tapentadol and Constipation

To compare efficacy and safety of tapentadol prolonged release (PR) vs oxycodone controlled release (CR) in younger patients (<65 years of age) and in elderly patients (≥65 and ≥75 years of age) in the treatment of moderate-to-severe chronic osteoarthritis (OA) knee pain.. Data from two double-blind, randomized, placebo-, and oxycodone CR-controlled phase 3 trials were pooled and stratified by age. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).. A total of 1357 patients <65 years, 653 patients ≥65 years, and 176 patients ≥75 years of age were assessed. The comparison between tapentadol PR and oxycodone CR showed numerically better pain relief under tapentadol PR for both primary end-points in all three age groups. More favorable improvements were also observed for patient global impression of change, the Short Form-36 physical component score, and EuroQoL-5Dimensions health status index. In the elderly, incidences of dizziness and somnolence were comparable between active treatments, but incidences of nausea, vomiting, and constipation were considerably lower under tapentadol PR. Treatment completion rates were lowest under oxycodone CR; > 50% of elderly oxycodone CR patients named side-effects as the main reason for discontinuation.. Tapentadol PR was effective in the treatment of moderate-to-severe chronic OA pain in elderly and younger patients. Compared to oxycodone CR, the overall and the gastrointestinal tolerability profile in particular were better in all tapentadol PR groups, regardless of age.

Topics: Aged; Chronic Pain; Clinical Trials, Phase III as Topic; Constipation; Delayed-Action Preparations; Double-Blind Method; Female; Health Status Indicators; Humans; Male; Middle Aged; Nausea; Osteoarthritis, Knee; Oxycodone; Randomized Controlled Trials as Topic; Tapentadol; Vertigo; Vomiting

To compare efficacy and safety of tapentadol prolonged-release (PR) and oxycodone-controlled release (CR) in moderate-to-severe chronic osteoarthritis knee pain.. Data from two double-blind, randomized, placebo- and oxycodone CR-controlled phase 3 studies with a 3-week titration period and 12-week controlled dose adjustment maintenance period were pooled. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).. A total of 2,010 patients were assessed. For both primary end-points, tapentadol PR was significantly more effective than oxycodone CR (LS mean difference of -0.41 [95% CI = -0.65, -0.16; p = 0.001] at week 12 and -0.35 [95% CI = -0.58, -0.12; p = 0.003] over 12 weeks of maintenance [last observation carried forward]). Significantly better outcomes than for oxycodone CR were also observed for patient global impression of change, both Short Form-36 component scores, and EuroQoL-5Dimensions health status index (all p < 0.001). Relative risk for vomiting, constipation, nausea, somnolence, and pruritus was lower for tapentadol PR than for oxycodone CR. A higher proportion of oxycodone CR patients discontinued treatment (64% vs 42.2% for tapentadol PR); time to treatment discontinuation due to an adverse event was significantly shorter for oxycodone CR (p < 0.001).. The analyses suggest that tapentadol PR provided superior pain relief and a more improved overall health status than oxycodone CR in a large patient population with moderate-to-severe chronic osteoarthritis pain. Compared to oxycodone CR, tapentadol PR showed a more favorable tolerability profile with better gastrointestinal tolerability.

Topics: Aged; Chronic Pain; Constipation; Delayed-Action Preparations; Double-Blind Method; Female; Health Status; Humans; Male; Middle Aged; Nausea; Osteoarthritis, Knee; Oxycodone; Phenols; Randomized Controlled Trials as Topic; Tapentadol; Vomiting

The aim of this review was to assess the role of tapentadol given at medium-high doses in opioid-tolerant patients for cancer pain management in place of step-3 analgesics.. A systematic literature search was performed out of which six studies and one secondary analysis provided data regarding tapentadol used as a step-3 analgesic for this review. Tapentadol, when used at ≥60 mg of oral morphine equivalents in opioid-tolerant patients with cancer pain, or passing from step-2 doses to ≥60 mg of oral morphine equivalents, was well tolerated and effective and could be considered as a flexible drug to be used for the management of moderate-to-severe cancer pain. The limited occurrence of gastrointestinal adverse effects may be a great advantage in the context of a disease like cancer, where multiple causes contribute to nausea, vomiting, or constipation; however, studies of tapentadol given at doses equivalent to step-3 level have some weaknesses, as data from prospective observational studies are poorly generalizable due to a small number of participants, controlled studies do not clearly show a superiority of tapentadol with respect to other opioids, and the sample size is often small.. More studies are necessary to confirm the role of tapentadol in cancer patients requiring strong opioids for their pain.

