buprenorphine and Constipation

To systematically assess efficacy and safety of buprenorphine patch versus fentanyl patch in patients with chronic moderate to severe pain.. Fifteen databases were searched up to December 2010. Randomised and quasi-randomised trials assessing the efficacy in patients with chronic pain were included. Quantitative methods for data synthesis were used and two network meta-analyses were conducted.. Fourteen unique trials (17 publications) were included. No head-to-head randomised trials of buprenorphine patch compared with fentanyl patch were identified. Therefore, less robust evidence from indirect comparisons was used. Results from a network meta-analysis of non-enriched designs (eight trials), using trials versus placebo and trials versus morphine for indirect comparisons, indicated that transdermal fentanyl, in comparison with transdermal buprenorphine, showed significantly more nausea (odds ratio [OR] 4.66, 95% confidence interval (CI) 1.07 to 20.39), a significantly higher number of treatment discontinuations due to adverse events (OR 5.94, 95% CI 1.78 to 19.87), and non-significant differences on all other outcomes, including pain measures. In comparison with morphine, transdermal buprenorphine had a significantly higher decrease of pain intensity (MD [mean difference] -16.20, 95% CI -28.92 to -3.48) while morphine caused more cases of constipation (OR 7.50, 95% CI 1.45 to 38.85) and a significantly higher number of treatment discontinuations due to adverse events (OR 5.80, 95% CI 1.68 to 20.11). All other outcomes showed non-significant differences between transdermal buprenorphine and morphine. The results were similar when also including six trials using enriched designs with the exception of more cases of vomiting for fentanyl (OR 17.32, 95% CI 4.43 to 67.71) and morphine (OR 15.85, 95% CI 3.92 to 64.13) compared to buprenorphine.. The findings indicate comparability of transdermal buprenorphine and transdermal fentanyl for pain measures with significantly fewer adverse events (nausea and treatment discontinuation due to adverse events) caused by transdermal buprenorphine.

Topics: Administration, Oral; Analgesics, Opioid; Buprenorphine; Chronic Pain; Constipation; Fentanyl; Humans; Morphine; Nausea; Pain; Pain Measurement; Transdermal Patch; Treatment Outcome

Buprenorphine is an opioid analgesic, derived from thebaine. Buprenorphine was initially classified as a "mixed agonist-antagonist analgesic" or a narcotic antagonist analgesic. The work of Martin et al (1976) on the animal model of the chronic spinal dog substantiated the substance's action as partial agonist at the mu-opioid receptor. These findings were underscored by the substance's general pharmacological profile. Further, buprenorphine was one of the first narcotic analgesics to be assessed for its abuse liability in humans. The lower abuse liability of the drug in humans soon turned it into a widely used therapeutic agent in patients with opioid dependence. Interest in buprenorphine spanning more than 30 years has been attributed to its unique pharmacological characteristics, including moderate intrinsic activity, high affinity to and slow dissociation from mu-opioid receptors. Early pharmacological studies demonstrated buprenorphine's strong binding to opioid receptors, and an inverted U-shaped dose-response curve in rodents. In the rat paw formalin test, although buprenorphine demonstrated a bell-shaped dose-response curve against an acute noxious stimulus, it showed a classic sigmoidal curve in the later phase of the assay. In most preclinical antinociceptive tests, buprenorphine was shown to be fully efficacious, with an antinociceptive potency 25 to 40 times higher than morphine. A ceiling effect for respiratory depression (but not for analgesia) has been demonstrated in humans. Current studies are focusing on norbuprenorphine, an N-dealkylated metabolite of buprenorphine. Norbuprenorphine is a likely contributor to the overall pharmacology of buprenorphine; in the mouse writhing test, norbuprenorphine provides antinociceptive efficacy similar to buprenorphine, with analgesic activity shown to be dose-dependent.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Constipation; Dose-Response Relationship, Drug; Gastrointestinal Transit; Humans; Mice; Nociceptors; Pain; Rats

