Diclofenac Epolamine Topical Patch Research Articles

Randomized, open-label, 5-way crossover study to evaluate the pharmacokinetic/pharmacodynamic interaction between furosemide and the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen in healthy volunteers

Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce renal complications in patients taking loop diuretics. This study investigated the pharmacokinetic/pharmacodynamic effects and safety profile of orally administered diclofenac sodium, ibuprofen and diclofenac epolamine topical patch (DETP) on furosemide in healthy adult subjects. This open-label, randomized, 5-way crossover study was conducted in 40 subjects (aged 19 - 45 y). Diclofenac (75 mg taken orally twice daily), DETP (1.3% applied topically twice daily), or ibuprofen (800 mg taken orally thrice daily) was administered for 3 consecutive days, followed by co-administration with furosemide (given intravenously as 20 mg/2 min). Plasma furosemide and NSAID concentrations, urine furosemide, sodium and potassium concentrations and urine output were determined throughout the 24 h period following furosemide administration. Orally administered ibuprofen significantly increased furosemide AUC(0-t) (37%) and AUC(0-inf) (36%) and decreased total body CL (27%), R(max) (19%) and CLR (23%) geometric mean ratios compared with furosemide control. Oral and topical diclofenac had no pharmacokinetic effects on furosemide. Ibuprofen increased sodium excretion (Ae(0-24), 16%) and decreased sodium R(max) (15%), and oral diclofenac decreased urine output (Vu(0-24), 15%). DETP had no effect on furosemide pharmacodynamics; total systemic exposure to diclofenac during DETP treatment was < 1% that of oral diclofenac. Treatments were generally safe, with 25 subjects reporting a total of 112 adverse events. Pharmacodynamic effects were seen with oral diclofenac (urine output) and ibuprofen (urine sodium excretion). Furosemide also affected plasma and urine pharmacokinetic profiles. Pharmacologic effects of DETP on furosemide were not observed under these conditions. Additional research is warranted to delineate the potential interactions of other NSAIDs with furosemide and other loop diuretics.

Pooled analysis of clinical trial data evaluating the safety and effectiveness of diclofenac epolamine topical patch 1.3% for the treatment of acute ankle sprain

This pooled analysis assessed the efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) for the treatment of acute mild-to-moderate ankle sprain. Data from 2 randomized, double-blind, placebo-controlled studies enrolling 274 male and female patients aged 18 to 65 years with acute ankle sprain were pooled and evaluated. The primary end point was pain reduction on movement assessed using a 100 mm visual analog scale (VAS). Safety and tolerability were also assessed. Beginning approximately 3 hours after initial treatment, DETP-treated patients experienced statistically significant and sustained lower mean VAS scores in pain intensity on movement (mean ± SD, 54.1 ± 20.0 mm versus 60.3 ± 16.8 mm) compared with placebo-treated patients, representing a 20% versus 13% reduction in VA S pain scores from baseline (P = 0.012). This statistically significant difference in mean VAS score was maintained through day 7 (9.4 ± 14.4 mm versus 18.4 ± 18.2 mm, P < 0.0001). The DETP and placebo patches were well tolerated. These results further confirm the efficacy and safety of DETP for the treatment of acute pain from ankle sprains.

Gastrointestinal Tolerability of Diclofenac Epolamine Topical Patch 1.3%: A Pooled Analysis of 14 Clinical Studies

Objective: The purpose of this investigation was to evaluate the gastrointestinal (GI) tolerability profile of diclofenac epolamine topical patch 1.3% (DETP) during short-term treatment in patients with mild-to-moderate pain. Design: Fourteen clinical trials of DETP were examined; 10 placebo-controlled studies were further integrated for analyses. All adverse event (AE) data were coded to the Medical Dictionary for Regulatory Activities. Outcome Measures: Frequency of GI AEs was summarized by treatment, preferred term, sex, and age group. Results: The percentage of patients reporting GI AEs were similar between patients treated with the DETP and placebo, with only 3 of the 10 placebo-controlled trials reporting events in > 2% of patients; there was no significant difference between DETP and placebo for any preferred GI term. The most common GI AE reported for both treatment groups was nausea (1.5% DETP, 1.1% placebo). There was no significant difference between treatment groups and sex in the number of reported events and no noted difference between age groups. Conclusion: This study provides evidence that DETP is a topical nonsteroidal anti-inflammatory drug that is a well-tolerated treatment option, demonstrating a low incidence of GI AEs across 14 clinical trials, making it a possible alternative to short-term oral NSAIDs, which are commonly associated with GI complications.

