Transdermal Fentanyl Research Articles

Long-Term Analgesia following a Single Application of Fentanyl Transdermal Solution in Pigs

Introduction: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fentanyl extended-release patches. However, as in all drugs with a short half-life time, repeated buprenorphine administrations are needed, leading to multiple injections that affect the research protocol. On the other hand, fentanyl patch efficacy is discussed in some species. These elements highlight the need of an optimal formulation of analgesic drugs for laboratory animals. In this study, we investigated how Recuvyra®, a fentanyl transdermal solution (FTS), validated in dog perioperative pain management, could provide sustained analgesia after a single topical administration in pigs in a surgical context. Methods: A total of 11 minipigs were used in this study. As a preliminary experiment, two different doses were tested as a single application on five pigs: two pigs at full dose (2.6 mg/kg) and three pigs at half dose (1.3 mg/kg). Plasma fentanyl dosages were performed during 4 consecutive days, using liquid chromatography with tandem mass spectrometry detection. The efficacy of FTS was then evaluated in a perioperative period. Six minipigs benefited from a surgical intervention comprising a laparotomy. The FTS was blotted on the skin in a single application 20 min before the surgical incision and plasma fentanyl dosages, clinical examination (body weight, food intake, heart rate, and body temperature) and pain assessment were performed for 7 consecutive days. Results: During the preliminary experiment, all fentanyl concentrations reached the minimum effective concentration (MEC) extrapolated in pigs (fentanylemia ≥0.2 ng/mL) throughout the 4 days. The half dose was chosen for the next step of the study. After the surgical intervention, all plasma fentanyl concentrations remained above the MEC up to 7 days post administration. Pig clinical examinations and pain evaluations showed efficient and constant pain control at the half dose, and few adverse events were observed. Discussion and Conclusion: This study confirms the pharmacological and clinical efficacy of FTS at 1.3 mg/kg in pigs throughout at least 7 postoperative days following laparotomy. The clinical analgesic effect of FTS appears more efficient and well-tolerated than the one observed with repeated injections of buprenorphine. This analgesic drug formulation could be universally used in animal research to provide optimal perioperative pain management and long-term analgesia.

Disproportionality Analysis of Safety Signals for a Wide Variety of Opioid-Related Adverse Events in Elderly Patients Using the Japanese Adverse Drug Event Report (JADER) Database.

Opioids are widely used for the treatment of moderate/severe pain in cancer and noncancer patients. In this study, we searched for safety signals for a wide variety of opioid-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Data from the JADER database from April 2004 to May 2018 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection of opioid-related AEs in elderly patients was defined using the relative elderly reporting odds ratio (ROR). Among the analyzed AEs, opioid-induced neurotoxicity (OIN) was assessed based on the time to onset using the Weibull shape parameter. The following safety signals were detected in elderly patients: respiratory depression, somnolence, hallucinations, akathisia and OIN. Fentanyl, tramadol, oxycodone and morphine exhibited a large relative elderly ROR for OIN. The median time to onset of OIN of transdermal fentanyl, oral tramadol, oral oxycodone and oral morphine was 13.5, 6, 9, and 6 d, respectively. These opioids were classified as early failure types using the Weibull distribution. Our results showed that elderly patients who are administered opioids should be closely monitored for AEs, such as respiratory depression, OIN and akathisia.

Comparison of Transdermal Fentanyl Patch and Intravenous Fentanyl for Postoperative pain relief in patients undergoing major abdominal surgeries under general Anaesthesia

