Buprenorphine Transdermal System Research Articles

Buprenorphine for pain management vs. chronic hydrocodone-acetaminophen therapy when comorbidities increase the risk of opioid-related side effects

A clinical decision report using: Gordon A, Callaghan D, Spink D, et al. Buprenorphine transdermal system in adults with chronic low back pain: a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase. Clin Ther. 2010;32(5):844-860. https://doi.org/10.1016/j.clinthera.2010.04.018 for a patient on long-term opioid therapy with high risk factors for adverse effects

In Vitro-In Vivo Correlation of Buprenorphine Transdermal Systems Under Normal and Elevated Skin Temperature.

Application of external heat using a heating pad over buprenorphine transdermal system, Butrans® has been shown to increase systemic levels of buprenorphine in human volunteers. The purpose of this study was to perform in vitro permeation studies at normal as well as elevated temperature conditions to evaluate the correlation of in vitro data with the existing in vivo data. In vitro permeation tests (IVPT) were performed on human skin from four donors. The IVPT study design was harmonized to a previously published clinical study design and skin temperature was maintained at either 32 ± 1°C or 42 ± 1°C to mimic normal and elevated skin temperature conditions, respectively. IVPT studies on human skin were able to demonstrate heat induced enhancement in flux and cumulative amount of drug permeated from Butrans® which was reasonably consistent with the corresponding enhancement observed in vivo. Level A in vitro-in vivo correlation (IVIVC) was established using unit impulse response (UIR) based deconvolution method for both baseline and heat arms of the study. The percent prediction error (%PE) calculated for AUC and Cmax values was less than 20%. The studies indicated that IVPT studies performed under the same conditions as those of interest in vivo may be useful for comparative evaluation of the effect of external heat on transdermal delivery system (TDS). Further research may be warranted to evaluate factors, beyond cutaneous bioavailability (BA) assessed using an IVPT study, that can influence plasma exposure in vivo for a given drug product.

Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM).

BackgroundChronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia.ObjectiveThe objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms.MethodsWe conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events.ResultsThe mean depression change was − 0.66 (95% confidence interval − 2.27 to 0.94) in the active group (n = 80) and − 3.30 (− 4.68 to −1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55–4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by − 1.11 (− 2.16 to − 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (− 0.11 to 6.19), p = 0.059] or pain [0.47 (− 0.77 to 1.71), p = 0.456] from 0 to 13 weeks. Thirty-five patients were withdrawn from the study because of adverse reactions, deterioration or death: 25 (31.3%) during active treatment [23 (52.3%) who received buprenorphine], and ten (12.2%) in the placebo group. The most frequently occurring adverse events were psychiatric (17 adverse reactions) and neurological (14 adverse reactions).ConclusionAnalgesic treatment did not reduce depression while placebo appeared to improve depressive symptoms significantly by comparison, possibly owing to the adverse effects of active buprenorphine. The risk of adverse events warrants caution when prescribing buprenorphine for people with advanced dementia.Trial registrationClinicalTrials.gov NCT02267057 (registered 7 July, 2014) and Norwegian Medicines Agency EudraCT 2013-002226-23.Electronic supplementary materialThe online version of this article (10.1007/s40266-018-0546-2) contains supplementary material, which is available to authorized users.

Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM).

PurposeBuprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population.Patients and methodsOne hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome.ResultsOf the 44 patients who received active buprenorphine 5 µg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group (p<0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95–182, p=0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45–235, p=0.006). Daytime activity dropped significantly during the second day of active treatment (−21.4%, p=0.005) and decreased by 12.9% during the first week (p=0.053).ConclusionActive buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.

Perioperative analgesia with a buprenorphine transdermal patch for hallux valgus surgery: a prospective, randomized, controlled study.

