Patch Formulation May Provide New Option for Clinicians Concerned About
Systemic Exposure When Using an Oral NSAID
TAMPA, Fla., May 8 /PRNewswire-FirstCall/ -- Alpharma Inc. (NYSE: ALO), a leading global specialty pharmaceutical company, announced today that two studies to be presented this week at the American Pain Society annual meeting demonstrate the efficacy, tolerability and positive pharmacokinetic profile of Alpharma Pharmaceuticals' FLECTOR(R) Patch (diclofenac epolamine topical patch) 1.3%, the first and only prescription anti-inflammatory pain relief patch in the United States. FLECTOR(R) Patch has been available since January in the United States for the topical treatment of acute pain due to minor strains, sprains and contusions.
Results of one study, to be presented Friday, May 9, show that FLECTOR(R) Patch offered greater pain reduction and resolution of pain versus placebo patch. Results of another study, to be presented Thursday, May 8, demonstrate that the systemic exposure to diclofenac, or amount of active drug circulating in the bloodstream, with FLECTOR(R) Patch used topically every 12 hours over a period of four days was approximately 1 percent of a single 50-mg oral dose of the non-steroidal anti-inflammatory drug (NSAID) Voltaren(R) (diclofenac sodium enteric-coated tablets).
"Many physicians and patients would prefer a targeted approach to treating pain at the site of an injury, for a number of reasons," said Joseph W. Stauffer, D.O., Chief Medical Officer, Senior Vice President, Clinical Research and Medical Affairs, Alpharma Pharmaceuticals. "In addition to supporting the effectiveness of FLECTOR(R) Patch in reducing pain, these data confirm that the targeted delivery of FLECTOR(R) Patch results in minimal systemic absorption of diclofenac, one of the best selling and most widely used orally administered NSAIDs worldwide."
Acute pain is a common problem, with one in four adult Americans suffering an episode of pain lasting longer than 24 hours.(1)
Efficacy and Tolerability of FLECTOR(R) Patch in the Treatment of Minor Soft Tissue Injury Pain (Abstract #8332/Poster #278)(2)
The efficacy and tolerability of FLECTOR(R) Patch was evaluated in a randomized, double-blind, placebo-controlled, parallel-group trial of 418 patients, aged 18-65 years who rated the minor soft tissue injuries they sustained within seven days of study entry as having a pain intensity of greater than or equal to five on a zero to 10 scale. Patients self-administered FLECTOR(R) Patch every 12 hours to the injury site. The primary study outcome was post-treatment pain, expressed as a proportion of the baseline pain score, which was recorded on a visual analog scale of zero to 10 in a diary, twice-daily for 14 days, or until pain resolution. The secondary study outcomes included end-of-treatment Investigator Global Assessment of Response to Therapy (a five-point scale, "none" to "excellent"), and time to pain resolution (four scores less than or equal to two).
Patients treated with FLECTOR(R) Patch experienced improved mean pain scores (40.4 percent of baseline score) versus patients using placebo patch (47.4 percent, p<0.05); overall pain reduction was 14.8 percent. FLECTOR(R) Patch patients also reached pain resolution three days sooner than those in the placebo patch group (median, 10.0 versus 13.5 days, p=0.01). Additionally, at the conclusion of the study, the Investigator Global Assessment of Response to Therapy significantly favored the FLECTOR(R) Patch: patient response to treatment was rated "good" to "excellent" for 57.8 percent of FLECTOR(R) Patch patients, versus 48.4 percent of placebo patch patients, and a "no"/"poor" response was given for only 24 percent of FLECTOR(R) Patch patients versus 34.4 percent of placebo patch patients (p<0.01).
Of the 418 patients randomized in the study, 49.3 percent were men and 99.5 percent were white. The mean age of the study participants was 38.9 years. The most common injuries reported were contusions (42.6 percent), strains (31.1 percent), and sprains (24.4 percent); the most common injury sites were ankle, shoulder, knee and foot (67.3 percent). Efficacy was evaluated in 384 (91.9 percent) patients (greater than or equal to one post- baseline pain assessment). Adverse events were similar between FLECTOR(R) Patch and placebo patch; the most common were application-site conditions, generally of mild severity (FLECTOR(R) Patch 7.9 percent, placebo patch 5.8 percent). The study was supported by a grant from Alpharma Pharmaceuticals LLC.
Comparison of Plasma Pharmacokinetics of FLECTOR(R) Patch and Oral Voltaren(R) in Healthy Volunteers (Abstract #8383/Poster #279)(3)
In order to compare the bioavailability of two formulations containing diclofenac, FLECTOR(R) Patch and Voltaren(R), a single-center, open-label, crossover study was conducted in 24 healthy volunteers. All study subjects received one FLECTOR(R) Patch every 12 hours for four consecutive days; 12 study subjects received a single 50-mg oral dose of Voltaren(R) in a two-way crossover fashion. Blood was collected at selected times post-dose to determine diclofenac plasma levels.
Results indicated that the systemic exposure to diclofenac with topical FLECTOR(R) Patch at a steady state (every 12 hours for four days) was approximately 1 percent of a single dose of Voltaren(R) (50-mg oral).
