Transdermal Therapeutic System Fentanyl Research Articles

Predicting Opioid Therapy Safety In Pancreatic Cancer Patients

Background — Obligatory use of strong opioids for treating chronic pain syndrome in patients with pancreatic cancer provides the implementation of opioid-associated adverse reactions. Genetic and non-genetic risk factors are predictive of the opioid therapy safety. Contemporary methods of information analysis allow using prognostic risk models for practical application. Objective — Identification of significant risk factors for the development of opioid-associated adverse drug reactions in patients with chronic pain syndrome against the background of pancreatic cancer. Material and Methods — The study included 90 patients with chronic pain against the background of pancreatic cancer, randomized at a ratio of 1: 1. Group 1 received morphine sulfate (MS), group 2 received fentanyl transdermal therapeutic system (FTTS) with standard adjuvant therapy (ketoprofen, diazepam, amitriptyline). To assess pain level, the 10-point Digital Rating Scale, the Visual Analogue Scale and the pain questionnaires were used. The assessment of the treatment safety was conducted by the Naranjo Scale. Assessment of prognostic genetic and non-genetic factors was carried out using ROC analysis with calculation of AUC (the area under the ROC-curve). Results — Prognostic models of good quality were determined with the optimal ratio of sensitivity and specificity for the influence of genetic and non-genetic risk factors on the development of opioid-associated adverse drug reactions (OA-ADRs) in comparison groups. Various prognostic factors, complementing each other, were identified in the comparison groups. Conclusion — The following OA-ADRs predicting factors were identified: for FTTS-associated nausea and vomiting – age and carriage of rs7438135 AG genotype of UGT2B7 gene; for local reactions – the sum of points on the ESAS scale and carriage of rs7438135 AA genotype of UGT2B7 gene; for difficulty urinating – the level of glomerular filtration rate; for neurotoxicity – the level of AST and bilirubin, and the carriage of rs1128503 GG genotype of ABCB1 gene; for pruritus – carriage of rs1045642642 AA genotype of ABCB1 gene. The prognostic factors for the implementation of MS-associated neurotoxicity were age and comorbidity; for dry mouth was predicted best from the sum of points on the MMCE scale; weakness was predicted by the carriage of rs7668258 TT genotype of UGT2B7 gene.

A patient with fever and delirium while wearing a fentanyl transdermal therapeutic system (TTS) showed marked improvement following intravenous naloxone hydrochloride administration

A patient with fever and delirium while wearing a fentanyl transdermal therapeutic system (TTS) showed marked improvement following intravenous naloxone hydrochloride administration

Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naïve patients with severe chronic noncancer pain

Chronic noncancer pain is often undertreated. To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain. A total of 215 patients with chronic (> or =6 months), severe (VAS > or = 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 microg/h fentanyl TTS was titrated in 25 microg/h increments to a visual analog scale (VAS) score < or = 4. OTFC was administered as single-unit doses of 400 microg. The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 microg/h dose in 48 percent of patients, the 75 microg/h dose in 18 percent, and the 100 microg/h dose in 5 percent (only two patients required >100 microg/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two. Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naïve patients with severe chronic nonmalignant pain.

Pain relief in pediatric palliative care: the place of fentanyl transdermal therapeutic system (according to the materials of Advisory Board Meeting)

Pain relief in pediatric palliative care: the place of fentanyl transdermal therapeutic system (according to the materials of Advisory Board Meeting)

The use of fentanyl in pain management in head and neck cancer patients: a narrative review.

Head and neck (H&N) cancers account for about 5% of all malignant tumours. Pain is one of the most feared consequences of H&N neoplasms and is experienced by up to 80% of patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing. Nevertheless, pain is still often underestimated and undertreated. The role of opioids in cancer pain has been well established but evidences about the role and the relative effectiveness of opioids such as fentanyl in the context of H&N cancer pain remains unclear. A literature review based on the guidance of the Centre for Reviews and Dissemination was conducted. An iterative approach was used starting with an electronic search in the MEDLINE database. The search terms (('Neoplasms'[Mesh]) AND 'Head and Neck Neoplasms'[Mesh]) AND 'Fentanyl'[Mesh] were used. A total of 18 publications were found by the first performed search on PubMed. Other publications concordant with our aim were found by cross-reference. Considering inclusion and exclusion criteria for our review, eight papers resulted eligible for analysis. Fentanyl transdermal therapeutic system (TTS) seems to be an important option, thanks to the way of administration, the good safety and tolerability profiles to control baseline pain. For breakthrough cancer pain (BTcP), several formulations of transmucosal fentanyl are available. All the formulations seem to be active and safety but we lack head-to-head studies of fentanyl versus other strong opioids, as well as with different formulation of fentanyl, particularly for BTcP where H&N cancer population is very poorly represented.