PurposeHallux valgus surgery often results in significant postoperative pain. Adequate control of pain is essential for patient satisfaction and improves the outcome of the procedure. This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent hallux valgus surgery.Patients and methodsA total of 90 patients were randomly divided into the following three groups based on the perioperative analgesic method: flurbiprofen axetil intravenous injection (Group F), oral celecoxib (Group C), and buprenorphine transdermal delivery system (BTDS) (Group BTDS). The pain status, degree of satisfaction, adverse effects, and administration of tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 2, and postoperative day 3.ResultsThe BTDS could effectively control perioperative pain for patients undergoing hallux valgus surgery. The analgesic effect of the BTDS was better than that of oral celecoxib. In addition, statistically significant differences were not observed in the visual analog scale (VAS) scores, adverse effects, and rescue analgesia between the patients who received the BTDS and the patients who received the flurbiprofen axetil intravenous injection. However, the degree of patient satisfaction of the BTDS group was significantly higher (P<0.05) than that of the other two groups.ConclusionThe BTDS (a preemptive analgesia regimen) could exert an analgesic effect during the perioperative period for patients who had received hallux valgus surgery, and this effect is beneficial for sustaining postoperative physiological and psychological states and promoting functional rehabilitation.

Long-Term Pain Treatment Did Not Improve Sleep in Nursing Home Patients with Comorbid Dementia and Depression: A 13-Week Randomized Placebo-Controlled Trial.

Objective: Previous research indicates that pain treatment may improve sleep among nursing home patients. We aimed to investigate the long-term effect of pain treatment on 24-h sleep patterns in patients with comorbid depression and dementia.Design: A 13-week, multicenter, parallel-group, double-blind, placebo-controlled randomized clinical trial conducted between August 2014 and September 2016.Setting: Long-term patients from 47 nursing homes in Norway.Participants: We included 106 patients with comorbid dementia and depression according to the Mini Mental Status Examination (MMSE) and the Cornell Scale for Depression in Dementia (CSDD).Intervention: Patients who were not using analgesics were randomized to receive either paracetamol (3 g/day) or placebo tablets. Those who already received pain treatment were randomized to buprenorphine transdermal system (maximum 10 μg/h/7 days) or placebo transdermal patches.Measurements: Sleep was assessed continuously for 7 days by actigraphy, at baseline and in week 13. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), wake after sleep onset (WASO), early morning awakening (EMA), and number of wake bouts (NoW) were evaluated. In addition, daytime total sleep time (DTS) was estimated. Pain was assessed with Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2).Results: The linear mixed model analyses for TST, SE, SOL, WASO, EMA, NoW and DTS showed no statistically significant differences between patients who received active pain treatment and those who received placebo. Post hoc subgroup analyses showed that there were no statistically significant differences between active treatment and placebo from baseline to week 13 in patients who were in pain (MOBID-2 ≥ 3) at baseline, or in patients who had poor sleep (defined as SE < 85%) at baseline. Patients who received active buprenorphine showed an increase in TST and SE compared to those who received active paracetamol.Conclusion: The main analyses showed that long-term pain treatment did not improve sleep as measured with actigraphy. Compared to paracetamol, TST and SE increased among patients who received buprenorphine. This could indicate that some patients had beneficial effects from the most potent pain treatment. However, based on the present findings, long-term pain treatment is not recommended as a strategy to improve sleep. Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02267057.

Effects of pain treatment on sleep in nursing home patients with dementia and depression: A multicenter placebo-controlled randomized clinical trial.

