buprenorphine and Neoplasms

Opioids are an important treatment in managing cancer pain. Uncontrolled pain can be detrimental to function and quality of life. Common adverse effects of opioids such as sedation, constipation and nausea are well recognised, but opioid effects on the endocrine and immune systems are less apparent. The evidence for the immunomodulatory effects of opioids suggest that some opioids might be immunosuppressive and that their use might be associated with reduced survival and increased rates of infection in patients with cancer. However, the quality of this evidence is limited. Opioid-induced endocrinopathies, in particular opioid-induced hypogonadism, may also impact cancer survival and impair quality of life. But again, evidence in patients with cancer is limited, especially with regard to their management. There are some data that different opioids influence immune and endocrine function with varying outcomes. For example, some opioids, such as tramadol and buprenorphine, demonstrate immune-sparing qualities when compared to others. However, most of this data is preclinical and without adequate clinical correlation; thus, no opioid can currently be recommended over another in this context. Higher opioid doses might have more effect on immune and endocrine function. Ultimately, it is prudent to use the lowest effective dose to control the cancer pain. Clinical presentations of opioid-induced endocrinopathies should be considered in patients with cancer and assessed for, particularly in long-term opioid users. Hormone replacement therapies may be considered where appropriate with support from endocrinology specialists.

Topics: Analgesics, Opioid; Buprenorphine; Cancer Pain; Humans; Neoplasms; Quality of Life

Pain is a common symptom in pediatric patients with cancer, and most patients in palliative care will receive opioids. Traditional opioids have several drawbacks, including their adverse effects, inconsistent or diminishing efficacy, and limited available routes of administration. Buprenorphine is an attractive option for pain management because of its safety profile, unique pharmacology, and availability in transdermal, buccal, parenteral, and sublingual (SL) dosage forms. Unfortunately, data supporting the use of buprenorphine in pediatric pain patients, particularly SL buprenorphine, are lacking. This case report describes the feasibility of SL buprenorphine use in pediatric patients with complex cancer-related pain.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Cancer Pain; Child; Humans; Neoplasms; Pain

Clinical studies demonstrate that buprenorphine is a pharmacologic agent that can be used for the treatment of various types of painful conditions. This study investigated the efficacy of 5 different types of buprenorphine formulations in the chronic pain population. The literature was reviewed on PubMed/MEDLINE, EMBASE, Cochrane Database, clinicaltrials.gov, and PROSPERO that dated from inception until June 30, 2017. Using the population, intervention, comparator, and outcomes method, 25 randomized controlled trials were reviewed involving 5 buprenorphine formulations in patients with chronic pain: intravenous buprenorphine, sublingual buprenorphine, sublingual buprenorphine/naloxone, buccal buprenorphine, and transdermal buprenorphine, with comparators consisting of opioid analgesics or placebo. Of the 25 studies reviewed, a total of 14 studies demonstrated clinically significant benefit with buprenorphine in the management of chronic pain: 1 study out of 6 sublingual and intravenous buprenorphine, the only sublingual buprenorphine/naloxone study, 2 out of 3 studies of buccal buprenorphine, and 10 out of 15 studies for transdermal buprenorphine showed significant reduction in pain against a comparator. No serious adverse effects were reported in any of the studies. We conclude that a transdermal buprenorphine formulation is an effective analgesic in patients with chronic pain, while buccal buprenorphine is also a promising formulation based on the limited number of studies.

Topics: Administration, Buccal; Administration, Cutaneous; Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Disease; Chronic Pain; Clinical Trials as Topic; Humans; Methadone; Neoplasms; Pain Management; Pain Measurement; Risk; Treatment Outcome

Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it.. This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route.. 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best.. Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.

Topics: Analgesics, Opioid; Buprenorphine; Cancer Pain; Chronic Pain; Fentanyl; Germany; Humans; Hydromorphone; Morphine; Neoplasms; Oxycodone; Pain Management

Refractory cancer pain that does not respond to standard opioid and/or co-analgesic therapy occurs in 10-20 % of patients. Risk factors include young age, neuropathic pain type, incident pain, psychological distress, previous opioid use, high tolerance, a history of addiction and impaired cognition. The management of patients with refractory pain remains a challenge. Treatment options include opioid manipulation (parenteral delivery, rotation, combination, methadone and buprenorphine), non-opioids and co-analgesics (paracetamol, non-steroidal anti-inflammatory agents, antidepressants and anticonvulsants), NMDA receptor antagonists, cannabinoids, lignocaine and corticosteroids. The evidence of benefit for any of these agents is weak, and each additional agent increases the risk of adverse events. Evidence-based guidelines cannot, therefore, be developed at present. New approaches are recommended including targeted opioid therapy, multimodal analgesia, a goal-oriented approach to pain management and increasing use of the multidisciplinary team and support services.

Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Buprenorphine; Drug Therapy, Combination; Drug Tolerance; Humans; Methadone; Neoplasms; Pain Management; Pain, Intractable

Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong opioids used for cancer pain relief. However, strong opioids are ineffective as pain treatment in all patients and are not well-tolerated by all patients. The aim of this Cochrane review is to assess whether buprenorphine is associated with superior, inferior or equal pain relief and tolerability compared to other analgesic options for patients with cancer pain.. To assess the effectiveness and tolerability of buprenorphine for pain in adults and children with cancer.. We searched CENTRAL (the Cochrane Library) issue 12 or 12 2014, MEDLINE (via OVID) 1948 to 20 January 2015, EMBASE (via OVID) 1980 to 20 January 2015, ISI Web of Science (SCI-EXPANDED & CPCI-S) to 20 January 2015, ISI BIOSIS 1969 to 20 January 2015. We also searched ClinicalTrials.gov (http://clinicaltrials.gov/; metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/) and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain (IASP; via European Journal of Pain Supplements) on 16 February 2015. We checked the bibliographic references of identified studies as well as relevant studies and systematic reviews to find additional trials not identified by the electronic searches. We contacted authors of included studies for other relevant studies.. We included randomised controlled trials, with parallel-group or crossover design, comparing buprenorphine (any formulation and any route of administration) with placebo or an active drug (including buprenorphine) for cancer background pain in adults and children.. Two review authors independently extracted data pertaining to study design, participant details (including age, cancer characteristics, previous analgesic medication and setting), interventions (including details about titration) and outcomes, and independently assessed the quality of the included studies according to standard Cochrane methodology. As it was not feasible to meta-analyse the data, we summarised the results narratively. We assessed the overall quality of the evidence for each outcome using the GRADE approach.. In this Cochrane review we identified 19 relevant studies including a total of 1421 patients that examined 16 different intervention comparisons.Of the studies that compared buprenorphine to another drug, 11 studies performed comparative analyses between the randomised groups, and five studies found that buprenorphine was superior to the comparison treatment. Three studies found no differences between buprenorphine and the comparison drug, while another three studies found treatment with buprenorphine to be inferior to the alternative treatment in terms of the side effects profile or patients preference/acceptability.Of the studies that compared different doses or formulations/routes of administration of buprenorphine, pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository. However, the average severity of dizziness, nausea, vomiting and adverse events as a total were all significantly higher in the intramuscular group relatively to the suppository group (one study).Sublingual buprenorphine was associated with faster onset of pain relief compared to subdermal buprenorphine, with similar duration analgesia and no significant differences in adverse event rates reported between the treatments (one study).In terms of transdermal buprenorphine, two studies found it superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine.The studies that examined different doses of transdermal buprenorphine did not report a clear dose-response relationship.The quality of this evidence base was limited by under-reporting of most bias assessment items (e.g., the patient selection items), by small sample sizes in several included studies, by attrition (with data missing from 8.2% of the enrolled/randomised patients for efficacy and from 14.6% for safety) and by limited or no reporting of the expected outcomes in a number of cases. The evidence for all the outcomes was very low quality.. Based on the available evidence, it is difficult to say where buprenorphine fits in the treatment of cancer pain with strong opioids. However, it might be considered to rank as a fourth-line option compared to the more standard therapies of morphine, oxycodone and fentanyl, and even there it would only be suitable for some patients. However, palliative care patients are often heterogeneous and complex, so having a number of analgesics available that can be given differently increases patient and prescriber choice. In particular, the sublingual and injectable routes seemed to have a more definable analgesic effect, whereas the transdermal route studies left more questions.

Topics: Administration, Cutaneous; Administration, Oral; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Child; Humans; Neoplasms; Pain; Randomized Controlled Trials as Topic

This study aimed to synthesize the available evidence on the efficacy and safety of transdermal (TD) buprenorphine.. We searched studies in electronic databases. Randomized controlled trials (RCTs) assessing the efficacy of TD buprenorphine comparing with placebo or other comparator drug in relieving cancer pain were included. The primary end points are patient-reported pain intensity and pain relief. For dichotomous data, the summary relative risk (RR) and its 95 % confidence interval (CI) were derived using random-effect model in view of heterogeneity testing.. Eight clinical trials (n = 909) were included in the analysis. Only a few studies reported the same outcome in similar way, which created difficulty in the pooling of outcome data. Two studies (n = 288) assessed 'responders' and showed a significant difference between TD buprenorphine and placebo in all three doses of TD buprenorphine, 35.5, 52.5, or 70 μg/h (RR 1.74, 95 % CI 1.31-2.32; I (2) 0 %); the numbers-needed-to-treat was 5.8 (3.9-11). Two studies (n = 331) showed a comparable requirement for rescue SL buprenorphine between TD buprenorphine and placebo (RR 1.25, 95 % CI 0.84-1.88; I (2) 0 %). The preferred outcome measure '50 % pain relief' was not reported in any included studies. On the basis of summary quality, further research is likely to have an important impact on our confidence in the estimate.. Transdermal buprenorphine has an increasing role for the relief of cancer pain. Further research in this field is needed. Multicentre studies in this field using a common protocol and strict supervision will be more practicable.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Humans; Neoplasms; Pain; Palliative Care; Randomized Controlled Trials as Topic; Treatment Outcome

Cancer patients with moderate-to-severe pain require opioids for analgesia. Whereas early guidelines recommend oral morphine as the 'drug of choice', newer synthetic opioids can be given by a reliable and effective nonoral transdermal route. We examine the mode of action of transdermal patches and we review the evidence on two drugs, which are currently available in this formulation - buprenorphine and fentanyl - covering physicochemical characteristics and pharmacokinetics of the patches, clinical efficacy data and adverse effects.. Both buprenorphine and fentanyl possess ideal characteristics for transdermal delivery, being small molecules with high lipophilicity. Studies of buprenorphine patches show benefits but there is poor randomized controlled trial evidence comparing them with oral opioids. Fentanyl patches have been used for longer and have a larger body of evidence supporting their use, with data to suggest improved pain relief and reduced opioid side effects compared with sustained release oral morphine. Patients who have used both oral morphine and transdermal fentanyl express a preference for the patch drug.. Transdermal buprenorphine and fentanyl are now established for moderate-to-severe cancer pain. There is still a need for further comparative studies with other opioids, especially for buprenorphine.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Evidence-Based Medicine; Fentanyl; Humans; Neoplasms; Pain; Pain Management

To identify users and use of opioids in Denmark three databases were combined. The latest fifteen years an increase in users has been noted, and the costs of opioids have increased from 175 million DKK (1994) to 540 million DKK (2008). Oxycodone and transdermal fentanyl constitute 60% of the total annual costs, and together with the increasing costs of buprenorphine, the three opioids constitute 70% of the total costs in the primary health care sector. The largest group of users is individuals with acute pain, however, the highest consumption is generated by individuals with chronic non-malignant pain.

Topics: Analgesics, Opioid; Buprenorphine; Databases, Factual; Denmark; Drug Costs; Drug Utilization; Fentanyl; Humans; Neoplasms; Oxycodone; Pain; Substance-Related Disorders

To assess the adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison with slow release oral morphine.. A systematic review of the literature in the MEDLINE and EMBASE databases from 1966 to June 2007 was independently performed by two authors. All phase 3 randomized trials comparing transdermal opiates and slow-release oral morphine in the treatment of moderate-severe cancer pain were considered eligible and included in the analysis. The primary end point was the overall adverse effects odds ratio (OR); secondary end points were the overall gastrointestinal adverse effects, constipation, nausea, somnolence, patients' preference, and trial withdrawal. Heterogeneity was analyzed using the Mantel-Haenszel test, and outcome analysis was performed using a random effect model; an alpha error lower than 5% was assumed as statistically significant.. Four trials met the selection criteria. The safety of transdermal opiates (fentanyl and buprenorphine) and slow-release oral morphine was analyzed in 425 patients. A significant difference in favor of transdermal opiates was observed for constipation (OR=0.38, p<0.001), and patients' preference (OR=0.43, p=0.014, in the three trials investigating transdermal fentanyl). No significant differences were observed for overall adverse effects, overall gastrointestinal adverse effects, overall neurologic adverse effects, nausea, somnolence, hypoventilation, trial withdrawal, and changes in opiate treatments.. Although no difference in the overall adverse effect profile exists between transdermal opiates and slow release oral morphine, the difference in some adverse effects (mainly constipation) seems to favor transdermal opiates in the preference of patients with moderate-severe cancer pain.

Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Fentanyl; Humans; Morphine; Neoplasms; Pain; Randomized Controlled Trials as Topic

Pain in older cancer patients is a common event, and many times it is undertreated. Barriers to cancer pain management in the elderly include concerns about the use of medications, the atypical manifestations of pain in the elderly, and side effects related to opioid and other analgesic drugs. The care of older cancer patients experiencing pain involves a comprehensive assessment, which includes evaluation for conditions that may exacerbate or be exacerbated by pain, affecting its expression, such as emotional and spiritual distress, disability, and comorbid conditions. It is important to use appropriate tools to evaluate pain and other symptoms that can be related to it. Pain in older cancer patients should be managed in an interdisciplinary environment using pharmacologic and nonpharmacologic interventions whose main goals are decreasing suffering and improving quality of life. In this two-part article, the authors present a review of the management of pain in older cancer patients, emphasizing the roles of adequate assessment and a multidisciplinary team approach.

Topics: Age Factors; Aged; Aged, 80 and over; Analgesics; Analgesics, Opioid; Buprenorphine; Female; Fentanyl; Humans; Male; Neoplasms; Pain; Pain Management

Patients with moderate to severe malignancy-related pain frequently require the use of opioid pharmacotherapy. Unfortunately, many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undo suffering and diminished quality of life. The choice of analgesic pharmacotherapy should be individualized and based on the intensity and etiology of pain reported by the patient. Health care providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal fentanyl is effective and well tolerated pharmacotherapy for the cancer pain patients. However, clinicians need to be cognizant that the U.S./U.K. manufacturer's recommendations for equilalagesic dosing of transdermal fentanyl may result in initial doses that produce subtherapeutic levels and unrelieved pain in some patients. A more aggressive dosing algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine: mcg/hr of transdermal fentanyl) conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualize cancer pain pharmacotherapy. Transdermal buprenorphine is now being prescribed in Europe and Australia for chronic and cancer pain management. Buprenorphine's mixed agonist/antagonist activity, dosage ceiling, and high affinity to the opiate receptor limits its use to those patients who do not already require large daily doses of opioids. Thus, buprenorphine may not be an appropriate medication for some patients with advanced unremitting cancer pain.

Topics: Administration, Cutaneous; Administration, Oral; Algorithms; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Fentanyl; Humans; Neoplasms; Pain, Intractable; Palliative Care; Titrimetry

Transdermal buprenorphine has been assessed as a therapy for chronic cancer and non-cancer pain in both clinical and postmarketing surveillance studies. Data from 239 patients who had participated in a follow-up study of up to six years have shown efficacy and safety, and good tolerability over prolonged treatment periods with a marked stability of doses. From the cancer pain population (134 patients), 20% stayed on transdermal buprenorphine until the end of their lives. Postmarketing surveillance study data from 13,179 patients, including 3690 cancer patients assessed during a 10-week observation period, showed that 81% of patients achieved good/very good pain relief with transdermal buprenorphine. Furthermore, 49.6% of patients did not require any analgesic comedication or rescue therapy, a point that is particularly important in the elderly population. Results from the Spanish Pain Society on transdermal buprenorphine in chronic non-cancer, neuropathic and cancer-related pain, and on switching from morphine, also confirmed its beneficial efficacy and safety, and showed that buprenorphine does not antagonize pain relief, or cause withdrawal when combined with full micro-agonists. The effectiveness of buprenorphine is further supported by evidence of its pronounced anti-hyperalgesic effect in a human pain model, which may be a factor in explaining the efficacy of buprenorphine in neuropathic pain. When switching of opioids is indicated to improve pain relief or reduce adverse events, equipotency dosage ratios are important. The equipotency ratio for morphine to buprenorphine, previously established as 75:1, is now being questioned as new data from a retrospective cohort study were published indicating a ratio of 100:1. Moreover, transdermal buprenorphine has superior safety in respect to respiratory depression, immunological and renal effects compared with standard World Health Organization step III opioids, which makes it highly suitable for treating moderate-to-severe pain also in cancer patients, a per se vulnerable patient population requiring a sensible selection of potent analgesics.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Drug Interactions; Fentanyl; Humans; Narcotic Antagonists; Neoplasms; Pain; Pain Measurement; Palliative Care

In most cancer patients pain can be successfully treated with pharmacological measures using opioid analgesics alone or in combination with adjuvant analgesics (coanalgesics). Weak opioids are usually recommended in the treatment of moderate cancer pain. There is still a debate as to whether the second step of the WHO analgesic ladder comprising opioid analgesics such as tramadol, codeine, dihydrocodeine, and dextropropoxyphene is still needed for the treatment of cancer pain. On the basis of our experience and review of the literature we think that there is definitely a place for weak opioids in the treatment of moderate cancer pain. One of the most interesting and useful weak opioids is tramadol (Adolonta, Contramal, Nobligan, Top-Algic, Tramal, Tramal Long, Tramal Retard, Tramundin, Trodon, Ultram, Zydol). Its unique mechanism of action, analgesic efficacy and profile of adverse reactions have been the reason of performing many experimental and clinical studies with tramadol. In this article we summarize data on pharmacology, mechanisms of action, pharmacokinetics, side effects and clinical experience assessing analgesic efficacy, adverse reactions and safety of tramadol in cancer pain.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Humans; Neoplasms; Pain; Pain Measurement; Tramadol

Buprenorphine is a broad spectrum, highly lipophilic, and long-acting partial mu opioid receptor agonist that is noncross tolerant to other opioids. Buprenorphine can be given by several routes. Metabolism is through CYP3A4 and CYP2C8 and by conjugases. Constipation and sexual dysfunction appear to be less with buprenorphine than with other opioids. The recent development of a polymer matrix patch delivery system for buprenorphine prevents "dose dumping" and facilitates pain management in those unable to take oral analgesics. Sublingual buprenorphine has been combined with naloxone to prevent illicit conversion to parenteral administration. Buprenorphine has been used extensively to control cancer pain. In certain clinical situations, buprenorphine may have particular advantages over other opioids.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Neoplasms; Pain

Although the optimal route of administration of opioids is by mouth, some patients may require alternative routes during the course of their illnesses for several reasons. These include bowel obstruction, severe emesis, or severe dysphagia. In these cases, the alternatives include the subcutaneous or rectal route. The transdermal route also provides a simple, comfortable method that produces stable blood drug concentrations. The high potency and lipid solubility of fentanyl make it suitable for this route of administration. Iontophoresis can provide a rapid drug delivery rate, but no clinical studies exist to document the long-term effectiveness of this method in controlling pain. The transmucosal route is recommended only for those opioids with high solubility, such as buprenorphine, the fentanyl series, and methadone. Oral transmucosal fentanyl (Actiq) provides a rapid onset of pain relief and is appropriate for treating episodes of breakthrough pain.

Topics: Administration, Oral; Administration, Topical; Analgesics, Opioid; Buprenorphine; Fentanyl; Humans; Injections, Subcutaneous; Neoplasms; Pain; Treatment Outcome

The present-day problem is the development of effective methods of general anesthesia and postoperative anesthesia on the basis of nonopiate central analgesics possessing no hazardous side effects of opiates. A study was made of synthetic analgesics of the last generation as agents for intra- and postoperative anesthesia as compared with conventional opiates. It has been established that synthetic analgesics belonging to the class of opiate agonists-antagonists, namely moradol and norphine, compare favourably enough with fentanyl. They are superior to fentanyl in antistressor properties, provide for a more powerful and longer analgesic effect and can replace conventional opiates in all the stages of surgical treatment of the patients. This is particularly important for the oncological clinic where opiates are to be preserved as reserve for the treatment of chronic painful syndrome.

Topics: Analgesics; Anesthesia, General; Buprenorphine; Butorphanol; Humans; Narcotics; Neoplasms; Promedol; Tramadol

To compare the effects of oral morphine and oxycodone and transdermal fentanyl and buprenorphine on quality of life (QoL) of cancer patients with severe pain.. Cancer patients with severe pain (NRS 6-10) treated at home and in outpatient clinics who failed to respond to non-opioids and/or "weak" opioids were randomized to morphine, oxycodone, fentanyl, or buprenorphine treatment for 28 days. Immediate-release oral morphine was rescued analgesic and 10-ml lactulose twice daily was prophylaxis of constipation; no antiemetics were used for prophylaxis.. Above all, 62 patients participated and 53 patients completed the study. Good analgesia was obtained with all 4 opioids. Morphine was associated with the less negative impact of pain on the ability to walk and normal work, and tendency on activity (BPI-SF) and lower consumption of rescue morphine. All 4 opioids elicited similar adverse effects. According to ESAS, the intensity of nausea and drowsiness increased at the beginning but decreased as treatment continued. Appetite, well-being, anxiety, depression, and fatigue improved. No changes were seen in constipation, vomiting and dyspnea. Constipation was rarely observed with all opioids (BFI). Any opioids improved overall QoL and emotional functioning with tendency improving physical functioning (EORTC QLQ-C15-PAL). Activity improved (Karnofsky). Morphine induced greater improvement in physical functioning and trend in improvement mood (HADS).. All opioids significantly improved patients' QoL. Morphine induced less negative impact of pain on daily activities and greater improvement in physical functioning with trends of better mood and less intense fatigue.

Topics: Analgesics, Opioid; Buprenorphine; Cancer Pain; Delayed-Action Preparations; Female; Fentanyl; Humans; Male; Morphine; Neoplasms; Oxycodone; Quality of Life

The current study investigated the efficacy, safety, tolerability, and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population.. Sixteen pediatric patients with moderate to severe cancer-related pain not satisfactorily controlled with previous non-opioid therapies were enrolled. Transdermal buprenorphine was administered following a 72 hour schedule and rescue medication (tramadol) was allowed for breakthrough pain. Pain intensity was assessed using the Wong-Baker faces pain rating scale (WBS) and other parameters related to the global quality of life were evaluated. Children's evaluations of efficacy, compliance, and tolerability were recorded using numerical scales. Adverse events were monitored during the study and the medications needed to control opioid-related nausea and constipation were recorded.. Eleven patients (68.75%) responded to transdermal buprenorphine after 2 weeks of treatment. Pain intensity measured with WBS decreased from 6.25 at baseline to 1.38 at Day +60 (P < 0.001). All outcome measures of global quality of life (quality of sleep, alimentation, play and activity, speech, and crying) significantly improved over the 60-day study period. Children's evaluations of compliance and tolerability of the drug were always positive over the entire period of treatment. No severe adverse events were recorded. Opioid-related nausea was well controlled with medication on request, and the need for laxative therapy was greater at the end of the second month of treatment.. Transdermal buprenorphine was found to represent an efficient, safe and well tolerated approach to the management of children's chronic cancer pain.

Topics: Administration, Cutaneous; Adolescent; Analgesics, Opioid; Buprenorphine; Child; Child, Preschool; Female; Humans; Male; Neoplasms; Pain

Buprenorphine and fentanyl transdermal patches are used widely for the management of persistent malignant and nonmalignant pain. Buprenorphine and fentanyl transdermal patches, both potent opioids, are considered to be equally efficacious in managing persistent pain. Various retrospective studies comparing dosage changes of buprenorphine and fentanyl patches in persistent pain patients have been completed; however, no long-term prospective, randomized, clinical study has compared the effectiveness of these patches. The objective of the present study was to satisfy this need.. This study aims to compare prospectively the long-term efficacy, acceptability, and side effects of both of these patches in patients with persistent pain. This study would examine the feasibility and lay the groundwork for a larger, multicenter study where such efficacy and safety outcomes of the two medications can be adequately assessed.. The participants were 46 adults (range 22-80 years.) with nonmalignant persistent pain (mean = 11 years), predominantly with lower back pain. Data were obtained monthly for 12 months. Participants recruited were opioid-naïve patients, having pain for the greater part of the day and night, and appropriate for treatment with transdermal patches. After initial assessment, participants were randomly allocated to either buprenorphine or fentanyl patch treatment. Participants were then titrated to optimal doses of medication. Patients with adverse effects or unsatisfactory pain relief were treated alternatively and discontinued from the study.. Nearly one-third of all patients, 41% (8 of 22) of the transdermal buprenorphine (TDB) group and 37.5% (8 of 24) of the transdermal fentanyl (TDF) group stopped treatment due to unacceptable side effects or inadequate pain relief. The remaining participants showed a similar trend in the improvement of pain intensity, physical activity, sleep, and mood throughout the study. Significant relief in the intensity of pain was achieved for the initial 6 months and the effects stabilized in the remainder of the study in both groups. There were no significant group differences over time. However, a higher equipotent dose of fentanyl was required for comparable pain relief. Compared with TDF group, the TDB group initially experienced relatively less side effects. However, a greater number of buprenorphine users suffered from local skin reactions. Buprenorphine users had significant improvement in mood. Thirty-one percent (5 of 16) of the buprenorphine group and 57% (8 of 14) of the fentanyl users needed additional pain relief medications by the end of 3 months. By the end of 12 months, a significant number 78% (7 of 9) of buprenorphine users but comparatively fewer 44% (4 of 9) of the fentanyl group used rescue medicines. Both had more doctor visits in the latter half of the study.. Thirty percent of the total number of patients discontinued treatment because of side effects or unsatisfactory pain relief. For those continuing treatment, clinical improvements were seen in the initial 6 months in both groups. Fifty percent of the TDB and 43% of TDF groups had significant relief in 3 months, which persisted up to 6 months. Only 11% and 13% of patients, respectively, had sustained relief after 6 months. Twenty percent more patients in the TDB group benefited significantly in symptoms of depression from TDB compared with the TDF group. Interestingly, switching of patches seemed to increase acceptability by preventing adverse effects and tolerance. Confirmation of these effects should be studied in future with a multicenter study and larger sample.