Topics: Analgesics, Opioid; Cancer Pain; Constipation; Humans; Morphine; Nausea; Neoplasms; Pain Measurement; Phenols; Tapentadol; Vomiting

The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients' daily functioning.. Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments.. Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = -3.60; 95% credible interval, -5.36 to -2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42-0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies.. Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life.

Topics: Chronic Pain; Constipation; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Headache; Humans; Naloxone; Nausea; Oxycodone; Phenols; Quality of Life; Tapentadol; Vomiting

Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with advanced illness. Some studies have reported that OIC is so intolerable in some patients that they skip their opioid medications and bear pain instead of OIC. Laxatives have commonly been used as a prophylaxis and treatment of OIC but they are frequently ineffective because the commonly available laxatives do not target the underlying mechanism of OIC, which is the blockade of peripheral mu-receptors. Recently, there have been a number of advances in the treatment of OIC, which any physician involved with opioid-prescribing discipline should be aware of. This review will update the new options and strategies available for treating OIC along with the relevant clinical trials. Finally, this review also provides a recommendation on the preferred way to approach a patient with OIC in the modern era as well as highlight on the importance of doctor-patient communication in this setting.

Topics: Chloride Channel Agonists; Chronic Pain; Constipation; Humans; Laxatives; Lubiprostone; Naloxone; Oxycodone; Peptides; Phenols; Receptors, Opioid, mu; Tapentadol

There has been an alarming increase in the prescription of opiates and opioids for chronic non-cancer pain in the past 15 years. It is estimated that opiate-induced constipation (OIC) is experienced by ~40% of these patients, and that constipation and other gastrointestinal symptoms may dissuade patients from using the required analgesic dose to achieve effective pain relief. Opiates have several effects on gastrointestinal functions, and the inhibition of colonic transit and intestinal and colonic secretion results in constipation. Several different pharmacological approaches are being developed to prevent or treat OIC: prolonged release formulations that contain naloxone (a less specific opiate antagonist that is widely distributed) and a new class of peripherally restricted μ-opiate receptor antagonists, including methylnaltrexone, alvimopan, tapentadol, NKTR-118, and TD-1211. Novel patient response outcomes have been developed to facilitate demonstration of efficacy and safety of drugs in development for OIC.

Topics: Analgesics, Opioid; Constipation; Humans; Naloxone; Narcotic Antagonists; Pain; Phenols; Receptors, Opioid, mu; Tapentadol

Opioids are often used in treatment of severe pain, although many patients experience gastrointestinal side-effects like constipation. The aim of the current study was to investigate changes in colonic volume, as the result of both colonic motility and fluid transport, in healthy volunteers during opioid treatment with tapentadol as compared with oxycodone and placebo.. In a randomized, double-blind, cross-over study, 21 healthy male volunteers were administered equianalgesic dosages of oral tapentadol (50 mg bid), oxycodone (10 mg bid) or corresponding placebo for 14 days. Segmental colonic volumes were quantified using T2-weighted magnetic resonance images, and gastrointestinal side-effects were assessed with questionnaires.. Total colonic volume increase during treatment was higher during tapentadol and oxycodone treatment (median 48 and 58 mL) compared to placebo (median -14 mL, both p≤0.003). Tapentadol (and placebo) treatment resulted in more bowel movements (both p<0.05) and softer stool consistency as compared with oxycodone (both p<0.01). Only oxycodone treatment was associated with increased constipation, straining during defecation, and tiredness (all p≤0.01). The colonic volume increase during treatment was directly associated with softer stools during tapentadol treatment (p=0.019).. Tapentadol treatment increased colonic volume without leading to harder stools, likely as the opioid sparing effects result in less water absorption from the gut lumen. Oxycodone treatment also increased colonic volume, but with a simultaneous increase in stool dryness and gastrointestinal and central nervous system side-effects. The results confirm that tapentadol treatment may be advantageous to oxycodone regarding tolerability to pain treatment.