ObjectiveTo investigate the effects of pain treatment on sleep in nursing home (NH) patients with dementia and depression.MethodsA multicenter, 2‐armed, double‐blinded, placebo‐controlled, randomized clinical trial conducted between August 2014 and September 2016. One hundred six long‐term patients from 47 NHs in Norway with dementia and depression according to the Mini‐Mental State Examination and the Cornell Scale for Depression in Dementia were included. Patients received stepwise pain treatment in which those who did not use analgesics were randomized to receive either paracetamol (3 g/day) or placebo tablets; those who already used pain treatment were allocated to buprenorphine transdermal system (max. 10 μg/h/7 days) or placebo transdermal patches. Sleep was assessed continuously for 14 days by actigraphy, 1 week of baseline measurement, and 1 week of ongoing treatment. The following sleep parameters were evaluated: total sleep time, sleep efficiency (SE), sleep onset latency (SOL), wake after sleep onset, early morning awakening (EMA), and number of wake bouts.ResultsIn the intervention group (paracetamol/buprenorphine), SE (70%‐72%), SOL (32‐24 min), and EMA (50‐40 min) improved compared with the control group (SE, 70%‐67%; SOL, 47‐60 min; EMA, 31‐35 min). Treatment effects were significant (P < .01, P < .05, and P < .05, respectively).ConclusionCompared with placebo, pain treatment improved sleep as measured with actigraphy. This implies that sleep, pain, and depression in NH patients should be critically evaluated and that pain treatment should be considered to be a potentially beneficial treatment.

Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system.

BackgroundThe buprenorphine transdermal system (BTDS) is approved in the US for the management of chronic pain. Due to its high affinity for μ-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing μ-opioid-receptor agonists, including immediate-release (IR) opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable.Materials and methodsThis post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate–severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917). Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI) were recorded.ResultsThe most common supplemental IR opioids prescribed during BTDS treatment (n=354) were hydrocodone–acetaminophen and oxycodone–acetaminophen. The mean daily dose of IR opioids (morphine equivalents) for supplemental analgesia was 22 mg. At baseline, BPI – pain intensity and BPI – interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in both groups.ConclusionPatients who were prescribed IR opioids reported lower scores for BPI pain intensity and pain interference to levels similar to patients receiving BTDS without IR opioids, without increasing the rate or severity of treatment-emergent adverse events. Patients prescribed concomitant use of IR opioids with BTDS had greater treatment persistence. The results of this post hoc analysis provide support for the concomitant use of IR opioids for supplemental analgesia during the management of moderate–severe chronic pain with BTDS.

(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

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.

Safety of buprenorphine transdermal system in the management of pain in older adults

ABSTRACTObjectives: To evaluate whether buprenorphine transdermal system (BTDS; Butrans®) is an option for the treatment of chronic pain in older adults.Methods: This retrospective analysis of 16 placebo- and active-controlled and uncontrolled studies (N = 6566) evaluated the safety and tolerability profile in patients exposed to BTDS and compared the safety profiles associated with BTDS treatment in older patients ≥ 65 years of age (65 to 98 years) and younger patients < 65 years of age (18 to 64 years). Safety analyses included adverse events (AEs), laboratory values, and electrocardiograms.Results: Overall, the incidence of AEs was similar in the ≥ 65 year patient cohort (N = 1715) and the < 65 year patient cohort (N = 4843) (63.8% and 61.0%, respectively). The older patient cohort experienced more constipation, peripheral edema, and urinary tract infection, but fewer application-site AEs (eg, erythema, irritation, pruritus, rash) and headaches. A statistically significant treatment-by-age interaction was observed for fall, arthralgia, and localized and non-application site-related rash, suggesting a differential increase in the risk of these events among older patients treated with BTDS that cannot be explained by age or treatment alone. A similar trend was observed for accidents and injuries, and for falls, in patients treated with both BTDS and active controls (oxycodone/acetaminophen [OXY/APAP] and hydrocodone/acetaminophen [HCD/APAP]), suggesting an opioid class effect. However, due to small sample sizes of the active control groups, a statistical test of treatment-by-age interaction could not be conducted for the active controls. The incidences of serious AEs and of clinically significant increases in liver enzymes, such as AST, ALT and bilirubin were small, regardless of age.Conclusion: BTDS appears to be a viable option for the management of pain in older adults, but the benefits need to be tempered by potential risks among older adults.

