Topical Patch Research Articles

Skin permeability and pharmacokinetics of diclofenac epolamine administered by dermal patch in Yorkshire-Landrace pigs

PurposeThis study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire-Landrace pigs.Patients and methodsTwelve anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either the dermal patch (FLECTOR® patch, 10 × 14 cm; Alpharma Pharmaceuticals, a subsidiary of Pfizer Inc, New York, NY) or 50 mg oral diclofenac (Voltaren®; Novartis, East Hanover, NJ). Tissue (skin area of 2 × 2 cm and underlying muscles approximately 2–3 cm in depth) and blood (10 mL) samples were collected at timed intervals up to 11.5 hours after initial patch application or oral administration. The concentrations of diclofenac in plasma, skin, and muscle samples were analyzed using validated ultra performance liquid chromatography tandem mass spectrometric methods.ResultsPeak systemic exposure of diclofenac was very low by dermal application compared with oral administration (maximum concentration [Cmax] values of 3.5 vs 9640 ng/mL, respectively). Absorption of diclofenac into underlying muscles beneath the dermal patch was sustained, and followed apparently zero-order kinetics, with the skin serving as a depot with elevated concentrations of diclofenac. Concentrations of diclofenac in muscles beneath the patch application site were similar to corresponding tissues after oral administration (Cmax values of 879 and 1160 ng/mL, respectively). In contrast to the wide tissue distribution of diclofenac after oral administration, dermal patch application resulted in high concentrations of diclofenac only on the treated skin and immediate tissue underneath the patch. Low concentrations of diclofenac were observed in the skin and muscles collected from untreated areas contralateral to the site of dermal patch application.ConclusionDermal patch application resulted in low systemic absorption and high tissue penetration of diclofenac compared with oral administration.

Validation of the Self-Assessment of Treatment Questionnaire among Patients with Postherpetic Neuralgia

Introduction. A five-item Self-Assessment of Treatment (SAT) was developed to assess improvement and satisfaction with treatment associated with the application of a novel high concentration 8% capsaicin topical patch in clinical trials in patients with postherpetic neuralgia (PHN). This study evaluated the item performance and psychometric properties of the SAT. Methods. The SAT, Brief Pain Inventory, SF-36v2, Short-Form McGill Pain Questionnaire, and Patient and Clinician Global Impression of Change (PGIC; CGIC) scores were measured in two 12-week Phase 3 clinical trials. Factor analysis assessed the underlying factor structure, followed by examination of the reliability and validity of the multi-item domain. Results. Pooled data from 698 patients completing SAT after 12 weeks of treatment were analyzed. A one-factor model combining three of the five items emerged as the optimal solution. Internal consistency reliability of this treatment efficacy factor was high (Cronbach's alpha = 0.89). Construct validity was demonstrated by moderate to high correlations with change in other study endpoints. SAT mean scores consistently discriminated between patient change groups defined by PGIC and CGIC. Conclusions. The measurement properties of the three-item version of SAT are valid and reliable for assessment of treatment with a high concentration capsaicin patch among patients with PHN.

Treatment for Postoperative Wound Pain in Gynecologic Laparoscopic Surgery: Topical Lidocaine Patches

This article reports our early experience with the use of lidocaine patches for pain control in the immediate postoperative period after laparoscopic gynecologic surgery. A prospective, double-blind, placebo-controlled clinical trial was conducted on 40 patients undergoing a gynecologic laparoscopy who were randomized to receive either topical patches of 700 mg of lidocaine (n=20) or placebo patches (n=20). The patch was divided evenly into four smaller patches, which were applied at the four port sites and changed every 12 hours for 36 hours after surgery. Postoperative pain was evaluated using the visual analog scale (VAS) score and the Prince Henry and 5-point verbal rating pain scale (VRS), and the analgesic requirement was also evaluated at 1, 6, 12, 24, and 36 hours after surgery. The VAS score for wound pain was lower in the lidocaine patch group at 1 and 6 hours after surgery than the control group (P=.005 and <.0005, respectively). The VAS scores for postoperative pain were lower in the lidocaine patch group at rest 1 hour after surgery (P=.045). The 5-point VRS score for postoperative pain was lower in the lidocaine patch group at 6 and 12 hours after surgery (P=.015 and .035, respectively) than in the control group. Topical lidocaine patches at the laparoscopic port sites reduced postoperative pain, particularly postoperative wound pain after gynecological laparoscopic procedures.