Topics: Colon; Constipation; Cross-Over Studies; Healthy Volunteers; Humans; Male; Oxycodone; Tapentadol

To assess efficacy and safety of tapentadol prolonged release (PR) for moderate-to-severe chronic osteoarthritis knee pain.. Patients (n = 990) were randomized (1:1:1) to tapentadol PR, oxycodone controlled release (CR; reference compound for assay sensitivity), or placebo for a double-blind 3-week titration and 12-week maintenance period. Primary efficacy end-points were change from baseline in average pain intensity at week 12 of maintenance (US end-point) and over the entire maintenance period (non-US end-point) with "last observation carried forward" as imputation method for missing scores.. Both primary end-points were not significantly different for tapentadol PR nor for oxycodone CR vs placebo at week 12 (least squares [LS] mean difference = -0.3 [95% CI = -0.61-0.09]; p = 0.152 and 0.2 [95% CI = -0.16-0.54]; p = 0.279, respectively) and over the maintenance period (LS mean difference = -0.2 [95% CI = -0.55-0.07]; p = 0.135 and 0.1 [95% CI = -0.18-0.44]; p = 0.421, respectively). Considerably more patients receiving tapentadol PR than oxycodone CR completed the trial (58.3% vs 36.6%). This is consistent with better results with tapentadol PR on the overall health status (PGIC) compared to oxycodone CR. Indeed, respectively, 56% and 42.5% rated at least "much improved" at the end of treatment. Incidences of gastrointestinal adverse events were higher for both active treatments compared to placebo. Tapentadol PR was associated with a better gastrointestinal tolerability profile with incidences of constipation (17.9% vs 35%) and of the composite of nausea and/or vomiting (23.8% vs 46.8%) significantly lower vs oxycodone CR (p < 0.001).. The study did not demonstrate assay sensitivity. The finding that both primary end-points for tapentadol PR were not met can, thus, not be interpreted. Tapentadol PR was better tolerated than oxycodone CR, largely due to fewer gastrointestinal side-effects.

Topics: Aged; Chronic Pain; Constipation; Delayed-Action Preparations; Double-Blind Method; Female; Health Status; Humans; Male; Middle Aged; Nausea; Osteoarthritis, Knee; Oxycodone; Phenols; Tapentadol; Vomiting

High post-operative pain scores after "minor" orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery.. This randomized, observer-blinded, active-controlled prospective clinical trial had 2 co-primary endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale (NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score of the following events: Nausea, vomiting, constipation, sedation, vertigo, somnolence. The study was powered to detect superiority of tapentadol for at least one endpoint pending statistical proof of non-inferiority for both endpoints in a first step.. Two hundred sixty-six trauma patients were randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n = 133). Analgesic efficacy: Mean (±SD) daily pain levels in the first five post-operative days were 2.8 ± 1.3 in both groups. Mean maximum pain intensity during exercise in the first 24 h after surgery was 3.8 ± 1.9 (tapentadol) and 3.8 ± 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but not superior to oxycodone/naloxone.. Vomiting on day 1 occurred in 11%, constipation in 35% of the tapentadol patients and in 16% and 30% of the oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3, respectively). The sum score of side effect events was 51% in the tapentadol vs. 49% in the oxycodone/naloxone group; risk difference 3% [95% CI, -8 to 14%]; p = 0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non-inferiority margin was exceeded.. With both concepts, mean maximum pain intensity during exercise within the first 24 h after orthopedic/trauma surgery was reduced to a score of <4. This analgesic efficacy came at the cost of mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against nausea and vomiting and pre-emptive laxatives as part of these concepts.. https://eudract.ema.europa.eu (EudraCT- Nr. 2011-003238-15 ); October 24th, 2012.