Topics: Administration, Cutaneous; Adult; Analgesics, Opioid; Buprenorphine; Chronic Disease; Chronic Pain; Feasibility Studies; Female; Fentanyl; Humans; Longitudinal Studies; Male; Neoplasms; Pain Measurement; Prospective Studies; Transdermal Patch; Treatment Outcome

P-glycoprotein (P-gp) is expressed on the blood-brain barrier (BBB) and acts as a transporter regulating the analgesic effect of morphine. The P-gp is also expressed by different types of tumors. The aim of this study was to determine the potential association of the P-gp expression in malignant tumors with analgesic effects in patients.. The P-gp expression in 120 malignant tumors was examined by immunohistochemistry. The analgesic responses of individual patients to morphine and buprenorphine (BNP) were evaluated by visual analog scale (VAS). The levels of plasma morphine and BNP were determined by HPLC.. We found that there was no significant difference in the values of VAS between patients with P-gp(+) and P-gp(-) malignant tumors in responses to 0.000025 g x kg(-2) of BNP administered by patient-controlled intravenous analgesia (PCIA), accompanied by similar levels of plasma BNP in those patients. In contrast, the values of VAS in response to 0.00075 g x kg(-2) of morphine in patients with P-gp(+) tumors were significantly greater than those in the patients with P-gp(-) tumors, although similar levels of plasma morphine were detected in both groups of patients. Furthermore, treatment with a higher dose (0.0011 g x kg(-2)) of morphine effectively controlled pain in those with P-gp(+) tumors.. Our data indicated that patients with P-gp(+) tumors required a higher dose of morphine to achieve an analgesic effect and that the P-gp expression in tumors may be valuable for predicting the analgesic responses of patients with severe pain to morphine.

Topics: Aged; Analgesia, Patient-Controlled; Analgesics; ATP Binding Cassette Transporter, Subfamily B, Member 1; Buprenorphine; Chromatography, High Pressure Liquid; Female; Humans; Immunohistochemistry; Male; Middle Aged; Morphine; Neoplasms; Pain; Pain Measurement

This was a multicenter, non-interventional, post-marketing study that aimed to evaluate the analgesic activity, safety of use, safety profile and adverse drug reactions of transdermal buprenorphine (Transtec 35, 52.5 and 70 μg/h) during the treatment of moderate to severe chronic cancer and non-cancer pain. The study was performed in Poland by 339 doctors. The study involved 4,030 general practice outpatients (managed by primary care physicians), pain therapy center patients, specialist outpatient clinic patients as well as patients treated in inpatients units. The recruitment process began in September of 2007, and the study was completed in October of 2008. The study has been reported to the Central Register of Clinical Trials in Poland; it was also in accordance with the requirements of the Polish Pharmaceutical Law in force. The objective of the study was to evaluate the efficacy, safety of use and application of transdermal buprenorphine in patients with moderate to severe cancer pain and in patients with severe, non-malignant pain in the course of other diseases. Patients were enrolled if their pain was not well-controlled after using non-opioid analgesics. Another objective of the study was to monitor adverse drug reactions of transdermal buprenorphine reported by patients or noted by the doctors during the study visits. This first such multicenter study in Poland has confirmed high efficacy and good tolerability of buprenorphine and, therefore, confirmed its usefulness in the treatment of moderate to severe cancer pain as well as in the treatment of severe pain in patients with non-cancer pain that cannot be effectively treated with non-opioid analgesics.

Topics: Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Pain; Poland; Prospective Studies; Severity of Illness Index; Transdermal Patch

The purpose of this trial was to evaluate the effect of long-term treatment with oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine on nausea, emesis and constipation.. Randomly selected outpatients with cancer pain receiving one of the study medications were enrolled in a prospective, open-labeled, controlled trial (n=174). Mobility, pain, and gastrointestinal symptoms were assessed directly and per selected item on the ECOG (Eastern Cancer Oncology Group), EORTC (European Organisation for Research and Treatment of Cancer) questionnaires, NRS (Numerical Rating Scales), and analyzed statistically.. Demographic and medical data were comparable in all groups. Only 15% of patients suffered from constipation. 59% took the prescribed laxatives. The incidence of stool free periods >72 h was significantly higher with transdermal opioids (transdermal fentanyl: 22%; transdermal buprenorphine: 21%; oral hydromorphone: 2%; p=0.003). 21% of patients revealed nausea and emesis. The mean NRS for nausea (transdermal fentanyl:1.3; transdermal buprenorphine: 1.2; oral hydromorphone: 1.5; p=0.6), the consumption of antiemetics (transdermal fentanyl: 42%; transdermal buprenorphine: 33%; oral hydromorphone: 36%; p=0.6) and laxatives (transdermal fentanyl:53%; transdermal buprenorphine:66%; oral hydromorphone: 61%; p=0.2) did not differ significantly, in contrast to the score for emesis (transdermal fentanyl: 16%; transdermal buprenorphine:13%; oral hydromorphone: 33%; p=0.02). Morphine equivalent opioid doses differed (mg/d transdermal fentanyl: 183; transdermal buprenorphine: 89; oral hydromorphone: 143; p=0.001), because of obvious tolerance varying after long-term treatment.. Gastrointestinal symptoms of cancer pain patients undergoing an opioid therapy are related to multifactorial causes. Transdermal opioids showed no benefit over oral controlled-release hydromorphone with regard to gastrointestinal symptoms. The conversion ratios for transdermal fentanyl, transdermal buprenorphine, and oral hydromorphone did not accord to the literature, because of differing occurrences of opioid tolerance after long-term therapy.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Antiemetics; Buprenorphine; Cohort Studies; Constipation; Delayed-Action Preparations; Female; Fentanyl; Gastrointestinal Diseases; Humans; Hydromorphone; Laxatives; Male; Middle Aged; Nausea; Neoplasms; Pain, Intractable; Prospective Studies; Vomiting

Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy. To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.. A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks. Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 +/- 20.5 (mean +/- SD) to 3.75 +/- 8.06, and 33.8 +/- 18.9 to 3.75 +/- 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.. Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

Topics: Adult; Aged; Analgesia; Analgesics, Opioid; Buprenorphine; Chronic Disease; Female; Fentanyl; Humans; Male; Middle Aged; Neoplasms; Pain; Palliative Care

Pain still afflicts most cancer patients, mainly in the metastatic phases, and under-treatment is well documented. Transdermal delivery systems (TDS) containing fentanyl or buprenorphine could potentiality have advantages over oral and parenteral routes, but evidence from comparative trials are scanty. In the framework of a wider initiative, an Outcome Research Study was carried out in Italy in 2006 to evaluate the effects of various analgesic options, particularly buprenorphine TDS.. This is a multicenter, open-label, prospective, nonrandomized study. Data were collected using a web-based standardized system, with a follow-up up of to 3 months. Pain intensity, the primary outcomes of the study, was measured using 11-point numerical rating scales from the Brief Pain Inventory.. One-hundred ten centers recruited 1801 cases, most of which (60%) were receiving a strong opioid at the time of inclusion. Of these, 257 had TDS buprenorphine as first choice. Of the remaining 709 patients who at the time of inclusion were not on a strong opioid, 325 changed to a strong opioid and in 43% it was TDS buprenorphine. During the follow-up, physicians had to increase the dosage to control pain (average increase between 16% and 17%). About 34% of patients had an improvement of at least 2 points in worst pain, 15% had a 20% improvement in pain relief, and 40% in satisfaction. Results were in line with those of patients receiving other World Health Organization-level III opioids.. Despite the limitations owing to the observational design, these findings may be useful to clinicians to judge the value of the drug under evaluation better and to help researchers design further comparative studies.

Topics: Administration, Cutaneous; Aged; Analgesics, Opioid; Buprenorphine; Female; Humans; Italy; Karnofsky Performance Status; Male; Middle Aged; Neoplasms; Pain Measurement; Pain, Intractable; Prospective Studies; Treatment Outcome

The aim of this study was to evaluate the effect and tolerability of low doses of transdermal (TD) buprenorphine patches in opioid-naive patients with cancer pain.. This was a nonrandomized, open-label, uncontrolled study in consecutive opioid-naive patients with advanced cancer and moderate pain. TD buprenorphine was initiated at a dose of 17.5 microg/h (0.4 mg/d), with patch changes every 3 days. Doses were then adjusted according to the clinical response. Pain intensity, opioid-related adverse effects, TD buprenorphine doses, and quality of life were monitored over 4 weeks. The time to dose stabilization and indexes of dose escalation were also calculated.. Thirty-nine consecutive patients completed all 4 weeks of the study. Low doses of TD buprenorphine were well tolerated and effective in these opioid-naive patients with cancer pain. Pain control was achieved within a mean of 1.5 days after the start of TD buprenorphine therapy. The mean TD buprenorphine dose was significantly increased from baseline beginning at 2 weeks after the start of therapy and had doubled by 4 weeks (P < 0.05). Pain intensity was significantly decreased from baseline beginning at 1 week and continuing through the remaining weekly evaluations (P < 0.05). The mean buprenorphine escalation index, calculated as a percentage and in milligrams, was 41.2% and 0.2 mg, respectively. Quality of life improved significantly over the study period (P = 0.007). There were no significant changes in opioid-related symptoms between weekly evaluations.. Observations from this study suggest that randomized, controlled, double-blind studies of TD buprenorphine 17.5 microg/h in opioid-naive patients with cancer pain may be warranted.

Topics: Administration, Cutaneous; Aged; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neoplasms; Pain Measurement; Pain, Intractable; Quality of Life

Strong opioids are recommended for treating severe cancer pain in the advanced stages of the disease. Few data are available concerning the efficacy of buprenorphine in cancer pain. We compared transdermal buprenorphine 70 microg/h (BUP TDS) to placebo in an enriched design study. Opioid-tolerant patients with cancer pain requiring strong opioids in the dose range of 90-150 mg/d oral morphine equivalents entered a two-week run-in phase, during which they were converted to BUP TDS. Patients who could be stabilized on BUP TDS were randomized to BUP TDS or placebo patch for a two-week maintenance phase. Rescue medication (buprenorphine sublingual tablets 0.2mg) was allowed as required. Response was defined as a mean pain intensity of <5 (0-10 scale) and a mean daily buprenorphine sublingual tablet intake of < or =2 tablets during the maintenance phase. Of 289 patients who entered the run-in phase, 100 discontinued treatment due to lack of efficacy or adverse events; 189 patients continued treatment in the maintenance phase (94 BUP TDS, 95 placebo), of whom 31 discontinued treatment (7 BUP TDS, 24 placebo). A significant difference in the number of treatment responders was observed: 70 BUP TDS (74.5%, 65.7-83.3) vs. 47 placebo (50%, 39.9-60.1) (P=0.0003). This result was supported by a lower daily pain intensity, lower intake of buprenorphine sublingual tablets and fewer dropouts in the BUP TDS group. The incidence of adverse events was slightly higher for BUP TDS. In conclusion, BUP TDS 70 microg/h is an efficacious and safe treatment for patients with severe cancer pain.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Comorbidity; Double-Blind Method; Europe; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Placebo Effect; Treatment Outcome

The aim of this randomized open-label prospective study was to evaluate the analgesic activity of buprenorphine in a transdermal formulation for cancer chronic pain control versus sustained-release morphine, in all cases combined with oral tramadol. A transdermal system with 35 microg/h buprenorphine was applied to the first group of patients (BT); the second group received 60 mg/day of sustained-release morphine (MT). In both groups oral tramadol was administered to a maximum of 200 mg daily, in case of need. The administration of transdermal buprenorphine versus morphine resulted in significant differences in the physical pain (P = 0.01), mental health (P = 0.03) and vitality (P = 0.001). These data indicated that the BT group showed an improvement of pain and a positive effect on the quality life.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Delayed-Action Preparations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain; Quality of Life; Tramadol

When selecting the appropriate long-acting opioid to treat cancer pain, both analgesic efficacy and safety need consideration. Generally, opioids are well tolerated. However, of opioid-typical adverse events, respiratory depression is especially important because of the risk of a fatal outcome. Although all potent opioid analgesics act via the micro-opioid receptor system, they differ in how they affect respiratory control. Recently, the respiratory effects of fentanyl (1 7 microg/kg) and buprenorphine (0.7-9 microg g/kg) were compared in healthy opioid-naïve volunteers. Fentanyl produced dose-dependent depression of respiration with apnoea at doses > or = 3 microg/kg, while buprenorphine caused depression that levelled at approximately 50% of baseline with doses > or = 2 microg/kg. These findings indicate the occurrence of a ceiling in the respiratory depression induced by buprenorphine but not by fentanyl. Surprisingly few studies have addressed the clinically important ability to reverse the respiratory effects of opioids. A recent assessment of the naloxone dose required to reverse 0.2 mg intravenous buprenorphine-induced respiratory depression in healthy opioid-naïve volunteers, found that the accumulated naloxone dose causing 50% reversal of respiratory depression was 1.20 +/- 0.32 mg/70 kg (given in 30 min); 80% reversal was observed at 2.50 +/- 0.60 mg/70 kg (given in 30 min). At greater buprenorphine doses, full reversal is observed when the duration of naloxone infusion is increased. These findings indicate the need for a continuous rather than bolus administration of naloxone to reverse the respiratory effects of buprenorphine. In conclusion, buprenorphine is more favourable compared with fentanyl in respect to ventilatory control. Buprenorphine causes limited respiratory depression with a ceiling effect at higher doses, while fentanyl causes dose-dependent respiratory depression with apnoea at high dose levels. In the rare instance of respiratory depression, reversal is possible with a sufficient and continuous infusion of naloxone.