Analgesic Efficacy and Safety of the Diclofenac Epolamine Topical Patch 1.3% (DETP) in Minor Soft Tissue Injury

The diclofenac epolamine topical patch 1.3% was designed to deliver analgesic concentrations of diclofenac to an underlying soft tissue injury site, while limiting systemic exposure to diclofenac. This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of the diclofenac epolamine topical patch for the treatment of acute pain due to minor soft tissue injury. Patients (18-65 years, inclusive) with clinically significant minor soft tissue injuries (mild or moderate sprain, strain, or contusion) incurred within 7 days of study entry and having pain scores ≥ 5 on a Visual Analog Scale of 0-10 were enrolled. Patients were randomized to receive the diclofenac epolamine topical patch (n=207) or placebo patch (n=211) application twice daily for 14 days or until pain resolution. Patients recorded pain scores every 12 h at the time of patch removal using the Visual Analog Scale. Investigator-assessed global response to therapy was also evaluated. Safety data were collected throughout the study. Twice-daily treatment with diclofenac epolamine topical patch produced a statistically significant reduction in mean pain score relative to baseline by an additional 18.2% in the diclofenac epolamine topical patch group (0.435 ± 0.268) compared with the placebo group (0.532 ± 0.293) (p=0.002; overall) beginning after application of the second patch. Consistent with this treatment effect, median time to pain resolution was shortened by 2 days in the diclofenac epolamine topical patch group relative to the placebo group (p=0.007). These results were reinforced independently by investigators who reported treatment as good or excellent for 58% of diclofenac epolamine topical patch-treated patients compared with 49% in the placebo patch group (p=0.008). The most common adverse events were treatment site related (n=16, 7.9% diclofenac epolamine topical patch; n=12, 5.8% placebo patch). Most (80%) patients reported tolerability as excellent or good. In conclusion, the diclofenac epolamine topical patch provides effective, rapid pain relief for the treatment of acute pain from minor soft tissue injury and appears generally safe and well tolerated.

Pharmacokinetic and pharmacodynamic interaction between furosemide and the nonsteroidal anti-inflammatory drugs diclofenac and ibuprofen