Fentanyl Transdermal Therapeutic System Provides Rapid Systemic Fentanyl Absorption in Two Ball Pythons (Python regius)

Abstract Although our understanding of reptile analgesia continues to develop, μ-opioid receptor agonists are currently the most effective analgesics in a variety of reptile species. Fentanyl, a potent, short-acting, μ- and δ-opioid receptor agonist, is formulated for use as a transdermal therapeutic system (TTS) and was shown to be absorbed across the skin of prehensile-tailed skinks (Corucia zebrata). Snakes, which possess highly permeable skin, seem to be ideal candidates for effective transdermal analgesia. Fentanyl TTS (12 μg/h) was applied to the midbody, dorsal surface of two ball pythons (Python regius). Specimen mean body weight was 2.60 kg (2.20–2.99 kg). Cardiac blood samples were collected for 7 days, and plasma fentanyl concentrations were determined using high-performance liquid chromatography–mass spectroscopy. Therapeutic concentrations, as defined in mammals (1 ng/ml), were reached within 4 h of patch application, and they were sustained throughout the study. Plasma fentanyl steady-state ...

Transdermal Fentanyl for Cancer Pain Management in Opioid-Naive Pediatric Cancer Patients.

Transdermal therapeutic system fentanyl with a drug release rate of 12 µg/h should be of special value in pediatric cancer pain control. Such a fentanyl formulation allows for a stepwise dose increase, similar to that reported for sustained-release morphine. Sixty-four male and female pediatric patients with moderate to severe chronic cancer pain, ages ranging 2-14 years, were included. Patients did not receive opioids prior to enrollment. Patients were observed for pain relief using the Visual Analog Scale and the Wong-Baker FACES Pain Rating Scale, play performance score, and for side effects. There was significant improvement of visual analog scale and FACES pain scores from the baseline to the second day of application (P < 0.001). By the 15th day, scores reached 1.18 ± 0.393 and 1.13 ± 0.35, respectively (P < 0.001). Play performance scale improved from the third day of application of the patch when compared with the baseline (P < 0.001), reaching 55.02 ± 8.35 (P < 0.001) at the end of the study. The sedation score increased on the second day to 2 in 10 patients and to 3 in 54 patients. By the seventh day, 56 patients had a sedation score of 1. All patients returned to baseline by the 15th day. Itching was reported in 16 cases, and erythema occurred in 10 cases. No significant side effects were reported. Transdermal fentanyl was found to be an effective, safe, and well-tolerated treatment for pediatric cancer-related pain in opioid-naive patients with chronic moderate to severe pain. In this study population, evaluation of vital signs and physical examination did not suggest any safety concerns while using transdermal fentanyl.

The effectiveness of transdermal opioid in the management multiple rib fractures: randomized clinical trial.

The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p<0.05). The mean VASl and VASm scores measured on the 1(st), 2(nd), 3(rd), 4(th) and 5(th) days were found to be higher in Group IMO than in Groups IVPCA and TTS; however, these differences were not statistically significant (p>0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

フェンタニル貼布剤（デュロテップ&lt;SUP&gt;&amp;reg;&lt;/SUP&gt;MTパッチ）剥離後6時間で退薬症状が出現したと考えられる1症例

フェンタニル貼布剤（デュロテップ&lt;SUP&gt;&amp;reg;&lt;/SUP&gt;MTパッチ）剥離後6時間で退薬症状が出現したと考えられる1症例

Fentanyl Transdermal Therapy System (TTS-Patch) for Post-Traumatic Blunt Chest Injury