Topics: Analgesics, Opioid; Apnea; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Fentanyl; Humans; Naloxone; Narcotic Antagonists; Neoplasms; Pain; Respiratory Insufficiency

Supplemental dosing of an opioid is the main treatment suggested to manage breakthrough pain in cancer patients. The intravenous route has been proven to be safe and effective, providing rapid analgesia in patients receiving oral morphine. Transdermal buprenorphine (TTS-BUP) is increasingly used in cancer pain management, but this drug has been labeled as a difficult drug to use in combination with other opioids. The aim of this open-label study was to verify the safety and effectiveness of intravenous morphine (IV-MO) for the treatment of episodic pain in cancer patients receiving TTS-BUP. A consecutive sample of 29 cancer patients, who were treated with TTS-BUP, reported an acceptable basal analgesia, and presented with episodic pains were selected for the study. The IV-MO dose was one-fifth of the morphine equivalent oral daily dose calculated using a ratio of TTS-BUP/oral morphine of 1:75, and a morphine IV/oral ratio of 1:3. For each episode, pain intensity and opioid-related adverse effects were recorded when severe pain occurred (T0), and 15 minutes after. One hundred six breakthrough events in the 29 patients (3.7 episodes per patient, on average) were recorded during admission. The mean pain intensity decreased from an initial value of 7.3 (confidence interval [CI] 95% 7.0-7.5) to 2.9 (CI 95% 2.5-3.3) 15 minutes after IV-MO. Ninety-eight episodes (92.4%) were considered treated successfully, defined as a reduction of more than 33% within 15 minutes; 88 of these episodes (83.0%) had more than 50% pain intensity decrease. No differences in age, gender, pain mechanism, and time of events were found. Eight episodes (7.5%) did not respond effectively within 15 minutes, and required further doses. The occurrence of adverse effects for each episode treated was not frequent and intensity was not relevant. IV-MO was effective and safe in most cancer patients receiving TTS-BUP who experienced pain exacerbation.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Drug Combinations; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Neoplasms; Pain; Pain Measurement; Palliative Care; Secondary Prevention; Treatment Outcome

Buprenorphine, a potent opioid analgesic, has been available in parenteral and oral or sublingual(SL) formulations for >25 years. In 2001, the buprenorphine transdermal delivery system (TES) was introduced at 3 release rates (35, 52.5, and 70 microg/h) for the treatment of chronic cancer and noncancer pain.. This study compared the analgesic efficacy and tolerability of buprenorphine TES at a release rate of 35 microg/h with those of buprenorphine SL and placebo in patients with severe or very severe chronic cancer or noncancer pain.. This multicenter, double-blind, placebo-controlled, parallel-group trial was 1 of 3 Phase III studies involved in the clinical development of buprenorphine TDS. It comprised a 6-day open-label run-in phase in which patients received buprenorphine SL 0.8 to 1.6 mg/d as needed and a double-blind phase in which patients were randomized to receive 3 sequential patches containing buprenorphine TES 35 microg/h or placebo, each lasting 72 hours. Rescue analgesia consisting of buprenorphine SL 02-mg tablets was available as needed throughout the double-blind phase. The main outcome measures were (1) the number of buprenorphine SL tablets required in addition to buprenorphine TES during the double-blind phase compared with the placebo group and compared with the buprenorphine SL requirement during the run-in phase, and (2) patients' assessments of pain intensity, pain relief, and duration of sleep uninterrupted by pain in the double-blind phase compared with the run-in phase. Adverse events were documented throughout the study.. One hundred thirty-seven patients were included in the double-blind phase (90 buprenorphine TES, 47 placebo). The buprenorphine TES group included 47 men and 43 women (mean [SD] age, 56.0 [12.1] years), and the placebo group included 23 men and 24 women (mean age, 55.7 [12.9] years). Forty-five patients had cancer-related pain and 92 had noncancer-related pain. The 2 treatment groups were comparable with respect to sex distribution, age, height, and body weight Patients receiving buprenorphine TES significantly reduced their consumption of buprenorphine SL tablets in the double-blind phase compared with patients receiving placebo (reduction of 0.6 [0.4] mg vs 0.4 [0.4] mg; P = 0.03). The relationship between the buprenorphine SL dose in the run-in phase and the number of buprenorphine SL tablets required in the double-blind phase was dose dependent in the active-treatment group only. Patients' assessments of pain intensity and pain relief suggested better analgesia with buprenorphine TES than with placebo, although the differences did not reach statistical significance. The proportion of patients who reported sleeping for >6 hours uninterrupted by pain in the double-blind phase compared with the run-in phase increased by 6.4% in the buprenorphine TDS group (35.6% vs 292%, respectively), compared with a decrease of 5.9% in the placebo group (40.4% vs 463%); no statistical analysis of sleep duration data was performed. Buprenorphine TDS was well tolerated, with adverse events generally similar to those associated with other opioids. The incidence of systemic adverse events in the double-blind phase was similar in the 2 treatment groups (28.9% buprenorphine TDS, 27.6% placebo), with the most common adverse events being nausea, dizziness, and vomiting. After patch removal, skin reactions (mainly mild or moderate pruritus and erythema) were seen in 35.6% of the buprenorphine TDS group and 25.5% of the placebo group.. In the population studied, buprenorphine TDS provided adequate pain relief, as well as improvements in pain intensity and duration of pain-free sleep. It may be considered a therapeutic option for the treatment of moderate to severe chronic pain.

Topics: Administration, Cutaneous; Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Pain Measurement; Tablets

Buprenorphine is a potent opioid analgesic that is available in sublingual and parenteral formulations. A new formulation, buprenorphine transdermal delivery system (TDS), has been developed.. The aim of this study was to compare the analgesic efficacy and tolerability of the 3 available dosages of buprenorphine TDS (35.0, 52.5, and 70.0 microg/h) with placebo.. This was a randomized, double-blind, placebo-controlled, multicenter study. Patients with chronic, severe pain related to cancer or other diseases and inadequately controlled with weak opioids were randomized to receive buprenorphine TDS 35.0, 52.5, or 70.0 microg/h or placebo patch for up to 15 days. A new patch was applied every 72 hours, for a total of 5 patches. All patients were permitted rescue analgesia with sublingual buprenorphine tablets (0.2 mg) as required for breakthrough pain.. A total of 157 patients (86 women, 71 men; mean [SD] age, 58.7 [11.8] years) were initially enrolled in the study. Buprenorphine TDS was associated with significantly higher response rates than was placebo at the 35.0- and 52.5-microg/h dosages (36.6% and 47.5%, respectively, vs 16.2%; P=0.032 and P=0.003, respectively) and a numerically higher response rate at 70.0 microg/h (33.3%), although this difference did not reach statistical significance. Patients treated with buprenorphine TDS experienced a 56.7% reduction in use of sublingual rescue analgesic during the study compared with an 8% reduction with the placebo patch. A total of 43.5% of patients treated with buprenorphine TDS reported good or complete pain relief compared with 32.4% in the placebo group. Pain intensity decreased in a dose-dependent manner with buprenorphine TDS, and the duration of sleep uninterrupted by pain was improved by the end of the study. More than three fourths (78.8%) of patients in the placebo and buprenorphine TDS groups reported at least 1 adverse event (AE) during the study. The most common AEs were central nervous system and gastrointestinal symptoms. The majority of treatment-related AEs were mild or moderate in intensity and were typical of those occurring at the beginning of therapy with a strong opioid.. Buprenorphine TDS was shown to be an effective analgesic against chronic, severe pain in this study population. Patients treated with this new formulation of buprenorphine showed improved duration of sleep and reduced need for additional oral analgesics.

Topics: Administration, Cutaneous; Administration, Sublingual; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Disease; Dosage Forms; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Pain Measurement; Sleep

Opioid analgesics represent one of the most important tools in a sequential pharmacological approach to oncological pain relief. They are recommended by the WHO when nonsteroidal anti-inflammatory drugs (NSAIDs) no longer provide adequate analgesia. However, the use of opioids is limited because of their numerous and often severe adverse effects. This aspect of opioids has motivated continuous research projects aimed at discovering drugs that can provide maximum pain relief but with improved tolerability. Tramadol is a new, centrally acting analgesic with a dual mechanism of action. It shows a selective interaction with mu receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release. From a pharmacokinetic standpoint, tramadol offers high bioavailability, with similar patterns after oral or parenteral administration (half-life 5 to 7 hours, time to peak plasma concentration 3.1 hours, and approximately 20% plasma protein binding). Although the efficacy of tramadol is comparable to that of other drugs with similar modes of action, the incidence of side effects such as constipation and respiratory depression is lower. The frequency of euphoria and dysphoria is negligible, resulting in little risk of abuse or dependence. It therefore seemed appropriate to further investigate the efficacy and tolerability of tramadol, defined as having only weak potency, in comparison with a widely used opioid, in oncological pain. Buprenorphine was selected as an opioid with a potency equivalent to half that of morphine, but with tolerability that is partially limited by the fact that it frequently gives rise to adverse reactions considered typical of stronger opioids. To compare the analgesic effect and tolerability of tramadol and buprenorphine, 60 patients (44 men, 16 women; average age 61.4 years), all presenting with advanced tumours, were treated orally in a controlled crossover trial with randomised sequences. Patients took both drugs, each for a week, with a 24-hour washout period between treatments. Tramadol was prescribed at the daily dose of 300mg, orally, and buprenorphine at 0.6 mg/day, as a sublingual preparation. Assessments were made of Karnofsky performance status and severity of pain before and during t

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Tramadol

In this multicentre trial tramadol and buprenorphine were compared for the treatment of neoplastic pain no longer responsive to non-steroidal antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six months. Most patients started treatment with 2-3 tablets/day in both groups, and the mean treatment period was 58 days for tramadol and 51 for buprenorphine. Almost all dose changes needed were made in the first fortnight in both treatment groups, and the largest number of patients dropped out because of inadequate pain relief or progression of the underlying disease. The results achieved in the first two weeks persisted throughout the rest of the trial, and the investigator's assessments on each patient's clinical chart corresponded closely with those that patients made in their own daily diaries. In the four hours after the first dose both drugs virtually halved the severity of pain (measured using a visual analogue scale), and this relief lasted throughout treatment. By the end of the first week the proportion of patients with strong/unbearable pain in the tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also tended to improve in the tramadol group, with the proportion of patients enjoying good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life did not change in the tramadol group; in the buprenorphine group the Karnofsky index dropped slightly after a fortnight (p < 0.05 between treatments). In the first two months of the trial the number of patients with no/moderate pain rose continuously in the tramadol group (71% and 80% after one and two months); the rise was less marked in the buprenorphine group (number of patients with mild/moderate pain, 45% and 65%). In both the short term and in the longer term, it was found that the levels of efficacy and acceptability were always significantly better in the tramadol group than in the buprenorphine group. General and biological safety in both drugs was good. The most typical side-effects were those characteristic of opioids (nausea and/or vomiting, drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%) and in 16

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Neoplasms; Pain; Pain Measurement; Patient Compliance; Patient Satisfaction; Tablets; Tramadol

The time has come to evaluate critically our practice of cancer pain management and the assumptions on which it is based. We owe it to our patients to maximize the quality of their lives and to provide evidence for them that is based on a scientific approach rather than anecdotal experience. From the information available, opioids do have effects on cognitive and psychomotor function, and although many of these effects diminish once the patient is on a stable dose, the evidence suggests that baseline pretreatment levels are not achieved. In addition, the relationship between measurable effects and the performance of everyday tasks such as driving is unclear. The challenge we now face is to continue the improvements in cancer pain control achieved over the last 25 years. The management of the central adverse effects of opioids must be focused on accurate assessment and careful titration of opioids against pain. Adjuvant analgesic drugs and non-drug measures should be used whenever possible, and drugs should be chosen that will not contribute to existing difficulties. The appropriate use of psychostimulants has yet to be established as has the relative benefit of one opioid over another in cancer pain.