Topics: Analgesics, Opioid; Constipation; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Naloxone; Orthopedic Procedures; Oxycodone; Pain Measurement; Pain, Postoperative; Phenols; Postoperative Nausea and Vomiting; Prospective Studies; Single-Blind Method; Tapentadol

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

Constipation is a common side effect of opioid therapy. Tapentadol immediate release (IR) was better tolerated than oxycodone IR in 2 clinical trials involving patients with low back or osteoarthritis pain. The objective of this study was to examine patient-reported bowel function during those trials.. Bowel function was assessed during secondary post hoc analyses using: the bowel movement questionnaire (BMQ; 10-d trial); the Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM; 90-day trial); and laxative use (both trials). Random effects maximum likelihood regressions were run to examine PAC-SYM data. BMQ data were analyzed using 1-way analyses of variance and a multinomial logistic regression. Rates of laxative use were compared using χ(2) statistics.. The 10- and 90-day trials consistently showed that tapentadol IR caused less impairment of bowel function than oxycodone IR. BMQ data were comparable between patients receiving tapentadol IR and placebo, and better versus oxycodone IR including: lower proportion of days where bowel movement was absent (P<0.05); lower risks of reporting hard stools (P<0.001); and moderate or severe straining (P<0.001). All PAC-SYM summary scores (abdominal, rectal, stool, overall) indicated fewer symptoms among patients receiving tapentadol IR versus oxycodone IR (P<0.001). In both trials, rates of laxative use was lower for tapentadol IR treatment groups versus oxycodone IR (P<0.001).. Patient-reported bowel function associated with tapentadol IR treatment was similar to that associated with placebo (10-d trial) and significantly better than that associated with oxycodone IR treatment (10- and 90-d trials).

Topics: Adolescent; Adult; Analgesics, Opioid; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Gastroenteritis; Humans; Laxatives; Low Back Pain; Male; Osteoarthritis; Oxycodone; Pain; Phenols; Surveys and Questionnaires; Tapentadol; Time Factors; Young Adult

Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR's improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes.. In this double-blind study, patients with end-stage joint disease were randomized to tapentadol IR (50 mg or 75 mg), oxycodone HCl IR 10 mg, or placebo. Treatment with IR formulations (14 days) was followed by treatment (28 days) with extended-release (ER) formulations of active drugs (or placebo).. Oxycodone HCl IR treatment significantly decreased (P<0.001) mean (SD) number of spontaneous bowel movements over the 14-day period (average per week: [6.7 (5.44)] versus tapentadol IR 50 mg [9.0 (4.04)], tapentadol IR 75 mg [8.6 (4.65)], and placebo [9.9 (5.16)]) (primary measure), confirming the tolerability findings of the earlier studies. Additionally, incidences of nausea and vomiting were significantly lower over the 14-day period (nominal P<0.001) for tapentadol IR 50 and 75 mg, versus oxycodone HCl IR 10 mg. Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations.. Tapentadol IR (50 mg, 75 mg) consistently demonstrated superior gastrointestinal tolerability, including for the most commonly reported events, such as nausea, vomiting, and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg. These findings validate and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses.

Topics: Aged; Analgesics, Opioid; Chronic Disease; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Joint Diseases; Male; Middle Aged; Nausea; Oxycodone; Pain; Phenols; Tapentadol; Vomiting