Pain is a common feature for many disease processes which has association with actual or impending tissue damage. Acute postoperative pain, moderate-to-severe is still a problem, despite the progress in pain management. New technologies in pain management are being used as alternatives to IV routes because of its limitations. The transdermal route is a novel system which uses iontophoresis for the drug delivery directly via the skin by a low-intensity electrical field. Among opioids, fentanyl is the most common and because of its low molecular weight, smaller structure, high lipid solubility and high analgesic potency it could be a good choice for transdermal use. Objectives: The primary objective of this study is to evaluate the efficacy of fentanyl dermal patch with intravenous fentanyl for postoperative analgesia in major abdominal surgeries under general anaesthesia. The secondary objective is to assess the side effects associated with transdermal fentanyl patch. Methods: 50 patients of ASA I and II posted for elective abdominal surgeries, randomly allocated into two groups, IV group (n=25), received intravenous fentanyl and TFP group (n=25), receiving 25mcg/hr Duragesic patch applied on upper arm 10 hours before the surgery and were monitored for pain by VAS scale and for side effects i.e, respiratory depression, pruiritis, nausea and vomiting. The patients received inj. Paracetamol 1gm as rescue analgesia when the VAS score> 5. The pain scores, time for rescue analgesia, the complications were noted and analysed by using Windows SPSS 17 version. Results: Pain intensity scores showed a statistically significant difference between the two groups, with VAS score lower in TFP (3.80±0.12) when compared to I.V (4.67±1.18). The mean time interval for the first rescue analgesia was significantly greater in TFP (345.50±33.34) than in I.V (58.10±12.88). The side effects i.e, respiratory depression, pruritis, nausea and vomiting were significantly lower with TFP. Conclusion: Transdermal patch of fentanyl of 25 microgram/hour put 10hours prior to surgery provides an effective, safe and non-invasive method of postoperative pain relief after major abdominal surgery.

Intoxication in a pig (Sus scrofa domesticus) after transdermal fentanyl patch ingestion : case report

An experimental study on the effects of electroporation on pancreatic tissue was performed in pigs, and the fentanyl transdermal patch (FTP) was used postoperatively as part of multimodal pain management. Ingestion of an FTP, which resulted in fentanyl intoxication, was suspected 5 days after placement in one of the experimental pigs. The pig was first dysphoric, running in the stall, panting and vocalizing until it finally became depressed and it remained lying on the floor. Ingestion of an FTP was not observed but the fentanyl plasma concentration on the day of intoxication was 20.7 ng/ml, while at its peak after FTP administration it was only 0.492 ng/ml. The intoxication was successfully treated with a single intramuscular naloxone injection.

Comparative evaluation of analgesic efficacy of buprenorphine transdermal patch and fentanyl patch in management of postoperative pain after arthroscopic lower limb surgery: A randomized controlled trial.

Background and Aims:Transdermal opioids are newer modality in use for the control of postoperative pain, because of its noninvasiveness, longer duration of action, sustained blood levels, and with minimal side effects. The study was aimed to evaluate the efficacy of analgesia of buprenorphine patch 10, 20 μg·h-1 and fentanyl patch 25 μg·h-1 for relief of pain in the postoperative period in patients undergoing arthroscopic lower limb surgeries.Materials and Methods:It was a randomized, double-blinded, prospective study in which adult patients undergoing lower limb arthroscopic surgery were randomly segregated into three groups. In Group 1 (fentanyl patch 25 μg·h-1), Group 2 (buprenorphine patch 10 μg·h-1), and Group 3 (buprenorphine patch 20 μg·h-1), transdermal patches were applied 12 h prior to surgery. Mean NRS score, total rescue analgesic requirement, drug-related adverse effects, and hemodynamic status were evaluated till 72 h in the postoperative period.Results:Out of 175 screened patients, 150 patients were finally analyzed. Baseline characteristics were the same among all the three groups. Median NRS score was lowest in Group 3 [P value < 0.05 at 2, 4, 8, 12, and 24 h after surgery (Kruskal Wallis test). The total consumption of postoperative rescue analgesic diclofenac was the lowest in Group 3 as compared to other groups without any significant increase in adverse events.Conclusions:In arthroscopic lower limb surgery, buprenorphine patch (20 μg·h-1) applied 12 h prior to surgery is an effective postoperative analgesic and it is not associated with any significant adverse effects.

The pharmacokinetics of a fentanyl matrix patch applied at three different anatomical locations in horses.