Buprenorphine transdermal system utilization

ABSTRACTObjectives: To evaluate utilization patterns in patients initiating buprenorphine transdermal system (BTDS), CIII, and estimate the proportion decreasing their total opioid dose over time.Methods: This retrospective cohort study used data from the Truven Health Analytics MarketScan® Commercial Claims and Encounters Database from 1 January 2011 through 31 December 2015. Eligible individuals were adults aged 18–64 years newly dispensed BTDS (index prescription) who had at least six months of insurance coverage prior to (baseline period) and following (study period) the index prescription.Results: Back and neck pain was the most common pain condition in the study population (n = 31,533) and 88% were dispensed opioids in the baseline period. Nearly half (48%) received BTDS in a strength of 10 mcg/hour as their index prescription. Most (80%) patients prescribed BTDS had concomitant prescriptions for other opioids, chiefly immediate-release (IR) opioids (77%). During the baseline period, median opioid dose among patients prescribed opioids was 50 morphine-equivalent doses (MED), with 33% of patients using nonsteroidal anti-inflammatory drugs and 44% adjuvant analgesics. During the study period, BTDS use lasted a median 30 days and mean 100 days. Median dose of BTDS remained largely constant, and median dose of all opioids during continuous use of BTDS was 65.6 units MED. However, 24% of patients reduced total units MED from the baseline period (median mean dose, 74.5 units MED) until the end of the study period (42.8).Conclusions: Most patients initiating treatment with BTDS had a history of treatment with IR opioids. Though the average change in total opioid daily dose after patients were prescribed BTDS was modest, an important subpopulation of approximately one-quarter of patients were able to markedly reduce their total units MED compared with prior opioid therapy. BTDS should be investigated as an option to help patients step down from higher opioid doses.

Analysis of the Abuse and Diversion of the Buprenorphine Transdermal Delivery System.

Prescription opioid abuse and diversion are major causes of morbidity and mortality in the United States. The buprenorphine transdermal delivery system (BTDS) is indicated for the treatment of moderate to severe chronic pain and provides a continuous dose of 5, 7.5, 10, 15, or 20μg/h buprenorphine for 7days. Quarterly rates of abuse and diversion of BTDS were compared with 4 comparator groups: 1) other buprenorphine products, 2) fentanyl patches, 3) extended-release (ER) opioid tablets/capsules, and 4) ER tramadol. Data were obtained from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Treatment Programs Combined (Opioid Treatment and Survey of Key Informants' Patients Programs), and College Survey Programs. Rates were calculated using case counts per population and mentions per prescriptions filled. Poisson regression analysis was used to compare mean rates over time across drug groups after allowing for drug group-specific dispersion parameters. Population adjusted abuse rates were low for BTDS in all of the RADARS System programs compared with the other comparator groups. Findings were similar for the prescription adjusted rates, with BTDS reported at the lowest rates in all programs. Route of abuse differed slightly for BTDS and the comparator groups depending on the program. BTDS was abused and diverted at low rates compared with the other opioid groups in 5 programs of the RADARS System using either population-based rates or prescription dispensed rates. Data from the RADARS System show the BTDS is abused and diverted at low rates compared with other opioid groups including other forms of buprenorphine, fentanyl patches, ER opioid formulations, and ER tramadol.

A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.

Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy. Data were from opioid-naïve adult patients with moderate-to-severe CLBP who participated in a randomized, placebo-controlled, double-blind clinical trial of Butrans(®) (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental Health subscale scores. Patient-reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status. At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post-treatment favored the depressed group on nine of seventeen outcomes. Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient-reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients.

