The document discusses pain and its global burden. Some key points: - Chronic pain affects 30-50% of the world's population. - In the USA, chronic pain affects more people annually than diabetes, heart disease, and cancer combined. - Pain comes in different forms including neuropathic pain (caused by nervous system dysfunction), nociceptive pain (from tissue injury), and mixed pain (with both neuropathic and nociceptive components). - Scales like the numeric rating scale and visual analogue scale are used to measure pain levels.

3. The Global Burden of Disease Study 2016 reaffirmed that
the high prominence of pain and pain-related diseases is
the leading cause of disability and disease burden
globally.1
Global burden of Pain: Analysis of Worldwide Data
1. British Journal of Anesthesia, 123 (2): e273ee283 (2019)
2. Pain Research and Management Volume 2017, Article ID 4643830, 9 pages
3. Goldberg and McGee BMC Public Health 2011, 11:770
Chronic pain affects between 30% and 50% of the world
population.2
Pain is an enormous global health problem. Globally, it has
been estimated that 1 in 5 adults suffer from pain and
that another 1 in 10 adults are diagnosed with chronic
pain each year.3

4. In the USA, chronic pain affects more people every year
than diabetes, heart disease, and cancer combined.
Global burden of Pain: Analysis of Worldwide Data
4.Journal of Pain Research 2012:5;327-346
Chronic pain can occur in patients of any age, but it is
more common and challenging among older individuals.

5. Examples
Peripheral
• Postherpetic neuralgia
• Trigeminal neuralgia
• Diabetic peripheral neuropathy
• Postsurgical neuropathy
• Posttraumatic neuropathy
Central
• Poststroke pain
Common descriptors2
• Burning
• Tingling
• Hypersensitivity to touch or cold
Examples
• Pain due to inflammation
• Limb pain after a fracture
• Joint pain in osteoarthritis
• Postoperative visceral pain
Common descriptors2
• Aching
• Sharp
• Throbbing
Examples
• Low back pain with
radiculopathy
• Cervical
radiculopathy
• Cancer pain
• Carpal tunnel
syndrome
Mixed Pain
Pain with
neuropathic and
nociceptive
components
Neuropathic Pain
Pain initiated or caused by a
primary lesion or dysfunction
in the nervous system
(either peripheral or
central nervous system)1
Nociceptive Pain
Pain caused by injury to
body tissues
(musculoskeletal,
cutaneous or visceral)2
Presentation Across Pain States Varies
1. International Association for the Study of Pain. IASP Pain Terminology.
2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57

6. PAIN SCALES

7. Numeric Rating Scale (NRS)
Visual Analogue Scale (VAS)
0 10
Pain Scores

8. Wong-Baker “Faces Scale”
Verbal scale
No
Pain
Mild Moderate
Severe
Pain

11. WHO Pharmacological Pain management
ladder

12. World Health Organization; 2018

15. http://what-when-how.com/low-back-pain-pathogenesis-and-treatment/pharmacotherapy-for-chronic-low-back-
pain-conservative-treatment-part-2/

16. According to recent FDA Alert!
FDA strengthens warning that non-
aspirin non-steroidal anti-inflammatory
drugs (NSAIDs) can cause heart attacks
or strokes.
U.S. Food and Drug Administration , 7-9-2015

17. FDA Alert regarding NSAIDs!

18. U.S. Food and Drug Administration , 7-9-2015
FDA Alert regarding NSAIDs!

19. G.I.T and cardiac Safety of Tramadol
“Unlike NSAIDs, Tramadol doesn’t irritate gastro intestinal
mucosa and exacerbate hypertension and Congestive
Heart Failure”
Int J. Clinical Rheumatol (2010),5(1): 1-4

20. Increasing trends of Tramadol/Tramadol combo in
Asian Countries
Intercontinental Marketing Services Kilochem statistics show that – except for NSAIDs and paracetamol –
tramadol and tramadol-containing products are the analgesics most often used in clinical practice in a
large group of Asian countries, with increasing consumption over time.
Journal of Pain Research, Volume 11; 24 October 2018 Volume 2018:11 Pages 2567—2575

21. Experts Opinion regarding Tramadol
 According to the experts, tramadol is used in the management of moderate to severe acute
and chronic pain caused by a wide range of conditions.
 Almost all the specialists treat moderate cancer pain with tramadol, a modality that is
supported in the literature
Journal of Pain Research, Volume 11; 24 October 2018 Volume 2018:11 Pages 2567—2575

22. FDA Recommended Indications of Tramadol
“Tramadol is an Opioid agonist indicated for the
management of different varieties of moderate to
moderately severe chronic pain in adults.”