Matrix fentanyl patches have not been investigated in horses and may represent an effective means of providing analgesia over an extended time period without venous catheterisation. To describe the pharmacokinetics of a matrix transdermal fentanyl patch in horses. Randomised experiment, Latin-square design. Six adult horses were given each of three treatments with a 96-hour washout. For each treatment, two 100µg/h matrix fentanyl patches were applied to the inguinal region (TXA), metacarpus (TXM) or ventral tail base (TXT) for 72hours. Blood samples for fentanyl analysis were obtained and heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were measured at various time points for 96hours. Fentanyl plasma concentrations were measured with LC-MS/MS for pharmacokinetic analysis. A mixed-effects model was used to analyse pharmacodynamic variables. The time to maximum plasma concentration, maximum plasma concentration and area under the curve extrapolated to infinity were 10±3.79, 14.3±5.13 and 10.3±4.8hours; 2.07±0.74, 1.55±0.53 and 2.07±0.72ng/mL; and 46.6±9.3, 44.6±6.0 and 46.2±7.68nghours/mL for TXA, TXM and TXT respectively. There was no significant difference among groups. There was no significant change from baseline or among treatment groups with regard to HR, RR or RT (P>.1 for all). There was no intravenous treatment group for determination of bioavailability. Fentanyl was rapidly absorbed and persisted in the plasma for up to 96hours. No adverse effects of treatment on HR, RR or RT were observed. Further controlled prospective studies are needed to determine what plasma concentration, if any, of fentanyl achieves an analgesic effect in horses when administered via a transdermal patch system.

Fatal Transdermal Fentanyl Patch Overdose in a Child

Fatal Transdermal Fentanyl Patch Overdose in a Child

English

English

RS2: Assessing Conversion to Transdermal Fentanyl or Methadone during Transition on Hospice Admission

"RS2: Assessing Conversion to Transdermal Fentanyl or Methadone during Transition on Hospice Admission." Journal of Pain & Palliative Care Pharmacotherapy, 34(4), p. 164

Uso de la Escala de dolor de la Universidad de Melbourne para evaluar dos protocolos de analgesia posquirúrgica en perras sometidas a mastectomía

Breast tumors in dogs comprise about 52% of neoplasms in dogs. Complete surgical removal, called mastectomy, is considered the treatment of choice. Postoperative pain for this procedure can be classified as moderate to severe, therefore requiring treatment with drugs that minimize pain. Preemptive analgesia is a method that consists of administering medications before painful stimulus and, thus, has stood out among analgesic protocols. Scales capable of evaluating pain in animals arose in view of the difficulty in its recognition in Veterinary Medicine. The pain scale of the University of Melbourne (UMPS) consists of the assessment of specific physiological and behavioral parameters related to pain, increasing its sensitivity and specificity. Therefore, the present study aimed to evaluate the effectiveness of two different preemptive analgesia protocols in controlling postoperative pain in dogs undergoing mastectomy, using UMPS. For this, the research included 16 female patients who were randomly divided into two groups (G1 and G2). The G1 group regarding the preemptive analgesia protocol with firocoxib associated with the transdermal fentanyl patch, was composed of 8 females. Thus, the remaining 8 females constituted the G2 group receiving preemptive analgesia with carprofen associated with transdermal fentanyl. In the postoperative period, patients were evaluated by applying the UMPS in 5 stages (T1, T2, T3, T12 and T24). The analgesic rescue was only carried out when the evaluation reached a score higher than 13. Therefore, among the 16 female dogs who participated in the research, 11 of them (68.75%) demonstrated adequate pain control, therefore, there was no need for rescue, 4 patients (25%) required analgesic rescue and 1 patient (6.25%) was disqualified from the research. However, it is concluded that the Pain Scale at the University of Melbourne is a good method for assessing the degree of pain in dogs and that transdermal fentanyl patch (Durogesic®) demonstrated good performance in pain control in association with both anti-inflammatory drugs , as long as it is in total adherence to the skin surface.

The Role of Opioids in Pain Management in Elderly Patients with Chronic Kidney Disease: A Review Article.