Proper post-extubation pain control in traumatic blunt chest injury represents a challenge to provide adequate analgesia for proper lung inflation and to prevent re-intubation. In this case, the average opioid (Remifentanil) infusion drip in a traumatic blunt chest injury patient in the 48 hours prior to extubation was calculated and converted to the equivalent analgesic one of the Fentanyl Transdermal Therapeutic System (Fentanyl TTS Patch). The analgesic gap before the onset of action for the applied fentanyl patch was covered by frequent injections of tramadol. Evaluation of the Fentanyl TTS effect through the post-extubation period was carried out by measuring the analgesic effect on a visual analogue scale, the alertness status by simple sedation score, while the respiratory performance was followed by the negative inspiratory force. The outcome in this case showed that Fentanyl Patch is a reliable, favorable, safe and non-invasive method that produces a good analgesic effect and positive impaction on the post-extubation course of respiratory performance with a satisfactory outcome and no side effects.

Fentanyl transdermal patches: overview of cutaneous adverse effects in humans

Using Medline, Embase, and the Science Citation Index, we summarize the cutaneous adverse effects of transdermal and parenteral fentanyl. The fentanyl transdermal therapeutic system (TTS; patch) provides continuous systemic delivery of fentanyl (N-phenyl-N-(1-(2-phenylethyl)-4-piperidinyl) propanamide), a potent opioid analgesic, for 72 hours. Clinical studies of fentanyl TTSs demonstrated varying rates of irritation at the application site, ranging from none to 42%, with a median of 25%. Most descriptions of skin reactions included erythema at the application site, indicating irritant dermatitis. Skin testing in 2 subjects receiving parenteral doses concluded that although immunoglobulin E (IgE) antibodies to fentanyl exist, few cases of immediate-type allergic reactions to fentanyl have been substantiated. Comparing the reactions to anesthetic agents during allergenic testing demonstrated positive “wheal and flare” to fentanyl in only 1 of 50 patients (2%). Pruritus has been frequently reported during administration of epidural fentanyl, but allergenicity has not been shown. The few case reports of possible anaphylactic reactions to fentanyl have not clearly demonstrated fentanyl as the causal agent. In addition, transdermal and intravenous/epidural routes of administration may not be comparable because of large differences in plasma concentrations: When these results are taken together, fentanyl (TTS) has shown limited skin intolerance.

Pediatric Palliative Care

Pediatric palliative care (PPC) is provided to children experiencing life-limiting diseases (LLD) or life-threatening diseases (LTD). Sixty to 90% of children with LLD/LTD undergoing PPC receive opioids at the end of life. Analgesia is often insufficient. Reasons include a lack of knowledge concerning opioid prescribing and adjustment of opioid dose to changing requirements. The choice of first-line opioid is based on scientific evidence, pain pathophysiology, and available administration modes. Doses are calculated on a bodyweight basis up to a maximum absolute starting dose. Morphine remains the gold standard starting opioid in PPC. Long-term opioid choice and dose administration is determined by the pathology, analgesic effectiveness, and adverse effect profile. Slow-release oral morphine remains the dominant formulation for long-term use in PPC with hydromorphone slow-release preparations being the first rotation opioid when morphine shows severe adverse effects. The recently introduced fentanyl transdermal therapeutic system with a drug-release rate of 12.5 microg/hour matches the lower dose requirements of pediatric cancer pain control. Its use may be associated with less constipation compared with morphine use. Though oral transmucosal fentanyl citrate has reduced bioavailability (25%), it inherits potential for breakthrough pain management. However, the gold standard breakthrough opioid remains immediate-release morphine. Buprenorphine is of special clinical interest as a result of its different administration routes, long duration of action, and metabolism largely independent of renal function. Antihyperalgesic effects, induced through antagonism at the kappa-receptor, may contribute to its effectiveness in neuropathic pain. Methadone also has a long elimination half-life (19 [SD 14] hours) and NMDA receptor activity although dose administration is complicated by highly variable morphine equianalgesic equivalence (1 : 2.5-20). Opioid rotation to methadone requires special protocols that take this into account. Strategies to minimize adverse effects of long-term opioid treatment include dose reduction, symptomatic therapy, opioid rotation, and administration route change. Patient- or nurse-controlled analgesia devices are useful when pain is rapidly changing, or in terminal care where analgesic requirements may escalate. In this article, we present detailed pediatric pharmacokinetic and pharmacodynamic data for opioids, their indications and contraindications, as well as dose-administration regimens that include practical strategies for opioid switching and dose reduction. Additionally, we discuss the problem of hyperalgesia and the use of adjuvant drugs to support opioid therapy.

