morphinans has been researched along with Chronic-Pain* in 17 studies
6 review(s) available for morphinans and Chronic-Pain
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Analgesic Mechanism of Sinomenine against Chronic Pain.
Purified from the roots of the plant Topics: Analgesics; Animals; Chronic Pain; Humans; Morphinans; Neuroimmunomodulation | 2020 |
Evidence Based Review of Pharmacotherapy for Opioid-Induced Constipation in Noncancer Pain.
To summarize and evaluate the existing literature regarding medications to treat opioid-induced constipation (OIC) in patients with chronic noncancer pain (CNCP).. PubMed, EMBASE, and Web of Science were searched using the following terms: constipation, opioid, chronic, pain, noncancer, nonmalignant, methylnaltrexone, alvimopan, lubiprostone, naloxegol, and naldemedine.. The search was limited to randomized controlled trials reporting human outcomes. Data extracted included the following: study design, population, intervention, control, outcomes related to OIC and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of the 190 studies were included: methylnaltrexone (n = 4), naloxegol (n = 3), naldemedine (n = 2), lubiprostone (n = 3), and alvimopan (n = 4). Lubiprostone was the only nonperipherally acting µ-opioid receptor antagonist included. Only 1 study (naloxegol) used "usual care" (nonstudy laxative) rather than placebo as a comparator. Placebo-controlled trials demonstrated benefit for methylnaltrexone, naloxegol, naldemedine, and lubiprostone, with conflicting evidence for alvimopan. No data suggest that one agent is better than another. Overall risk of bias across all studies was low to moderate.. With risk of bias determined to be low to moderate, published data to date suggest that methylnaltrexone, naloxegol, and naldemedine may be appropriate to treat OIC in patients with CNCP. Topics: Analgesics, Opioid; Chronic Pain; Constipation; Evidence-Based Practice; Humans; Laxatives; Lubiprostone; Morphinans; Naltrexone; Narcotic Antagonists; Piperidines; Polyethylene Glycols; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic | 2018 |
[Management of adverse effects of opioid therapy].
More than 6 million people in Germany suffer from chronic pain which greatly impairs their wellbeing. Often the only therapeutic option is to use class 2 or 3 analgesic opioids in the WHO classification, as class 1 analgesics may be toxic or of limited efficacy. However, the high incidence of opioid side effects leads to high discontinuation rates. Thus, the success of opioid treatment is also highly dependent on the management of the safety and tolerability of the treatment. Most opioid side effects, such as nausea and sedation, predominantly occur in the initial phase of therapy. In contrast, opioid-induced constipation can last throughout opioid therapy. First-line treatment with laxatives does not solve the problem in all patients. Possible second-line therapies include opioid receptor antagonists, such as Naloxone, oral-administered Naloxegol, or subcutaneously given Methylnaltrexone. The discussion also covers the management of other common side effects of opioids, such as nausea, vomiting, sedation, pruritus, micturition disorder, and further symptoms. Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Chronic Pain; Constipation; Drug-Related Side Effects and Adverse Reactions; Germany; Humans; Morphinans; Naltrexone; Narcotic Antagonists; Polyethylene Glycols; Quaternary Ammonium Compounds; Treatment Outcome | 2017 |
Opioid-induced constipation in chronic noncancer pain.
