Tramadol extended-release in the management of chronic pain

Figures & data

Table 1 Morbidity associated with untreated chronic pain (APS 1996)

Decreased quality of life

Sleep disturbance

Adverse impact on:

Concentration

Ability to work

Ability to exercise

Physical function

Cognitive functions

Daily living

Social relationships

Depression

Increased anxiety

Inability to cope

Figure 1 ACR treatment guidelines for pharmacological management of noncancer chronic pain systemic agents (ACR 2000).

Abbreviations: ACR, American College of Rheumatology; COX-2, cyclooxygenase-2; NSAIDs, nonsteroidal antiinflammatory drugs.

Table 2 Limitations of pharmacologic therapy for chronic pain

Therapeutic class	Major limitations
Nonselective NSAIDs	Risk for gastrointestinal toxicitya
	Recommended use of concomitant gastroprotective agents
	increases costa
	Risk for renal toxicitya
	Cardiovascular safety issuesb
COX-2 Inhibitors	Increased risk
	Cardiovascular safety issuesc
	Renal toxicitya
Opioids	Associated with: Reduced cognitive and motor functiond
	Respiratory depressione
	Fear of dependence/tolerance/abusef
	Stringent regulatory requirements and potential for scrutiny maylimit adequate prescribingf

a Notes: ACR 2000

b Hudson et al. 2005

c Caldwell et al. 2006

d JCAHO 2001

e Stephens et al. 2003

f Weinstein et al. 2000.

Abbreviations: COX-2, cyclooxygenase-2; NSAIDs, nonsteroidal antiinflammatory drugs.

Figure 2 Structure of tramadol extended-release: (±) cis-2-[(dimethylamino) methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride (Ultram PI 2004).

Figure 3 Pharmacokinetics of tramadol ER 200 mg once daily (qd) versus tramadol IR 50 mg every 6 hours (q6h) (mean steady-state tramadol plasma concentrations in healthy subjects on day 8 post dose) (Ultram PI 2006).

Abbreviations: ER, extended-release; IR, immediate-release.

Figure 4 WOMAC pain responder analysis: patients with moderate to moderately severe pain due to osteoarthritis of the knee and/or hip achieving various levels of response with tramadol ER. Patients in the 100 mg and 200 mg treatment groups demonstrated a statistically significant improvement in pain compared with placebo (Ultram PI 2006).

Abbreviations: ER, extended release; WOMAC, Western Ontario and McMaster Universities.

Figure 5 Efficacy of tramadol ER in patients with osteoarthritis: mean change from baseline in Arthritis Pain Intensity VAS assessed through 12 weeks. Reprinted from Babul N, Noveck R, Chipman H, et al. 2004. Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee. J Pain Symptom Management, 28:59–71. Copyright © 2004 with permission from Elsevier.

Abbreviations: ER, extended release; VAS, Visual Analogue Scale.

Figure 6 Efficacy of tramadol ER in patients with osteoarthritis using the WOMAC pain, stiffness, and physical function subscales. Mean percentage change in subscales were assessed from baseline to 12 weeks of treatment. Tramadol ER significantly improved pain, stiffness, and physical function subscales, compared with placebo (p < 0.001). Reprinted from Babul N, Noveck R, Chipman H, et al. 2004. Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee. J Pain Symptom Management, 28:59–71. Copyright © 2004 with permission from Elsevier.

Abbreviations: ER, extended release; WOMAC, Western Ontario and McMaster Universities.

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