23. Sologesic

24. SR

25. “Drug Delivery system that are designed to achieve prolonged
therapeutic effect by continuously releasing medication over an
extended period of time after administration of single dose.”
ADVANTAGES OF SUSTAIN RELEASE DOSAGE
FORMS (Sologesic-SR)
Reduction in frequency of intakes.
Reduce side effects.
Uniform release of drug over time.
Better patient compliance
Unlike NSAIDs, don’t irritate Gastrointestinal
mucosa, exacerbate hypertension and CHF.

26. Better Control of Pain/Compliance/ Safety
ISRN pain, volume 2013 article ID:255346, page 16

28. In most of the conditions patients did not
get the desired response by use of single
analgesics
Journal of clinical pharmacy and therapeutics

29. Single Analgesics…
Most analgesics cannot prescribed at unlimited doses
due to the ceiling of efficacy and/ or safety and
tolerability concerns such as;
 Liver damage (paracetamol)
According to FDA all NSAIDs cause heart stroke or heart
attacks
Gastrointestinal and cardiovascular risks (both non
selective and cyclo-oxygenase -2 (COX & NSAIDS)
 Sedation, constipation and other effects opioids
agonists
Journal of clinical pharmacy and therapeutics

30. Combination Analgesic…..
Combining drugs from different classes offers effective analgesia at
reduced doses of individual agents which may reduced the severity of
dose related adverse events
A Rational Approach!
Journal of clinical pharmacy and therapeutics

31. Why Combinations is Better than Single
Agents?
Combination analgesics might reduce adverse
events.
Combining two or more agents may result in an
additive or synergistic analgesic effect.
Complementary pharmacokinetics of
tramadol/paracetamol in combination enhance the
probability of effective pain relief.

32. A rational approach …
Tramadol plus acetaminophen are a rational combination products in
that their mechanisms of action do not overlap
European journal of Anesthesiology. Supplement (2003, 28:13-17)

34. Fixed-dose Combination of
Tramadol/Paracetamol
Paracetamol blocks the production of chemicals in the
body that are responsible for pain and fever, while
Tramadol exerts its effect by acting on parts of the
central nervous system which process pain signals.

35. Advantages of FDC
Better Pain control
Lesser incidence of individual drug’s side effects
Increased patient compliance
Decrease cost of therapy

36. The clinically used combination of paracetamol 325mg plus tramadol
37.5mg utilizes a fixed dose ratio (8.7:1) that falls within this range of
synergy
Combination drug provide
synergistic effect…
Clinical Rheumatology July 2006, volume 25, issue 1 supplement , pp 16-21

37. Potential Advantages of a Fixed-dose
Tramadol/Paracetamol Analgesic Product Include:
Broader analgesic spectrum
Complementary pharmacokinetic profile
Potentially synergistic analgesic effect
Greater convenience (possibly resulting in better compliance,
thus, improved therapy)
Improved ratio of efficacy to adverse effects.

38. Rationale of Tramadol-APAP
Combination

39. Sologesic Extra

40. Sologesic Extra

41. Rapid & Persistent Pain Relief
Sologesic Extra combination provide more rapid pain relief than tramadol
alone, and more persistent pain relief than acetaminophen alone
Clinical Rheumatology July 2006, volume 25, issue 1 supplement , pp 16-21

43. NSAIDs Vs. Sologesic-Extra
in management of Osteo-arthritis

44. Ann Rheum Dis 2010;69(Suppl3):273
Sologesic-Extra in management of
Osteoarthritis

45. Study Protocols
Background
• NSAIDs are commonly prescribed for knee OA pain. However,
flare ups of OA pain or poor control with NSAIDs alone are
common and necessitate the addition of other analgesics with
different mechanisms, such as tramadol.
Study Design
• This was a randomized, multicenter, open comparative study in
out-patients at six sites.
Objectives
The purpose of this study is to compare the efficacy of tramadol
37.5 mg/acetaminophen 325 mg combination tablets
(tramadol/APAP) with that of NSAIDs as maintenance therapy
following tramadol/APAP and NSAID combination therapy in
knee osteoarthritis (OA) pain which was inadequately controlled
by NSAIDs.

