Transdermal Buprenorphine Research Articles

Transdermal buprenorphine for moderate chronic noncancer pain syndromes

ABSTRACTIntroduction: Chronic noncancer pain has remained a challenging clinical problem. Opioid analgesics are effective, but they are known to be associated with opioid use disorder and potentially treatment-limiting side effects. Buprenorphine is a Schedule III synthetic opioid in the USA with a chemical structure similar to that of morphine but with a longer duration of action, greater potency, and other unique pharmacological attributes. Its role in treatment of chronic noncancer pain may be broader than currently thought.Areas covered: The pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile of transdermal buprenorphine in moderate chronic noncancer pain syndromes patients will be discussed.Expert commentary: Buprenorphine offers effective analgesia in the form of a Schedule III drug (rather than Schedule II such as oxycodone or morphine) and transdermal buprenorphine is a convenient, accepted, around-the-clock pain reliever. Its lower potential for abuse should make it a more desirable pain reliever but many payers do not reimburse buprenorphine, driving prescribers and their patients to generic versions of the riskier Schedule II oral opioids such as oxycodone and morphine.

Manejo de conductas aberrantes inducidas por opioides en una consulta externa de «cuidados paliativos precoces»

ObjectiveTo audit the quality of the prevention, detection and management of aberrant opioid-induced behaviours (AB) in patients attending our Early Palliative Care outpatient clinic. MethodsWe report data belonging to patients with detected AB who participated in a second descriptive retrospective observational study, which was conducted on 100 consecutive cancer patients attending our outpatient clinic between November 2015 and June 2016. The nature and characteristics of the Early Palliative Care clinic, the methodology employed to perform the clinical audit (sample size and selection, variables chosen etc.) have already been described for the first audit and published elsewhere. ResultsOut of 100 patients in our audit sample, 52 patients were taking prescribed opioids chronically and 10 out of them presented AB whereas only 4 fulfilled DSM-V criteria for opioid addiction –therefore, in our series prevalence of AB was 19.2% and opioid addiction 7.7%. Common characteristics of patients with AB were: younger age (median 58 years), presence of known risk factors for AB (basically substance use disorder and psychiatric pathology), wide range of opioids used for basal pain (oral morphine extended release, oral oxycodone extended release, oral hydromorphone extended release, fentanyl transdermal, buprenorphine transdermal), large dose of opioids used (morphine equivalent daily dose 259.5mg) and long opioid treatment duration (median, 2.75 years). Eighty percent of the patients with AB were taking rapid onset opioids as rescue doses for breakthrough cancer pain, and rapid onset opioids were involved in the insidious development of the 4 addiction cases. Urine drug screens and screening – questionnaires for opioid misuse/abuse risk were found to be unhelpful in the prevention and detection of AB. An essential part in our therapeutic measures was the performing of opioid rotations to buprenorphine and/or methadone in 70% of the patients – these opioid rotations were found to be efficacious pain-wise and in the management of the AB, but also complicated and distressing for the patients, several of whom perceived persistent withdrawal symptoms. In 3 cases both rapid onset opioids and immediate release opioids, as rescue doses for breakthrough cancer pain, had to be strictly forbidden. Forty percent of the AB patients are still followed at our Early Palliative Care outpatient clinic, and we expect a prolonged follow-up given the fact that they are also long cancer survivors. DiscussionOur data support the emerging relevance of AB in the chronic cancer pain and breakthrough cancer pain population. In our series the prevalence of AB and opioid addiction double previous published figures. This might be explained by the widespread adequate medical use of opioids in our environment, but also might reflect the fact that it is very easy to send these complex cases early to our Early Palliative Care outpatient clinic. Based on our own clinical experience, it seems that good clinical practice performed by highly qualified professionals has been the key to our success in controlling the AB. We have found urine drug screens and screening questionnaires, suggested in the literature, not to be helpful. On the other hand, clinical expertise in the detection of AB and in performing complex opioid rotations to buprenorphine and/or methadone, have been key to analgesic success and in controlling AB, just as we had expected previously in our current internal protocol. ConclusionThe unquestionable emergence of AB seems to be, to a certain extent, a relatively unavoidable side – effect of adequate opioid consumption for the relief of cancer pain. Our data support our conviction that the problem is manageable with expert clinical practice. Therefore, we believe the answer to the problem is not to increase restrictions on cancer patients to access opioids (including rapid onset opioid) in order to avoid an expansion of AB, but to increase our efforts in order to prevent these behaviours, and once detected to organize adequate specialized care.