Topics: Adult; Amphetamines; Analgesics, Opioid; Buprenorphine; Central Nervous System Stimulants; Chronic Disease; Cocaine; Codeine; Cognition; Dextropropoxyphene; Dopamine Uptake Inhibitors; Humans; Methylphenidate; Morphine; Neoplasms; Pain; Psychomotor Performance; Randomized Controlled Trials as Topic; Reaction Time; Thiazoles

Topics: Administration, Oral; Administration, Sublingual; Adult; Aged; Aged, 80 and over; Buprenorphine; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain; Pain Measurement; Prospective Studies

The efficacy of phenytoin (PHT), buprenorphine (Bu), and Bu+PHT for the relief of cancer pain of various etiologies was evaluated in a randomized, double-blind study of 3 groups, each comprised of 25 patients. Treatment duration was 1 month. PHT (100 mg by mouth twice daily) provided greater than 50% pain relief to 18 patients (72%) and greater than 75% relief to 4 (16%). Bu (0.2 mg sublingually twice daily) gave 21 patients (84%) greater than 50% relief and 15 patients (60%) greater than 75% relief. Of the Bu-treated patients, 8 had major side effects, while none of the PHT-treated patients experienced significant untoward reactions. Combined therapy (PHT, 50 mg PO+Bu 0.1 mg SL twice daily) provided greater than 50% pain relief to 22 patients (88%) and greater than 75% to 18 (72%); only 3 patients experienced a significant side effect. This study suggests that phenytoin has mild-to-moderate pain-relieving properties of its own and can significantly enhance buprenorphine analgesia. By permitting a lower opioid dose, it may reduce the occurrence of opioid-related side effects. PHT's lack of serious side effects, as well as its documented anxiolytic and antidepressant actions, may add to its comparative usefulness. Further clinical trials of PHT as a coanalgesic and/or adjuvant agent in cancer pain are warranted.

Topics: Adult; Buprenorphine; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Phenytoin

Topics: Buprenorphine; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain Measurement; Palliative Care; Random Allocation

In a randomized cross-study analgesic activity and side effects of two narcotics, buprenorphine and pentazocine, administered orally in 91 advanced cancer patients whose pain intensity varied from moderate to severe, have been compared. The number of hours of sleep and hours standing after administration of both the drugs were also assessed and in 16 patients life activity was taken into consideration. The analysis of data showed: a better pain control with buprenorphine, than with pentazocine, with a statistically significant difference of P less than 0.001; an increase in the number of hours of sleep with buprenorphine, in comparison with pentazocine, with P less than 0.001; an increase in the number of hours standing with buprenorphine, in comparison with pentazocine; as for side effects, many more patients had to stop treatment with pentazocine than with buprenorphine.

Topics: Administration, Oral; Buprenorphine; Clinical Trials as Topic; Humans; Neoplasms; Pain; Pentazocine; Random Allocation; Time Factors

Twelve patients with intense or very intense pain of the non-incident type, secondary to neoplasia, were divided at random into two groups and treated with an epidural dose of 3 mg of morphine in 10 ml of glucose solution (6 patients = group M) or with 0.3 mg of buprenorphine in the same vehicle (6 patients = group B). None of the patients had previously been treated with opioids by any route. After first determining basal values, the following assessments were carried out: (1) evaluation of the analgesic effect of the drugs with checks at 30 min and at 1, 2, 3, 4, 6 and 18 h after administration, using a visual analogue scale, a numerical rating scale and a simple descriptive scale; and (2) evaluation of effects on respiration by means of checks at 30 and 90 min and at 6 and 18 h, on control of breathing indices (P0.1; VE; VA; Ti/Ttot; VT/Ti; RR), gas exchange indices (delta(A-a)O2; VD/VT; pAO2; R) and blood gas and acid-base indices (paO2; paCO2; pH; HCO3-). The data obtained were analyzed statistically using analysis of variance and Student's t test. The study results showed very similar analgesic efficacy for both treatments at a single dosage level of morphine (3 mg) compared to buprenorphine (0.3 mg), which was approximately 3 times greater than an equivalent parenteral dose of morphine (10 mg). Analysis of the results revealed statistically, though not clinically, significant changes in respiratory function indices, only in the buprenorphine-treated group. The effects of buprenorphine on respiratory function, when administered epidurally at the above dosage, are less favourable than those of morphine in the early measurements, probably because of its greater systemic absorption; nevertheless, the risk of delayed respiratory depression appears to be less after buprenorphine than after morphine.

Topics: Aged; Buprenorphine; Double-Blind Method; Female; Humans; Injections, Epidural; Male; Middle Aged; Morphine; Neoplasms; Pain; Prospective Studies; Pulmonary Gas Exchange; Random Allocation; Respiration

The analgesic efficacy and tolerability of a morphine agonist-antagonist buprenorphine are evaluated. The drug is compared to pentazocin. For this purpose, the drugs were randomly administered to 42 patients suffering from pain caused by advanced cancer. Buprenorphine demonstrated a significantly higher analgesic effect than pentazocin and was better tolerated.

Topics: Buprenorphine; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Morphinans; Neoplasms; Pain, Intractable; Pentazocine

Sublingual tablets of buprenorphine (Temgesic sublingual) were given in a controlled trial of 41 patients for 2804 patient-days. With a mean starting dose of 1.09 mg and a final dose of 1.53 mg buprenorphine daily there was a good pain-relieving effect. The interval between doses was six to eight hours. The trial did not reveal any direct pointers as to tolerance or addictiveness after long-term intake of the drug. Because of its effectiveness and good duration of action, as well as the absence of negative long-term effects, the drug can be recommended in the long-term management of cancer pain.

Topics: Buprenorphine; Clinical Trials as Topic; Drug Evaluation; Humans; Long-Term Care; Morphinans; Neoplasms; Pain, Intractable; Palliative Care

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Female; Humans; Male; Meperidine; Middle Aged; Morphinans; Morphine Derivatives; Neoplasms; Pain, Intractable; Palliative Care

Buprenorphine appears to have an analgesic effect (evaluated after a week of treatment) statistically superior to that of the comparative drug. On the whole, during buprenorphine treatment the normal activities of life of the individual patient improved. The percentage incidence of the side-effects is similar for the two drugs. Buprenorphine, however, caused less intense side-effects than pentazocine.

Topics: Adult; Aged; Buprenorphine; Humans; Middle Aged; Morphinans; Neoplasms; Pain; Pentazocine; Time Factors

Topics: Adult; Aged; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphine; Neoplasms; Palliative Care

1 Twenty-seven patients with moderate to severe chronic pain of malignant origin received buprenorphine (0.3 mg) and morphine (10 mg) intramuscularly in a double-blind, single dose within patient study. 2 Efficacy analysis demonstrated no significant differences in the peak analgesic effects or in the time to reach these effects. However, buprenorphine had a significantly longer duration of action than morphine. 3 Sedation was the most frequent unwanted effect with a similar incidence following each treatment. Buprenorphine was associated with a significantly higher incidence, greater severity, earlier onset, and longer duration of dizziness, nausea and vomiting than morphine. 4 Following both treatments there were small but significant decreases in pulse rate, blood pressure, and respiratory rate.

Topics: Adult; Aged; Buprenorphine; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Morphine; Neoplasms; Pain, Intractable; Time Factors

The therapeutic value of buprenorphine was investigated in 31 patients suffering from moderate to severe cancer pain by intramuscular administration at the single doses of 0.2 mg and 0.3 mg in comparison with pentazocine 30 mg. Analgesic effect of buprenorphine 0.3 mg was significantly superior to buprenorphine 0.2 mg and pentazocine 30 mg. The duration of analgesia with buprenorphine was 9 hours at 0.2 mg and 11 hours at 0.3 mg, which were markedly longer than pentazocine's 6 hours. Side effects most commonly observed in the three groups were nausea, vertigo, oral dryness, urinary retention, vomiting, sweating, and headache. The frequency of side effects was 54.8% for buprenorphine 0.2 mg, 50.0% for buprenorphine 0.3 mg and 58.3% for pentazocine 30 mg respectively, indicating no significant difference between the three groups. Blood pressure, heart rate and respiratory rate did not change appreciably, thereby suggesting a little effect of buprenorphine on the respiratory and cardiovascular systems. Buprenorphine was found a useful or extremely useful in 58% at 0.2 mg and 87.5% at 0.3 mg. As the result it was concluded that buprenorphine could be valuable as an analgesic for cancer pain.

Topics: Adolescent; Adult; Aged; Blood Pressure; Buprenorphine; Female; Humans; Male; Middle Aged; Morphinans; Neoplasms; Pain, Intractable; Pentazocine; Pulse; Respiration

1 Buprenorphine is a new antagonist analgesic which was offered sublingually to 141 patients with moderate cancer pain as an alternative to their current analgesic. These patients were not on regular strong morphine-like analgesics. 2 Forty-seven patients used the drug on demand in unit doses ranging from 0.15-0.8 mg for an average of 12 weeks. A full-time nurse-observer was used throughout the studies. 3 Good analgesic results were obtained. Certain difficult chronic dull aching pains in the head and neck were especially helped by the drug. There was no indication of dependence or tolerance in this study. 4 The main side-effect was drowsiness which lessened with usage of the drug. A major advantage of the drug was the absence of constipation as a side-effect. 5 This sublingual preparation seems worthy of addition to the commercially available range of analgesics in clinical practice.

Topics: Buprenorphine; Clinical Trials as Topic; Humans; Morphinans; Neoplasms; Pain

This study explored the effect of transdermal buprenorphine on quality of life and six symptoms in cancer patients with pain.. Transdermal opioids offer advantages over traditional routes of administration. The impact of transdermal buprenorphine on quality of life for patients with cancer in Asian populations is unknown.. This study employed a single-arm observational repeated measures design. Cancer patients with pain were evaluated prior to treatment (baseline). Over a 4-week treatment period, quality of life and symptoms were assessed at 2 and 4 weeks. This study adhered to the recommendations of STROBE guidelines.. This multi-site study was conducted in six hospitals located across northern, middle and southern Taiwan. Adult cancer patients whose pain was previously stable with opioid analgesics and, based on clinical judgement, were able to convert to transdermal buprenorphine treatment were invited to participate. Quality of life was measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).. Generalised estimating equations showed participants who completed at least one follow-up measurement (N = 80) over 4-weeks had a significant improvement in overall quality of life. Functional status only improved for social functioning. However, symptom severity decreased significantly for nausea/vomiting, pain, insomnia and constipation.. The study provides initial evidence supporting transdermal buprenorphine for providing beneficial effects of improving quality of life and reducing severity of symptoms in Asian patients with cancer.. The findings of this study can inform the clinical practice that the use of transdermal buprenorphine in cancer patients with pain may also reduce the severity of other symptoms and improve overall quality of life.. This study was registered in ClinicalTrials.gov. Identifier: NCT04315831.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Humans; Neoplasms; Pain; Quality of Life

Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population.. This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs).. A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain.. This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

Topics: Analgesics, Opioid; Buprenorphine; Cancer Pain; Humans; Neoplasms; Pain; Taiwan

Opioid misuse and opioid use disorder (OUD) are important comorbidities in people with advanced cancer and cancer-related pain, but there is a lack of consensus on treatment.. To develop consensus among palliative care and addiction specialists on the appropriateness of various opioid management strategies in individuals with advanced cancer-related pain and opioid misuse or OUD.. For this qualitative study, using ExpertLens, an online platform and methodology for conducting modified Delphi panels, between August and October 2020, we conducted 2 modified Delphi panels to understand the perspectives of palliative and addiction clinicians on 3 common clinical scenarios varying by prognosis (weeks to months vs months to years). Of the 129 invited palliative or addiction medicine specialists, 120 participated in at least 1 round. A total of 84 participated in all 3 rounds.. Consensus was investigated for 3 clinical scenarios: (1) a patient with a history of an untreated opioid use disorder, (2) a patient taking more opioid than prescribed, and (3) a patient using nonprescribed benzodiazepines.. Participants were mostly women (47 [62%]), White (94 (78 [65%]), and held MD/DO degrees (115 [96%]). For a patient with untreated OUD, regardless of prognosis, it was deemed appropriate to begin treatment with buprenorphine/naloxone and inappropriate to refer to a methadone clinic. Beginning split-dose methadone was deemed appropriate for patients with shorter prognoses and of uncertain appropriateness for those with longer prognoses. Beginning a full opioid agonist was deemed of uncertain appropriateness for those with a short prognosis and inappropriate for those with a longer prognosis. Regardless of prognosis, for a patient with no medical history of OUD taking more opioids than prescribed, it was deemed appropriate to increase monitoring, inappropriate to taper opioids, and of uncertain appropriateness to increase the patient's opioids or transition to buprenorphine/naloxone. For a patient with a urine drug test positive for non-prescribed benzodiazepines, regardless of prognosis, it was deemed appropriate to increase monitoring, inappropriate to taper opioids and prescribe buprenorphine/naloxone.. The findings of this qualitative study provide urgently needed consensus-based guidance for clinicians and highlight critical research and policy gaps.