Treatment with topical capsaicin: Experience from a pain clinic

Abstract Background Neuropathic pain is usually treated with antidepressants and anticonvulsant. The use of systemic treatment is, however, limited due to poor tolerability and low efficacy. Qutenza, a topical capsaicin patch (8%), is a relatively new treatment for patients with peripheral neuropathic pain (PNP) conditions. The indication for using topical capsaicin treatment is peripheral neuropathic pain in patients without diabetes. Aim To describe the use of topical capsaicin treatment in a pain clinic in patients with PNP. Methods Case series of patients in a neuropathic pain clinic. Results Since October 2010, 40 patients with PNP with different aetiologies have been treated with topical capsaicin; 14 patients had nerve injuries in feet or lower leg or polyneuropathy, 13 patients had nerve lesions related to fingers, hands or arms, seven patients had pain after thoracotomy, four patients postherpetic neuralgia, and two patients had other lesions. Almost half of the patients (47%) were responders and achieved a decrease in pain intensity as well as increased their quality of life (QoL). Responders received 1–6 treatments with capsaicin. Most responders were found in the post-thoracotomy group, of which 86% had a clinical significant reduction in pain. In the group with injuries to the hands, fingers and arms, 46% experienced a reduction in pain. Only 23% of patients with PNP in the feet and lower leg were responders; these patients had a clinical significant increase in QoL. Conclusion In 40 patients with PNP who were treated with topical capsaicin, we found an increase in QoL and a decrease in mean pain intensity of 3 measured on a VAS scale (0–10) in 47% of the treated patients.

Trigeminal postherpetic neuralgia responsive to treatment with capsaicin 8 % topical patch: a case report

Postherpetic neuralgia has been variably defined but is generally understood to be pain that persists for longer than a few months after an attack of herpes zoster. Pain persists for years in approximately 10 % of those afflicted with acute herpes zoster. The likelihood of postherpetic neuralgia increases with older age, severity of the zoster, trigeminal location, and other factors. Postherpetic neuralgia is a neuropathic pain and treatment usually involves sequential trials of topical and systemic drugs; a variety of other therapies may be considered in refractory cases. A new topical capsaicin 8 % patch has been approved for this indication based on the positive studies in patients with non-trigeminal postherpetic neuralgia. Experience with the use of the capsaicin 8 % patch for trigeminal distribution neuralgia is lacking. We report a case of trigeminal postherpetic neuralgia which was safely and effectively treated with capsaicin 8 % patch.

Addition of UVA-absorber butyl methoxy dibenzoylmethane to topical ketoprofen formulation reduces ketoprofen-photoallergic reaction

Topical application of ketoprofen (KP) clinically evokes the allergic type of photocontact dermatitis. To avoid this adverse reaction, we investigated the beneficial effect of each ultraviolet (UV) filter that was included in topical ketoprofen formulation. We first tested the inhibitory effects of four UVA filters by a modified local lymph node assay following KP application on the mouse skin and UVA irradiation on the same site. In this assessment, butyl methoxy dibenzoylmethane (BMDBM), when included in KP application, exerted the most effective inhibitory effect on stimulation with KP and UVA. We manufactured topical patch and gel KP applicants containing BMDBM, which retained KP penetration through the skin and KP stability toward UVA. The ability of BMDBM in these formulations to inhibit KP photosensitivity was evaluated by a modified adjuvant and strip method in guinea pigs, and the photoallergic reactions induced by the BMDBM-containing KP applicants were lower than the non-containing ones. It is known that KP has a cross-reactivity with benzophenone upon UVA exposure, but such a photocross-reactivity of BMDBM with KP was not observed in a mouse ear swelling model. The anti-inflammatory effect of the BMDBM-containing KP patch applicant was comparable to the non-containing one. These results suggest that the addition of BMDBM into KP topical formulations is efficacious for inhibition of KP photocontact dermatitis.

