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Hydrocodone is a semisynthetic opioid with analgesic and antitussive
properties qualitatively similar to other opioid agonists. Ibuprofen is a nonsteroidal antiinflammatory agent with analgesic
and antipyretic activity and is an effective, primarily peripheral-acting antiinflammatory analgesic. The objective of this
clinical trial was to determine the additive analgesic effect of the combination of 15 mg hydrocodone bitartrate with 400
mg ibuprofen, relative to 400 mg ibuprofen alone and placebo, in the treatment of postoperative pain. The single-dose analgesic
efficacy of the combination of hydrocodone bitartrate with ibuprofen was compared with ibuprofen alone and placebo in 120
patients with moderate or severe postoperative pain after abdominal surgery. Analgesia was measured during the 6-hour period
after dosing based on onset of relief, hourly and summary variables, and duration of effect. A significantly greater proportion
of patients treated with the hydrocodone/ibuprofen combination reported onset of relief compared with ibuprofen or placebo;
however, the distribution functions for time to onset of relief did not differ among treatments. Hydrocodone with ibuprofen
and ibuprofen alone were significantly more effective than placebo for all measures of analgesia. The combination of hydrocodone
with ibuprofen was significantly superior to ibuprofen for all hourly analgesic evaluations, weighted sum of pain intensity
differences (SPID), total pain relief (TOTPAR), and global rating of study medication. No patients in the hydrocodone with
ibuprofen group required analgesic remedication during the 6-hour study period, compared with 25% and 82% in the ibuprofen
and placebo groups, respectively. The analgesic superiority of 15 mg hydrocodone bitartrate combined with 400 mg ibuprofen
compared with 400 mg ibuprofen alone was demonstrated across many efficacy variables.
Clin Ther. 2000 Jul;22(7):879-92
Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain.
Palangio M, Damask MJ, Morris E, Doyle RT Jr, Jiang JG, Landau CJ, de Padova A.
Medical Affairs Department,
Knoll Pharmaceutical Company, Mount Olive,
New Jersey 07828-1234, USA.
palangm@basf.com
OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone
7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain.
BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid
and ibuprofen. METHODS: In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter
study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone
7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen
300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief
scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who
discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the 469 patients,
255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214;
45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic
neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior
to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean
daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P =
0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly
less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014).
The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than
in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued
treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group
(12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001
vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of
study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P =
0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005
vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between
HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse
events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued
treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P
= 0.013). CONCLUSIONS: The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen
200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg
and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective
as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.
Test shows that 5mg of hydrocodone is as effective as 30 mg of codeine, with somewhat less side effects.
1: Ann Emerg Med. 1991 Oct;20(10):1100-
Hydrocodone versus codeine in acute musculoskeletal pain.
Turturro MA, Paris PM, Yealy DM, Menegazzi JJ.
University
of Pittsburgh Affiliated Residency in Emergency Medicine, Pennsylvania.
STUDY
OBJECTIVES: To evaluate the efficacy and prevalence of side effects of hydrocodone versus codeine in acute pain syndromes.
TYPE OF PARTICIPANTS/SETTING: Sixty-two consecutive adult emergency department patients 18 to 70 years old with acute musculoskeletal
pain. Patients using other analgesics or having any contraindication to opioid therapy were excluded. In addition, 12 patients
were excluded because of insufficient data or study dropout. DESIGN/INTERVENTIONS: In a randomized, double-blind prospective
manner, patients received either 5 mg hydrocodone with 500 mg acetaminophen or 30 mg codeine with 500 mg acetaminophen to
take on discharge from the ED and every four hours thereafter as needed for pain. MEASUREMENTS: Pain intensity was evaluated
by a visual analog scale at zero, one, two, four, eight, 24, and 48 hours. Specific side effects were sought, along with the
number of patients reporting inadequate analgesia. MAIN RESULTS: Data were obtained on 50 subjects (25 per group). Mean and
median pain scores did not differ significantly at time zero (x vs y, 6.03 vs 5.99 and 6.8 vs 6.1, respectively) or subsequent
intervals. Side effects were noted in eight hydrocodone/acetaminophen and 18 codeine/acetaminophen patients (P = .005). No
significant differences in gastrointestinal side effects were reported; however, less nausea or vomiting was reported in the
hydrocodone group (P = .23). Central nervous system side effects (sedation or lightheadedness) were reported in six hydrocodone/acetaminophen
patients compared with 16 codeine/acetaminophen patients (P less than .005). In addition, no hydrocodone/acetaminophen patients
reported inadequate analgesia compared with six codeine/acetaminophen patients (P less than .05). CONCLUSION: Although pain
scores were not significantly different, hydrocodone may be a more effective analgesic than codeine in acute musculoskeletal
pain, as demonstrated by significantly fewer treatment failures. Central nervous system side effects are less common with
hydrocodone than with codeine.
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