Chronic kidney disease (CKD) is a global public health problem. Pain is one of the most generally experienced symptoms by CKD patients. Pain management is a key clinical activity; nonetheless, insufficient pain management by health professionals keeps it up. Opioids as pain relievers are a class of naturally-derived and synthetic medications. They act through interactions with receptors in peripheral nerves. Numerous pharmacokinetic alterations happen with aging that influence drug disposition, metabolism, and quality of life. Acetaminophen alone, or combined with low-potency opioid dose is regarded as the safest pain-relieving choice for CKD. Morphine and codeine are probably eluded in renal impairment patients and used with excessive carefulness. Tramadol, oxycodone, and hydromorphone can be used by patient monitoring, while methadone, transdermal fentanyl, and buprenorphine seem to be safe to use in older non-dialysis patients with renal impairment. Consistent with the available literature, the main aim of this review was to explore the occurrence of chronic pain and its opioid treatment in CKD patients. According to this review, more and well-made randomized controlled trials are necessary to find appropriate opioid doses and explore the occurrence of side effects.

Predicting Transdermal Fentanyl Delivery Using Mechanistic Simulations for Tailored Therapy.

Transdermal drug delivery is a key technology for administering drugs. However, most devices are “one-size-fits-all”, even though drug diffusion through the skin varies significantly from person-to-person. For next-generation devices, personalization for optimal drug release would benefit from an augmented insight into the drug release and percutaneous uptake kinetics. Our objective was to quantify the changes in transdermal fentanyl uptake with regards to the patient’s age and the anatomical location where the patch was placed. We also explored to which extent the drug flux from the patch could be altered by miniaturizing the contact surface area of the patch reservoir with the skin. To this end, we used validated mechanistic modeling of fentanyl diffusion, storage, and partitioning in the epidermis to quantify drug release from the patch and the uptake within the skin. A superior spatiotemporal resolution compared to experimental methods enabled in-silico identification of peak concentrations and fluxes, and the amount of stored drug and bioavailability. The patients’ drug uptake showed a 36% difference between different anatomical locations after 72 h, but there was a strong interpatient variability. With aging, the drug uptake from the transdermal patch became slower and less potent. A 70-year-old patient received 26% less drug over the 72-h application period, compared to an 18-year-old patient. Additionally, a novel concept of using micron-sized drug reservoirs was explored in silico. These reservoirs induced a much higher local flux (µg cm-2 h-1) than conventional patches. Up to a 200-fold increase in the drug flux was obtained from these small reservoirs. This effect was mainly caused by transverse diffusion in the stratum corneum, which is not relevant for much larger conventional patches. These micron-sized drug reservoirs open new ways to individualize reservoir design and thus transdermal therapy. Such computer-aided engineering tools also have great potential for in-silico design and precise control of drug delivery systems. Here, the validated mechanistic models can serve as a key building block for developing digital twins for transdermal drug delivery systems.

Transdermal Fentanyl Uptake at Two Different Patch Locations in Swiss White Alpine Sheep.

Simple SummaryProviding adequate and prolonged pain relief to sheep undergoing invasive orthopedic surgery while keeping side effects and stress for the animals at a minimum is challenging. Transdermal patches continuously releasing the synthetic opioid fentanyl through the skin, are a frequently used method in veterinary and human medicine. To refine the current analgesia protocol, we compared the uptake of fentanyl from a transdermal fentanyl patch applied at two different skin locations in sheep. The fentanyl plasma levels were measured at different time points over five days. The patch applied on the foreleg resulted in a faster fentanyl uptake with higher peaks and a longer time within or above the target fentanyl plasma concentration when compared to the one on the thorax. Additionally, it was easier to apply the patch at the foreleg than at the thorax. Our findings suggest that the fentanyl patch should be applied to the foreleg 3–6 h before the painful insult and that its effect should last at least 48 h.When using animals in biomedical research, investigators have the responsibility to ensure adequate analgesia. Currently, transdermal fentanyl patches (TFP) are often used to provide postoperative analgesia in large laboratory animals. The aim of this study was to compare the fentanyl uptake resulting from TFP applied at two different locations, namely the foreleg and the thorax, in healthy adult sheep. Twelve sheep received a TFP with an intended dosage of 2 ug/kg/h. Blood samples were taken at different time points over a period of five days and the fentanyl plasma levels were measured. The TFP applied on the foreleg allowed a faster fentanyl uptake with higher peaks and a longer time within or above the target concentration of 0.6–1.5 ng/mL, shown to be analgesic in humans, when compared to the one on the thorax. Assuming that the effective plasma concentration described for humans is providing analgesia in sheep as well, the present findings suggest that it should be sufficient to apply the TFP 3–6 h before the painful insult and that its effect should last at least 48 h. Furthermore, when TFP are used to provide postoperative analgesia in sheep, they should be placed on the foreleg rather than on the thorax.

