David P. Recker

A single preoperative oral dose of valdecoxib, a new cyclooxygenase-2 specific inhibitor, relieves post-oral surgery or bunionectomy pain.

BACKGROUND The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery. METHODS Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patients Global Evaluation of Study Medication. RESULTS In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patients Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events. CONCLUSIONS Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain.

Valdecoxib, a Cox-2–specific Inhibitor, Is an Efficacious, Opioid-sparing Analgesic in Patients Undergoing Hip Arthroplasty

Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects. Valdecoxib is a new, highly selective cyclooxygenase (COX)-2–specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain. The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty. This multicenter, multiple-dose, double-blind, parallel-group study compared the opioid-sparing effects, analgesic efficacy, and safety of 20-and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty. Study medication was first administered 1 to 3 hours preoperatively. The total amount of morphine administered, pain intensity, and patients global evaluation of study medication were assessed over a period of 48 hours. Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40% less morphine than those receiving placebo after hip arthroplasty. Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo. Valdecoxib and placebo were equally well tolerated. Pre-and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone. Thus, valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients.

Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis.

Objective To determine whether valdecoxib, at chronic arthritis doses, has the characteristics of a cyclo-oxygenase 2 (COX-2) specific inhibitor, as measured by a reduced incidence of upper-gastrointestinal ulceration compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Methods This double-blind, multicentre, placebo-controlled, parallel-group study compared the incidence of gastroduodenal ulcers associated with valdecoxib 10 mg daily (q.d.) and 20 mg q.d. with that of ibuprofen 800 mg three times daily (t.i.d.) or diclofenac 75 mg twice daily (b.i.d.) when administered over a 12-week period. The incidence of gastroduodenal ulcers was assessed by upper-gastrointestinal endoscopy, performed at baseline and again at the end of week 12 (or at early study termination). Efficacy assessments were performed at baseline and at weeks 2, 6 and 12 using Patients and Physicians Global Assessments of Arthritis. Results A total of 1052 osteoarthritis patients were enrolled into the trial. The incidence of gastroduodenal ulcers over 12 weeks was 5% in patients receiving valdecoxib 10 mg q.d., 4% in patients receiving valdecoxib 20 mg q.d., 7% in patients receiving placebo, 16% in patients receiving ibuprofen 800 mg t.i.d. (P < 0.05 v. placebo), and 17% in patients receiving diclofenac 75 mg b.i.d. (P < 0.05 v. placebo). The incidence of gastroduodenal ulcers at week 12 seen in the ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. groups was significantly higher than that in the valdecoxib 10 mg q.d. and valdecoxib 20 mg q.d. groups (P < 0.05). The incidence rates of gastroduodenal ulcers were not significantly different between the valdecoxib treatment groups or between valdecoxib- and placebo-treated patients. Efficacy responses to valdecoxib 10 mg and 20 mg q.d. were significantly greater than placebo and comparable with both ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. Conclusions The results of the study demonstrate that valdecoxib has an upper-gastrointestinal safety profile typical of a COX-2 specific inhibitor. Overall, the data indicate that administration of valdecoxib offers similar efficacy for the treatment of osteoarthritis but improved upper-gastrointestinal safety compared with the conventional NSAIDs, ibuprofen and diclofenac, based on the significantly lower incidence of gastroduodenal ulcers detected by endoscopy.

Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea

OBJECTIVE To compare the efficacy of the cyclooxygenase (COX)‐2‐specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea. METHOD This single‐center, double‐blind, placebo‐controlled, randomized, crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg, or placebo, with an option of treatment for up to 3 days, twice daily. Efficacy was assessed by time‐weighted sum of total pain relief, sum of pain intensity difference, time‐specific pain relief, and pain intensity difference over 12 hours, time to rescue medication or first re‐medication, the percentage of patients taking rescue medication, and patients global evaluation of study medication. RESULTS Mean time‐weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg (P < .01) and 40 mg (P < .001). Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures. Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance, with the exception of sum of pain intensity difference‐12. Both doses of valdecoxib were well tolerated. CONCLUSIONS Both valdecoxib 20‐ and 40‐mg doses were effective and well tolerated for the treatment of primary dysmenorrhea. Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy, based on onset, magnitude, and duration of analgesia that is similar to naproxen sodium, making it a potential choice for treating women with primary dysmenorrhea.

The COX-2 Specific Inhibitor, Valdecoxib, Is An Effective, Opioid-Sparing Analgesic in Patients Undergoing Total Knee Arthroplasty

This multicenter, randomized, double-blind, placebo-controlled study evaluated the analgesic efficacy and opioid-sparing effects of valdecoxib, a potent COX-2 specific inhibitor, in patients undergoing knee replacement. Patients received morphine by patient-controlled analgesia (PCA), and valdecoxib 40 mg or 80 mg daily, or placebo, for up to two days. Efficacy was assessed by the cumulative amount of morphine administered over 48 hours, pain intensity and patients evaluation of medication. Morphine consumption over 48 hours by patients receiving valdecoxib 40 mg or 80 mg daily plus morphine was 83.7% and 75.8% (P < 0.05) of the total amount consumed by patients receiving morphine alone. Patients receiving valdecoxib 40 mg and 80 mg daily experienced significantly lower maximum pain intensity on Day 2 (P < 0.05), and rated their study medication significantly higher than patients receiving morphine alone. Valdecoxib plus morphine was well tolerated. Thus, valdecoxib in combination with morphine provides multi-modal analgesia that reduces pain and opioid use and increases patient satisfaction following knee replacement surgery.

The COX-2 Selective Inhibitor, Valdecoxib, Does Not Impair Platelet Function in the Elderly: Results of a Randomized Controlled Trial

The effects of the new cyclooxygenase (COX)‐2 selective inhibitor, valdecoxib (40 mg bid; n = 17), on platelet function were evaluated, along with ibuprofen (800 mg tid; n = 15) and placebo (n = 15), in healthy elderly subjects (65–85 years) in this 7.5‐day, randomized, single‐center, double‐blind study. Platelet aggregation (to sodium arachidonate, collagen, and adenosine diphosphate), bleeding time, and serum thromboxane B2 (TxB2) concentrations were measured up to 8 hours postdose on Days 1 and 8. Valdecoxib had no platelet effects, while ibuprofen significantly decreased platelet aggregation, significantly increased bleeding time (2–4 h postdose on each day), and significantly decreased TxB2 levels at all time points. In conclusion, unlike ibuprofen, valdecoxib 40 mg bid spares platelet COX‐1 function in healthy elderly subjects. Valdecoxibs lack of effect on platelet aggregation and bleeding time suggests that it will have an improved clinical profile over nonselective NSAIDs, particularly in patients for whom bleeding complications are a concern.

A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects

Background : In long‐term outcomes studies, cyclooxygenase COX‐2 specific inhibitors spare COX‐1 at supratherapeutic doses and therefore demonstrate improved gastrointestinal safety over nonspecific nonsteroidal anti‐inflammatory drugs (NSAIDs). However, in clinical practice, anti‐inflammatory drugs are often used for short‐term treatment of pain.