Nonsteroidal anti-inflammatory drugs (NSAIDs) may blunt anti-hypertensive effects and alter renal-function of loop-diuretics.1,2 An open-label study in healthy volunteers (N=40) compared the pharmacokinetic/pharmacodynamic (PK/PD) profiles of furosemide administered intravenously (IV) alone (20mg/2min) vs after oral ibuprofen (800mg TID), oral diclofenac sodium (75mg BID), or topical diclofenac epolamine topical patch 1.3% (DETP) BID.3 Dextrose (5% in water) administered IV at 2mL/2min served as negative control. NSAIDs were administered for 3 days followed by 20mg furosemide IV on day-4. Plasma furosemide and NSAID, and urine furosemide, sodium, potassium, and prostaglandin E2 (PGE2) concentrations were measured at multiple intervals through 24h after furosemide-dose. Interactions between NSAIDs and furosemide vs furosemide alone were concluded if 90% confidence intervals (CIs) for ratios of PK/PD measures fell outside 80%-125%. Ibuprofen yielded greater furosemide systemic-exposure (AUC0-t, % mean ratio 137.2 [CIs 131.7-143.0]; AUCinf, 136.1 [131.2-141.1]), and decreased total body-clearance (CL 73.5 [70.9-76.2]), renal-clearance (CLR 76.6 [72.4-81.1]), and maximum excretion-rate (Rmax 81.3 [76.7-86.1]). Ibuprofen increased urine sodium-excretion (Ae0-24) and decreased Rmax (p<0.01); mean ratios and 90% CI ranges supported an interactive effect with furosemide. Oral diclofenac sodium and DETP had no clinically significant effect on furosemide PK. Oral diclofenac sodium decreased urine-output (14%, p=0.005; Vu0-24 84.7 [76.9-93.2]). DETP did not affect furosemide PD in any clinically significant manner. Urine PGE2 concentrations fell below the level of quantification (30pg/mL) following furosemide-administration. At steady-state, systemic-exposure to diclofenac after DETP was <1% vs oral diclofenac sodium (16.0 vs 2164 ng•h/mL). Overall, oral ibuprofen affected furosemide PK and PD; oral diclofenac sodium affected PD; and DETP did not affect PK or PD in healthy subjects. Additional drug-interaction studies between NSAIDs and loop-diuretics are needed to identify interactions and determine clinical significance. Research supported by King Pharmaceuticals®, Inc. (1. Brater, Am J Medicine, 1986; 2. Müller, Eur J Clin Pharmacol, 1995; 3. Flector Patch PI, 2009). Nonsteroidal anti-inflammatory drugs (NSAIDs) may blunt anti-hypertensive effects and alter renal-function of loop-diuretics.1,2 An open-label study in healthy volunteers (N=40) compared the pharmacokinetic/pharmacodynamic (PK/PD) profiles of furosemide administered intravenously (IV) alone (20mg/2min) vs after oral ibuprofen (800mg TID), oral diclofenac sodium (75mg BID), or topical diclofenac epolamine topical patch 1.3% (DETP) BID.3 Dextrose (5% in water) administered IV at 2mL/2min served as negative control. NSAIDs were administered for 3 days followed by 20mg furosemide IV on day-4. Plasma furosemide and NSAID, and urine furosemide, sodium, potassium, and prostaglandin E2 (PGE2) concentrations were measured at multiple intervals through 24h after furosemide-dose. Interactions between NSAIDs and furosemide vs furosemide alone were concluded if 90% confidence intervals (CIs) for ratios of PK/PD measures fell outside 80%-125%. Ibuprofen yielded greater furosemide systemic-exposure (AUC0-t, % mean ratio 137.2 [CIs 131.7-143.0]; AUCinf, 136.1 [131.2-141.1]), and decreased total body-clearance (CL 73.5 [70.9-76.2]), renal-clearance (CLR 76.6 [72.4-81.1]), and maximum excretion-rate (Rmax 81.3 [76.7-86.1]). Ibuprofen increased urine sodium-excretion (Ae0-24) and decreased Rmax (p<0.01); mean ratios and 90% CI ranges supported an interactive effect with furosemide. Oral diclofenac sodium and DETP had no clinically significant effect on furosemide PK. Oral diclofenac sodium decreased urine-output (14%, p=0.005; Vu0-24 84.7 [76.9-93.2]). DETP did not affect furosemide PD in any clinically significant manner. Urine PGE2 concentrations fell below the level of quantification (30pg/mL) following furosemide-administration. At steady-state, systemic-exposure to diclofenac after DETP was <1% vs oral diclofenac sodium (16.0 vs 2164 ng•h/mL). Overall, oral ibuprofen affected furosemide PK and PD; oral diclofenac sodium affected PD; and DETP did not affect PK or PD in healthy subjects. Additional drug-interaction studies between NSAIDs and loop-diuretics are needed to identify interactions and determine clinical significance. Research supported by King Pharmaceuticals®, Inc. (1. Brater, Am J Medicine, 1986; 2. Müller, Eur J Clin Pharmacol, 1995; 3. Flector Patch PI, 2009).