The primary objective of this study was to assess the efficacy and tolerability of tapentadol immediate release (IR) in patients who were candidates for joint replacement surgery due to end-stage joint disease. A secondary objective was to compare tapentadol IR with oxycodone HCl IR with respect to efficacy and prespecified tolerability end points.. This 10-day, Phase III, randomized, double-blind, active- and placebo-controlled study compared the efficacy and tolerability of tapentadol IR, oxycodone HCl IR, and placebo in patients with uncontrolled osteoarthritis pain who were candidates for primary replacement of the hip or knee as a result of end-stage degenerative joint disease. Patients received tapentadol IR 50 mg, tapentadol IR 75 mg, oxycodone HCl IR 10 mg, or placebo every 4 to 6 hours during waking hours. The primary end point was the sum of pain intensity difference (SPID) over 5 days. Secondary efficacy end points included 2- and 10-day SPID; 2-, 5-, and 10-day total pain relief (TOTPAR); and the sum of total pain relief and pain intensity difference (SPRID). Prespecified noninferiority comparisons with oxycodone HCl IR were performed with respect to efficacy (based on 5-day SPID) and tolerability (based on incidence of the reported adverse events (AEs) of nausea and/or vomiting and constipation).. Of 666 patients originally enrolled, 659 were included in the efficacy analysis (51% male; 91% white; mean age, 61.2 years; mean weight, 97 kg). Five-day SPID was significantly lower in those treated with tapentadol IR (tapentadol IR 50 mg: least squares mean difference [LSMD] = 101.2 [95% CI, 54.58- 147.89]; tapentadol IR 75 mg: LSMD = 97.5 [95% CI, 51.81-143.26]) or oxycodone HCl IR (LSMD = 111.9 [95% CI, 66.49-157.38]) (all, P < 0.001). Tapentadol IR 50 and 75 mg and oxycodone HCl IR 10 mg were associated with significant reductions in pain intensity compared with placebo, based on 2- and 10-day SPID and 2-, 5-, and 10-day TOTPAR and SPRID (all, P < 0.001). The efficacy of tapentadol IR 50 and 75 mg was noninferior to that of oxycodone HCl IR 10 mg; however, the incidence of selected gastrointestinal AEs (nausea, vomiting, and constipation) was significantly lower for both doses of tapentadol IR compared with oxycodone HCl IR 10 mg (nominal P < 0.001). The odds ratios for nausea and/or vomiting for tapentadol IR 50 and 75 mg relative to oxycodone HCl IR 10 mg were 0.21 (95% CI, 0.128-0.339) and 0.32 (95% CI, 0.204-0.501), respectively; for constipation, the corresponding odds ratios were 0.13 (95% CI, 0.057-0.302) and 0.20 (95% CI, 0.098-0.398). Rates of treatment discontinuation were 18% (28/157) in the tapentadol IR 50-mg group, 26% (43/168) in the tapentadol IR 75-mg group, 35% (60/172) in the oxycodone HCl IR 10-mg group, and 10% (17/169) in the placebo group. In a post hoc analysis, tapentadol IR 50 mg was associated with a significantly lower incidence of treatment discontinuation than was oxycodone HCl IR 10 mg (P < 0.001).. In these patients with uncontrolled osteoarthritis pain who were awaiting joint replacement surgery, tapentadol IR 50 and 75 mg were associated with analgesia that was noninferior to that provided by oxycodone HCl IR 10 mg. Tapentadol treatment was associated with improved gastrointestinal tolerability.

Topics: Adult; Aged; Analgesics, Opioid; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Osteoarthritis, Hip; Osteoarthritis, Knee; Oxycodone; Pain; Phenols; Tapentadol; Vomiting; Young Adult

Topics: Analgesics, Opioid; Cancer Pain; Chronic Pain; Constipation; Delayed-Action Preparations; Drug Combinations; Female; Humans; Morphine; Naloxone; Oxycodone; Pharmacogenomic Testing; Quality of Life; Tapentadol

Tapentadol shares with tramadol a mixed mechanism of action. It has no identified analgesically active metabolite and is not significantly metabolised by CYP450, thus overcoming some limitations of tramadol, including potential for pharmacokinetic drug-drug interactions and inter-individual variability due to genetic polymorphisms of CYP450. It is likely to expose less to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) and more to opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. As a conclusion, tapentadol represents an additional analgesic which some patients may benefit from after careful examination of their clinical situation, comorbidities and comedications.. Le tapentadol partage avec le tramadol un mode d’action mixte. Il n’a pas de métabolite actif identifié et n’est pas significativement métabolisé par le cytochrome P450 (CYP450), ce qui lui permet de contourner certaines limites du tramadol (interactions pharmacocinétiques, variabilité due aux polymorphismes génétiques du CYP450). Il expose potentiellement moins aux effets indésirables sérotoninergiques (nausées, vomissements, hypoglycémie) et davantage aux effets opioïdergiques (constipation, dépression respiratoire, abus) que le tramadol. Le niveau de preuve des données disponibles sur l’efficacité du tramadol et du tapentadol dans les douleurs chroniques est globalement faible. Le tapentadol représente un antalgique supplémentaire dont certains patients peuvent bénéficier après un examen attentif de leurs comorbidités, de leurs comédications et de la situation clinique.