Opioid-based management of noncancer pain has become much more prevalent over the last 2 decades and is responsible for a wide range of side-effects, particularly affecting the intestinal tract causing opioid-induced constipation (OIC). This review will consider results of recent clinical trials that have provided evidence of new pharmacological management options for the treatment of OIC.. Supportive use of conventional agents, such as stool softeners, osmotic laxatives, and stimulating laxatives in OIC has limited efficacy. The peripheral μ-opioid receptor antagonist (PAMORA) methylnaltrexone (MNTX) was first FDA approved for OIC in patients with advanced illness and later also for OIC in noncancer pain patients; clinical trial results indicated MNTX did not reverse opioid analgesia and did not trigger central opioid withdrawal. Another PAMORA, the orally available naloxegol, has also gained recent FDA approval for the treatment of OIC in adults with chronic, noncancer pain. Lubiprostone, a bicyclical fatty acid acting via activation of intestinal chloride channel-2 (ClC-2), was also approved for OIC treatment in patients with noncancer pain.. PAMORA MNTX and naloxegol and the intestinal chloride channel-2 (ClC-2) activator lubiprostone represent additional possible therapeutic options for the management of OIC in patients with chronic noncancer pain. Topics: Analgesics, Opioid; Chloride Channel Agonists; Chronic Pain; Constipation; Humans; Lubiprostone; Morphinans; Naltrexone; Narcotic Antagonists; Polyethylene Glycols; Quaternary Ammonium Compounds; Receptors, Opioid, mu | 2016 |
Novel Oral Therapies for Opioid-induced Bowel Dysfunction in Patients with Chronic Noncancer Pain.
Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are needed to further define their role in therapy. Topics: Administration, Oral; Analgesics, Opioid; Chronic Pain; Constipation; Humans; Lubiprostone; Morphinans; Narcotic Antagonists; Polyethylene Glycols; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Treatment Outcome | 2016 |
Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain.
To describe the effectiveness of naloxegol for the treatment of opioid-induced constipation (OIC) in chronic non-cancer pain patients.. Citations in PubMed, Google Scholar, Cochrane Library, CINAHL, ScienceDirect, and ProQuest were obtained. Reference lists from individual articles obtained were reviewed for additional sources.. All English-language publications available as poster presentations, abstracts, and peer-reviewed articles ranging from preclinical to phase III trials and published between 2007 and September 14, 2014, were reviewed and summarized.. Naloxegol was shown to be effective for increasing the average weekly number of spontaneous bowel movements (SBMs) in a single phase II trial enrolling 208 patients. Phase III trials (KODIAC-04/-05) enrolling a total of 1352 patients developed a new primary end point with a more strict responder criteria. This entailed a mean increase in SBMs, at least 3 SBMs per week, efficacy in 9 of 12 weeks, and efficacy in 3 of the final 4 weeks of the study period. Both groups receiving naloxegol 25 mg had significant improvement over the placebo group. The improvement was similar in patients who reported failure with laxatives in the past and regardless of daily opioid dose. A long-term trial (KODIAC-08) showed safety over 52 weeks.. OIC affects many individuals treated with opioids for chronic non-cancer pain. Previous over-the-counter or prescription treatment options were limited by a lack of adequate and well-controlled studies, multiple daily dosing, or need for injections. Cost issues may limit therapy with naloxegol to select patients. Topics: Adult; Aged; Analgesics, Opioid; Chronic Pain; Constipation; Female; Humans; Laxatives; Male; Morphinans; Narcotic Antagonists; Polyethylene Glycols | 2015 |
3 trial(s) available for morphinans and Chronic-Pain
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Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS).
To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP).. Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181).. Multicenter, long-term clinical research study.. NKTR-181 administered at doses of 100-600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF).. The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events.. The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP. Topics: Analgesics, Opioid; Chronic Pain; Double-Blind Method; Humans; Low Back Pain; Morphinans; Pain Measurement; Treatment Outcome | 2020 |
Treatment with Naloxegol Versus Placebo: Pain Assessment in Patients with Noncancer Pain and Opioid-Induced Constipation.