Comparison of Post-Operative Analgesia with Transdermal Fentanyl Patch and Epidural Fentanyl in Lower Limb Orthopaedic Surgeries: A Prospective Randomised Trial

Comparison of Post-Operative Analgesia with Transdermal Fentanyl Patch and Epidural Fentanyl in Lower Limb Orthopaedic Surgeries: A Prospective Randomised Trial

A Novel Clinical Consideration to Conserve Parenteral Fentanyl During the COVID-19 Pandemic.

A Novel Clinical Consideration to Conserve Parenteral Fentanyl During the COVID-19 Pandemic.

Utilização da escala composta Glasgow short form para avaliação de dois diferentes protocolos de analgesia pós-cirúrgica em cadelas submetidas à mastectomia

The concern with the treatment of postoperative pain is based on the prevention of unnecessary suffering of the patient, in addition to providing many physiological benefits. Post-surgical pain can be minimized more easily when preemptive analgesia is applied, that is, the administration of analgesics before tissue damage occurs. However, the association of non-steroidal anti-inflammatory drugs with opioids in anti-pain protocols is seen as a way to reduce the doses of each medication and ensure a greater coverage of inflammatory mediators. The modified Glasgow Scale (Short Form of the Glasgow Composite Pain Scale -CMPS-SF), allows the assessment of six behavioral categories. In view of this, the present study aims to evaluate and compare, by applying the modified Glasgow Scale, the effectiveness of two different preemptive analgesia protocols using transdermal fentanyl patch associated with two non-steroidal anti-inflammatory drugs (firocoxib and carprofen) for the control of postoperative pain in dogs undergoing mastectomy surgery. Thus, 16 bitches participated in the research and were randomly divided into two groups with 8 females constituting the 1 group and receiving preemptive analgesia with firocoxib associated with transdermal fentanyl patch and another 8 females constituting the 2 group receiving analgesia preemptive with carprofen associated with transdermal fentanyl. Postoperatively, patients were evaluated using the Glasgow Modified Scale in 5 steps (T1, T2, T3, T15 and T24). The analgesic rescue was only performed when the assessment exceeded 6 points on the scale. Among the 16 patients who participated in the research, 11 of them (68.75%) demonstrated adequate pain control, therefore, there was no need for rescue, 4 patients (25%) needed analgesic rescue and 1 patient (6.25%) was disqualified from the search. It was concluded that there was no difference in analgesic control with both protocols. The Glasgow Modified Scale is a useful method for assessing the degree of pain in bitches undergoing mastectomy. Transdermal fentanyl has demonstrated good performance in pain control simultaneously associated with both anti-inflammatory drugs, however it is of utmost importance that the patch is correctly attached to the skin for proper release of the active ingredient.

Comparison of analgesic efficacy and fetal effects between transdermal administration of fentanyl and intramuscular administration of buprenorphine in pregnant sheep.

To compare analgesic efficacy and fetal effects between transdermal administration of fentanyl and IM administration of buprenorphine in pregnant sheep. 12 healthy pregnant ewes. Before study initiation, each ewe was confirmed pregnant with a single fetus between 113 and 117 days of gestation. Ewes were randomly assigned to receive buprenorphine (0.01 mg/kg, IM, q 8 h for 48 hours beginning 1 hour before anesthesia induction; n = 6) or fentanyl (a combination of transdermal fentanyl patches sufficient to deliver a dose of 2 μg of fentanyl/kg/h applied between the dorsal borders of the scapulae 24 hours before anesthesia induction; 6). Ewes were anesthetized and underwent a surgical procedure to instrument the fetus with an arterial catheter and place a catheter in utero for collection of amniotic fluid samples. Physiologic variables and behavioral changes indicative of pain were assessed, and amniotic fluid and blood samples from ewes and fetuses were collected for determination of drug concentrations at predetermined times. Both protocols provided acceptable postoperative analgesia with no adverse effects observed in the ewes or fetuses. Compared with the buprenorphine protocol, the fentanyl protocol induced more profound analgesia, decreased the requirement for isoflurane during surgery, and was associated with a shorter anesthesia recovery time. Fetal indices did not differ significantly between the 2 analgesic protocols. Results indicated that both protocols provided acceptable analgesia. However, the fentanyl protocol was superior in regard to the extent of analgesia induced, inhalant-sparing effects, and anesthesia recovery time.