The study included an equal number of males and females, all Caucasian, with a mean age of 24.1 years. Subjects were required to have no skin disorders or abnormalities at the patch application site. Mean Cmax for FLECTOR(R) Patch (steady state) was 1.7 plus or minus 0.9ng/mL versus Voltaren(R) (single dose), 1214 plus or minus 750ng/mL. Area under the plasma concentration curve (AUC) for zero to 12 hours was FLECTOR(R) Patch at 15.2 plus or minus 6.9ng*h/mL versus Voltaren(R), 1754 plus or minus 1060 ng*h/mL. The dose-adjusted relative percent bioavailability of diclofenac after treatment with FLECTOR(R) Patch versus Voltaren(R) was 0.7 plus or minus 0.4 (i.e., <1 percent). The study was supported by a grant from Alpharma Pharmaceuticals LLC.
About FLECTOR(R) Patch
Each FLECTOR(R) Patch measures approximately 4 inches by 5.5 inches and contains 180-mg of diclofenac epolamine, which has demonstrated both anti-inflammatory and analgesic (pain-relieving) activities. The recommended dose of FLECTOR(R) Patch is one patch to the most painful area twice a day (12 hours at a time). FLECTOR(R) Patch should be applied to intact or non-damaged skin.
Although the prescribing information does not specify a limit on the duration of use for FLECTOR(R) Patch, it recommends that FLECTOR(R) Patch be used at the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
FLECTOR(R) Patch delivers significant pain relief with rates of common adverse events with FLECTOR(R) Patch similar to placebo patch observed in clinical trials for up to two weeks with approximately 600 patients. In addition, the incidence of gastrointestinal side effects such as nausea and upset stomach were comparable to placebo patch.
In the clinical trials, 3 percent of patients in both the FLECTOR(R) Patch and placebo patch groups discontinued treatment due to an adverse event. The most common adverse events leading to discontinuation were application site reactions, occurring in 2 percent of both the FLECTOR(R) Patch group and the placebo patch group.
Outside the U.S., the diclofenac patch has an extensive track record of
safety, having been introduced in Switzerland in 1993, and is currently
approved in 43 countries. FLECTOR(R) Patch has been used in more than six
million patients with a total of approximately 175 million patches
Important Safety Information
-- NSAIDs may cause an increased risk of serious cardiovascular thrombotic
events, myocardial infarction, and stroke, which can be fatal. This
risk may increase with duration of use. Patients with cardiovascular
disease or risk factors for cardiovascular disease may be at greater
-- FLECTOR(R) Patch is contraindicated for the treatment of peri-operative
pain in the setting of coronary artery bypass graft (CABG) surgery.
-- NSAIDs cause an increased risk of serious gastrointestinal adverse
events including bleeding, ulceration, and perforation of the stomach
or intestines, which can be fatal. These events can occur at any time
during use and without warning symptoms. Elderly patients are at
greater risk for serious gastrointestinal events.
Carefully consider the potential benefits and risks of FLECTOR(R) Patch and other treatment options before deciding to use FLECTOR(R) Patch.
FLECTOR(R) Patch is contraindicated in patients with known hypersensitivity to diclofenac. FLECTOR(R) Patch should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
FLECTOR(R) Patch should not be applied to non-intact or damaged skin resulting from any etiology, eg, exudative dermatitis, eczema, infected lesion, burns or wounds.
NSAIDs, including FLECTOR(R) Patch, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
In late pregnancy, as with other NSAIDs, FLECTOR(R) Patch should be avoided because it may cause premature closure of the ductus arteriosus. Please see complete prescribing information for FLECTOR(R) Patch available at http://www.FlectorPatch.com.
Alpharma press releases are also available at our website: http://www.alpharma.com.
Alpharma Inc. (NYSE: ALO) is a global specialty pharmaceutical company with leadership positions in products for humans and animals. Alpharma is presently active in more than 80 countries. Alpharma has a growing branded pharmaceutical franchise in the U.S. pain market with its KADIAN(R) (morphine sulfate extended-release) Capsules, and the FLECTOR(R) Patch (diclofenac epolamine topical patch) 1.3%. Alpharma is also internationally recognized as a leading provider of pharmaceutical products for poultry and livestock.
Voltaren(R) is a registered trademark of a third party.
ALPHARMA(R) is a registered trademark of Alpharma Inc.
(C)2008 Alpharma Pharmaceuticals LLC. All rights reserved.
FLECTOR(R) is a registered trademark of Institut Biochimique SA.
(1) National Center for Health Statistics. Health, United States, 2006.
With Chartbook on Trends in the Health of Americans. Hyattsville, MD:
2006. (Reporting on data from 1999-2002)
(2) Carr, et al. "Efficacy and tolerability of FLECTOR(R) Patch
(diclofenac epolamine topical patch) in the treatment of minor soft
tissue injury pain." Abstract #8332. Presented May 9, 2008, at the
American Pain Society 27th Annual Meeting. (3) Rusca, et al.
"Comparison of plasma pharmacokinetics of FLECTOR(R) Patch (diclofenac
epolamine topical patch) and oral Voltaren(R) (diclofenac sodium
enteric-coated tablets) in healthy volunteers."
Abstract #8383. Presented May 8, 2008, at the American Pain Society
27th Annual Meeting.
|SOURCE Alpharma Inc.|
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