoskeletal Pain: A Phase III, 5 Day Open Label Study. J Exerc Sports Orthop 4(1): 1-6.
 Comparative Efficacy and Safety Evaluation of Tramadol plus Diclofenac versus Copyright:
Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to © 2017 Billa et al.
Severe Acute Musculoskeletal Pain: A Phase III, 5 Day Open Label Study
received tramadol-diclofenac had good tolerability while 88%
patients in the tramadol-paracetamol group had moderate to
good tolerability ( table 3; p<0.0001). The global assessment of
tolerability as evaluated by patients was good in 92.31% and
24% patients who received tramadol-diclofenac and tramadol-
paracetamol respectively ( table 3; p<0.0001).
The overall incidence of adverse events was 11.54% and 24%
with tramadol-diclofenac and tramadol-paracetamol respectively.
The rate of adverse events was less in tramadol-diclofenac group
on both days (day 3: 7.69% vs 20%; day 5: 11.54% vs 16%;
table 5)). All the adverse events were gastrointestinal (gastritis,
nausea and vomiting) in nature except drowsiness reported by
one patient receiving tramadol-paracetamol on day three. No
Figure 3: Comparison of mean (SEM) VAS score for pain on movement-
serious adverse event was reported in this study. between tramadol-diclofenac and tramadol-paracetamol
Discussion
Table 4: Comparison of global assessment of tolerability between
The combination of diclofenac and tramadol provides
tramadol-diclofenac and tramadol-paracetamol
advantage of different mechanisms of action with potential for
Tramadol + Tramadol +
wider spectrum of pain relief. Our group has recently published Diclofenac (n=26) Paracetamol (n=25)
Global assessment of tolerability by physiciana
Poor, n (%) 1 (3.85%) 3 (12.00%)
Moderate, n (%) 2 (7.69%) 15 (60.00%)
Good, n (%) 23 (88.46%) 7 (28.00%)
Global assessment of tolerability by patientb
Poor, n (%) 1 (3.85%) 7 (28.00%)
Moderate, n (%) 1 (3.85%) 12 (48.00%)
Good, n (%) 24 (92.31%) 6 (24.00%)
χ = 19.462, p’<0.0001; bχ2 =24.598, p’<0.0001
a 2

Table 5: Comparative incidence of adverse events between tramadol-

diclofenac and tramadol-paracetamol
Figure 2: Comparison of mean (SEM) VAS score for pain at rest be-
Tramadol + Tramadol +
tween tramadol-diclofenac and tramadol-paracetamol
Diclofenac (n=26) Paracetamol (n=25)
Day 3
Table 3: Comparison of global assessment of efficacy between
tramadol-diclofenac and tramadol-paracetamol Nausea, n (%) 1 (3.85) 2 (8%)
Tramadol + Tramadol + Vomiting, n (%) - 1 (4%)
Diclofenac (n=26) Paracetamol (n=25) Gastritis, n (%) 1 (3.85) 1 (4%)
Global assessment of efficacy by physiciana Drowsiness, n (%) - 1 (4%)
Poor, n (%) 0 (0.00%) 0 (0.00%) Day 5
Satisfactory, n (%) 0 (0.00%) 15 (60.00%) Nausea, n (%) 2 (7.69) 2 (8%)
Good, n (%) 3 (11.54%) 4 (16.00%) Vomiting, n (%) - 1 (4%)
Very good, n (%) 8 (30.77%) 3 (12.00%) Gastritis, n (%) 1 (3.85) 1 (4%)
Excellent, n (%) 15 (57.69%) 3 (12.00%)
Global assessment of efficacy by patientb a phase three Indian study which demonstrated that tramadol-
Poor, n (%) 0 (0.00%) 5 (20.00%) diclofenac FDC results in significantly greater analgesia compared
Satisfactory, n (%) 0 (0.00%) 10 (40.00%)
to tramadol-paracetamol in patients with moderate to severe
pain due to acute musculoskeletal conditions, postoperative pain
Good, n (%) 1 (3.85%) 5 (20.00%)
following orthopaedic surgery, or acute flare of osteoarthritis and
Very good, n (%) 15 (57.69%) 2 (8.00%) rheumatoid arthritis [13]. In this paper, we com­pared the safety
Excellent, n (%) 10 (38.46%) 3 (12.00%) and efficacy of tramadol-diclofenac with tramadol-paracetamol,
χ =25.406, p’<0.0001; bχ2 =32.914, p’<0.0001
a 2 as an analgesic agent in subgroup population of moderate to