Transdermal Fentanyl patch: An approach to enhance tolerance of conscious proning in COVID-19 patients.

The COVID-19 ARDS appears to have worse outcomes than ARDS from other causes. It is a predictable serious complication and the key strategy is to maintain oxygenation. Adopting the prone position for conscious COVID-19 patients requiring basic respiratory support, is shown to benefit patients in terms of improving oxygenation, reducing the need for invasive ventilation and potentially even reducing mortality. Cough and myalgia are the common and most distressing symptoms seen in conscious COVID-19 patients which can impair tolerance to awake proning. Modified awake proning with application of transdermal fentanyl patch (TFP) can improve the compliance to conscious proning in COVID-19 patients.

Transdermal Fentanyl in Hospitalized Patients with Severe Pain

The Journal of Anesthesia & Intensive Care Medicine (JAICM) is a globally accepted journal that aims to publish innovative scientific developments and high quality information on anesthesia and intensive care medicine.

A single-arm, prospective, multicenter study on the efficacy and safety of low-dose transdermal fentanyl patch in opioid-naive patients with moderate to severe cancer pain.

e24149 Background: The efficacy and safety of low-dose fentanyl transdermal patch (TDF) in the treatment of opioid-naive patients with moderate-to-severe cancer pain has no tyet been confirmed. There are little international studies, and none in mainland China. The aim of this study was to explore the effect and tolerability of low dose of TDF in opioid-naive patients with Chinese moderate-to-severe cancer pain, and evaluate the influence on quality of life and cognitive function. Methods: A prospective, single-arm, non-randomized, open-label, multicenter trial was conducted with 285 opioid-naivepatients with moderate-to-severe cancer pain in 14 tertiary hospitals in mainland China. The initial analgesic dose of TDF was 12.5 µg/h, pain assessment (pain score, pain relief and pain response rate) was performed every 3 days for a total of 9 cycles.Adverse reactions and events were monitored over 24 days. In the meantime, quality of life and cognitive function of patient were evaluated with EORTC QLQ-C30 and MMSE. Results: 285 patients with 267(92.00%) completed the trial were enrolled. The average age was 60 (range 28-87) and the average effective therapeutic dose was 6.3±6.08mg.The total pain relief rate was 98.12% (mean pain score ±SD, 5.7±0.89 vs 3.9±1.28; P &lt; 0.001). The efficacy of low-dose TDF on pain relief was consistent in groups separated by gender (p &lt; 0.001), age (p &lt; 0.001), types of cancer (p &lt; 0.001), and baseline pain intensity (p &lt; 0.001). There were 79 patients (29.59%) in the low-dose subgroup, and the pain response rate of the low-dose subgroup was better than other dose groups within one week (p = 0.0018).The adverse effects were mild. The most common adverse reactions are constipation 7.87%, followed by nausea 11.24%, vomiting 4.12%, drowsiness 1.87% and urine retention 1.5%.There was no difference in the incidence of adverse reactions between the low-dose subgroup and the other groups (p &gt; 0.05). Meanwhile, TDF improved the quality of life of patients with moderate-to-severe cancer pain (mean± SD: 46.44±16.96 vs. 67.04±18.02;p &lt; 0.05), without impairing cognitive function(mean ±SD, 29.13±1.54 vs. 28.98±1.99; p &gt; 0.05). Conclusions: Low-dose TDF is effective for opioid-naive patients with moderate-to-severe cancer pain. Adverse reactions are mild and the quality of life of patients is improvedwith little losson cognitive function. Further randomized controlled studies are warranted to investigate the value of low-dose TDF in the treatment of opioid intolerant cancer pain. Clinical trial information: ChiCTR-ONC-17014080 .