Effect of Opioids on Testosterone Levels: Cross-Sectional Study using NHANES.

Objective: Opioids can suppress gonadal hormone production, which may result in low testosterone levels. To date, there have been no large-scale population-based studies examining the extent to which opioid use may contribute to changes in testosterone levels.

Design: Cross-sectional study.

Does tapentadol affect sex hormone concentrations differently from morphine and oxycodone? An initial assessment and possible implications for opioid-induced androgen deficiency.

Objectives: Opioid-induced androgen deficiency (OPIAD) affects patients treated with opioid analgesics. The norepinephrine reuptake inhibitor (NRI) and µ-opioid receptor (MOR) agonist activities of tapentadol may result in tapentadol having less effect on serum androgen concentrations than analgesics acting through the MOR alone, such as morphine and oxycodone. The objectives of this publication are to 1) evaluate the effects of tapentadol (NUCYNTA and NUCYNTA extended release [ER]) on sex hormone concentrations in healthy male volunteers (vs placebo and morphine) and patients with osteoarthritis (vs placebo and oxycodone), and 2) present a mechanistic hypothesis explaining how the combined MOR agonist and NRI activities of tapentadol may result in less impact on androgen concentrations.

Development and preliminary validation of an integrated efficacy-tolerability composite measure for the evaluation of analgesics.

The goal of this analysis was to develop and evaluate integrated measures of benefit and tolerability of analgesic drugs in clinical trials. We evaluated an efficacy-tolerability composite (ETC) measure combining different cutoff values for daily pain reduction (≥20%, ≥30%, or ≥50% pain reduction) and adverse events (AEs) (no AE, no or mild AEs, no or mild drug-related AEs). Nine ETC cutoff values (3 × 3) were tested using data from a randomized double-blind trial comparing tapentadol extended release (ER) (n = 310), oxycodone controlled release (CR) (n = 322), and placebo (n = 314) in subjects with chronic low back pain.

Evaluation of the tamper-resistant properties of tapentadol extended-release tablets: results of in vitro laboratory analyses.

Objective: To evaluate tamper-resistant properties of tapentadol tablets formulated with polyethylene oxide (PEO) matrix.

Design: Analytical and physical tests to characterize tablets.

Interventions: Tapentadol extended release (ER) 50, 100, 150, 200, and 250 mg.

Tapentadol, oxycodone or placebo for acute pain of vertebral compression fractures: a randomized Phase IIIb study.

Unlabelled: SUMMARY 

Aim: Tapentadol is a centrally acting analgesic that combines µ-opioid receptor agonism with norepinephrine reuptake inhibition. This study evaluated the efficacy and safety of tapentadol immediate-release (IR), oxycodone IR or placebo in subjects with acute pain from vertebral compression fracture (VCF) associated with osteoporosis.

Patients & Methods: Study patients were adults with new onset of pain or acute exacerbation of previous pain from VCF associated with osteoporosis, radiographic confirmation of VCF and back pain intensity of 5 or greater on an 11-point scale from 0 (no pain) to 10 (pain as bad as you can imagine).

Physician management of moderate-to-severe acute pain: results from the Physicians Partnering Against Pain (P³) study.

Objective: To evaluate differences among physician specialties in the management of acute pain including prescribing practices and management of opioid-related side effects.

Design And Participants: The Physicians Partnering Against Pain (P³) survey was a nationwide study of US physicians and their patients with severe to moderate acute pain (<3 months).

Main Measures: Physicians were surveyed about volume of patients with moderate-to-severe acute pain in their practice, frequency of prescribing opioid analgesics, percentage of these patients returning for a follow-up visit after treatment, reasons patients discontinue treatment, frequency of recommending or prescribing treatment for opioid-related gastrointestinal (GI) side effects, and frequency of patients taking opioid analgesics that take additional treatments to manage GI side effects.

Immediate-release tapentadol or oxycodone for treatment of acute postoperative pain after elective arthroscopic shoulder surgery: a randomized, phase IIIb study.

Objective: Arthroscopic shoulder surgery can result in substantial postoperative pain. This study evaluated the efficacy and safety of tapentadol immediate release (IR) or oxycodone IR in this setting for the treatment of acute pain.

Design: Subjects received tapentadol IR 50 or 100 mg or oxycodone IR 5 or 10 mg every 4-6 hours as needed for pain up to 7 days after arthroscopic shoulder surgery.

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations.

As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately.

Opioids before and after initiation of pregabalin in patients with diabetic peripheral neuropathy.

Objectives: To examine opioid prescription claims before and after initiation of pregabalin in patients with a diagnosis of diabetic peripheral neuropathy (DPN).

Methods: This retrospective analysis used a national commercial database of integrated inpatient, outpatient, and prescription claims to identify adults with a DPN diagnosis code within 360 days prior to the first claim for pregabalin between January 1, 2006 and March 31, 2008. Prescription claims for pregabalin or opioids were analyzed in nine consecutive 60-day periods from 180 days before through 360 days after the first pregabalin claim.