Citation: Billa G, Chandanwale AS, Sundar S, Latchoumibady K, Biswas S(2017) Comparative Efficacy and Safety Evaluation Page 4 of 6
of Tramadol plus Diclofenac versus Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to Severe Acute
Musculoskeletal Pain: A Phase III, 5 Day Open Label Study. J Exerc Sports Orthop 4(1): 1-6.
 Comparative Efficacy and Safety Evaluation of Tramadol plus Diclofenac versus Copyright:
Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to © 2017 Billa et al.
Severe Acute Musculoskeletal Pain: A Phase III, 5 Day Open Label Study
severe pain in acute musculoskeletal conditions. The results of All the adverse events in our study were mild to moderate
this subgroup analysis confirm that tramadol and diclofenac is in nature, with self-limiting gastrointestinal adverse events
the rational combination for management of moderate to severe (gastristis, nausea and vomiting) being most common.
pain in acute musculoskeletal conditions.
This study has some limitations. Small sample size limits
In acute musculoskeletal pain, tramadol-diclofenac the extrapolation of the results to entire population with acute
administration resulted in greater reduction of swelling and musculoskeletal pain. The results of this paper are limited
total score of inflammation compared to tramadol-paracetamol only to patients with acute musculoskeletal pain. A separate
both at day three and five. Diclofenac is a non-steroidal anti- subgroup analysis needs to be conducted to see whether similar
inflammatory agent [16]. The anti-inflammatory property trend of results were seen in acute flare of osteoarthritis, acute
of diclofenac provides an advantage in acute inflammatory flare of rheumatoid arthritis and postoperative pain. The study
musculoskeletal pain as paracetamol does not have any effect on was conducted in controlled setting to evaluate the role of co
the inflammatory mediators [17]. morbidities in these patients; a study in real-world settings is
required. Lastly, though the study was conducted in controlled
The VAS score for overall pain was significantly reduced setting with randomization, an open label study design leaves an
after combination therapy of tra­madol and diclofenac. Mitra et area for suspecting bias.
al [18] have showed that diclofenac-tramadol and diclofenac-
Conclusion
paracetamol combinations are effective in providing post-
operative pain control after caesarean section. The investigators The tramadol-diclofenac combination resulted in
demonstrated that the overall efficacy of diclofenac-tramadol significantly greater reduction in VAS scores for overall pain,
combination is better than diclofenac-paracetamol. pain at rest and pain on movement on day five compared to
tramadol-paracetamol combination. Mean score for swelling
Similarly, another comparative study has evaluated the and total score for inflammation, was significantly better with
efficacy and safety of diclofenac-tramadol [19]. Compared to tramadol-diclofenac combination compared with the tramadol-
diclofenac alone, the combination has been shown to provide paracetamol combination both at day three and five. Both the
faster and longer pain relief in patients after unilateral hallux formulations caused mainly GI side effects of mild to moderate
valgus surgery. The combination was found to be well tolerated intensity without any serious adverse event warranting discon­
in acute inflammatory pain of moderate to severe intensity [19]. tinuation of treatment.
We did not find any comparative study of tramadol-diclofenac Acknowledgement
combination in acute musculoskeletal pain. In this regards, our
The authors of this study wish to thank Dr. Anant D Patil for
study results provide unique insights about efficacy and safety
assistance in writing and editing the manuscript.
of combination in subset of population with moderate to severe
pain. Declaration
Both the combinations were well tolerated by patient Financial support for the project, along with the study drug,
population in our study. The incidence of adverse events was Dura pain® (tramadol 50 mg immediate release with diclofenac
less in patients receiving the tramadol-diclofenac combination sodium 75 mg sustained release), was provided by Abbott
compared with those receiving the tramadol-paracetamol Healthcare Pvt Ltd, India. Pvt Ltd, India. B Gauri and B Swati are
combination, on both day 3 and day 5. The difference in rate employees of Abbott Healthcare Pvt Ltd, India. The other authors
of adverse events can partly be explained by higher number report no conflict of interest.
of patients receiving concomitant medication in tramadol-
Trial registration number: CTRI/2011/091/000150
paracetamol group. The dose of tramadol in FDC with diclofenac
[Registered on: 01/02/2011]
sodium was 100 mg per day versus 150-225 (up to maximum
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Citation: Billa G, Chandanwale AS, Sundar S, Latchoumibady K, Biswas S(2017) Comparative Efficacy and Safety Evaluation Page 5 of 6
of Tramadol plus Diclofenac versus Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to Severe Acute
Musculoskeletal Pain: A Phase III, 5 Day Open Label Study. J Exerc Sports Orthop 4(1): 1-6.
 Comparative Efficacy and Safety Evaluation of Tramadol plus Diclofenac versus Copyright:
Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to © 2017 Billa et al.
Severe Acute Musculoskeletal Pain: A Phase III, 5 Day Open Label Study
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