Buprenorphine transdermal system compared with placebo reduces interference in functioning for chronic low back pain

Objective: This study examines the efficacy of the buprenorphine transdermal system (BTDS) for reducing the interference of pain on physical and emotional functioning associated with chronic low back pain (CLBP). Methods: A post-hoc analysis used data from a randomized, placebo-controlled, double-blind trial of patients with moderate-to-severe CLBP. The Brief Pain Inventory (BPI) measured pain interference at screening, following a run-in period, and during the 12-week double-blind treatment phase. Statistical analyses examined treatment arm differences (BTDS vs placebo) for the following: BPI Interference subscale items and subscale scores at the trial end point (week 12); patterns of change in the Interference subscale scores over time; proportions of patients indicating mild or no interference following treatment; and proportions of patients showing improvement (30%, 50%, 2-point, or 4-point change in score from screening to week 12) for each item and subscale. Results: Mean scores for BPI Interference items and Interference subscale were significantly lower (ie, indicated less interference) for BTDS than for placebo (all P < 0.001). Treatment arm differences in Interference subscale scores emerged within 4 weeks of treatment. The BTDS patients were significantly more likely to indicate mild/no interference on 5 of 7 Interference subscale items following treatment (P < 0.05). For most comparisons, BTDS patients were significantly more likely to show criterion-level improvements in Interference item and subscale scores (P < 0.05 for differences). Discussion: Results indicate the efficacy of BTDS treatment, compared with placebo, for reducing the interference of pain on physical and emotional functioning in patients with moderate-to-severe CLBP. The advantage of BTDS was observed within 4 weeks of treatment, and was maintained throughout the 12-week treatment phase.

The Impact of Buprenorphine Transdermal Delivery System on Activities of Daily Living Among Patients With Chronic Low Back Pain

The buprenorphine transdermal delivery system (BTDS) is indicated for reduction of pain in moderate to severe chronic low back pain (CLBP), which can affect patients' ability to perform routine activities of daily living (ADLs). This post hoc analysis of clinical trial data examines the impact of BTDS treatment on CLBP patients' ability to perform ADLs that relate to functioning with low back pain. Data are drawn from a multicenter, enriched enrollment, randomized, placebo-controlled, double-blind 12-week trial of BTDS for pain control among opioid-naive patients with moderate to severe CLBP. The 23 selected ADLs are those that (1) appear in the Low Back Pain Core Set of the International Classification of Functioning, Disability and Health and (2) link to the content of 3 patient-reported outcome instruments administered during the trial. Logistic regression models estimated the odds ratios (ORs) of BTDS patients' ability to perform each ADL at 12 weeks, controlling for baseline ability, relative to placebo. The ORs for 10 ADLs related to sleeping, lifting, bending, and working reached multiplicity-adjusted statistical significance and indicated a greater ability to perform ADLs among BTDS users than among the placebo group. These 10 ORs ranged from 1.9 (no physical health-related restrictions on the kind of work performed) to 2.4 (being able to sleep undisturbed by pain). These results suggest that for patients with moderate to severe CLBP, 12 weeks use of BTDS improves the ability to carry out certain ADLs related to sleeping, lifting, bending, and working.

US practitioner prescribing practices and patient characteristics of those newly treated with a buprenorphine transdermal patch system

Objectives:Medication prescribing information provides guidance to healthcare providers on how to prescribe a drug properly. Oftentimes patient factors in addition to the prescribing information are considered when selecting medications. Utilizing real-world pharmacy and medical claims data, this study assessed US practitioner prescribing practices of US approved transdermal buprenorphine system (BTDS) in relation to BTDS’s full prescribing information (FPI) as well as the relationship between patient factors and initial BTDS dose.Research design and methods:Patients aged ≥18 years initiating BTDS between 1 January 2011 and 30 November 2011 were identified in the IMS Pharmacy and Private Practitioner Medical Claims databases. The index date was defined as the first filled BTDS prescription. Demographics, chronic pain-related medical conditions in the 12 months pre-index and prior medication use in the 6 months pre-index were assessed. Initial BTDS dosing strength, receipt of approved initial BTDS dose per the FPI, and concomitant medications were assessed in the post-index 6 month period.Results:The study included 10,457 patients newly treated with BTDS. The majority of patients were female (69.9%) with a mean (±SD) age of 54.5 (±15.2) years. Within the 6 months prior to the index BTDS prescription, 91.7% of the patients used opioids. Overall, 48.9% of patients were prescribed the FPI approved BTDS dose. When stratified, 73.5% of opioid-naïve patients received the FPI approved initial dose compared to 46.0% of those with prior opioid experience of ≤80 mg morphine-equivalent daily dose. Patients on BTDS alone (i.e. monotherapy) had a higher rate of receiving the FPI approved initial BTDS dose compared to patients on BTDS concomitant regimens (p < 0.05).Conclusions:Practitioners demonstrated that they prescribe in accordance with BTDS’s prescribing information in the majority of opioid-naïve patients and in approximately half of opioid-experienced patients. The initial opioid dose is a critical step in treatment, setting the stage for preventing side-effects and improving treatment effectiveness. Understanding practitioner prescribing practices with regard to the initial dose selection of BTDS may provide insight on how to improve outcomes of care and reduce healthcare resource utilization and costs associated with pain management.Limitations:Data obtained from prescription claims reflect only the activities of prescriptions filled, not medication use or other clinical characteristics observed by physicians when treating patients.