46. Results
WOMAC:WESTERN ONTARIO AND
MCMASTER OSTEOARTHRITIS INDEX
(WOMAC)
NRS: (Numerical Pain Scale)

47. Conclusion
In conclusion, when added to NSAID, tramadol/APAP was
generally well tolerated and significantly improved knee OA
pain which was previously refractory to NSAID therapy.
In those subjects who showed favorable response to
tramadol/APAP and NSAID combination therapy, both
tramadol/APAP and NSAIDs were effective at maintaining
the pain-reduced state and there was no significant
difference in efficacy between tramadol/APAP and NSAIDs
Ann Rheum Dis 2010;69(Suppl3):273

48. Impact on Fibromyalgia Pain

49. Impact of Fibromyalgia Pain on Health-Related Quality of
Life Before and After Treatment With
Tramadol/Acetaminophen
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 53, No. 4, August 15, 2005, pp 519–527

50. Health Related Quality Of Life
(HRQOL)

51. According to American college of Rheumatology,
Tramadol/ Acetaminophen significantly increases
Health-related quality of life (HRQOL)
European journal of pain Jan 2012

52. Role in Diabetic Peripheral
Neuropathic Pain(DPNP)

54. AMERICAN ACADEMY OF NEUROLOGISTS
(ANN) GUIDELINES 2011
Pharmacological Treatment of Painful
Diabetic Peripheral Neuropathy.
TheAAN recognizesthat specificcaredecisions are the prerogativeof the patient and the
physician caring forthe patient, based on all of the circumstances involved.
AAN =AmericanAcademy ofNeurology
Bril Vet al. Neurology 2011;76(20):1758-65.
1st line
(levelA)
2nd line
(level B)
• Pregabalin
• Gabapentin
• Duloxetine
• Amitriptyline
• Opioids
• Tramadol

55. Comparison of the efficacy and safety of
Tramadol/Acetaminophen combination therapy and
Gabapentin in the treatment of painful diabetic neuropathy
Diabet. Med. 27, 1033–1040 (2010)
This study suggests that the T⁄A combination treatment is as effective as gabapentin in
the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.
The T⁄A and gabapentin
groups both showed
significant
improvement on the 36-
item Short form Health
Survey
questionnaire in terms of
both quality of life and
mood. There was no
significant difference
between the
groups.

56. Effective Relief from Migraine Pain

57. Tramadol/Acetaminophen for the Treatment of
Acute Migraine Pain
Headache 2005;45:1317-1327
In summary,
tramadol/APAP relieves
pain, photophobia,
and phonophobia more
effectively than a
placebo in patients with
migraine headache, and
it might provide greater
reductions in functional
disability as well.

58. Treatment of Breakthrough Pain in
Cancer Patients

59. Efficacy and safety of tramadol/acetaminophen in the
treatment of breakthrough pain in cancer patients.
The effective rates, defined by more than 30%
reduction of the VAS score
After 10 minutes of administration of tramadol/acetaminophen was 74.6%,
30 minutes 86.4%, and one hour 94.9%
CONCLUSION:
Tramadol/acetaminophen might be efficacious and safe in the treatment
of breakthrough pain in cancer.
Saudi Med J.2010 Dec;31(12):1315-9.

60. Treatment of CLBP Pain with
Sologesic-Extra Vs. Celecoxib

61. Effect of Sologesic-Extra (Tramadol/APAP) on
Motivation in Patients with Chronic Low Back
Pain
Study Design
four-week study compared the efficacies of tramadol/acetaminophen
and celecoxib in the treatment of patients with chronic LBP.
This was a retrospective case-control study, in which the case group
consisted of patients treated with tramadol-acetaminophen tablets (𝑛 = 36),
and the control group consisted of patients treated with celecoxib (𝑛 = 37)
for four weeks.
Population
A total of 73 patients (23 men, 50 women) with chronic LBP were included.
Inclusion criteria
individuals whose pain had persisted for >3 months and who agreed to
answer the questionnaire.
Pain Research and Management Volume 2016, Article ID
7458534, 7 pages