Diclofenac epolamine topical patch relieves pain associated with ankle sprain

Background:Sports-related injuries, such as sprains and strains, commonly occur during exercise and athletic events. Current therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs), which have a high incidence of upper gastrointestinal side effects. The present study assessed the efficacy and safety of the diclofenac epolamine topical patch (DETP, 1.3%), a topical NSAID for the treatment of acute minor sprains and strains.Methods:This multicenter, randomized, placebo-controlled clinical study enrolled adult patients (n = 134) with acute ankle pain (due to a minor sprain) occurring less than 48 hours prior to entering the study. Patients were treated with either the DETP or a placebo topical patch daily for seven days. Pain intensity was evaluated during the first six hours after application of the patch, and on treatment days 1, 2, 3, and 7.Results:Patients treated with the DETP experienced a significantly greater reduction in pain associated with their ankle injury compared with placebo, beginning four hours after the first patch application (P = 0.02). The DETP was well tolerated and was comparable with placebo in terms of safety.Conclusion:Overall, the results of this study demonstrate that the DETP is an effective analgesic for local treatment of pain in mild acute ankle sprain.

Effectiveness and Safety of Diclofenac Epolamine Topical Patch 1.3% for the Treatment of Acute Pain Due to Back Strain: An Open-Label, Uncontrolled Study

The diclofenac epolamine topical patch 1.3% (DETP) is indicated for topical treatment of acute pain due to minor strains, sprains, and contusions. This exploratory, multicenter, open-label study evaluated effectiveness and safety of DETP in patients with acute pain due to back strain. Patients aged ≥ 18 years with acute pain due to nonradicular back strain with an average pain intensity of ≥ 4 (0 = no pain, 10 = pain as bad as you can imagine) entered a 3-day observation/washout period and completed daily diary modified Brief Pain Inventory assessments. At baseline, patients with an average pain intensity of ≥ 4 started DETP treatment (q12h). Patients were treated for 7 or 14 days, depending on investigator and patient assessment of pain resolution. Primary endpoint was mean change from baseline to end of treatment in average pain intensity. Key secondary endpoints included changes from baseline in least, worst, and current pain scores and Beck Depression Inventory(®) II scores. Patients and investigators assessed patch satisfaction and global pain relief. In 123 enrolled patients, baseline mean ± standard deviation average pain score was 6.5 ± 1.3, which decreased to 2.5 ± 2.4 (P < 0.0001) at end of treatment. Similarly, least, worst, and current pain scores were also reduced (P < 0.0001). Sixty-three percent of patients achieved ≥ 50% pain reduction from baseline. At the end of treatment, most patients (88%) were satisfied or very satisfied with DETP. For 85% of patients, investigators also reported being satisfied or very satisfied with DETP. Most patients (87%) and investigators (88%, rating the patient's response) rated global pain relief as moderate to complete. Fifteen patients experienced a total of 19 adverse events (AEs), 17 of which were mild to moderate, and 2 of which were severe. Three AEs were treatment related (application site rash, nausea, and tachycardia); 1 patient had a serious AE (noncardiac chest pain) considered unrelated to DETP. In this exploratory study, patients experienced well-tolerated relief for acute pain due to back strain, with ≥ 85% of patients and their investigators expressing satisfaction with DETP treatment.

Effectiveness and Safety of Diclofenac Epolamine Topical Patch 1.3% for the Treatment of Acute Pain Due to Back Strain: An Open-Label, Uncontrolled Study