Use of the Low-Dose Buprenorphine Patch: A Response

Dear Editor: As the NDA holder and distributor of Butrans® (buprenorphine) Transdermal System, Purdue Pharma L.P. works to ensure the dissemination of accurate and complete information regarding our products. Purdue commends the Journal of Palliative Medicine on its commitment to end-of-life care and patients with intractable pain; however, we are writing to notify you of misinformation published in Fast Fact #268, “Low-Dose Buprenorphine Patch for Pain.” While the review was well written and informative, there are several statements about Butrans (i.e., low-dose buprenorphine patch) that warrant correction or clarification. Listed below by section of the article and article statement in quotes is a summary of significant misinformation that can lead to safety concerns and/or the improper use of Butrans. • Background: ∘ In addition to being approved for use in treatment of opioid addiction, buprenorphine is approved, as an injectable, for relief of moderate to severe pain, as referenced in the Equianalgesic Ratios section. The U.S. approval for this pain indication predates approval for use in addiction treatment by over 20 years (12/29/1981).1 • Pharmacology: ∘ Buprenorphine is described as providing “analgesia with decreased incidence of sedation, euphoria, and respiratory depression compared to other opioids.” There are no head-to-head studies evaluating these outcomes with Butrans in comparison to other opioids. Although buprenorphine is considered a partial agonist at mu opioid receptors, it can be expected to produce pharmacological effects similar to those of full mu-agonists, especially at the buprenorphine doses delivered by Butrans.2 Therefore, sedation, euphoria, and respiratory depression can occur. In fact, respiratory depression is the primary risk of Butrans.3 • Using the low-dose buprenorphine patch: ∘ This section states, “The U.S. formulation of the buprenorphine transdermal system is recommended for opioid tolerant patients requiring up to 80 mg/day of oral morphine equivalents.” The use of Butrans is not limited to opioid-tolerant patients. Butrans has been studied and is approved for use in opioid-naive patients or in opioid-experienced patients requiring up to 80 mg/day of oral morphine equivalents.3–5 ∘ Butrans is described as being “available in strengths of 5, 10, and 20 mcg/hour.” Butrans 15 mcg/hour was approved in July 2013 and Butrans is now available in four dosage strengths.3 We understand that the reason for this omission is because the new strength became available after the writing of this article. ∘ Withdrawal symptoms are described as “symptoms tend to be milder than with other long-acting opioids.” Although this has been demonstrated with other buprenorphine formulations, clinical studies comparing withdrawal symptoms with Butrans to other long-acting opioids have not been conducted. When a patient no longer requires therapy with Butrans, a gradual downward titration of the dose every seven days to prevent signs and symptoms of withdrawal in the physically dependent patient is recommended. Butrans should not be abruptly discontinued.3 ∘ The article states, “Use of more than one patch at a time is not recommended due to risk of QT prolongation.” Although applying more than one patch at a time is not recommended, it is important to clarify that QTc interval prolongation is not dependent on the number of patches worn, but rather on the buprenorphine dose delivered. The maximum dose of Butrans is 20 mcg/hour due to the risk of QTc interval prolongation (which was detected at a dose of 40 mcg/hour).3 • Clinical applications: ∘ This section states, “Other advantages of buprenorphine include a decreased risk of respiratory depression.” While this effect may have been demonstrated with other buprenorphine products, it has not been demonstrated with Butrans. Respiratory depression is the primary risk of Butrans.3 • Summary: ∘ The article concludes by stating, “The low-dose transdermal buprenorphine patch is effective for mild to moderate chronic pain, both malignant and nonmalignant.” Butrans is not recommended for use in treating mild chronic pain. Butrans is indicated for the management of moderate to severe chronic pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.3 ∘ The low-dose buprenorphine patch is described as being “a reasonable second- or third-line option in patients with low opioid requirements who experience intolerable side effects with other opioids.” Categorizing Butrans as an option for patients only with low opioid requirements misrepresents the patient population for which Butrans is approved. Butrans is approved for use in opioid-naive patients as the first opioid analgesic, as well as in opioid-experienced patients requiring up to 80 mg/day of oral morphine equivalents.3–5 This article provides clinicians with a concise overview of the low-dose buprenorphine patch. We would appreciate a correction that accurately presents the product information in order for clinicians to have the necessary information to use Butrans safely and effectively.