The Experiences of Buprenorphine (Sovenor®) via Transdermal Patch in Elderly with Poor Renal Function

Transdermal buprenorphine is an opioid analgesic used in the management of moderate-severe pain via transdermal pathway. The case series is to discuss the efficacy and safety of transdermal buprenorphine (Sovenor®) in elderly patients with chronic low back pain under renal function impairment condition. We presented 4 cases demonstrating successful therapy in management of chronic severe low back pain in elderly, who were with poor renal function. Transdermal buprenorphine benefited significantly in those patients’ symptoms, and the elderly tolerated transdermal buprenorphine well under good compliance.. In conclusion, transdermal buprenorphine is effective in treating chronic neuropathic pain, and to be a safe analgesic for the elderly. In light of evidence for efficacy, safety, tolerability, and cost, physicians may consider transdermal buprenorphine as the priority choice as pain management in the elderly.

Comparison of efficacy and safety of transdermal buprenorphine patch applied 48 versus 72 hours preoperatively in providing adequate postoperative analgesia following major abdominal surgeries

Introduction: A transdermal drug delivery system provides steady and continuous drug delivery. As the onset of action is delayed, it has to be applied preoperatively to provide optimal postoperative analgesia. Aim: To compare the efficacy and safety of transdermal buprenorphine patches applied 48 and 72 h preoperatively in providing adequate postoperative analgesia following major abdominal surgeries and the incidence of side effects. Materials and Methods: This prospective randomized, double-blinded study was conducted in a tertiary care institution. Thirty patients undergoing laparotomy were recruited. Group A (n = 15) received a transdermal buprenorphine 10 mg patch with a delivery rate of 10 μg/h, which was applied approximately 48 h before surgery, whereas in group B (n = 15) buprenorphine 10 mg patch was applied 72 h preoperatively. All patients received general anesthesia following standardized protocol. Postoperative pain was assessed using numerical rating scale (NRS). The Mann–Whitney U test and independent t-test were used for statistical analysis. Results: NRS was significantly high in group A for up to 30 h postoperatively as compared to group B. From 36 to 48 h, it was comparable. The need for rescue analgesia was significantly high in group A as compared to group B. Significant number of patients in group B experienced nausea and vomiting (53.33% vs. 26.67%) and sedation (20% vs. 13.33%) in the preoperative period. Conclusion: Transdermal buprenorphine patch applied 72 h preoperatively provided better analgesia than the one applied 48 h before surgery. However, its preoperative use in patients without painful conditions predisposes them to develop side effects.

A Comparative Study of Transdermal Buprenorphine and Oral Morphine in the Treatment of Chronic Pain of Malignant Origin.