To compare analgesia and adverse effects during oral morphine and oxycodone and transdermal fentanyl and buprenorphine administration in cancer patients with pain.. Cancer patients treated at home and in outpatient clinics with severe pain (numerical rating scale score 6-10) fail to respond to non-opioids and/or weak opioids. All patients were randomized to either morphine, oxycodone, fentanyl or buprenorphine and divided into subgroups with predominant neuropathic and nociceptive pain component. Doses of opioids were titrated to satisfactory analgesia and acceptable adverse effects intensity. Patients were assessed at baseline and followed for 28 days. In all patient groups, immediate-release oral morphine was the rescue analgesic and lactulose 10 mL twice daily was the prophylaxis of constipation; no antiemetics were used as prophylaxis.. A total of 62 patients participated and 53 patients completed the study. Good analgesia was obtained for all 4 opioids, for both nociceptive and neuropathic pain. The use of co-analgesics was greater in patients with neuropathic pain. Morphine treatment was associated with less negative impact of pain on ability to walk, work and activity (trend) according to Brief Pain Inventory-Short Form scores and less consumption of rescue morphine. The most common adverse effects included nausea and drowsiness, which increased at the beginning of the treatment and gradually decreased over the days to come. Appetite, well-being, anxiety, depression, and fatigue improved. There was no constipation (the Bowel Function Index scores were within normal range) during the treatment with all opioids. No changes were seen for constipation, vomiting and dyspnea.. All opioids were effective and well-tolerated. Morphine was the most effective in the improvement in some of the Brief Pain Inventory-Short Form items regarding negative impact of pain on patients' daily activities. Prophylaxis of constipation was effective; antiemetics may be considered for nausea prevention.

Topics: Administration, Cutaneous; Administration, Oral; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Cancer Pain; Constipation; Delayed-Action Preparations; Drug Therapy, Combination; Fentanyl; Humans; Lactulose; Male; Middle Aged; Morphine; Oxycodone; Pain Measurement; Severity of Illness Index

This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50-250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to World Health Organization (WHO) step III opioids but tolerating treatment poorly. Equianalgesic ratios for tapentadol to prior strong opioids were calculated.. Patients rotated directly from prior WHO step III opioids to tapentadol. Patients received tapentadol PR (50-250 mg b.i.d.) during 5-week titration and 7-week maintenance periods. Tapentadol immediate release (IR) 50 mg (≤ twice/day, ≥ 4 h apart) was allowed (total daily dose of tapentadol PR and IR ≤ 500 mg/day). The primary endpoint was responder rate 1 at week 6 (percentage of patients with the same or less pain intensity [11-point numerical rating scale (NRS; 3-day average)] vs week -1).. Responder rate 1 at week 6 (last observation carried forward [LOCF]) was 80.9% (76/94; P < 0.0001 vs. the null responder hypothesis rate [<60%]), resulting in a positive trial despite premature termination (136 recruited of 180 planned). Significant improvements from baseline in pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR (P < 0.05). Equianalgesic ratios were calculated for PR formulations alone and for PR and IR formulations combined for tapentadol to oxycodone, buprenorphine, fentanyl, morphine, and hydromorphone. The prevalences of adverse events reported as the reason for switching to tapentadol (most commonly constipation and nausea) decreased over time.. Tapentadol PR (50-250 mg b.i.d.) provided at least comparable pain relief and improved tolerability versus prior strong opioids in patients with severe, chronic low back pain responding to WHO step III therapy. Conversion from strong opioids to tapentadol PR, with its two mechanisms of action, went smoothly considering overall effectiveness and tolerability outcomes. Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Chronic Pain; Constipation; Delayed-Action Preparations; Female; Fentanyl; Humans; Hydromorphone; Low Back Pain; Male; Middle Aged; Morphine; Neuralgia; Oxycodone; Pain Measurement; Phenols; Severity of Illness Index; Tapentadol

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

To investigate the pharmacological profile and side effects of buprenorphine administered as a sustained-release formulation in horses.. Pilot trial.. A total of four experimental horses, aged 18-27 years and weighing 508-578 kg.. Buprenorphine (0.1 mg kg. All four horses developed colon constipation requiring medical therapy, together with increased locomotor activity. One horse, requiring surgical treatment of colon constipation, was euthanized during recovery from anaesthesia for weakness and severe lower airway obstruction. The three other horses recovered fully within 5-7 days. Plasma buprenorphine concentrations were between 1 and 8 ng mL. Administration of the sustained-release formulation of buprenorphine at a dose of 0.1 mg kg

Topics: Analgesics, Opioid; Animals; Buprenorphine; Colonic Diseases; Constipation; Delayed-Action Preparations; Horse Diseases; Horses; Pilot Projects