Predicting Medication Persistence to Buprenorphine Transdermal System

Persistence, the duration a patient remains on therapy, in chronic, symptomatic conditions plays an important role in therapy effectiveness. Understanding the duration and patient factors associated with prescribed medication persistence is, therefore, an important step toward better treatment and health outcomes for patients. In the following study, an analysis of such factors associated with buprenorphine transdermal system (BTDS) persistence was conducted utilizing a large US private practitioner and pharmacy claims database and is herein reported. Patients aged ≥ 18 years initiating BTDS during January 1, 2011-November 30, 2011 were identified in the IMS Private Practitioner Medical Claims and Pharmacy Claims databases. An index date was defined as the first prescription of BTDS during the studied interval. During the preindex period, Charlson Comorbidity Index (CCI), chronic pain-related conditions, and prior medication use were assessed. Concomitant medications and various treatment patterns (eg, last dose strength and dose adjustments) were assessed in the postindex 6-month period. Persistence was measured as the duration of BTDS from initiation to the 1st >28-day refill gap in the postindex 6-month period. Descriptive statistical and survival analysis was used to assess the predictors of BTDS persistence. During the study period, 10,457 patients newly treated with BTDS were identified. Patients' mean (± SD) age was 54.5 (± 15.2) years; 69.9% were women, and the mean (± SD) CCI was 1 (± 1.4). Utilizing a hierarchical approach, patients were separated into different cohorts based on the initial analgesic prescription identified during postindex period with 91.7%, 34.7%, and 59.0% of the patients using opioids, NSAIDs and adjuvant analgesics, respectively. Multivariate regression analyses showed that patients with prior opioid and adjuvant analgesic use were 21% and 5% less likely to discontinue BTDS (P < 0.05), respectively, as compared to patients not using these agents. Patients with concomitant use of adjuvant analgesics were 15% less likely to discontinue therapy (P < 0.05) as compared to patients without concomitant use of these agents. Long-term BTDS persistence was also observed in patients who had a dose change or a last dose strength >5 mcg/hour. Sensitivity analyses for those with 30-day prior opioid use and patients with ≥ 2 claims of BTDS confirmed these findings. Prior and concomitant use of adjuvant analgesics, prior use of opioids, and dose adjustments were associated with significantly longer persistence among patients initiating BTDS. The results suggest that patients are less likely to discontinue BTDS early if practitioners account for prior treatment history and dose titration.

PSY53 - Impact of dosage strength on medication persistence among patients treated with buprenorphine transdermal system

PSY53 - Impact of dosage strength on medication persistence among patients treated with buprenorphine transdermal system