Background: The diclofenac epolamine topical patch 1.3% (DETP) is indicated for topical treatment of acute pain due to minor strains, sprains, and contusions. This exploratory, multicenter, open-label study evaluated effectiveness and safety of DETP in patients with acute pain due to back strain. Methods: Patients aged ≥ 18 years with acute pain due to nonradicular back strain with an average pain intensity of ≥ 4(0 = no pain, 10 = pain as bad as you can imagine) entered a 3-day observation/washout period and completed daily diary modified Brief Pain Inventory assessments. At baseline, patients with an average pain intensity of ≥ 4 started DETP treatment (q12h). Patients were treated for 7 or 14 days, depending on investigator and patient assessment of pain resolution. Primary endpoint was mean change from baseline to end of treatment in average pain intensity. Key secondary endpoints included changes from baseline in least, worst, and current pain scores and Beck Depression Inventory® II scores. Patients and investigators assessed patch satisfaction and global pain relief. Results: In 123 enrolled patients, baseline mean ± standard deviation average pain score was 6.5 ± 1.3, which decreased to 2.5 ± 2.4 (P < 0.0001) at end of treatment. Similarly, least, worst, and current pain scores were also reduced (P < 0.0001). Sixty-three percent of patients achieved ≥ 50% pain reduction from baseline. At the end of treatment, most patients (88%) were satisfied or very satisfied with DETP. For 85% of patients, investigators also reported being satisfied or very satisfied with DETP. Most patients (87%) and investigators (88%, rating the patient's response) rated global pain relief as moderate to complete. Fifteen patients experienced a total of 19 adverse events (AEs), 17 of which were mild to moderate, and 2 of which were severe. Three AEs were treatment related (application site rash, nausea, and tachycardia); 1 patient had a serious AE (noncardiac chest pain) considered unrelated to DETP. Conclusion: In this exploratory study, patients experienced well-tolerated relief for acute pain due to back strain, with ≥ 85% of patients and their investigators expressing satisfaction with DETP treatment.

Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions.

Update on the Use of Topical NSAIDs for the Treatment of Soft Tissue and Musculoskeletal Pain: A Review of Recent Data and Current Treatment Options

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have an emerging role in the treatment of certain types of acute pain. In addition to their convenience, efficacy, and safety, they are an attractive option, particularly when considering current concerns about the safety of traditional NSAIDs and cyclooxygenase-2 (COX-2) inhibitors (coxibs). Topical analgesics act largely within the peripheral nervous system. Studies have demonstrated that topical NSAIDs penetrate the skin and distribute to the target tissues underlying the application site. Because the pharmacologically effective dose is delivered at the site of pain, there is minimal systemic absorption and risk of related adverse events. Topical NSAIDs have been used for many years in Europe, with extensive post-marketing data available for some of the agents. Three topical NSAID formulations have recently been approved for use in the United States: the diclofenac epolamine topical patch 1.3% (DETP), diclofenac sodium 1% gel, and diclofenac sodium topical solution 1.5%. Topical NSAIDs provide a therapeutic option for treatment of acute, localized, soft tissue injuries or painful conditions in areas of the body that can be readily treated using the topical route of administration. This article reviews available data on the use of topical NSAID therapy.

Poster 239: Efficacy of Diclofenac Epolamine Topical Patch in the Treatment of Mild to Moderate Acute Pain Due to Ankle Sprain

Poster 239: Efficacy of Diclofenac Epolamine Topical Patch in the Treatment of Mild to Moderate Acute Pain Due to Ankle Sprain

104: Time to Resolution of Pain from Minor Soft Tissue Injury With Diclofenac Epolamine Topical Patch

104: Time to Resolution of Pain from Minor Soft Tissue Injury With Diclofenac Epolamine Topical Patch

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Treatment of Minor Soft Tissue Injury Using Diclofenac Epolamine Topical Patch.

Treatment of Minor Soft Tissue Injury Using Diclofenac Epolamine Topical Patch.

Efficacy and Tolerability of Diclofenac Epolamine Topical Patch for Treatment of Minor Soft-Tissue Injury Pain

Efficacy and Tolerability of Diclofenac Epolamine Topical Patch for Treatment of Minor Soft-Tissue Injury Pain

(279) Comparison of plasma pharmacokinetics of FLECTOR Patch (diclofenac epolamine topical patch) and oral Voltaren (diclofenac sodium enteric-coated tablets) in healthy volunteers

(279) Comparison of plasma pharmacokinetics of FLECTOR Patch (diclofenac epolamine topical patch) and oral Voltaren (diclofenac sodium enteric-coated tablets) in healthy volunteers

(278) Efficacy and tolerability of FLECTOR Patch (diclofenac epolamine topical patch) in the treatment of minor soft tissue injury pain

(278) Efficacy and tolerability of FLECTOR Patch (diclofenac epolamine topical patch) in the treatment of minor soft tissue injury pain