Background and Objective:The study was designed to compare the efficacy and adverse effects of buprenorphine transdermal (TD) against oral morphine in pain management of cancer patient.Methods:A randomized open-labeled prospective study was done in palliative cancer pain clinic in a tertiary care medical college between August 2017 and January 2018, to compare the efficacy (pain assessed by VAS) and adverse events (CTCAEv4) between arm A, buprenorphine TD, (20 μg/h, extended 7 days formulation) and arm B, oral morphine (10mg immediate releasing formulation). Patients with solid tumour malignancies with VAS score >40 (moderate to severe pain) were included in study.Results:63 patients were analyzed. Commonest primary cancers were breast in females and head and neck in male individuals in both arms. Initial VAS score of arm A and arm B were 81.25 and 82.26 respectively. By 1st week, 11 arm A patients were relieved from pain. Another 17 patients of arm A became pain free by 2nd week, total dose of 40 μg/h. Only 4 patients needed 60 μg/h for pain relief. In arm B, 2 patients were relieved by 1 week with total 30mg/day morphine, 11patients were relieved with 60 mg/day by 2nd week and 12 patients with 90 mg/day. 6 patients were relieved with 120 mg/day dose at the end of 4th week. Nausea and constipation were stastically higher in Arm B compared to that of Arm-A.Conclusions:TD Buprenorphine had similar efficacy with oral morphine, with better toxicity profile and better compliance.

Transdermal buprenorphine poorly tolerated in people with dementia

Transdermal buprenorphine poorly tolerated in people with dementia

Effectiveness and tolerability of transdermal buprenorphine patches: a multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain

BackgroundWe examined the effectiveness and tolerability of transdermal buprenorphine (TDB) treatment in real-world setting in Asian patients with musculoskeletal pain.MethodsThis was an open-label study conducted in Hong Kong, Korea, and the Philippines between June 2013 and April 2015. Eligible patients fulfilled the following criteria: 18 to 80 years of age; clinical diagnosis of osteoarthritis, rheumatoid arthritis, low back pain, or joint/muscle pain; chronic non-malignant pain of moderate to severe intensity (Box-Scale-11 [BS-11] pain score ≥ 4), not adequately controlled with non-opioid analgesics and requiring an opioid for adequate analgesia; and no prior history of opioid treatment. Patients started with a 5 μg/h buprenorphine patch and were titrated as necessary to a maximum of 40 μg/h over a 6-week period to achieve optimal pain control. Patients continued treatment with the titrated dose for 11 weeks. The primary efficacy endpoint was the change in BS-11 pain scores. Other endpoints included patients’ sleep quality and quality of life as assessed by the 8-item Global Sleep Quality Assessment Scale (GSQA) questionnaire and the EuroQol Group 5-Dimension Self-Report Questionnaire-3 Level version (EQ-5D-3 L), respectively. Tolerability was assessed by collecting adverse events.ResultsA total of 114 eligible patients were included in the analysis. The mean BS-11 score at baseline was 6.2 (SD 1.6). Following initiation of TDB, there was a statistically significant improvement in BS-11 score from baseline to visit 3 (least squares [LS] mean change: -2.27 [95% CI -2.66 to −1.87]), which was maintained till the end of the study (visit 7) (LS mean change: −2.64 [95% -3.05 to −2.23]) (p < 0.0001 for both). The proportion of patients who rated sleep quality as ‘good’ increased from 14.0% at baseline to 26.9% at visit 6. By visit 6, the mean EQ VAS score increased by 7.7 units (SD 17.9). There were also significant improvements in patients’ levels of functioning for all EQ-5D-3 L dimensions from baseline at visit 6 (p < 0.05 for all). Seventy-eight percent of patients reported TEAEs and 22.8% of patients discontinued due to TEAEs. TEAEs were generally mild to moderate in intensity (96.5%).ConclusionsTDB provides effective pain relief with an acceptable tolerability profile over the 11-week treatment period in Asian patients with chronic musculoskeletal pain. More studies are needed to examine the long-term efficacy and safety of TBD treatment in this patient population.Trial registrationClinicalTrials.gov NCT01961271. Registered 7 October 2013 (retrospectively registered; first patient was enrolled on 28 June 2013 and last patient last visit date was 26 Apr 2015).

Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review.

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion.