To summarize results from pain and opioid use assessments with naloxegol in adults with opioid-induced constipation (OIC) and chronic noncancer pain.. Two phase 3 randomized, double-blind, 12-week studies evaluated the efficacy and safety of oral naloxegol (12.5 or 25 mg daily) in adults (18 to < 85 years) with confirmed OIC and chronic noncancer pain: KODIAC-04 (NCT01309841) and KODIAC-05 (NCT01323790). Pain level was assessed daily (11-point numeric rating scale [NRS]; 0 = no pain, 10 = worst imaginable pain). Changes from baseline in mean weekly pain scores and opioid dose (weeks 1 through 12) were analyzed using mixed-model repeated measures.. At baseline, mean daily NRS average pain scores ranged from 4.5 to 4.8 for all groups in KODIAC-04 (N = 652) and were 4.6 for each group in KODIAC-05 (N = 700). Respective mean ± SD changes from baseline average pain for placebo, naloxegol 12.5 mg, and naloxegol 25 mg were -0.2 ± 1.07, -0.3 ± 1.05 (P = 0.773 vs. placebo), and 0.2 ± 0.95 (P = 0.837 vs. placebo; KODIAC-04) and -0.1 ± 0.94, -0.1 ± 0.87 (P = 0.744), and 0.0 ± 1.18 (P = 0.572; KODIAC-05). At baseline, mean daily opioid doses ranged from 135.6 to 143.2 morphine equivalent units (MEUs)/day in KODIAC-04, and from 119.9 to 151.7 MEUs/day in KODIAC-05. Respective mean ± SD changes from baseline dose were -1.8 ± 30.19, -2.3 ± 20.52 (P = 0.724 vs. placebo), and 0.4 ± 13.01 (P = 0.188 vs. placebo; KODIAC-04) and -0.3 ± 17.14, -1.3 ± 17.11 (P = 0.669 vs. placebo), and 0.1 ± 8.54 (P = 0.863 vs. placebo; KODIAC-05). Changes in maintenance opioid dose were few; reasons for such changes were similar across treatment groups.. Centrally mediated opioid analgesia was maintained during treatment with naloxegol in patients with noncancer pain and OIC. Topics: Administration, Oral; Adult; Aged; Analgesics, Opioid; Chronic Pain; Constipation; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Narcotic Antagonists; Polyethylene Glycols | 2018 |
Population Exposure-Response Modeling Supported Selection of Naloxegol Doses in Phase III Studies in Patients With Opioid-Induced Constipation.
Naloxegol is approved for the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain. Population exposure-response models were developed using data from a phase II study comprising 185 adults with OIC. The weekly probability of response defined as having ≥3/week spontaneous bowel movements (SBMs) and ≥1 SBM/week increase over baseline was characterized by a longitudinal mixed-effects logistic regression dose-response model, and the probability of time to discontinuation was modeled with a Weibull distribution function. The predicted probability of SBM in a given week increased with increasing naloxegol dose. The model predicted that 12.5, 25, and 37.5 mg doses would produce median response rates of 40%, 50%, and 60%, and dropout rates of 13.3%, 16.7%, and 23.3%, respectively. The large overlap of predicted difference of the response rate between placebo and the 25 or 37.5 mg doses suggested little utility of using a 37.5 mg dose in phase III studies. Topics: Algorithms; Analgesics, Opioid; Chronic Pain; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Models, Statistical; Morphinans; Narcotic Antagonists; Polyethylene Glycols; Regression Analysis | 2017 |
8 other study(ies) available for morphinans and Chronic-Pain
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Cardiovascular Safety of the Selective μ-Opioid Receptor Antagonist Naloxegol: A Novel Therapy for Opioid-Induced Constipation.