Improved Cancer Pain Treatment Using Combined Fentanyl‐TTS and Tramadol

The aim of the study was to facilitate dose escalation of strong opioids. In this randomized open-label study the influence of tramadol on dose adjustment of transdermal fentanyl in advanced cancer pain control was prospectively evaluated. Seventy patients affected by intractable cancer disease with visual analog scale (VAS) score >3 were enrolled. Thirty-five patients were treated conventionally with increasing transdermal fentanyl dosage as required (group F) and 35 patients received oral tramadol added to their transdermal fentanyl before each increment of the transdermal opioid dosage (group T). Pain control was equally satisfactory in the two groups. VAS scores at baseline (T: 4.36 +/- 1.53; F: 4.51 +/- 1.36; n.s.) and at the end of the study (T: 1.8 +/- 1.6; F: 1.6 +/- 1.5; n.s.) did not differ. However, in the tramadol group this level of pain control was achieved with much slower dose escalation of fentanyl. The mean application time of the fentanyl-Transdermal Therapeutic System patch for each dosage (25, 50, 75 microg/hour) was significantly greater in patients receiving tramadol. No patient in group T escalated to the 100 microg/hour patch, while in 12 patients of group F the 100 microg/hour patch was applied after a 75 microg/hour patch mean application period of 18.6 +/- 4.7 days. The number of fentanyl-TTS dosage changes was significantly lower in group T (1.2 +/- 0.4 vs. 2.3 +/- 0.5; P < 0.05). The mean total duration of treatment in group T, was 37.1 +/- 11.6 days. The amount of fentanyl used at study end was 56.6 +/- 11.2 microg/hour plus 141.1 +/- 151.9 mg tramadol per day (median: 200 mg/day) in group T patients compared with 84.1 +/- 12.2 microg/hour in group F patients (P < 0.05). The combination of a strong opioid with a weak opioid to treat severe cancer pain allowed a more gradual increase of analgesic delivery than was possible using fentanyl-TTS alone, minimizing periods of under- and overdosing. In addition, it considerably slowed the pace of fentanyl dose escalation. In conclusion, this TTS fentanyl-tramadol analgesic protocol provides a useful alternative to the usual treatment of cancer pain with fentanyl-TTS alone, especially in case of quick progression of disease and pain.

Transdermal Fentanyl in Childhood and Adolescence: A Comprehensive Literature Review

The recently introduced fentanyl transdermal therapeutic system (TTS) with a drug release rate of 12.5 microg/h matches the lower dosing requirements of cancer pain control in children. It is likely that fentanyl TTS will be used in pediatrics with increasing frequency. We compiled the published evidence on pediatric applications of this drug formulation to help physicians get the most benefit from its use. Within this systematic review, a total of 11 observational clinical or pharmacokinetic studies were identified. There are no pediatric randomized or controlled cohort studies. Pharmacokinetic studies poorly described time-concentration profiles after application. The time to reach steady-state serum drug concentrations seems to be longer, clearance (expressed as liters per kilogram per hour) higher, and elimination half-life shorter in children than in adults. There are no fundamental differences in effect or profile of adverse effects compared with adults. Fentanyl TTS may be associated with less constipation compared with morphine use. Frequently, pediatric patients need supplemental mechanical fixation of the fentanyl TTS by means of medical tape. Younger patients tend to have a higher fentanyl requirement when referenced to body weight. Both parents and medical professionals are satisfied with fentanyl TTS to a higher degree than with individual analgesic pretreatment regimens. Fentanyl TTS is a promising option for chronic pain control in children. An approximate conversion factor of 45 mg/day oral morphine to 12.5 microg/h fentanyl TTS is used for initial therapy dose estimation in children receiving long-term morphine therapy. This is conservatively low to avoid respiratory depression. Daily oral morphine equivalent dose should be at least 30 mg/d before fentanyl TTS therapy is started with 12.5 microg/h. Evidence for superiority of fentanyl TTS treatment above conventional opioid administration is both scarce and of low quality. The article gives a comprehensive overview of all pediatric data concerning the fentanyl TTS. Children may take longer to reach steady-state fentanyl serum concentrations than adults, and younger children may require higher doses referenced to body weight than older children or adults. Consequently, there is a need to provide sufficient medication in the phase of therapy initiation to prevent breakthrough pain. The 72-hour dosing schedule recommended by the manufacturers may not be applicable to children because of poor patch adhesiveness. The authors suggest to ensure firm fixation of the fentanyl TTS with additional medical tape if necessary and to change the fentanyl TTS after 48 hours. Transdermal fentanyl in children may exhibit fewer side effects when compared with other opioids, especially constipation. Randomized studies are urgently needed to definitively answer this question.