Injectable naltrexone, oral naltrexone, and buprenorphine utilization and discontinuation among individuals treated for opioid use disorder in a United States commercially insured population

We investigated prescribing patterns for four opioid use disorder (OUD) medications: 1) injectable naltrexone, 2) oral naltrexone, 3) sublingual or oralmucosal buprenorphine/naloxone, and 4) sublingual buprenorphine as well as transdermal buprenorphine (which is approved for treating pain, but not OUD) in a nationally representative claims-based database (Truven Health MarketScan®) of commercially insured individuals in the United States. We calculated the prevalence of OUD in the database for each year from 2010 to 2014 and the proportion of diagnosed patient months on OUD medication. We compared characteristics of individuals diagnosed with OUD who did and did not receive these medications with bivariate descriptive statistics. Finally, we fit a Cox proportional hazards model of time to discontinuation of therapy as a function of therapy type, controlling for relevant confounders.From 2010 to 2014, the proportion of commercially insured individuals diagnosed with OUD grew by fourfold (0.12% to 0.48%), but the proportion of diagnosed patient-months on medication decreased from 25% in 2010 (0.05% injectable naltrexone, 0.4% oral naltrexone, 23.1% sublingual or oralmucosal buprenorphine/naloxone, 1.5% sublingual buprenorphine, and 0% transdermal buprenorphine) to 16% in 2014 (0.2% injectable naltrexone, 0.4% oral naltrexone, 13.8% sublingual or oralmucosal buprenorphine/naloxone, 1.4% sublingual buprenorphine, and 0.3% transdermal buprenorphine). Individuals who received medication therapy were more likely to be male, younger, and have an additional substance use disorder compared with those diagnosed with OUD who did not receive medication therapy. Those prescribed injectable naltrexone were more often male, younger, and diagnosed with additional substance use disorders compared with those prescribed other medications for opioid use disorder (MOUDs). At 30 days after initiation, 52% for individuals treated with injectable naltrexone, 70% for individuals treated with oral naltrexone, 31% for individuals treated with sublingual or oralmucosal buprenorphine/naloxone, 58% for individuals treated with sublingual buprenorphine, and 51% for individuals treated with transdermal buprenorphine discontinued treatment. In the Cox proportional hazard model, use of injectable naltrexone, oral naltrexone, sublingual buprenorphine, and transdermal buprenorphine were all associated with significantly greater hazard of discontinuing therapy beginning >30days after MOUD initiation (HR=2.17, 2.54, 1.15, and 2.21, respectively, 95% CIs 2.04–2.30, 2.45–2.64, 1.10–1.19, and 2.11–2.33), compared with the use of sublingual or oralmucosal buprenorphine/naloxone.This analysis demonstrates that the use of evidence-based medication therapies has not kept pace with increases in OUD diagnoses in commercially insured populations in the United States. Among those who have been treated, discontinuation rates >30days after initiation are high. The proportion treated with injectable naltrexone, oral naltrexone, and transdermal buprenorphine grew over time but remains small, and the discontinuation rates are higher among those treated with these medications compared with those treated with sublingual or oralmucosal buprenorphine/naloxone. In the face of the opioid overdose and addiction crisis, new efforts are needed at the provider, health system, and policy levels so that MOUD availability and uptake keep pace with new OUD diagnoses and OUD treatment discontinuation is minimized.

(276) An open-label, Multicenter Study of the Safety, Pharmacokinetics, and Effectiveness of Buprenorphine Transdermal System (BTDS) in Children from 7 to 16 years of age, Inclusive, who Required Continuous Opioid Analgesia for Moderate to Severe Pain

(276) An open-label, Multicenter Study of the Safety, Pharmacokinetics, and Effectiveness of Buprenorphine Transdermal System (BTDS) in Children from 7 to 16 years of age, Inclusive, who Required Continuous Opioid Analgesia for Moderate to Severe Pain

Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. Descriptive, cross-sectional study, utilising a 7-day medication diary. Community-based treatment settings, Australia. A sample of 1101 people prescribed opioids for chronic non-cancer pain. Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd.

Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus)

ObjectiveTo determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine. Study designA randomized comparative experimental trial. AnimalsTwenty-four Yorkshire gilts weighing 27.8±2.2 kg (mean±standard deviation). MethodsAnimals were randomly assigned to different doses of transdermal patches (TPs) of fentanyl (50 μg hour−1, 75 μg hour−1 and 100 μg hour−1) or buprenorphine (35 μg hour−1 and 70 μg hour−1), once or twice. Thirteen blood samples were obtained for each TP applied. Plasma concentrations were determined, and the area under the curve, peak serum concentration (Cmax) and time to Cmax were calculated. ResultsFentanyl: Cmax was observed at different time points: for the first TP application: 30 hours for 50 μg hour−1, 6 hours for 75 μg hour−1 and 100 μg hour−1 patches; and for the second TP application: 30 hours for 50 μg hour−1 and 36 hours for 75 μg hour−1 patches. Buprenorphine: serum concentrations were not detected for the 35 μg hour−1 patch; Cmax was observed at different times for the 70 μg hour−1 patch: 18 hours (n = 1), 24 hours (n = 3), 30 hours (n = 1) and 42 hours (n = 1) after application of the first patch and 12 hours after the second patch. Conclusions and clinical relevanceA relevant serum concentration obtained with fentanyl TP dosed at 75 μg hour−1 or 100 μg hour−1suggests that TPs could represent an analgesia option for laboratory pigs weighing 25–30 kg. As concentrations of buprenorphine were variable, this study does not support the use of buprenorphine TPs in pigs. Consecutive fentanyl or buprenorphine TPs did not provide reliable serum concentrations. Further pharmacokinetic studies and analgesiometric tests in swine are needed to confirm the clinical adequacy of TPs.

Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data

ABSTRACTObjective: Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases.Methods: Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database.Results: There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 −0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia.Conclusions: The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

Effects of buprenorphine on QT intervals in healthy subjects: results of 2 randomized positive- and placebo-controlled trials

ABSTRACTObjectives: To study the effect of transdermal buprenorphine on QTc prolongation at dose levels of 10, 40, and 80 mcg/h, (BTDS 10, BTDS 40, BTDS 80).Methods: Two randomized, placebo- and positive-controlled, parallel-group, dose-escalating clinical studies evaluated healthy adult subjects randomized to BTDS, placebo, or moxifloxacin in the first study; and to BTDS only, BTDS plus naltrexone, naltrexone alone at the same dose, placebo, or moxifloxacin in the second study. QT intervals were corrected for heart rate using data from each individual subject (QTcI).Results: In the first study (n = 44), the maximum upper bounds of the 90% confidence interval (CI) for mean placebo-corrected change from baseline in QTcI across 13 time points over 24 h were: 10.0 msec for BTDS 10 (Day 6) and 13.3 msec for BTDS 40 (Day 13); and 17.0 msec (Day 6) and 15.5 msec (Day 13) for moxifloxacin, respectively. Similarly, in the second study (n = 66), the upper bound of the 90% CI for mean placebo-corrected change from baseline for QTcI was under 10 msec at all time points for BTDS 10 (maximum upper bound, 5.63 msec), over 10 msec at 5 time points for BTDS 40 (maximum 11.81 msec) and over 10 msec at all 13 time points for BTDS 80 (maximum, 14.14 msec). Naltrexone administered with BTDS eliminated the QTcI prolongation seen with supratherapeutic BTDS doses (BTDS 40, BTDS 80) administered without naltrexone.Conclusions: At the therapeutic dose of 10 mcg/h, BTDS has no clinically significant effect on QTc. At supratherapeutic doses of 40 and 80 mcg/h, BTDS treatment produces prolongation of QTcI similar in magnitude to that produced by a 400 mg dose of moxifloxacin. Despite the modest, dose-dependent increase in QTcI noted in these studies, transdermal buprenorphine has not been associated with proarrhythmic effects.