Topics: Analgesics, Opioid; Chronic Pain; Constipation; Humans; Tapentadol; Tramadol

The distinct properties of the centrally-acting analgesic tapentadol derive from the combined contributions of an opioid component and a nonopioid component. However, the opioid component's relative contribution to analgesic and adverse effects has not previously been elucidated. Tapentadol's analgesic effect derives from the combined contribution of an opioid mechanism and a nonopioid mechanism, the extent of which can vary for different pains. Likewise, the interaction can vary for various adverse effects. Hence, the contribution of each mechanism to adverse effects can be different from the contribution to analgesia. We here estimate the percent contribution of each component of the mechanism of action to analgesia and to adverse effects.. Several approaches to in vitro and in vivo data to estimate the contribution of tapentadol's opioid component to analgesia and to the two important opioid adverse effects, respiratory depression and constipation. The results are then compared with clinical data.. Traditional opioids, such as morphine, oxycodone, and others, produce their analgesic effects primarily through a single mechanism-the activation of µ-opioid receptors (MOR). Therefore, the contribution of the opioid component to adverse effects is 100%. In contrast, the newer strong analgesic tapentadol produces its analgesic effect via two separate and complementary analgesic mechanisms, only one of which is µ-opioid. We applied standard drug-receptor theory and novel techniques to in vitro and in vivo data to estimate by several different ways the μ-load of tapentadol (the % contribution of the opioid component to the adverse effect magnitude relative to a pure/classical µ-opioid at equianalgesia) in respiratory depression and constipation, and we compared the results to clinical evidence. The estimate is remarkably consistent over the various approaches and indicates that the μ-load of tapentadol is ≤ 40% (relative to pure MOR agonists, which have, by definition, a µ-load of 100%).. Grünenthal GmbH.

Topics: Analgesia; Analgesics, Opioid; Animals; Constipation; Humans; Mathematical Concepts; Pain; Pain Management; Pain Measurement; Receptors, Opioid, mu; Respiratory Insufficiency; Tapentadol; Treatment Outcome

To compare the effects of tapentadol-extended release versus oxycodone-controlled release for pain relief on productivity by combining evidence from different sources.. Multiparameter evidence synthesis. Three sources were used. The first consisted of 3 randomized double-blind controlled trials that evaluated the efficacy and safety of tapentadol and oxycodone for the management of chronic pain. The second was published data on the incidence of constipation in patients exposed to opioids, and the third was a published survey that evaluated the effect of opioid-induced constipation on productivity. In the trials, a patient was classified as constipated if constipation was reported at any time during the 15 weeks of double-blinded assessment after randomization. In the survey, the effect of constipation on productivity was measured using the Work Productivity and Activity Impairment Questionnaire. All analyses were performed using Bayesian Markov chain Monte Carlo simulations in WinBUGS.. The odds of developing constipation were 60% lower with tapentadol than with oxycodone (odds ratio=0.40, 95% credible interval, 0.32-0.50). Tapentadol was associated with less time missed from work, less impairment while working, and a lower overall loss in work productivity compared with oxycodone. The gain in overall work productivity with tapentadol was 1.92% compared with oxycodone (95% credible interval, 1.32-2.59), which translates to a gain of almost 1 hour per week worked.. Tapentadol was associated with increases in all productivity dimensions compared with oxycodone. Multiparameter evidence synthesis capitalizes on available evidence, so that better informed medical decisions can be made.

Topics: Adult; Aged; Chronic Pain; Cohort Studies; Constipation; Cross-Sectional Studies; Delayed-Action Preparations; Double-Blind Method; Efficiency; Female; Humans; Male; Markov Chains; Middle Aged; Narcotics; Oxycodone; Phenols; Randomized Controlled Trials as Topic; Retrospective Studies; Surveys and Questionnaires; Tapentadol