Validated GC–MS analysis for the determination of residual fentanyl in applied Durogesic ® reservoir and Durogesic ® D-Trans ® matrix transdermal fentanyl patches

The method development and validation characteristics are described of a simple gas chromatographic–mass spectrometric (GC–MS) analytical procedure to determine residual fentanyl in used Durogesic ® reservoir patches and Durogesic ® D-Trans ® matrix technology based systems to estimate the actual rate of transdermal fentanyl delivered in individual patients. The sample preparation protocol constituting a saline based extraction of sets of new patches of each nominal dose available, resulted in fentanyl extraction recoveries to increase steadily as a function of increasing extraction time. For the reservoir type transdermal therapeutic system (TTS), fentanyl extraction efficiencies at equilibrium (16 h) ranged from approximately 60% (100-μg/h TTS) to 95% (25-μg/h TTS), whereas for the matrix type system considerable lower recoveries were demonstrated for the highest nominal dose rates (35%–52%), while reaching 90% for the 25-μg/h system. For the latter type of fentanyl TTS, an optimized methanol based extraction protocol yielded virtually quantitative fentanyl recoveries for each matrix patch nominal dose level at substantially shorter extraction periods (15 min). The GC–MS analytical method using selected ion monitoring (SIM) and deuterated fentanyl as internal standard was shown to be adequately selective with regard to the presence of other compounds in the Durogesic ® patches. It was further demonstrated that the developed analytical protocols provided highly reproducible and accurate estimates of the initial fentanyl content of each patch type at all available nominal doses, with coefficients of variation and relative errors generally below 10%. These advantageous assay validation characteristics can be further transposed to the application of residual fentanyl level estimates in used patches, provided that with each batch of samples also a set of new TTSs with equal dose is assayed to perfectly mimic extraction phenomena. Finally, the presented GC–MS analytical protocol was successfully applied for the determination of residual fentanyl in a subset of 57 reservoir type patches obtained from four palliative patients.

Regional differences in transdermal penetration of fentanyl through equine skin

The rate and regional differences for the penetration of fentanyl through equine skin was investigated in vitro using a commercial transdermal therapeutic system (TTS) or ‘patch’. Skin collected from the thorax, groin and leg (dorsal metacarpal) regions of five horses was placed in diffusion cells and a fentanyl TTS applied to each skin sample. Drug penetration through each skin sample over 48 h measured using high performance liquid chromatography (HPLC). Cumulative penetration (μg/cm 2) was plotted against time (h) and used to regress the steady state flux (μg/cm 2/h) of fentanyl through each skin site. Results showed similar fluxes for both the thorax (2.32 ± 0.17 μg/cm 2/h and groin (2.21 ± 0.11 (μg/cm 2/h) regions, but significantly lower flux ( P = < 0.05) for the leg region (1.56 ± 0.120 μg/cm 2/h. Interestingly, there was a significantly longer lag time for the penetration of fentanyl through the groin region (7.87 ± 0.51 h) compared to the other two sites (5.66 ± 0.97 h and 5.75 ± 0.43 h for the thorax and leg regions respectively). The results suggest that a fentanyl TTS applied to the leg region may have a small but significantly lower amount of fentanyl available systemically, compared to patches applied to the thorax or groin regions, which may affect the level of analgesia subsequently achieved in the horse.