Safety and efficacy of transdermal buprenorphine versus oral tramadol for the treatment of post-operative pain following surgery for fracture neck of femur: A prospective, randomised clinical study.

Background:Transdermal buprenorphine, which is used in chronic pain management, has rarely been studied for use in acute pain management. The aim of this study was to compare the safety and efficacy of transdermal buprenorphine patch to oral tramadol for post-operative analgesia, following proximal femur surgeries.Methodology:Fifty adult patients undergoing surgery for hip fracture under spinal anaesthesia were included in this study. One group (Group TDB) received transdermal buprenorphine 10 mcg/h patch applied a day before the surgery and other group received oral tramadol 50 mg three times a day for analgesia (Group OT). They were allowed to take diclofenac and paracetamol tablets for rescue analgesia. Pain scores at rest, on movement, rescue analgesic requirement and side effects were compared between the groups over 7 days. Chi-square and independent sample t-test were used for categorical and continuous variables, respectively.Results:Resting pain scores and pain on movement were significantly lower in TDB Group on all 7 days starting from 24 h post-operatively. Rescue analgesic requirement was significantly lower in TDB Group compared to OT Group. All the patients needed rescue analgesic in OT Group whereas 68% of the patients needed the same in TDB Group. Incidence of vomiting was less and satisfaction scores were much higher in TDB Group as compared to OT Group (79% vs. 66%, P < 0.001).Conclusion:Transdermal buprenorphine can be safely used for post-operative analgesia and is more efficacious in reducing post-operative pain after 24 hours, with fewer side effects when compared to oral tramadol.

Efficacy of transdermal buprenorphine patch on post-operative pain relief after elective spinal instrumentation surgery.

Background and Aims:Transdermal buprenorphine patch (TDB) is increasingly used for chronic pain management because of non-invasive dosing, longer duration of action and minimal side effects. However its role in acute post-operative pain management for spinal instrumentation surgery is not well established. The aim of this study was to evaluate the analgesic efficacy of buprenorphine patch for postoperative pain relief in patients undergoing spinal instrumentation surgery.Methods:In this randomised, placebo-controlled, double-blinded, prospective study, 70 adult patients undergoing elective spinal instrumentation surgery were randomly allocated into two groups-TDB Group (buprenorphinepatch) and TDP Group (placebo patch). Time to first rescue analgesic requirement was the primary outcome. All patients also were monitored for total rescue analgesic requirement, drug-related adverse effect and haemodynamic status till 48 h after surgery. Statistical analysis was carried out using student independent t-test if normally distributed or with Mann–Whitney U-test if otherwise.Results:Time to first post-operative rescue analgesic (tramadol) requirement was much delayed in TDB Group than TDP Group (708.0 ± 6.98 min vs 54 ± 0.68 min, P < 0.001) and the total tramadol requirement was higher in TDB Group (490.60 ± 63.09 averagevs. 162.93 ± 63.91 mg, P < 0.001). Intra-and post-operative haemodynamic status was also stable in TDB Group without any adverse event.Conclusion:A TDB patch (10 μg/hour) applied 24 hours before surgery can be used as a postoperative analgesic for lumber fixation surgery without any drug-related adverse effect.

The role of transdermal buprenorphine in the treatment of chronic pain in elderly patients