Topics: Analgesics, Opioid; Benzodiazepines; Buprenorphine; Cancer Pain; Consensus; Female; Humans; Male; Methadone; Naloxone; Neoplasms; Opioid-Related Disorders

Although buprenorphine is widely accepted as a treatment option for opioid use disorder (OUD), it is underutilized as a treatment for cancer-related pain. Owing to its decreased side effect profile, various formulations (depending on FDA indication of pain versus OUD), and ability to simultaneously address OUD and pain, buprenorphine is gaining popularity in the outpatient palliative medicine setting. Despite these compelling benefits, there are significant barriers to initiating therapy. These barriers include clinician experience, insurance authorization, pharmacy supply, and stigma. We present a complicated case to describe the practical clinical experience of an attempt at low-dose initiation of buprenorphine to treat cancer-related pain in a patient with concurrent OUD and to discuss ways to start overcoming the encountered barriers.

Topics: Buprenorphine; Cancer Pain; Humans; Neoplasms; Opioid-Related Disorders

Most patients with cancer-related pain are managed using opioids; cancer-related pain in the setting of pregnancy can be challenging to address owing to risk to the fetus associated with

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cancer Pain; Female; Humans; Neoplasms; Opioid-Related Disorders; Pain Management; Pregnancy; Pregnancy Complications

Chemotherapy-induced mucositis is an extremely painful condition that occurs in 40-60% of patients undergoing chemotherapy. As mucositis currently has no effective treatment, and due to the self-limiting nature of the condition, the major treatment aims are to manage symptoms and limit pain with significance placed on improving patient quality of life. Rodent models are frequently used in mucositis research. These investigations typically assess pathological outcomes, yet fail to include a measure of affective state; the key therapeutic goal. Assessment of cognitive biases is a novel approach to determining the affective state of animals. Consequently, this study aimed to validate a cognitive bias test through a judgement bias paradigm to measure affective state in a rat model of chemotherapy-induced intestinal mucositis. Rats with intestinal mucositis demonstrated a negative affective state, which was partially ameliorated by analgesic administration, whilst healthy rats showed an optimistic response. This study concluded that the judgement bias test was able to evaluate the emotional state of rats with chemotherapy-induced mucositis. These findings provide a foundation for future refinement to the experimental design associated with the animal model that will expedite successful transitioning of novel therapeutics to clinical practice, and also improve humane endpoint implementation.

Topics: Affect; Analgesics, Opioid; Animals; Antineoplastic Agents; Buprenorphine; Disease Models, Animal; Drug Evaluation, Preclinical; Fluorouracil; Intestinal Mucosa; Mucositis; Neoplasms; Quality of Life; Rats

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Buprenorphine; Female; Humans; Male; Morphine; Neoplasms; Pain

To evaluate the use of a buprenorphine transdermal patch (Transtec*) in routine clinical practice, including dosage, indications, efficacy and tolerability.. This prospective, open-label, non-comparative, non-interventional, post-marketing study was performed in Poland by 339 investigators in a range of clinical practice settings. Patients with chronic moderate to severe cancer pain, or chronic severe non-cancer pain that was insufficiently controlled by non-opioids, were prescribed buprenorphine transdermal patch 35, 52.5 or 70 μg/hour (changed twice weekly), and followed up for 3 months. Additional analgesia, and adjuvant/supportive treatments were allowed at the discretion of the physician.. The study enrolled 4030 patients, with a mean age of 62.8 years. Most patients had cancer-related pain (80.7%). Non-cancer pain was generally musculoskeletal or neuropathic. A starting dose of 35, 52.5 or 70 μg/hour was used in 73.4%, 21.5%, and 4.8% of patients, respectively. Buprenorphine dose was increased in 44.7% of patients during the observation, generally from 35 to 52.5 μg/hour. Mean pain intensity (using a 100 mm visual analogue scale) decreased by 73.5% from 62.3 mm at baseline to 16.5 mm after 3 months. Most patients rated pain relief as 'very good' (41.4%) or 'good' (44.5%). Sleep quality also improved. 48.1% of patients needed no additional analgesics during buprenorphine treatment. Most patients (96%) rated the buprenorphine transdermal patch as 'very easy' or 'easy' to change. The most common treatment-related reasons for discontinuation were lack of analgesic effect (3.3% of patients) and adverse drug reactions (ADRs, 0.8%). ADRs, all non-serious, occurred in 34 patients (0.8%), most commonly local skin reactions or vomiting. At study end, it was planned to continue treatment with transdermal buprenorphine in 70.1% of patients. The main limitations related to the observational study design, balanced by advantages gained from the 'real life' exploration of transdermal buprenorphine use.. In routine Polish clinical practice, transdermal buprenorphine was effective and generally well-tolerated in patients with chronic moderate to severe cancer pain or chronic severe non-malignant pain insufficiently controlled by non-opioids.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Disease; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Poland; Product Surveillance, Postmarketing; Prospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

We present three cases of children (aged 3-5 years) in which cancer-related pain was adequately controlled by Transdermal Buprenorphine. The endpoints for evaluating analgesic efficacy consisted of the assessment of pain using a visual scale and the possibility of reducing other pain treatment. Improvement of pain level was demonstrated by the decrease in pain scores, by reduction of the overall amount of medications, especially opioids, and by improvement of uninterrupted sleep. Only limited data is available on the use of Transdermal Buprenorphine in children. In our experience, Transdermal Buprenorphine allowed good analgesia without significant side effects in these three children with cancer-related pain.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Child, Preschool; Humans; Male; Neoplasms; Pain

The aim of this study was to evaluate the equianalgesic ratio of transdermal buprenorphine (TD BUP) with oral morphine and TD fentanyl in a sample of consecutive cancer patients receiving stable doses of 120-240 mg of oral morphine or 50-100 microg of TD fentanyl, reporting adequate pain and symptom control.. Patients receiving daily stable doses of opioids for more than 6 days, with no more than two doses of oral morphine (20 and 40 mg, respectively) as needed, were switched to TD BUP using a fentanyl-BUP ratio of 0.6:0.8 and an oral morphine-BUP ratio of 70:1. Opioid doses, pain and symptom intensity, global satisfaction, and number of breakthrough medication were recorded before switching (T0), 3 days after (T3), and 6 days after (T6). Eleven patients were recruited in a period of 1 year, and data were complete for ten patients. The mean age was 61.6 (SD 9.5), and five patients were males. No significant changes in pain and symptom intensity were found, except improvement in reported constipation (p = 0.014), as well as in global satisfaction with the analgesic treatment. No significant changes in breakthrough pain medication were observed.. The results of this study suggest that stable patients receiving relatively high doses of oral morphine or TD fentanyl could be safely switched to TD BUP, by using a ratio of 70:1 and 0.6:0.8, respectively, maintaining the same level of analgesia.

Topics: Administration, Cutaneous; Aged; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Fentanyl; Humans; Male; Middle Aged; Neoplasms; Pain; Patient Satisfaction; Prospective Studies

Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Drug and Narcotic Control; Drug Prescriptions; Fentanyl; Guideline Adherence; Humans; Italy; Morphine; Neoplasms; Oxycodone; Pain; Practice Guidelines as Topic; Practice Patterns, Physicians'; Time Factors

The semi-synthetic opioid, buprenorphine, has the general structure of morphine but differs from it in significant ways, both pharmacologically and clinically. A number of long-term studies have shown effective, long-lasting analgesia in moderate to severe cancer and non-cancer pain, including neuropathic pain, with a low incidence of constipation, nausea, dizziness and tiredness. The treatment of moderate to severe chronic pain has improved as a result of the development of new methods of administration of this substance, particularly the introduction of the transdermal drug delivery system, which offers a number of advantages over the usual oral and parenteral routes.. A panel of experts specialising in palliative care and pain treatment was convened in November 2007 to discuss their clinical experiences with transdermal buprenorphine and other analgesics. The aim was to provide practical guidance on the treatment of cancer pain with transdermal buprenorphine, particularly when there is a need for increasing pain relief leading to high and increasing doses. A literature search on the use of transdermal buprenorphine was carried out for the panel meeting (based on a search of PubMed to November 2007 - since updated by an additional search for the period to February 2009) and a number of case histories were presented and discussed. This commentary article presents this evidence and the consensus findings of the expert panel.. The Panel reached consensus that transdermal buprenorphine was a valuable treatment for chronic cancer pain, including its neuropathic components. A number of general recommendations were made. Large-scale, randomised clinical studies are needed to provide product comparisons on the use of analgesics in the treatment of neuropathic pain although it was recognised that such studies may not be practicable. Data on the treatment of acute and chronic pain should be kept separate in general. Physicians should be made more aware of the problem of hyperalgesic effects of some opioids in long term use. Buprenorphine in contrast has been described to exert an antihyperalgesic effect. The development of analgesic tolerance with some opioids in long term use and the lack of it with buprenorphine requires further studies. The registered dose range of 35-140 microg/h was considered adequate to achieve sufficient pain relief in most patients although some members of the panel presented data showing that increases beyond this dose range provided improved pain relief if slow titration is used. However, it was generally felt that more evidence was needed before this could become generally acceptable.. The consensus was that transdermal buprenorphine has a valuable role to play in the treatment of chronic cancer pain because of its efficacy and good safety and tolerability profile, including a low risk of respiratory depression, a lack of immunosuppression and a lack of accumulation in patients with impaired renal function.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Consensus; Expert Testimony; Guidelines as Topic; Humans; Neoplasms; Pain; Palliative Care

Topics: Administration, Topical; Aged; Analgesics, Opioid; Buprenorphine; Cholestasis; Chronic Disease; Drug Combinations; Female; Humans; Injections, Intravenous; Naloxone; Narcotic Antagonists; Neoplasms; Pain; Pain Measurement; Palliative Care; Pruritus; Treatment Outcome

To obtain information on the efficacy, tolerability and safetyofa transdermal buprenorphine patch (Transtec PRO) in patients with moderate to severe chronic pain. In addition it should be evaluated to what extent the two fixed patch change days per weekare simplifyingthe therapy.. In this prospective multi-center post marketing surveillance study patients with chronic cancer and non-cancer pain were treated with transdermal buprenorphine for up to eight weeks. The evaluation included pain intensity, the dosage of the applied analgesics and additional therapies, the renal function (by serum creatinine) and adverse events.. 3654 patients were treated for a mean of 50.4 days. Using the NRS-11 the mean pain intensity decreased from 6.3 at the time when patients were switched to the transdermal buprenorphine patch to 2.6 at the last treatment evaluation. The matrix patch was safe and well tolerated also in patients with advanced renal insufficiency. Adverse events were reported in 6.7% of the patients. 89.3% of the physicians quoted to prefer transdermal buprenorphine with the two fixed patch change days per week compared to the pre-treatment.. The buprenorphine-containing matrix patch was effective and well tolerated in patients with moderate to severe chronic cancer and noncancer pain. From the physicians view the two fixed patch change days per week facilitate the guidance of therapy. In patients with advanced renal insufficiency a dose adjustment is not necessary.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Product Surveillance, Postmarketing; Prospective Studies

Pain still afflicts most cancer patients, mainly in the metastatic phases, and undertreatment is well documented. Transdermal delivery systems (TDS) could potentially have advantages over oral and parental routes, but evidence from comparative trials are scanty. In the framework of a wider initiative, an Outcome Research Study was carried out in Italy in 2006 to evaluate the effects of various analgesic options, particularly TDS Buprenorphine. Despite the limitations due to the observational design, these findings may be useful to clinicians to better judge the value of the drug under evaluation and to help researchers to design further comparative studies.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Chronic Disease; Dose-Response Relationship, Drug; Female; Humans; Italy; Male; Middle Aged; Neoplasms; Outcome Assessment, Health Care; Pain; Pain Measurement; Palliative Care; Prospective Studies; Quality of Life; Research Design; Surveys and Questionnaires; Treatment Outcome

The aim of this preliminary study was to explore the possibility of using higher doses of transdermal buprenorphine (TD-BUP) than those commonly used and available as manufactured patches, which are based on the assumption that BUP may have a ceiling effect that has never been determined yet.. Ten patients who were already receiving TD-BUP (70 microg/h, which is about 1.6 mg/day) and were no longer responsive to this dosage were administered higher doses up to a maximum of 140 microg/h within 6 days, when the study was completed.. In six patients, dose increments of TD-BUP were effective, and patients achieved adequate analgesia within 6 days. Four patients discontinued the treatment due to inefficacy of TD-BUP 140 microg/h and were switched to other opioids until achieving stabilization (oxycodone 320 and 400 mg/day, methadone 120 mg/day, transdermal fentanyl 200 microg/h). This group of patients required higher doses than those chosen for TD-BUP, underlying the need to escalate the dose rapidly, a modality not accomplished with transdermal drugs. Adverse effects did not change and were similar to those observed before increasing the dose of TD-BUP. On the basis of these preliminary data, patients requiring doses higher than 70 microg/h of TD-BUP, in the range of 105-140 microg/h, may still have an analgesic benefit without important consequences in terms of adverse effects. It cannot be excluded that even higher doses may be effective, as some patients required rapid titration with higher morphine equivalent doses, and according to the protocol, other opioids were provided to facilitate this process. Further studies should clarify the role and the benefit of TD-BUP in specific clinical circumstances.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Maximum Tolerated Dose; Neoplasms; Pain; Pilot Projects; Treatment Outcome