Post hoc analyses of data from a 90-day clinical trial evaluating the tolerability and efficacy of tapentadol immediate release and oxycodone immediate release for the relief of moderate to severe pain in elderly and nonelderly patients.

Objective: To evaluate the tolerability and efficacy of tapentadol immediate release (IR) and oxycodone IR for relief of moderate to severe pain in elderly and nonelderly patients.

Methods: Post hoc data analyses were conducted on a 90-day randomized, phase 3, double-blind, flexible-dose study (ClinicalTrials.gov: NCT00364546) of adults with moderate to severe lower back pain or osteoarthritis pain who received tapentadol IR 50 mg or 100 mg, or oxycodone HCl IR 10 mg or 15 mg every 4 h to 6 h as needed for pain relief.

Evaluation of study discontinuations with tapentadol inmmediate release and oxycodone immediate release in patients with low back or osteoarthritis pain.

Objective: To examine discontinuations due to nausea and/or vomiting or constipation with tapentadol immediate release (IR) or oxycodone IR treatment.

Design: Post hoc analyses of a 90-day, phase 3, randomized, double-blind, flexible-dose study.

Setting: United States, Canada, United Kingdom.

Effects of extended-release tramadol on pain-related sleep parameters in patients with osteoarthritis.

Objective: To examine the effects of extended release tramadol (tramadol ER) on reducing pain-related sleep disturbances (PRSDs) in patients (20-80 years) with moderate to moderately severe pain with radiographically confirmed osteoarthritis (OA) of the knee or hip.

Methods: A post hoc analysis of two 12-week, double-blind, placebo-controlled, randomized, parallel-group studies was conducted. In Study A, patients (n = 1,020) received tramadol ER 100, 200, 300, or 400 mg, or placebo.

Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain.

Background: This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain, using an open-label run-in followed by, without washout, a randomized controlled study design.

Methods: Adults with scores > or = 40 on a pain intensity visual analog scale (VAS; 0 = no pain; 100 = extreme pain) received open-label tramadol ER, initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in. Patients completing run-in were randomized to receive tramadol ER 300 mg, 200 mg, or placebo once daily for 12 weeks.

Post hoc analysis of a randomized, double-blind, placebo-controlled efficacy and tolerability study of tramadol extended release for the treatment of osteoarthritis pain in geriatric patients.

Background: Once-daily tramadol extended release (ER) was evaluated for 12 weeks in a randomized, double-blind, placebo-controlled, parallel-group study in 1020 patients with osteoarthritis of the knee or hip. As previously reported, compared with placebo, the results of the study showed that patients treated with tramadol ER had significant improvement in the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and in pain-related sleep parameters.

Objective: Because chronic/persistent arthritis pain is common in geriatric patients, this post hoc analysis evaluated the efficacy and tolerability of tramadol ER in geriatric patients 65 years or older (n=317) from this study.

Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain.

Background: Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain.

Methods: Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61).

Pharmacokinetic model and simulations of dose conversion from immediate- to extended-release tramadol.

Objective: Extended-release tramadol (tramadol ER) is a once-daily formulation of tramadol approved in the United States for moderate to moderately severe chronic pain in adults. This modeling and simulation analysis was conducted to support dosing recommendations for switching patients receiving immediate-release tramadol (tramadol IR) to tramadol ER.

Research Design And Methods: Monte Carlo simulations based on steady-state data from three Phase 1 studies predicted minimum plasma concentration (C(min)), maximum plasma concentration (C(max)), and area under the plasma-concentration-versus-time curve (AUC).

Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy.

Objective: To examine the efficacy and safety of tramadol/acetaminophen (APAP) for the management of painful diabetic peripheral neuropathy (DPN).

Methods: Adults with painful DPN involving the lower extremities received 37.5 mg tramadol/325 mg APAP or placebo, up to 1-2 tablets four times daily, for 66 days.

Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Objective: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain.

Methods: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily.

An observational study of health-related quality of life and pain outcomes in chronic low back pain patients treated with fentanyl transdermal system.

Background: The analgesic effect of long-acting opioids, such as transdermal fentanyl, has been demonstrated in patients with cancer, neuropathic pain and chronic low back pain (CLBP). However, the broader effect of long-acting opioids on the patient's health-related quality of life (HRQoL) is less well known.

Objective: To evaluate HRQoL outcomes in CLBP patients treated with transdermal fentanyl.

Neuropsychological effects of long-term opioid use in chronic pain patients.

Opioids are thought to worsen the performance of psychomotor tasks due to their sedating and mental-clouding effects. As a result, some safety regulations currently restrict the use of opioids when driving or using heavy equipment. We investigated the psychomotor effects of long-term opioid use in 144 patients with low back pain.