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Article Excerpt
Business Editors/Health & Pharmaceutical Writers
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--March 4, 2002
In a new study designed to examine the analgesic effects of Merck's acute pain medicine Vioxx(R) (rofecoxib), Vioxx 50 mg provided superior pain relief over six hours compared to oxycodone 5 mg combined with acetaminophen 325 mg in patients with moderate to severe acute pain following dental surgery.
The total pain relief score over the first six hours for patients taking Vioxx was 11.7 compared to 5.9 for those who took oxycodone with acetaminophen based on a standard patient response to therapy reporting scale. The study results were presented during the 18th Annual Meeting of the American Academy of Pain Medicine.
The study compared a single dose of Vioxx 50 mg, the recommended dose for the management of acute pain in adults, to a single dose of oxycodone 5 mg combined with acetaminophen 325 mg, and to placebo. For acute pain, Vioxx 50 mg is dosed once daily, as needed. The management of acute pain beyond five days has not been studied. For acute pain in adults, oxycodone with acetaminophen is available in formulations from 2.5/325 mg to 10/650 mg; doses may be repeated every six hours as needed.
A total of 212 patients who experienced moderate to severe acute pain following the surgical removal of at least two wisdom teeth, of which at least one was impacted, were randomly assigned to receive either Vioxx (n=90), oxycodone with acetaminophen (n=91) or placebo (n=31). The primary endpoint of the study was total pain relief over the first six hours after dosing as measured by TOPAR6(1), a measure of overall pain relief. Other measures included patients' assessment of the medicines and the use of additional pain-relieving medicine ("rescue medication"). Patients rated pain intensity and pain relief at prescribed times and recorded time to perceptible pain relief and time to meaningful pain relief. Patients were allowed to take an additional pain reliever during the study if needed, but were encouraged not to do so in the first 90 minutes of the study.
Multiple endpoints evaluated
In this study, Vioxx (rofecoxib) achieved its primary endpoint, reducing pain to a greater degree over six hours compared to oxycodone with acetaminophen. For all measurements, both Vioxx and oxycodone with acetaminophen reduced pain to a greater degree compared to placebo. A second study confirming these results has been completed but not yet presented.
More specifically, results of the study were:
- Overall pain relief (primary endpoint): Vioxx provided significantly greater total pain relief over six hours compared to oxycodone with acetaminophen. The mean TOPAR6 score for Vioxx was 11.7 compared to 5.9 for oxycodone with acetaminophen and 1.9 for placebo (p less than 0.001). Compared to oxycodone with acetaminophen, Vioxx also demonstrated greater peak pain relief. - Initial pain relief: At 30 minutes, the time of initial pain relief measurement, mean pain relief scores statistically favored oxycodone with acetaminophen (p=0.002). - Patient assessment of study medication: Significantly more patients taking Vioxx reported a "very good" or "excellent" response six hours after initial dosing compared to patients taking oxycodone with acetaminophen and compared to patients taking placebo. Of patients taking Vioxx, 62 percent reported a "good" to "excellent" response to the study medication at six hours versus 40 percent of patients taking oxycodone with acetaminophen and 3 percent of patients taking placebo (both p less than 0.001) (oxycodone with acetaminophen versus placebo, p less than 0.001). - Use of additional medication: Over the first six hours post-dosing, significantly fewer patients on Vioxx (37 percent) used additional pain relief medication compared to patients on oxycodone with acetaminophen (68 percent) and compared to patients on placebo (90 percent) (p less than 0.001 for both).
Important Information about Vioxx
In rare cases, serious stomach problems, such as bleeding, can occur without warning symptoms. People who have had an allergic reaction, such as asthma, to Vioxx, aspirin or other arthritis medicines should not take Vioxx. People who have had liver or kidney problems, or are pregnant, should tell their doctors. Also, Vioxx should not be used by women in late pregnancy. Vioxx is not a substitute for aspirin for cardiovascular prophylaxis. Vioxx does not interfere with the effects of low-dose aspirin on platelets.
Common side effects reported in osteoarthritis clinical trials with Vioxx were upper-respiratory infection, diarrhea, nausea and high blood pressure.
Vioxx is approved in the United States for the relief of the signs and symptoms of osteoarthritis, management of acute pain in adults, and treatment of menstrual pain.
Merck & Co., Inc. is a leading research-driven pharmaceutical products and services company. Merck discovers, develops, manufactures and markets a broad range of innovative products to improve human and animal health, directly and through its joint ventures. Merck-Medco manages pharmacy benefits for employers, insurers and other plan sponsors, encouraging the appropriate use of medicines and providing disease management programs.
Full prescribing information for Vioxx(R) is attached and is also available by calling 1-800-546-8173.
(1) TOPAR6, or Total Pain Relief Score over 6 hours, is a time-interval weighted sum of pain relief scores as recorded over the initial 6 hours after taking the study medication, and can range from (no pain relief at all at any time point) to 24 (complete pain relief at all 6 time points).
Vioxx(R) is the Merck registered trademark for rofecoxib.
VERSION: 9183809 - July 2001
VIOXX(R) (rofecoxib tablets and oral suspension)
DESCRIPTION
VIOXX* (rofecoxib) is described chemically as 4-(4-(methylsulfonyl)phenyl)-3-phenyl-2(5H)-furanone. It has the following chemical structure:
(GRAPHIC OMITTED)
Rofecoxib is a white to off-white to light yellow powder. It is sparingly soluble in acetone, slightly soluble in methanol and isopropyl acetate, very slightly soluble in ethanol, practically insoluble in octanol, and insoluble in water. The empirical formula for rofecoxib is C17H14O4S, and the molecular weight is 314.36.
Each tablet of VIOXX for oral administration contains either 12.5 mg, 25 mg, or 50 mg of rofecoxib and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, lactose, magnesium stearate, microcrystalline cellulose, and yellow ferric oxide. The 50 mg tablets also contain red ferric oxide.
Each 5 mL of the oral suspension contains either 12.5 or 25 mg of rofecoxib and the following inactive ingredients: citric acid (monohydrate), sodium citrate (dihydrate), sorbitol solution, strawberry flavor, xanthan gum, and purified water. Added as preservatives are sodium methylparaben 0.13% and sodium propylparaben 0.02%.
CLINICAL PHARMACOLOGY
Mechanism of Action
VIOXX is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of VIOXX is believed to be due to inhibition of prostaglandin synthesis, via inhibition of cyclooxygenase-2 (COX-2). At therapeutic concentrations in humans, VIOXX does not inhibit the cyclooxygenase-1 (COX-1) isoenzyme.
Pharmacokinetics
Absorption
The mean oral bioavailability of VIOXX at therapeutically recommended doses of 12.5, 25, and 50 mg is approximately 93%. The area under the curve (AUC) and peak plasma level (C max) following a single 25-mg dose were 3286 (+/-843) ngohr/mL and 207 (+/-111) ng/mL, respectively. Both Cmax and AUC are roughly dose proportional across the clinical dose range. At doses greater than 50 mg, there is a less than proportional increase in Cmax and AUC, which is thought to be due to the low solubility of the drug in aqueous media. The plasma concentration-time profile exhibited multiple peaks....
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