Possible role of sodium channels and NMDA receptors in painful patellar tendinopathy: an open-label pilot study using a heated lidocaine/tetracaine topical patch

Possible role of sodium channels and NMDA receptors in painful patellar tendinopathy: an open-label pilot study using a heated lidocaine/tetracaine topical patch

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.

Intravenous Lidocaine for Acute Pain Treatment

Lidocaine’s versatility is seen in the many routes by which it can be administered. It is given topically or by infiltration for procedural pain, such as for venous punctures and laceration repairs, and is available in a topical patch formulation for peripheral types of pain, such as postherpetic neuralgia. Lidocaine may be delivered epidurally and by single injection or continuous peripheral nerve block infusion. It has been administered for many years by the intravenous (IV) route for regional anesthesia (Bier block) for surgical procedures and increasingly by brief IV infusion as a third-line option for the treatment of refractory neuropathic and postoperative pain.

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.

Biphasic Vesicles for Topical Delivery of Interferon Alpha in Human Volunteers and Treatment of Patients with Human Papillomavirus Infections

PURPOSE. Topical biphasic vesicle delivery system encapsulating interferon alpha (IFN α) was developed as an alternative to injections used to treat human papillomavirus (HPV) infections. METHODS. Biphasic lipid vesicles encapsulating increasing doses of IFN α (biphasic IFN α) were characterized for encapsulation efficiency, size, zeta potential and vesicle structure by centrifugation, dynamic light scattering, confocal microscopy and small-angle x-ray scattering. Biphasic IFN-α delivery into human skin in vivo and topical efficacy in patients with genital warts were evaluated. RESULTS. Average encapsulation efficiency of IFN α was 81-91%. The average particle size was 1000-1100 nm and zeta potential +70 to +78 mV. After application of 5, 15 and 40MU/g biphasic IFN α formulation in a topical patch on the upper inner arm in healthy volunteers, skin IFN α levels increased to 120±30, 380±60 and 400±80 IU/mg protein in skin homogenates (n=5, 5, and 7), respectively. Topical application of biphasic IFN α (1 MU/dose) twice daily for two weeks in a pilot study with 12 patients with external condylomata acuminata resulted in a decrease in lesion size, in 2',5'-oligoadenylate synthetase activity and in tissue viral load. CONCLUSIONS. Biphasic vesicles delivered clinically significant levels of IFN α across intact human skin and elicited marked therapeutic effect in patients.

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).

Capsaicin 8% Topical Patch (Qutenza)—A Review of the Evidence

ABSTRACTQutenza is a high-potency capsaicin (8%) topical patch, labeled for treating pain associated with postherpetic neuralgia (PHN). Qutenza decreases pain sensation by reducing transient receptor potential vanilloid 1 (TRPV1) expression and decreasing the density of epidermal nerve fibers in the application area. Systemic absorption from Qutenza is low. Qutenza has not been directly compared to any other medications for the treating PHN. Two pivotal clinical trials compared Qutenza to a control patch (0.04% capsaicin) in PHN. The primary endpoint of both trials was the reduction in numeric pain rating scale (NPRS) score. Qutenza reduced pain from baseline to weeks 2 to 8 (29.6% and 32% reductions) compared to control (19.9% and 24.4% reductions; P ≤ .01). The improvement in NPRS scores persisted, with score reductions greater with Qutenza (29.9% and 32.3% reductions) compared to control (20.4% and 25% reductions; P ≤ .03) for the period 2 to 12 weeks. Safety and efficacy of capsaicin 8% has been demonstrated in open-label trials for up to 48 weeks. The most common adverse drug reactions occurring with capsaicin 8% are application site erythema (63%) and application site pain (42%). Some patients experienced transient increases in blood pressure during Qutenza application. Qutenza must be administered by a physician or under the close supervision of a physician. Prior to application, pretreat the affected area with a topical anesthetic to reduce application site pain. Some patients may require systemic analgesics during and after treatment for treatment-associated pain. Applications of Qutenza can be repeated no sooner than once every 3 months, as needed.

Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs

The study was performed to evaluate the percutaneous penetration of ketoprofen after transdermal administration using a microdialysis technique in pigs, in comparison with rats. Ketoprofen release from patches was determined by analysis of the remaining drug content after application to hairless rats and pigs. Skin and knee joint penetration of ketoprofen was tested by microdialysis, and recovery was determined by retrodialysis. Residual rates in hairless rats and pigs were 68.1 ± 1.6% and 81.7 ± 4.4%, respectively, at 10 h. The average recoveries of ketoprofen over 480 min in the skin and knee joint cases were 72.0 ± 3.4% and 9.8 ± 6.2% in rats and 72.3 ± 2.5% and 57.6 ± 3.1% in pigs, respectively. In rats, ketoprofen was rapidly absorbed with transdermal administration, with C max values of 191.7 ± 76.2 and 35.5 ± 21.7 ng/mL and AUC 0–8h values of 918.2 ± 577.5 and 195.9 ± 137.1 ng h/mL, respectively, for the skin and knee joint. The C max values for the pig were 20.9 ± 18.5 and 3.7 ± 3.0 ng/mL, with AUC 0–8h values of 73.1 ± 69.2 and 16.1 ± 16.1 ng h/mL. Ketoprofen concentrations within skin and knee joint of non-application sites in rats and pigs were less than 0.8 ng/mL. Transdermal administration of ketoprofen significantly reduced prostaglandin E2 levels in the skin of the application site and showed a tendency for inhibition in the knee joint. We thus demonstrated that topical patches containing ketoprofen can deliver the drug through the skin and knee joint of pigs and rats via direct diffusion, and microdialysis data with the pig may be useful for the prediction of human tissue penetration of drugs with transdermal administration.

Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia

Objective:The purpose of this study was to compare the cost effectiveness of a new 8% capsaicin patch, compared to the current treatments for postherpetic neuralgia (PHN), including tricyclic antidepressants (TCAs), topical lidocaine patches, duloxetine, gabapentin, and pregabalin.Methods:A 1-year Markov model was constructed for PHN with monthly cycles, including dose titration and management of adverse events. The perspective of the analysis was from a payer perspective, managed-care organization. Clinical trials were used to determine the proportion of patients achieving at least a 30% improvement in PHN pain, the efficacy parameter. The outcome was cost per quality-adjusted life-year (QALY); second-order probabilistic sensitivity analyses were conducted.Results:The effectiveness results indicated that 8% capsaicin patch and topical lidocaine patch were significantly more effective than the oral PHN products. TCAs were least costly and significantly less costly than duloxetine, pregabalin, topical lidocaine patch, 8% capsaicin patch, but not gabapentin. The incremental cost-effectiveness ratio for the 8% capsaicin patch overlapped with the topical lidocaine patch and was within the accepted threshold of cost per QALY gained compared to TCAs, duloxetine, gabapentin, and pregablin. The frequency of the 8% capsaicin patch retreatment assumption significantly impacts its cost-effectiveness results. There are several limitations to this analysis. Since no head-to-head studies were identified, this model used inputs from multiple clinical trials. Also, a last observation carried forward process was assumed to have continued for the duration of the model. Additionally, the trials with duloxetine may have over-predicted its efficacy in PHN. Although a 30% improvement in pain is often an endpoint in clinical trials, some patients may require greater or less improvement in pain to be considered a clinical success.Conclusions:The effectiveness results demonstrated that 8% capsaicin and topical lidocaine patches had significantly higher effectiveness rates than the oral agents used to treat PHN. In addition, this cost-effectiveness analysis found that the 8% capsaicin patch was similar to topical lidocaine patch and within an accepted cost per QALY gained threshold compared to the oral products.

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.