Buprenorphine is a synthetic opioid with partially agonist effects on μ (MOR) receptors and slightly less internal activity compared to morphine. Buprenorphine binds with κ1 (KOR 1), κ2 (KOR 2), δ (DOR) receptors and with ORL–1 (orphan–related ligand–1, NOR) receptors. The drug is absorbed after transmucosal (approximately 30–50%) and transdermal (biological bioavailability equals approximately 50%) route of administration due to significant lipophilicity. Buprenorphine concentration in plasma slowly increases after transdermal patch application reaching minimal effective concentrations after approximately 12–24 h and maximal concentrations of the drug in the serum after approximately 60–80 h. The drug is metabolized in the liver, mainly through CYP3A4 to an active metabolite – norbuprenorphine. Both buprenorphine and norbuprenorphine undergo subsequently glucuronidation through conjugates and in this forms are excreted with the bile. The majority of the drug is excreted with the stool in the form of unbound buprenorphine or norbuprenorphine with 10–30% of the drug excreted with the urine. Buprenorphine metabolism causes that the risk of pharmacokinetic drug interactions is low. Moreover, buprenorphine is safe drug in patients with renal impairment. Mild and moderate hepatic impairment do not significantly influence buprenorphine pharmacokinetics. In this paper a review of buprenorphine clinical studies (with randomization and nonrandomized) conducted in elderly patients was undertaken. Buprenorphine administered in patches by the transdermal is frequently used in the treatment of chronic pain in cancer patients and in the course of other diseases. Buprenorphine may be used successfully in the treatment of neuropathic pain. Buprenorphine administered by transdermal route is preferred opioid analgesic in elderly patients with moderate to severe chronic pain due to beneficial pharmacodynamics and pharmacokinetics

Insights into Chronic Postsurgical Pain

Most postsurgical patients experience moderate to severe acute pain which, in some patients, transitions to chronic postsurgical pain (CPSP). Optimal pain control of acute surgical pain will likely blunt or prevent the transition of acute postsurgical pain (APSP) to CPSP. While there are known risk factors for such chronification of pain type, and certain surgeries (such as limb amputation) and approaches (open versus laparoscopic) are associated with higher rates, it is impossible to predict which patients will transition to CPSP. Additionally, despite knowledge and an armamentarium of analgesics, APSP may be suboptimally controlled. Opioid analgesics can be safe and effective for APSP, but there are legal, social, governmental, clinical, and even cultural barriers to their use. Patients may be reluctant to take opioid agents even when available. Effective APSP control is essential to promote speedy recovery, rapid ambulation, good rehabilitation, and, ultimately, hospital discharge. Since, pain can be multimechanistic, multimodal or combination therapy may be required. Fixed-dose combination products are available that may reduce total opioid consumption by combining a small amount of opioid with an NSAID or paracetamol (acetaminophen). For CPSP, transdermal buprenorphine appears to offer certain advantages in that it is an effective analgesic, can be safely used without dosage adjustment in the elderly and in those with compromised renal function, and the patch delivery system reduces pill burden and reduces the problem of non-compliance. Since tolerability is an important consideration for any pain relievers, side effects should be managed proactively and promptly.

The switch from buprenorphine to tapentadol: is it worth?

Opioid analgesia continues to be the primary pharmacologic intervention for managing acute pain and malignant pain in both hospitalized and ambulatory patients. The increasing use of opioids in chronic nonmalignant pain is more problematic. Opioid treatment is complicated with the risks raised by adverse effects, especially cognitive disturbance, respiratory depression but also the risk of tolerance, opioid abuse and drug-disease interactions. Despite the growing number of available opioids within the last years, adequate trials of opioid rotation are lacking and most of the information is anecdotal. This article reviews the clinical evidence surrounding the switch from transdermal buprenorphine to tapentadol in malignant and non-malignant pain. Tapentadol acts on both the μ-opioid receptors (MOR) and on the neuronal reuptake of noradrenaline with a limited usefulness in acute pain management while buprenorphine is a mixed agonist-antagonist, and both present some advantages over other opioids. Both drugs show particular pharmacodynamic and pharmacokinetic properties which reduce the risks of development of tolerance, opioid abuse, diversion and determine fewer hormone changes than the "classical opioids" making these opioids more attractive than other opioids in long term opioid treatment. However, in the absence of powered clinical trials, the evidence to support the method used for transdermal buprenorphine rotation to tapentadol is weak.

Transdermal buprenorphine for OA pain increases satisfaction

Transdermal buprenorphine for OA pain increases satisfaction