Opioid substitution treatment (OST) is often continued long-term and, therefore, opioid-associated symptoms are of interest. Symptoms associated with methadone maintenance treatment (MMT) in men are well described, but there are fewer reports concerning symptoms associated with buprenorphine maintenance treatment (BMT) and very few reports among women.. Recipients of BMT (n=113) and MMT (n=184), non-opioid users (n=105) and opioid users not receiving OST (n=87) completed the Patient Assessment of Constipation (PAC-SYM) and a general symptom checklist. Multivariate analysis included other potential moderators of opioid-associated symptoms.. Opioid users reported a higher frequency and severity of symptoms than non-opioid users. Constipation, dry mouth, decreased appetite, sweating and fatigue were highly prevalent in the previous 30days (51-80%). Nausea, itchy skin, trouble urinating, menstrual problems, lightheadedness, blurred vision, heart racing were also common (30-50%). Non-OST opioid users had significantly higher frequency and severity than OST recipients of nausea, vomiting, diarrhoea, decreased appetite, sweating and itchy skin. Sweating was significantly more common in MMT than BMT. Constipation scores were higher in women, otherwise most sex differences were small. Higher PAC-SYM scores were associated with vomiting (OR=1.04) and sweating (OR=1.06). Cannabis use was associated with vomiting (OR=2.19). Constipation (OR=1.07), insomnia (OR=2.5) and depression (OR=2.82) were associated with fatigue.. Men and women receiving OST report similarly high rates of somatic symptoms, though less than opioid users not receiving OST. There were few differences between BMT and MMT. Buprenorphine might be preferred where sweating is problematic. Several modifiable factors were identified.

Topics: Adult; Analgesics, Opioid; Australia; Buprenorphine; Case-Control Studies; Constipation; Depression; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Sex Factors; Young Adult

Objectives To evaluate prevalence and severity of constipation and quality of life (QoL) in a cohort of opioid-addicted patients treated with opioid substitution treatments (OST).. A total of 1057 heroin-dependent patients treated with methadone or buprenorphine were enrolled in a multicenter observational study. Constipation was assessed by Wexner Constipation Scoring System (Wexner CSS), QoL by General Health Questionnaire (GHQ-12).. 38.5% patients reported mild constipation, 33.3% reported moderate constipation, 14.8% severe constipation and 5.1% very severe constipation. Mean Wexner CSS score was 6.6 ± 4.8. 44.9% patients showed a GHQ-12 score ≥14; of these 18.3% patients showed a GHQ-12 score ≥20. Mean GHQ score was 13.8 ± 6.5. Mean Wexner CSS score was significantly higher in methadone patients (p = 0.004), in those taking psychoactive drugs (p = 0.0001) and in female (p < 0.0001) with respect to counterparts. Similarly, GHQ-12 mean scores were higher methadone group (p = 0.003), in those taking psychoactive drugs (p < 0.0001), and in female (p = 0.039) with respect to counterparts. ANOVA and ANCOVA showed a significant influence of methadone and female gender on Wexner CSS score while psychoactive drugs significantly influenced both tests.. The present study shows that patients affected by opioid-dependence in OST with methadone and buprenorphine have a high prevalence of constipation and reduced QoL.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Constipation; Female; Heroin Dependence; Humans; Italy; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Quality of Life

For patients experiencing inadequate analgesia and intolerable opioid-related side effects on one strong opioid analgesic, pain relief with acceptable tolerability is often achieved by rotation to a second strong opioid. These observations suggest subtle pharmacodynamic differences between opioids in vivo. This study in rats was designed to assess differences between opioids in their in vivo profiles.. Male Sprague Dawley rats were given single i.c.v. bolus doses of morphine, morphine-6-glucuronide (M6G), fentanyl, oxycodone, buprenorphine, DPDPE ([D-penicillamine(2,5) ]-enkephalin) or U69,593. Antinociception, constipation and respiratory depression were assessed using the warm water tail-flick test, the castor oil-induced diarrhoea test and whole body plethysmography respectively.. These opioid agonists produced dose-dependent antinociception, constipation and respiratory depression. For antinociception, morphine, fentanyl and oxycodone were full agonists, buprenorphine and M6G were partial agonists, whereas DPDPE and U69,593 had low potency. For constipation, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, morphine produced a bell-shaped dose-response curve, whereas DPDPE and U69,593 were inactive. For respiratory depression, morphine, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, whereas DPDPE and U69,593 were inactive. The respiratory depressant effects of fentanyl and oxycodone were of short duration, whereas morphine, M6G and buprenorphine evoked prolonged respiratory depression.. For the seven opioids we assessed, no two had the same profile for evoking antinociception, constipation and respiratory depression, suggesting that these effects are differentially regulated. Our findings may explain the clinical success of 'opioid rotation'.. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Topics: Analgesics, Opioid; Animals; Benzeneacetamides; Buprenorphine; Castor Oil; Constipation; Diarrhea; Enkephalin, D-Penicillamine (2,5)-; Fentanyl; Hot Temperature; Male; Morphine; Morphine Derivatives; Oxycodone; Pain; Pyrrolidines; Rats, Sprague-Dawley; Respiratory Insufficiency