Abstracts P29

(212) Withdrawn by author (214) Symptoms of opioid withdrawal after discontinuation

of tapentadol immediate release, an analgesic with mu-
opioid receptor agonism
D Upmalis, A Okamoto, C Oh, M Buzoianu, J Stegmann, M Halel; Johnson &
Johnson Pharmaceutical Research and Development, Titusville, NJ
Tapentadol is a single molecule with a dual mode of action: mu-opioid
receptor agonism and norepinephrine reuptake inhibition. The contri-
bution of mu-opioid receptor agonism to opioid withdrawal symptoms
following 90-days treatment with tapentadol immediate release (IR)
was compared with oxycodone IR in a randomized, double-blind, mul-
ticenter trial of patients with low back pain or pain from osteoarthritis.
Patients (878 randomized, 849 received study drug) were randomly as-
signed in a 4:1 ratio to a flexible dose of either tapentadol IR (50 or 100
mg/dose; maximum 600 mg/day) or oxycodone IR (10 or 15 mg/dose;
maximum 90 mg/day) every 4 to 6 hours. Withdrawal symptoms after
abrupt study medication discontinuation were examined using the Clin-
ical Opioid Withdrawal Scale (COWS) and the Subjective Opioid With-
drawal Scale (SOWS) questionnaires. Most patients completed these
questionnaires within 2 to 4 days after study medication was discontin-
ued and without replacement opioid therapy. Treatment with daily
doses (mean ⫾ SD) of tapentadol IR (284 ⫾ 156 mg) and oxycodone IR
(42 ⫾ 25 mg) showed similar pain scores throughout the study. Based on
the COWS assessment (n⫽306 tapentadol IR, 66 oxycodone IR), signifi-
cantly fewer patients reported mild-to-moderate withdrawal symptoms
in the tapentadol IR group (17%) than in the oxycodone IR group (29%;
nominal P ⬍0.05). The mean SOWS score was lower for the tapentadol IR
group (6.9) than the oxycodone IR group (8.7, no significant difference).
For patients assessed ⱖ5 days after study drug was discontinued (n⫽183
tapentadol IR, 43 oxycodone IR), the mean SOWS score was 6.3 and 7.0
for the tapentadol IR and oxycodone IR groups, respectively (no signif-
icant difference). These findings suggest in this patient population, opi-
oid withdrawal was infrequent and of limited intensity after abrupt
discontinuation of 90-day therapy. This study was supported by Johnson
& Johnson Pharmaceutical Research and Development and Grünenthal
GmbH.

(213) Low-dose intrathecal naloxone to enhance intrathecal (215) Withdrawn by author

morphine analgesia in the treatment of refractory se-
vere chronic low back pain
S Hamann, W Witt, P Sloan; University of Kentucky, Lexington, KY
Ultra low-doses of opioid antagonists (naloxone) block excitatory opioid
receptor pathways and may paradoxically enhance morphine analge-
sia.1,2 The purpose of this case study was to evaluate the safety and
efficacy of ultra-low dose intrathecal (IT) naloxone added to IT mor-
phine for the treatment of refractory severe chronic low back pain. A
56-yr old man with a history of severe chronic low back pain (post-
laminectomy syndrome; 9/10 pain rating) was evaluated. Prior treat-
ments included physical therapy, antidepressants, oral opioid analgesic
trials, adjuvant analgesics, steroid epidural injections, lumbar laminec-
tomy, and spinal cord stimulation. Initial therapy at our clinic was a
lumbar IT trial of morphine (unsuccessful) up to 50 mg/d. The addition of
IT clonidine (up to 75 mcg/d) and ketamine (6 mg/d) were without ben-
efit. With patient consent and approval, we administered an IT bolus of
morphine 2 mg combined with IT naloxone 20 ng. Onset of pain relief
was within 20 minutes and peaked at 1 hour with a 50% reduction in
VAS pain score. The initial IT morphine 2mg/naloxone 20ng dose was
repeated and the patient followed in hospital overnight. There were no
signs of adverse drug toxicity or hemodynamic compromise. An IT infu-
sion of daily morphine 5 mg and naloxone 50 ng was started. Through-
out the 3-yr follow up period the patient maintained pain reduction of
60-80%, with a return to daily activities and no further hospitalizations.
Conclusions: 1.) Ultra-low dose IT naloxone added to IT morphine infu-
sion provided effective analgesia in the management of severe refrac-
tory chronic low back pain. 2.) IT morphine/naloxone infusion appeared
to be safe without obvious side effects. 3.) No evidence of opioid antag-
onist toxicity or opioid withdrawal was observed. (1. Sloan, Opioid Man-
age 2006; 2. Hamann, J Opioid Manage, 2007.)