62. Effect of Sologesic-Extra (Tramadol/APAP) on
Motivation in Patients with Chronic Low Back
Pain
Primary Outcome
The primary outcome measure was apathy after four weeks of treatment.
Secondary outcome
measures included pain, physical disability, anxiety, depression, and pain
catastrophizing assessment after four weeks of treatment.
Pain Assessment
The numerical rating scale (NRS) for pain self-assessment.
Results
The Apathy Scale score was significantly lower in the tramadol group than
in the celecoxib group after treatment (P<0.05).
Pain Research and Management Volume 2016, Article ID
7458534, 7 pages

63. Effect of Sologesic-Extra (Tramadol/APAP) on
Motivation in Patients with Chronic Low Back
Pain
The NRS was significantly lower in the tramadol group than in the celecoxib
group after treatment (P<0.05), suggesting enhancement of internal pain
control by tramadol-acetaminophen
Conclusion
The results of the study suggest that tramadol-acetaminophen in tablet form
may represent an attractive alternative treatment option for chronic LBP
patients with depression or apathy.
Pain Research and Management Volume 2016, Article ID
7458534, 7 pages

64. Treatment of CLBP Pain with
Sologesic(Tramadol)

65. Efficacy of tramadol in treatment of
chronic low back pain
Study Design
 An open label, a 4 week, randomized, placebo controlled, double blind
treatment phase.
Three hundred eighty outpatients between 21 and 79 years with chronic
low back pain with no or a distant history of back surgery enrolled in the
open label phase and were treated with tramadol up to 400 mg/day.
VAS was selected to asses pain relief.
Results
There were significantly lower (p < or = 0.0001) mean pain visual analog
scores (10 cm scale) among tramadol patients (3.5 cm) compared to
placebo patients (5.1 cm)
Conclusion
Tramadol was effective for the treatment of chronic low back pain
J Rheumatol. 2000 Mar;27(3):772-8

66. Treatment of Post-Operative/
Musculoskeletal/Diabetic Neuropathy
Pain with Sologesic-Extra

67. Sologesic-Extra Tramadol/paracetamol fixed-dose
combination: a review of its use in the management
of moderate to severe pain
In several well designed, clinical studies, single- or multiple-dose
tramadol/paracetamol was effective in providing pain relief in adult patients
with postoperative pain after minor surgery, musculoskeletal pain (acute, sub
acute or chronic), painful diabetic peripheral neuropathy or migraine pain.
 It was also effective as an add-on analgesic in patients who were experiencing
moderate to severe musculoskeletal pain (e.g. osteoarthritis or rheumatoid
arthritis pain) despite ongoing NSAID and/ anti rheumatic drug therapy.
Moreover, in patients with postoperative pain, ankle sprain pain or sub acute
lower back pain, the analgesic efficacy of tramadol/paracetamol was better
than that of paracetamol.
Tramadol/paracetamol had no additional tolerability issues relative to its
components
Conclusion
Clinical data suggest that tramadol/paracetamol is a useful treatment option
for providing multimodal analgesia in patients with moderate to severe pain.
Clin Drug Investig. 2010;30(12):866

68. Effect of Sologesic(Tramadol) in
Dento alveolar Surgical Pain

69. The effect of Sologesic (Tramadol) on dento-
alveolar surgical pain
Study Design
Four-hundred and fifty-two (452) patients over the age of 18 years who were to
undergo removal of impacted teeth (n = 362), removal of root (n = 79), or
alveolectomy, enucleation of cysts, or removal of soft tissue (n = 11) under local
anesthesia were studied.
 Patients were randomly allocated to receive tramadol 100 mg or 50 mg four
times daily, or 50 mg twice daily, or placebo.
Results
More patients given tramadol reported complete pain relief than the placebo
group.
The advantages of tramadol continued over the next 2 days. There were no
serious or unexpected adverse effects.
Conclusion
It is concluded that tramadol is an effective analgesic after dento-alveolar
operations.
British Journal of Oral and Maxillofacial Surgery Volume 35, Issue 1, February 1997, Pages 54-58