Naloxegol is a novel selective, peripherally acting μ-opioid receptor antagonist for treating opioid-induced constipation (OIC) in patients with chronic pain syndromes. We analyzed the cardiovascular (CV) safety of naloxegol based on data from its development program prior to approval by the US Food and Drug Administration in 2015.. Comprehensive CV safety analyses were performed in 4 clinical studies of naloxegol (12.5 and/or 25 mg) in patients with noncancer pain and OIC: two 12-week, double-blind, randomized studies; a 12-week, double-blind, extension study; and a 52-week, randomized, open-label study versus usual care. Evaluations of baseline CV risk were obtained from medical histories and clinical findings at the time of study initiation.. Across the 4 studies (N = 2135), 68% of patients had ≥1 CV risk factor and 41% had a history of CV disease, diabetes, or ≥2 other CV risk factors. There were no increases in blood pressure, heart rate, or the rate-pressure product with naloxegol versus placebo. The rates of major adverse cardiovascular events (MACE) per 100 patient-years of exposure were 1.13 (95% confidence interval [CI], 0.31-2.89) for placebo/usual care and 0.75 (95% CI, 0.24-1.75) for naloxegol. The relative risk of MACE for all doses of naloxegol versus placebo was 0.67 (95% CI, 0.14-3.36).. These data demonstrate that naloxegol has a CV safety profile comparable to placebo/usual care in patients with OIC. Although the observed number of events was low, the data show no CV signal in patients with OIC treated with naloxegol. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Cardiovascular System; Chronic Pain; Clinical Trials, Phase III as Topic; Constipation; Defecation; Evidence-Based Medicine; Female; Humans; Male; Middle Aged; Morphinans; Narcotic Antagonists; Polyethylene Glycols; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Recovery of Function; Risk Assessment; Risk Factors; Signal Transduction; Treatment Outcome; Young Adult | 2018 |
Naloxegol for managing opioid-induced constipation.
Naloxegol is a peripherally acting mu-opioid receptor antagonist for opioid-induced constipation in adults with chronic noncancer pain. This drug's once-daily oral formulation can be used as monotherapy and helps to decrease the constipating effects of opioid therapy; however, it has been associated with abdominal pain. Topics: Abdominal Pain; Adult; Analgesics, Opioid; Chronic Pain; Constipation; Female; Humans; Male; Morphinans; Narcotic Antagonists; Polyethylene Glycols; Receptors, Opioid, mu | 2017 |
Sinomenine attenuates chronic inflammatory pain in mice.
Topics: Analgesics; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Chronic Pain; Freund's Adjuvant; Gyrus Cinguli; Inflammation; Mice; Morphinans; Phosphorylation; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Up-Regulation | 2017 |
Dialyzability of Oxycodone and Its Metabolites in Chronic Noncancer Pain Patients with End-Stage Renal Disease.
Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking.. We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis.. Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased.. While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future. Topics: Adult; Analgesics, Opioid; Chronic Disease; Chronic Pain; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Morphinans; Oxycodone; Oxymorphone; Renal Dialysis | 2017 |
Cost Effectiveness of Naloxegol for Opioid-Induced Constipation in the UK.
Opioid-induced constipation (OIC) is the most common adverse effect reported in patients receiving opioids to manage pain. Initial treatment with laxatives provides inadequate response in some patients. Naloxegol is a peripherally acting µ-opioid receptor antagonist used to treat patients with inadequate response to laxative(s) (laxative inadequate responder [LIR]). A cost-effectiveness model was constructed from the UK payer perspective to compare oral naloxegol 25 mg with placebo in non-cancer LIR patients receiving opioids for chronic pain, and a scenario analysis of naloxegol 25 mg with rescue laxatives compared with placebo with rescue laxatives in the same patient population.. The model comprised a decision tree for the first 4 weeks of treatment, followed by a Markov model with a 4-week cycle length and the following states: 'OIC', 'non-OIC (on treatment)', 'non-OIC (untreated)' and 'death'. Two phase III trials with a follow-up period of 12 weeks provided data on treatment efficacy, transition probabilities, adverse event frequency and patient utility. Resource utilisation data were sourced from a UK-based burden of illness study and physician surveys. A UK National Health Service and Personal Social Service perspective was adopted; costs and health-related quality of life gains were discounted at a rate of 3.5 %. The model was run over a time horizon of 5 years, reflecting the average period of opioid use.. Naloxegol has an incremental cost-effectiveness ratio of £10,849 per quality-adjusted life-year gained versus placebo, and £11,179 when rescue laxatives are made available in both arms (2014 values). Model outcomes were only sensitive to variations in utility inputs. However, the probabilistic sensitivity analyses indicate that naloxegol has a 91 % probability of being cost effective at a £20,000 threshold when compared with placebo.. Naloxegol is likely a cost-effective treatment option for LIR patients with OIC. This assessment should be supported by further work on the utility of patients with OIC, including how utility varies with more granular measures of OIC. Topics: Analgesics, Opioid; Chronic Pain; Constipation; Cost-Benefit Analysis; Decision Trees; Humans; Laxatives; Markov Chains; Models, Economic; Morphinans; Narcotic Antagonists; Polyethylene Glycols; Quality of Life; Quality-Adjusted Life Years; Receptors, Opioid, mu; United Kingdom | 2017 |
Population Exposure-Response Modeling of Naloxegol in Patients With Noncancer-Related Pain and Opioid-Induced Constipation.