The aim of this study was to confirm that the concomitant presence of transdermal fentanyl (TTS FE) and buprenorphine (TTS BU) may be feasible without important consequences, using doses presumed to be equianalgesic. A prospective "N of 1" study was carried out in a sample of volunteers with cancer pain receiving stable doses of TTS FE or TTS BU, with adequate pain and symptom control. In the study design, each patient provided data before and after a switch from one opioid to the other and then back to the previous one. Sixteen patients receiving daily stable doses of 0.6 or 1.2mg of TTS FE were switched to TTS BU using an FE-BU ratio of 0.6-0.8. After three days, the TTS BU patch was removed and TTS FE patch was placed for another three days. Six patients receiving TTS BU were switched to TTS FE and then rotated back to TTS BU with the same dosing considerations. No statistical differences in changes in pain and symptom intensity during switching and between the two different sequences were observed. No significant changes in rescue doses of oral morphine were reported at the same intervals. Cancer patients receiving stable doses of TTS FE or TTS BU can be safely switched to the alternative transdermal opioid. Further studies should be performed to gather data about the use of TTS BU with other opioids, at different doses, and in different clinical conditions.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Fentanyl; Humans; Male; Middle Aged; Neoplasms; Pain Measurement; Pain, Intractable; Prospective Studies

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Neoplasms; Pain; Randomized Controlled Trials as Topic; Treatment Outcome

We evaluated patterns of use of opioids in palliative care across one region in Italy by cross-referencing a cancer registry with unique patient identifiers, with prescription databases. There were 90 803 patients in the registry, of whom 39 597 died during the study period. Only 8539 (21%) of these were prescribed opioids at the time of their death. Prescribed daily doses of oral morphine used (45 mg) and of buprenorphine (0.71 mg) were low compared with injected morphine (28.6 mg, equivalent to approximately 90 mg of oral morphine) and especially with doses of transdermal fentanyl (1.13 mg, equivalent to approximately 180 mg morphine). The reasons for this acceptance of transdermal fentanyl and reluctance to use oral morphine are unclear, but it seems that more effort in educating healthcare professionals and patients about the use of morphine would be useful. The use of more detailed prescribing data such as prescribed or received daily doses can add to our understanding of headline prescribing data.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Aged; Buprenorphine; Child; Child, Preschool; Drug Prescriptions; Female; Fentanyl; Humans; Infant; Infant, Newborn; Italy; Male; Middle Aged; Morphine; Narcotics; Neoplasms; Palliative Care; Registries; Retrospective Studies

Previous studies have suggested that buprenorphine may have a low association with tolerance development compared with other strong opioids. In a previous study by our group, mean cohort and intraindividual dosage increases over an entire course of treatment and on a per-day basis were significantly lower with transdermal (TD) buprenorphine than with TD fentanyl. However, no information concerning the relationship between qualitative and quantitative dose changes is available.. The aim of this study was to compare TD buprenorphine and TD fentanyl with respect to dosage increases, dosage stability, and the nature of dosage changes.. This retrospective analysis used data from the IMS Disease Analyzer-Mediplus database, which contains patient-related data documented by 400 medical practices in Germany. Data from patients with noncancer or cancer pain treated with TD buprenorphine or TD fentanyl for at least 3 months between May 2002 and April 2005 were analyzed. Daily dosages were directly determined from the prescribed patch strength, taking into account the possibility of multiple patches applied simultaneously. To determine dosage stability, patients were classified based on the type of dosage change (stable, increase, alternating, or decrease) of the prescribed dosages. From the prescribed daily dosages, mean percentage increases were calculated on a per-patient basis for the entire treatment period and per day, and these were assessed in relation to the type of dosage change.. In total, 631 patients with noncancer pain and 605 patients with cancer pain were included in the analysis (782 women, 454 men; mean age, 76.3 years [range, 29-100 years]). Treatment indications included osteoarthritis, low back pain, osteoporosis (noncancer groups), and neoplasm (cancer groups). Patients had similar analgesic premedication requirements based on steps 1 to 3 of the World Health Organization analgesic ladder. Comedication requirements for breakthrough pain were also similar between the TD buprenorphine and TD fentanyl groups. The mean percentage increases per day were 0.10% (TD buprenorphine) and 0.25% (TD fentanyl) in the noncancer groups and 0.19% (TD buprenorphine) and 0.47% (TD fentanyl) in the cancer groups (both, P < 0.05). A significantly larger proportion of patients receiving TD buprenorphine had stable dosages over the entire treatment period compared with patients receiving TD fentanyl (noncancer groups: 56.9% vs 41.6%; cancer groups: 50.0% vs 26.2% [both, P < 0.05]). Compared with TD buprenorphine, the proportion of patients with alternating dosage changes was significantly greater in patients receiving TD fentanyl (noncancer groups: 22.7% vs 13.1%; cancer groups: 30.6% vs 11.8% [both, P < 0.05]).. In this retrospective data analysis, compared with TD buprenorphine, the increase in mean daily dosage was significantly greater in patients treated with TD fentanyl. Also, compared with TD buprenorphine, alternating dosage changes were seen in a significantly greater proportion of patients receiving TD fentanyl. On the other hand, a significantly greater proportion of patients treated with TD buprenorphine had stable dosages over their entire treatment periods.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Female; Fentanyl; Humans; Male; Middle Aged; Neoplasms; Pain; Pain, Intractable; Retrospective Studies

The equipotency ratio of transdermal (TD) fentanyl to oral morphine has been established as 1:100; for buprenorphine TD, a ratio of 1:75 has been proposed, although this ratio has not been confirmed in clinical studies. Growing evidence from clinical practice, in which much lower doses of buprenorphine are used, suggests that this conversion ratio may be too high.. The aim of this study was to compare calculated equipotent oral morphine doses of fentanyl TD with equipotent oral morphine doses of buprenorphine TD prescribed in clinical practice.. This retrospective study identified patients with cancer and noncancer pain who had received > or =1 prescription for fentanyl TD or buprenorphine TD (the all-patients groups) from the German IMS Disease Analyzer-mediplus database, which contains all relevant data concerning drug prescriptions from 400 practices in Germany. Also identified were subgroups of the all-patients groups who had received long-term treatment with fentanyl TD or buprenorphine TD and were considered to have similar pain intensity, as they had previously received similar analgesic medication (the identical-cohort groups). Mean prescribed daily doses for the all-patients and identical-cohort groups were calculated based on the distribution of prescribed patch strengths. Because patients could have applied >1 patch, mean prescribed daily doses were also calculated based on an assumption of double application when appropriate. Equipotent oral morphine doses were estimated using equipotency ratios of 1:100 for fentanyl TD and 1:75 for buprenorphine TD.. The all-patients groups consisted of 2198 patients with noncancer pain and 2544 patients with cancer pain; the identical-cohort groups consisted of 380 patients with noncancer pain and 496 patients with cancer pain (529 women, 347 men; mean age, 74 years [range, 25-101 years]). Equipotent doses of oral morphine were significantly lower in patients receiving buprenorphine TD compared with those receiving fentanyl TD (P < 0.001). In cancer patients, the equipotent oral morphine doses of fentanyl TD and buprenorphine TD were 130.9 to 138.9 mg and 85.2 to 88.8 mg, respectively; in noncancer patients, the corresponding values were 117.0 to 118.3 mg and 80.2 to 80.9 mg. Based on these results, an equipotency ratio of 1:110 to 1:115 for buprenorphine TD would appear to be more appropriate than the proposed ratio of 1:75.. The fact that this retrospective analysis conducted in identical cohorts showed lower calculated equipotent oral morphine doses in the buprenorphine TD groups compared with the fentanyl TD groups calls into question the proposed 1:75 ratio for conversion of buprenorphine TD to equipotent oral morphine doses. Based on the findings of the present study, an equipotency ratio of 1:110 to 1:115 may be more appropriate. However, confirmative data from prospective randomized clinical trials are needed.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Disease; Cohort Studies; Female; Fentanyl; Hospitalization; Humans; Male; Middle Aged; Neoplasms; Pain; Referral and Consultation; Retrospective Studies

A new transdermal delivery system (TDS) for the rate-controlled systemic delivery of buprenorphine is available in 3 patch strengths, with release rates of 35, 52.5, and 70 microg/h over 72 hours, delivering daily amounts of 0.8, 1.2, and 1.6 mg, respectively. Randomized, double-blind, placebo-controlled, Phase III clinical trials in >400 patients with severe pain of malignant or nonmalignant origin have shown the analgesic efficacy of buprenorphine TDS.. This study investigated the effectiveness and tolerability of buprenorphine TDS for the relief of chronic pain in routine clinical practice.. This was a multicenter, open-label, uncontrolled, prospective, observational, 3-month follow-up study in patients who were beginning buprenorphine TDS treatment for moderate to severe cancer or noncancer pain that had not responded to nonopioid analgesics. Patches were to be changed every 72 hours. Patients were evaluated at 1 and 3 months after the start of treatment. Those who dropped out were considered treatment failures. Pain relief was assessed on a 5-category verbal rating scale, and quality of life was assessed using the European Quality of Life 5D (EQ-5D) questionnaire. Tolerability was determined based on adverse events recorded during the follow-up period.. The study recruited 1223 patients, most of whom were outpatients. Of the 1212 patients for whom sex data were available, 820 (67.7%) were women. In the 1188 patients with age data, the mean (SD) age was 64.9 (12.9) years. In the 1175 patients with data on the etiology of pain, 82.4% had noncancer pain. Six hundred eighty-eight (56.3%) patients completed the 3-month follow-up period. The median daily amount of buprenorphine TDS received at the beginning of the study was 0.8 mg (corresponding to 35 microg/h). Over the study period, there was a significant increase in the proportion of patients reporting very good or good pain relief (P < 0.001), from 3.6% (43/1205) at baseline to 63.2% (762/1205) after 1 month and 56.8% (685/1205) after 3 months. Quality of life also improved, from a mean (SD) EQ-5D score of 40.6 (20.5) at baseline to 56.8 (23.5) at 3 months (P < 0.001). Five hundred seventeen (42.3%) of the original 1223 patients experienced adverse events; the investigator judged 397 (32.5%) of these events possibly or probably related to study drug. The likelihood of experiencing a drug-related adverse event was greater in noncancer patients than in cancer patients. The most common adverse events were nausea (11.0%), vomiting (9.2%), and constipation (7.8%); the most common local adverse events were pruritus (1.4%), dermatitis (1.3%), and erythema (1.3%).. In the population studied, buprenorphine TDS was effective in alleviating cancer and noncancer pain and was well tolerated overall.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Pain; Pain Measurement; Quality of Life

During long-term therapy with strong opioids (step III opioids according to the World Health Organization [WHO] analgesic ladder), dose increases are often necessary because of deterioration of the primary disease or development of tolerance.. The purpose of this study was to compare changes in dosages of transdermal (TD) fentanyl and TD buprenorphine in patients with cancer and non-cancer pain.. In a retrospective study, patients with cancer and noncancer pain being treated with TD fentanyl or TD buprenorphine for at least 3 months between January 2001 and December 2003 were identified from the IMS Disease Analyzer-mediplus database, which contains all patient-related data documented from 400 medical practices in Germany. The indications for treatment were defined according to the International Classification of Diseases, 10th Revision, and included neoplasm (cancer groups), and osteoarthritis, low back pain, and osteoporosis (noncancer groups). The cohort patients were considered to have comparable pain intensity because they had received similar analgesic premedication classified according to steps I to III of the WHO analgesic ladder (cohort groups). The mean prescribed daily doses on first and last prescription were documented, and the mean percentile increases were calculated over the whole treatment duration and per day. Additionally, the mean percentile intraindividual increases (on a per-patient basis) were estimated.. The cohort groups consisted of 448 patients with noncancer pain and 446 patients with cancer pain (552 women and 342 men; mean age, 74 years; range, 25-101 years). The mean percentile increases in dosages over the whole treatment duration and adjusted per day were significantly higher in patients taking TD fentanyl (P < 0.05). Differences were even greater for the mean percentile intraindividual increases per day, which totaled 0.42%and 0.17% for cancer patients taking TD fentanyl and TD buprenorphine, respectively; corresponding values were 0.25% and 0.09%in noncancer patients (P < 0.001).. This retrospective analysis showed a significantly higher increase in the mean daily doses of TD fentanyl as compared with TD buprenorphine. The results must be verified in prospective, randomized clinical studies.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Cohort Studies; Dose-Response Relationship, Drug; Female; Fentanyl; Germany; Humans; Male; Middle Aged; Neoplasms; Pain; Retrospective Studies