70. Journal of Minimally Invasive Gynecology Volume 19, Issue 5, September–October 2012, Pages 581-584
Comparison of the Analgesic Effects of Oral Tramadol and
Naproxen Sodium on Pain Relief During IUD Insertion

71. Design
Randomized, double-blinded, clinical trial
Setting
University-affiliated hospital. Single-center.
Patients
One hundred three patients scheduled for insertion of an IUD.
Interventions
Patients were randomly assigned to receive oral tramadol 50 mg
capsules (n = 35) or naproxen sodium 550 mg tablets (n = 34) or placebo
(n = 34) 1 hour before insertion of the IUD. After insertion of the IUD,
pain intensity was evaluated using a visual analog scale(VAS, 0–10).
Adverse effects, patient satisfaction with the medication, and preference
for using it during future insertions were also recorded.
Journal of Minimally Invasive Gynecology Volume 19, Issue 5, September–October 2012, Pages 581-584
Comparison of the Analgesic Effects of Oral Tramadol and
Naproxen Sodium on Pain Relief During IUD Insertion

72. Conclusion
Prophylactic analgesia using 50 mg tramadol and 550 mg naproxen
delivered orally, can be used to relieve pain during IUD insertion.
However, tramadol capsules were found to be more effective than
naproxen tablets.
Journal of Minimally Invasive Gynecology Volume 19, Issue 5, September–October 2012, Pages 581-584
Comparison of the Analgesic Effects of Oral Tramadol and
Naproxen Sodium on Pain Relief During IUD Insertion

73. Conclusion
• Sologesic(Tramadol) is effective in wide range of acute & chronic pain
,including neuropathic pain.(Int j. of clin Rheum 2010)
• Sologesic (Tramadol) is an effective analgesic after dento-alveolar
operations.(British Journal of Oral and Maxillofacial Surgery )
• Sologesic provide better control, increased compliance, improved
tolerability and Safety.(ISRN Pain)
• Sologesic provides rapid onset of pain relief only in 17 mins and
faster duration of action.(Clinical Rheumatology July 2006)
• Sologesic-Range Unlike NSAIDs, doesn’t disturb Gastro-intestinal mucosa
and exacerbate hypertension and CHF.(Int j. of clin Rheum 2010)
• Sologesic is a useful treatment option for providing multi-model
analgesia in wide variety of musculoskeletal pain, DPNP, Post operative pain,
migraine, fibromyalgia and Cancer pain.
• Sologesic has been recommended as safe with no drug abuse or
tolerance. .(Clin drug Invest 2010)
SR
Extra
Extra
Extra

74. Sologesic (Tramadol 50mg) Capsule
Sologesic (Tramadol 100 mg)Tablet
Sologesic (Tramadol 37.5 mg + Paracetamol
325 mg) Tablet
Extra
SR

75. Mode of Action of Tramadol
Biomedicine & Pharmacotherapy 111 (2019) 443–451

76. Mode of Action of Paracetamol

77. Pharmacokinetics:
PARACETAMOL
Bioavailability (Orally) 70-90%
T max 0.5-1 hrs
C max 12.3µg/L
Metabolism 90-95% Hepatic by cytochrome P450 (isoenzyme CYP2E1)
Excretion Renal
Protein Binding Negligible
t ½ 1-3 hrs
TRAMADOL
Absorption 75%
Bioavailability 75%, irrespective of food intake.
T max 2 hours (After oral absorption)
C max (100mg) 0.08 mg/L.30.31
Metabolism CYP2D6 and CYP3A4, as well as by conjugation of parent
and metabolites.
Excretion Renal 90%; Fecal 10%
Protein Binding 20%
t ½ 6.3hrs
M1 (O-demethylated metabolite)
T max 3hrs
C max (100mg) 15-25% those of tramadol
Metabolism CYP2D6 and CYP3A4, as well as by conjugation of parent
and metabolites.
t ½ 7.4hrs

78. Note:
The pharmacokinetics of oral and intravenous
tramadol does not differ significantly between
adults and children.
Half-lives may be prolonged in people with
decreased liver or kidney function.
Approximately 30% of the dose is excreted in
the urine as unchanged drug, whereas 60% of
the dose is excreted as metabolites
Pharmacokinetics:

