New Drug Update 2009-2010 - LAFP

19% unchanged in urine 3% unchanged in urine 30% unchanged in
urine
COMPARATIVE EFFICACY: Tapentadol efficacy as an analgesic was established in several pain
conditions, including postoperative bunionectomy pain, dental extraction pain, and osteoarthritis. The
extended-release formulation (NOT FDA approved) has been studied in osteoarthritis, chronic low back
pain, and diabetic neuropathic pain.
Tapentadol immediate-release was assessed in a randomized, double-blind study enrolling 269 patients
with moderate to severe pain following bunionectomy surgery. Eligible patients had a postoperative pain
score of at least 4 on an 11-point numerical-rating scale and an increase in pain of at least 1 point on the
11-point scale within 9 hours after regional anesthesia was discontinued on the first postoperative day.
Patients received tapentadol 50 or 100 mg, oxycodone immediate-release 10 mg, or placebo, with study
drug taken every 4 to 6 hours over a 72-hour period starting 1 day after surgery. Oxycodone was included
to demonstrate model sensitivity; the study was not powered for comparison of tapentadol with
oxycodone. Rescue medication was available for patients requiring pain medication within 4 hours after
the second or subsequent dose of study drug. The primary end point was the sum of pain intensity over
24 hours (SPI-24) on the second day after randomization (study day 3). Mean SPI-24 values on the day 3
were 33.6 for tapentadol 50 mg (P = 0.0133 vs placebo), 29.2 for tapentadol 100 mg (P = 0.0001 vs
placebo), and 35.7 for oxycodone 10 mg (P = 0.0365 vs placebo) compared with 41.9 for placebo.
Results from this study are summarized in Table 2. Tapentadol 50 mg was associated with a lower
incidence of dizziness than oxycodone (32.8% vs 56.7%), but a similar incidence of somnolence (28.4%
vs 26.9%). Tapentadol 100 mg was associated with higher rates of dizziness (64.7%) and somnolence
(36.8%). GI side effects also appeared less frequently with tapentadol; however, the study was not
powered for these comparisons (Curr Med Res Opin. 2008;24(11):3185-3196).
Table 2. Efficacy of Tapentadol Immediate-Release Formulation in the
Treatment of Postsurgical Bunionectomy Pain
Tapentadol 50
mg
(n = 67)
Tapentadol 100
mg
(n = 68)
Oxycodone 10
mg
(n = 67)
Mean SPI-24 on day 2 41.2 a 36.9 a 43.3 a 53.9
Mean SPI-24 on day 3 33.6 b 29.2 a 35.7 b 41.9
Mean SPI-24 on day 4 24.9 23.4 b 25 30.1
Median time to
perceptible pain
relief
Median time to
50% pain relief
Percentage rating
study drug “good,”
“very good,” or
“excellent” on day 3
Percentage receiving
rescue medication
Placebo
(n = 67)
43 min 31 min 31 min 2 h 40 min
2 h 1 h 1.5 h 3.5 h
64.1% 86.5% 74.2% 45.4%
80.6% 76.5% 80.6% 98.5%
Tapentadol immediate-release was also assessed in a subsequent randomized, double-blind, placebocontrolled
study enrolling 603 patients with moderate to severe pain following bunionectomy. Patients
received tapentadol 50, 75, or 100 mg, oxycodone 15 mg, or placebo every 4 to 6 hours over a 72-hour
period following bunionectomy. Patients receiving rescue medication were withdrawn from the study. The
primary end point was the sum of pain intensity difference (SPID) over 48 hours in the modified intent-totreat
population. Mean SPID48 values were higher for all tapentadol doses and oxycodone compared
71