Safety and efficacy of transdermal fentanyl in patients with cancer pain: phase IV, Turkish oncology group trial

We have performed a prospective evaluation of the efficacy, safety and convenience of the transdermal therapeutic system - fentanyl (TTS-F) in Turkish cancer patients when it was newly available in Turkey. Ninety-nine patients with historically confirmed malignancy and pain entered the study; the mean age was 55.1 (16-58) years. The study duration was 28 days. Transdermal therapeutic system - fentanyl was used in opioid-naïve or pre-treated patients. Most patients reported a decrease in pain severity. Use of rescue medication decreased from day 4 to day 28. The majority of patients rated patch convenience of use as excellent. A total of 22.2% of patients experienced adverse events that were either probably related or very likely to be related to the study drug. The majority of the adverse events mentioned were related to the digestive system. Eighteen serious adverse events were reported by 13 patients. Six events were doubtfully related, and 12 events were not related to the study drug. Four patients died during the trial. None of these deaths was attributed to the study drug. In conclusion, the trial showed that TTS-F is easily managed, effective and will help to enable the appropriate opioid administration to patients who are suffering from cancer pain in Turkey.

Effectiveness of Transdermal Fentanyl Patch for Treatment of Acute Pain Due to Oral Mucositis in Patients Receiving Stem Cell Transplantation

The current study was performed to evaluate the effectiveness and safety of transdermal therapeutic system (TTS) fentanyl in the management of acute pain due to oral mucositis in patients receiving stem cell transplantation. A cohort of consecutive patients with painful oral mucositis were enrolled. Initially, 25 μg/h of TTS fentanyl was administered for the treatment of oral mucositis pain. The pain score, based on a visual analogue scale, and mood and quality of sleep as determined by EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Cancer 30), were all recorded before the treatment, then 2, 6, and 10 days later. Twenty-two patients with hematologic malignancies were enrolled. Three patients were excluded from the response assessment, as their TTS fentanyl treatment was stopped owing to related complaints, including severe dizziness, severe vomiting, and an extensive body rash. The total duration of the treatment was 8 days (range, 6–15 days) and the total amount of TTS fentanyl administered per patient was 2.21 at 25 μg/h and 0.63 at 50 μg/h. Six (31.6%) of the remaining 19 patients required an escalated dose of TTS fentanyl at 50 μg/h. The mean pain scores before treatment and 2, 6, and 10 days later were 6.68, 5.17, 3.42, and 2.13, respectively ( P < .001). Eight (42.1%) and seven (36.8%) patients experienced improved sleep and mood after treatment, respectively. The TTS fentanyl was effective in both relieving oral mucositis pain with an excellent tolerability and improving the quality of life for hematological patients receiving high-dose chemotherapy with stem cell transplantation.

Transdermal Fentanyl Combined with Nonsteroidal Anti‐Inflammatory Drugs for Analgesia in Horses

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti‐inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 μg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2 1.1 ng/mL (mean ± SD) and a time to peak serum concentration of 26 ± 13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P &lt; .05), but lameness scores were not significantly different (P± .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.

Long-term cancer pain management in morphine pre-treated and opioid naive patients with transdermal fentanyl.

There is emerging data supporting the use of TTS-F (transdermal therapeutic system-fentanyl) in opioid naive patients. Our study examines the safety and efficacy of TTS-F in the long-term control of cancer pain in opioid naive patients and those transferring from oral morphine. Pain was assessed in 589 patients (Group A: 268 opioid naive, Group B: 321 transferring from morphine) using a Visual Analogue Scale (VAS; 0-10), based on selected questions from the Greek Brief Pain Inventory (GBPI). Overall treatment satisfaction was assessed on a 4-point scale. Quality of Life (QOL) and ECOG (0-4) status were also recorded. These were assessed in relation to TTS-F dose, pain type (neuropathic, combined, nociceptive), concomitant use of anti-inflammatory drugs and other demographic data. Of 589 patients, 59 (10%) withdrew as a result of inadequate pain satisfaction or for other reasons. There were no discontinuations due to side effects; no Grade 3-4 events occurred. A total of 530 continued on-study, 211 patients died during study period and 295 departed; all (506; 89%) were satisfied with their pain relief. Analysis of patients at baseline, 28 days, 6 and 12 month time points (n = 153 Group A; n = 214 Group B) with respect to QOL and pain measures indicated a statistically significant (p < 0.001) improvement in all measures across time independent of pain type, or any other patient characteristic(s). In patients with intolerable pain, transfer to TTS-F offers an efficient and safe long-term analgesic option. TTS-F offers durable long-term maintenance of pain relief with acceptable side effects in opioid naive patients. In general, TTS-F as a first line analgesic approach for carefully selected and monitored patients experiencing moderate to severe cancer pain should be considered.