79. Osteoarthritis
Rheumatoid arthritis
Ankylosing spondylitis
CLBP
DPNP
Cancer Pain
Strain/sprain
Knee & joint pain
Post operative pain
Dental pain
Musculoskeletal pain
Fibromyalgia
Renal & Biliary colic.
Migraine etc
Sologesic 50 mg Capsule: for mild to moderate Pain (Acute)
Sologesic SR Tablet: for Prolong Pain (Chronic)
Sologesic-Extra Tablet: for moderate to severe Pain(Acute)
Following are key indications:
Indications

80. DOSAGE
&
ADMINISTRATION
Usual Adult Dose for Pain (Tramadol)
Adults (17 years or older): 50 to 100 mg orally every 4 to
6 hours as needed for pain.
Maximum dose: 400 mg per day
Usual Adult Dose for Chronic Pain
Tramadol Sustained-Release (SR):
18 years or older: 100 mg orally once a day
Renal Dose Adjustments
Immediate-release:
-CrCl less than 30 mL/min:
Increase dosing interval to every
12 hours; Maximum dose should
not exceed 200 mg per day
Sustained-release:
-CrCl less than 30 mL/min: Use
is not recommended
Liver Dose Adjustments
Immediate-release:
-Patients with cirrhosis: 50
mg orally every 12 hours
Sustained-release:
-Severe hepatic impairment
(Child-Pugh Class C): Use is
not recommended

81. DOSAGE
&
ADMINISTRATION
Usual Adult Dose for Pain (Sologesic-Extra=Tramadol/APAP)
Adults (17 years or older):
 The usual starting dose is two tablets.
 If required, further doses can be taken after every six hours, as
recommended by your doctor.
 Do not take more than 8 tablets per day (equivalent to 300 mg
tramadol hydrochloride and 2600 mg paracetamol).
 The dosage should be adjusted to the intensity of your pain and
your individual pain sensitivity.
 In general the lowest pain-relieving dose should be taken
Maximum dose for adult of Tramadol: 400 mg per day
Maximum dose for Geriatric of Immediate-release: 300 mg per day

82. Contra-Indications
Patients who have previously demonstrated hypersensitivity to
tramadol, any other component of this product or opioids.
Patients with significant respiratory depression in unmonitored
settings or the absence of resuscitative equipment.
Patients with acute or severe bronchial asthma or hypercapnia
(also known as hypercarbia and CO2 retention) in unmonitored
settings or the absence of resuscitative equipment.
All other opioid contraindications, including intoxication with
alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or
psychotropic drugs.

83. Drug
Interaction
SSRI/SNRI antidepressants or anorectics, TCA
antidepressants, other tricyclic compounds, other
opioids, MAOIs, neuroleptics or other drugs that lower
seizure threshold: Risk of seizures increased with
concomitant use of tramadol.
CYP2D6 and/or CYP3A4 Inhibitors: May result in
increased tramadol concentrations.
Serotonergic Drugs, Triptans, and CNS Depressants:
Enhanced risk of adverse reactions.
Carbamazepine: Reduces analgesic effects of tramadol.
Quinidine: May result in increased concentration of
tramadol and reduced concentrations of its active
metabolite, M1.
Digoxin and Warfarin: Rare reports of digoxin toxicity;
altered warfarin effect and elevation of prothrombin time.

84. “Sologesic Extra provides Rapid and
Sustain relieve from pain when compare
with NSAIDs, &
doesn’t have NSAIDs like side effects”
Brand Slogan

85. Summary
 Preferred treatment choice for management of wide range
of Moderate to severe pain, including musculoskeletal,
post operative, dental, DPNP, migraine, cancer and
dental pain.
 Sologesic. Is multi-model analgesic
provides strict relief from different varieties of
pain.
 Sologesic provides better control with better
patient compliance, tolerability and safety.
 Sologesic provides quick relief from pain and
has longer duration of action.
Extra
SR
Extra

86. Price
Product Company Strength Pack Size RP Per Tablet
SOLOGESIC cap. Werrick 5o mg 1*10s 120 12.50
SOLOGESIC SR Werrick 100mg 1*10s 195 19.5
SOLOGESIC EXTRA Werrick
325mg/37.5
mg
1*10s 115 11.50