Naloxegol is a polyethylene glycol derivative of naloxone approved in the US as a once-daily oral treatment for opioid-induced constipation (OIC) in adults with chronic noncancer pain. Population exposure-response models were constructed based on data from two phase III studies comprising 1,331 adults with noncancer pain and OIC. In order to characterize the protocol-defined naloxegol responder rate, the number of daily spontaneous bowel movements (SBMs) was characterized by a longitudinal ordinal nonlinear mixed-effects logistic regression dose-response model, and the incidence of diary entry discontinuation was described by a time-to-event model. The mean number of SBMs per week increased with increasing naloxegol dose. The predicted placebo-adjusted responder rates (90% confidence interval) were 10.4% (4.6-13.4%) and 11.1% (4.8-14.4%) for naloxegol 12.5 and 25 mg/day, respectively. Model-predicted response to naloxegol was influenced by the baseline SBM frequency and characteristics of the opioid treatment. Topics: Adult; Analgesics, Opioid; Chronic Pain; Clinical Trials, Phase III as Topic; Constipation; Defecation; Double-Blind Method; Female; Humans; Male; Medical Records; Middle Aged; Models, Statistical; Morphinans; Multicenter Studies as Topic; Narcotic Antagonists; Polyethylene Glycols; Randomized Controlled Trials as Topic; Treatment Outcome | 2016 |
GI relief may come sooner than later for patients with chronic noncancer pain.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Constipation; Drug Approval; Humans; Morphinans; Naltrexone; Narcotic Antagonists; Polyethylene Glycols; Quaternary Ammonium Compounds; United States; United States Food and Drug Administration | 2014 |
Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study.
Opioids are recommended by the World Health Organization for moderate to severe cancer pain. Oxycodone is one of the most commonly used opioids and is metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross-sectional study was to assess the relationship between oxycodone pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes "poor metaboliser" (PM), "extensive metaboliser" (EM) and "ultra-rapid metaboliser" (URM) in a cohort of patients with cancer pain.. The patients were genotyped for the most common CYP2D6 variants and serum concentrations of oxycodone and metabolites were determined. Pain was assessed using the Brief Pain Inventory (BPI). The EORTC QLQ-C30 was used to assess the symptoms of tiredness and nausea. Cognitive function was assessed by the Mini Mental State (MMS) examination. Associations were examined by analyses of variance (ANOVA) and covariance (ANCOVA), or ordinal logistic regressions with and without covariates.. The sample consisted of 27 PM, 413 EM (including heterozygotes) and 10 URM. PM had lower oxymorphone and noroxymorphone serum concentrations and oxymorphone to oxycodone ratios than EM and URM. No differences between PM, EM and URM in pain intensity, nausea, tiredness or cognitive function was found.. CYP2D6 genotypes caused expected differences in pharmacokinetics, but they had no pharmacodynamic consequence. CYP2D6 genotypes did not influence pain control, the adverse symptoms nausea and sedation or the risk for cognitive failure in this study of patients treated with oxycodone for cancer pain. Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Biotransformation; Chronic Pain; Cohort Studies; Cross-Sectional Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Drug Monitoring; Europe; Female; Genetic Association Studies; Humans; Male; Middle Aged; Morphinans; Neoplasms; Oxycodone; Oxymorphone; Polymorphism, Genetic; Severity of Illness Index | 2012 |