A retrospective survey of the opioid prescriptions issued for cancer outpatients (2125) of the Treviso district (Veneto Region, northern Italy) during the time period 1993-2000 was carried out with the specific aims to establish the rate of opioid prescription and verify whether terminally ill outpatients (1697) who had died by the end of December 2000 received adequate opioid prescription, as compared with the Defined Daily Doses (DDDs) of opioids suggested by the World Health Organization (WHO) for a standard population. For both women and men, the maximum rate of opioid prescription was at the age of beyond 90 years. Men were more prescribed than women between 60 and 79 years of age, whereas women were more prescribed than men beyond 90 years. Opioid prescriptions concerned only morphine, buprenorphine, and pentazocine. The Anatomical Therapeutic Chemical (ATC)/DDDs analysis of opioid prescriptions indicated that total opioid use increased about 1.7-fold between 1993 and 1996, mainly because of an increase (55.4%) in morphine prescriptions. Afterwards, total opioid use remained stable, with an estimated mean annual value of 108.2+/-6.4 DDDs/million inhabitants/day. Considering terminally ill outpatients who had died by the end of December 2000, oral morphine turned out to be the most commonly prescribed opioid (64% of patients) and, among the three opioids, pentazocine was more prescribed to older patients. From the comparison between the number of "expected opioid DDDs" (i.e. days for which patients should have been prescribed opioids at the WHO recommended DDDs) and the number of prescribed opioid DDDs (i.e. days for which patients had been offered adequate opioid treatment) for individual patients, it could be estimated that only 38.1% of opioid prescriptions were adequate and a mean of 55.8 DDDs of opioids per patient were not prescribed. The opioid prescription inadequacy increased with the length of time from first prescription to patient death. In addition, a questionnaire investigation, conducted in 2001 among general practitioners of the Treviso district to evaluate their attitudes toward opioid prescribing, evidenced insufficient knowledge of general practitioners in theory and use of opioid analgesics in cancer pain management. A total of 104 (32.5%) general practitioners responded and most of them feared opioid side effects, such as respiratory depression (49.6%), constipation (41.7%), and addiction (8.7%). Furthermore, many of the responde

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Analgesics, Opioid; Attitude of Health Personnel; Buprenorphine; Drug Utilization; Female; Humans; Italy; Male; Middle Aged; Morphine; Neoplasms; Pentazocine; Practice Patterns, Physicians'; Retrospective Studies; Surveys and Questionnaires; Terminal Care; Terminally Ill

Patients with moderate to severe pain were treated with buprenorphine patches in one of 3 concentrations: 35 micrograms/h, 52.5 micrograms/h and 70 micrograms/h (= 0.8 mg/d, 1.2 mg/d and 1.6 mg/d respectively). The aim of this review was to assess the efficacy and tolerability of this transdermal system (TDS) in patients with chronic pain. A total of 445 patients were included in 3 double-blinded studies. The dosage titration with buprenorphine patches followed pretreatment with buprenorphine sublingual tablets, higher doses of weak opioids (level 2 substances), low dose morphine (level 3) or other analgesics. Patients with chronic tumour or non-tumour pain were recruited for these studies and treated with buprenorphine patches or placebo for 6 to 15 days. All patients were offered, in addition, buprenorphine sublingual tablets to be taken as required for supplementary pain relief. Pain intensity, analgesia, consumption of buprenorphine sublingual tablets and sleep duration were all assessed. All patients in the double-blinded studies were between the ages of 22 and 88. 249 patients suffered from tumour pain and 196 patients suffered from non-tumour pain. To examine long-term efficacy and tolerability of the transdermal system, treatment was expanded, if the patients were interested in participating in an open-label-study. In all 3 studies, the number of patients with moderate, severe and very severe pain increased in the placebo-patch treated group, while the patients in the buprenorphine transdermal system treated group had a greater incidence of mild or no pain. A further benefit in the buprenorphine transdermal system treated group was evidenced by a great number of patients with a daily sleep duration of more than 6 hours compared to the placebo group--an indicator of greater well-being. The systemic side-effects were typically opioid in nature and rare and usually only mild. Of particular note was the very low incidence of constipation in only 5.3% of cases. Dermatological reactions to the patches were only rarely encountered. The dermatological reactions consisted mainly of erythema and pruritus with a mild to moderate extent. Half the cases of erythema and more than on third of the cases of pruritus were spontaneously reversible. More than half the patients (53.7%) in the double blind studies wished to continued treatment with buprenorphine transdermal system. These results demonstrate that buprenorphine patches achieved a very good analgesic effe

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Humans; Long-Term Care; Neoplasms; Pain; Pain Measurement; Randomized Controlled Trials as Topic; Treatment Outcome

A new method for administration of opiates into the ventriculo-cisternal system for intractable pain due to cancer is presented. Five patients suffering from such pain underwent the permanent implantation of a subcutaneous reservoir connected to a thin catheter inserted into the trigeminal cistern. The indications are those of the intraventricular way. Percutaneous trigeminal opiates administration (PTO) proved to be a valid and simple alternative method to intrathecal and intraventricular morphine.

Topics: Analgesia; Buprenorphine; Catheters, Indwelling; Female; Humans; Male; Middle Aged; Neoplasms; Pain Measurement; Pain, Intractable; Palliative Care; Trigeminal Ganglion

This report concerns 23 patients, the majority of whom are suffering from low back and chest pain caused by chest, urological or gynaecological cancer. These patients were treated with subarachnoid buprenorphine, administered in a single bolus or by slow infusion from micropumps, at a daily dose adapted to patients need (0.06-0.15 mg). The painful symptomatology was successfully controlled in all the cases treated, allowing the patients to live a virtually normal life. In no cases was respiratory depression or tolerance observed.

Topics: Adult; Aged; Buprenorphine; Drug Administration Schedule; Female; Humans; Infusion Pumps, Implantable; Male; Middle Aged; Neoplasms; Pain, Intractable; Subarachnoid Space; Thermography

The continuous subcutaneous infusion of buprenorphine, a new approach to the relief of severe cancer pain, has been carried out using a portable infusion pump. The efficacy of this method was examined in 30 patients by visual analogue scale. An infusion rate of 4 micrograms/kg/day following intramuscular administration of 0.004 micrograms/kg gave satisfactory pain relief without serious complications. The minimum effective blood concentration was not detectable by high-performance liquid chromatography. Advantages of this therapy are its simplicity, applicability in many types of cancer, multiple sites of administration, and easier training on the part of health personnel.

Topics: Adult; Aged; Blood Pressure; Buprenorphine; Female; Humans; Infusion Pumps; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pain Measurement; Pain, Intractable

During a trimester time-course, pain and the efficiency of analgesic interventions were carefully analyzed over 4 weeks in 50 consecutive medical oncology patients with chronic cancer pain. Pain self-assessment was performed with help of a semi-verbal linear analogue scale (VAS). During the initial hospital stay a mean reduction in pain intensity of "40-50%" on VAS in (largely insufficiently pretreated) cancer patients was recorded within 3-7 days. Optimizing pain therapy was not accompanied by more prominent side-effects from more potent analgesic measures, which consisted in regular "pain prophylaxis" instead of PRN-orders, more frequent use of analgesics with a central analgesic action, combination of analgesics with antidepressants or neuroleptic agents and diligent use of still available potentially effective causal pain relief from palliative chemo-hormonotherapy, irradiation and supportive surgery. The (most frequent) skeletal pain situations were usually managed effectively by prostaglandin-synthetase inhibitors, and also by liberal use of palliative antitumor therapy. Visceral cancer pain was more effectively controlled by analgesics only (opiates/opioids). Strong emphasis is placed on critical interpretation of VAS pain scores and on concomitant psychosocial issues.

Topics: Adult; Aged; Analgesics; Buprenorphine; Chronic Disease; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain; Pain Measurement; Prospective Studies

Epidural administration of opiates as a long-term treatment of cancer pain, even for out-patients, is now well established. Most reports describe intermittent injections given several times a day, which may have technical and personal disadvantages. Continuous epidural infusion may be preferable. This report describes 16 patients who were treated with epidural opiates delivered by plastic infusion pumps. Pain relief was effective, the equipment was inexpensive and home treatment was easily accomplished.

Topics: Anesthesia, Epidural; Buprenorphine; Catheters, Indwelling; Humans; Infusion Pumps; Meperidine; Morphine; Neoplasms; Pain

The efficacy of continuous subcutaneous infusion of buprenorphine for the treatment of terminal cancer pain was studied. Continuous subcutaneous administration of 4-8 micrograms/kg/day of buprenorphine, examined by the visual analogue scale was revealed to have satisfactory analgesic potency for control of every type of terminal cancer. This therapy can be undertaken by any member of the medical staff because of its safety and simplicity. The indications for this method are almost unlimited when the subcutaneous tissue can absorb the drug at a constant rate. Continuous subcutaneous buprenorphine administration via a portable infusion pump allows patients with severe pain from cancer the opportunity to move about freely.

Topics: Buprenorphine; Humans; Injections, Subcutaneous; Morphinans; Neoplasms; Pain, Intractable

Epidural opiates were administered to 139 patients with pain due to malignant diseases via a chronic indwelling catheter inserted percutaneously. So far, 9,716 days of treatment can be evaluated. In 87% of the patients whose pain previously could not be controlled with conventional analgesic approaches, epidural opiates resulted in remarkable pain relief. With a mean daily dose of 15.6 mg morphine (range 2-290 mg) or 0.86 mg buprenorphine (range 0.15-7.2 mg) half of the patients could be treated as outpatients. The mean duration of therapy was 72 days (range 1-700 days), 26 catheters being in place for more than 100 days and one catheter being in place for 510 days. Two severe side-effects (meningitis) were observed, both patients being free of symptoms after catheter removal and antibiotic therapy. Epidural opiates proved to be a valuable method of pain control in terminal illness. The method should be reserved for those patients, for whom oral opiates fail to produce effective pain relief.

Topics: Adult; Aged; Anesthesia, Epidural; Buprenorphine; Catheters, Indwelling; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Neoplasms; Pain, Intractable

Topics: Adolescent; Buprenorphine; Child; Child, Preschool; Female; Humans; Male; Morphinans; Neoplasms; Pain; Retrospective Studies

Systemic administration of opioids is one of the traditional, but by no means optimized therapeutic procedures in cancer pain. Besides the underlying pathophysiology, appropriate treatment has to take into account the psychodynamics and behavior of the patient as well as his life expectancy. In view of this, therapy with centrally acting analgesics can be considered after administration of analgesics with peripheral action first and then of psychoactive agents. Nefopam is a centrally (but not spinally) acting analgesic with a novel activity profile. Its advantages and disadvantages in the treatment of carcinoma pain are outlined. The opiate agonist-antagonist principle has the advantage of a lower dependence and tolerance potential. In addition, the preparations pentazocine, tilidine plus naloxone, and buprenorphine deviate from the morphine derivatives in various constituent effects. Their actions and side effects are outlined. The optimization of control of cancer pain is not possible without taking into account the time dimension. In 50 pain patients with advanced cancer, the following main errors were observed in previous treatment of pain syndromes: (1) too early parenteral administration in the course of the disease; (2) underdosage; (3) application intervals that were too long; and (4) use of analgesics as needed by the patient or on request and not according to a time schedule.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Middle Aged; Morphine; Nefopam; Neoplasms; Pain; Pentazocine; Tilidine; Tramadol

Buprenorphine sublingual tablets (0.2 mg) were investigated in therapy of cancer pain. In 67 patients there was a good analgetic effect in 60%, even in those cases treated with other opiates before. The induction time was quite long (60 min.) but is no problem in chronic administration. Effective pain relief was obtained even in final stages of cancer. The mean daily dose of buprenorphine had been 1.2-1.7 mg, the mean duration of analgesia being 6-8 hours with a single dose of 0.2-1.0 mg buprenorphine. Typical opiate-side-effects were registered and well tolerated after some days' treatment. There was no respiratory depression. Buprenorphine sublingual tablets are certainly a good alternative in orally available opioids.

Topics: Administration, Oral; Adult; Aged; Buprenorphine; Female; Humans; Long-Term Care; Male; Middle Aged; Morphinans; Neoplasms; Pain, Intractable

Topics: Buprenorphine; Humans; Morphinans; Neoplasms; Pain, Intractable; Palliative Care; Postoperative Period; Respiration, Artificial

In that study we compared the analgesic effects of equianalgesic doses of buprenorphine and morphine taken as the narcotic of reference. The experiment has been undertaken in ten adults having severe cancer pain. The results have been analysed by statistical non parametric tests. We found that buprenorphine and morphine have the same pattern of action despite the fact that intramuscular buprenorphine has a clinical duration of approximately 9 hours.

Topics: Adolescent; Adult; Analgesics; Buprenorphine; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Neoplasms; Pain; Statistics as Topic; Time Factors

Topics: Buprenorphine; Humans; Injections, Intramuscular; Morphinans; Neoplasms; Pain, Intractable