No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Methadone in Participants Receiving Maintenance Opioid Agonist Therapy.

We conducted two phase I trials to evaluate the pharmacokinetic interactions between elbasvir (EBR), grazoprevir (GZR), and methadone (MK-8742-P010 and MK-5172-P030) in non-hepatitis C virus (HCV)-infected participants on methadone maintenance therapy. Coadministration of EBR or GZR with methadone had no clinically meaningful effect on EBR, GZR, or methadone pharmacokinetics. The geometric mean ratios (GMRs) for R- and S-methadone AUC were 1.

No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Buprenorphine/Naloxone in Healthy Participants and Participants Receiving Stable Opioid Agonist Therapy.

The aims of these phase I trials were to evaluate the pharmacokinetic interaction between elbasvir (EBR) or grazoprevir (GZR) and buprenorphine/naloxone (BUP/NAL). Trial 1 was a single-dose trial in healthy participants. Trial 2 was a multiple-dose trial in participants on BUP/NAL maintenance therapy.

Evaluation of the analgesic efficacy of AZD1940, a novel cannabinoid agonist, on post-operative pain after lower third molar surgical removal.

Aim To evaluate the analgesic efficacy of AZD1940, a novel peripherally acting cannabinoid CB1/CB2 receptor agonist, in patients undergoing third molar surgical removal. Methods This was a randomized, double-blind, placebo-controlled study in patients scheduled for surgical removal of an impacted lower third molar. Patients received a single oral dose of 800 μg AZD1940, 500 mg naproxen or placebo 1.

Medical management of chronic low back pain: efficacy and outcomes.

Objectives:   Chronic low back pain (CLBP) is common and contributes to significant disability and healthcare costs. The mechanism and etiology of CLBP are frequently unclear, and treatment choices vary.

Materials And Methods:   The scientific literature, including expert-generated treatment guidelines, was reviewed and evaluated for data regarding CLBP prevalence and predictors and for evidence of outcomes from pharmacologic and nonpharmacologic therapies.

A randomized, double-blind, multiple-dose study of the pan-genotypic NS5A inhibitor samatasvir in patients infected with hepatitis C virus genotype 1, 2, 3 or 4.

Background & Aims: Samatasvir is a pan-genotypic inhibitor of the hepatitis C (HCV) non-structural protein 5A (NS5A). This study evaluated the antiviral activity, pharmacokinetics and safety of samatasvir monotherapy in treatment-naïve subjects infected with HCV genotype 1-4.

Methods: Thirty-four genotype 1 and thirty genotype 2, 3 or 4 subjects were randomized to receive for 3days placebo or samatasvir 25-100mg per day.

Randomized, double-blind, placebo-controlled study of the abuse potential of different formulations of oral oxycodone.

Objective: The objective of this study was to evaluate the pharmacokinetics and abuse potential of different formulations of oxycodone.

Design: The participants completed an 8-day, placebo-controlled trial with four phases: naloxone challenge, double-blind drug discrimination, double-blind abuse liability, and discontinuation.

Subjects: Nineteen healthy, male, recreational drug abusers participated in this study.

Review and critique of opioid rotation practices and associated risks of toxicity.

Objectives: A dramatic increase in unintentional deaths from opioids has occurred over the past decade with strong inference that many of these deaths may be resulting from prescriber's error. Recent evidence suggests that the use of dose conversion ratios published in equianalgesic tables may lead to fatal or near-fatal opioid overdoses. The objective of this review was to determine whether the current practice of opioid rotation may be contributing to high rate of unintentional deaths.

Overdose deaths demand a new paradigm for opioid rotation.

Objective: An increasing number of deaths have been inferred to be associated with current opioid rotation practices and evidence is mounting that the use of widely accepted protocols for opioid rotation is an important contributing factor. Based on the findings of a literature review published in conjunction with this article, we propose a new paradigm for a potentially safer method of opioid rotation and present a case study illustrating the paradigm. This new paradigm suggests three easy-to-remember steps in opioid rotation and obviates the need to use a conversion table.

Efficacy and safety of dual-opioid therapy in acute pain.

Background: Although opioids are widely accepted as standard therapy for treating acute postoperative pain, the frequent occurrence of adverse events (AEs) and the substantial burden on the patient and the costs of care are a barrier to optimal dosing and adherence to prescribed treatment. Coadministration of two opioids is not often recommended as a multimodal treatment option for moderate to severe acute pain because of lack of knowledge about the potential benefit of such combinations and due to potential concerns about side effects and doubts about the added benefits. Study results on the coadministration of two or more opioids demonstrate synergistic analgesia with a similar or lower incidence of opioid-related AEs.

Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain.

Background: The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain.

Methods: This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.

Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users.

Background: Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users.

Tolerability of NGX-4010, a capsaicin 8% dermal patch, following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with post-herpetic neuralgia.

Background: Post-herpetic neuralgia (PHN) is a common type of neuropathic pain that can severely affect quality of life. NGX-4010, a capsaicin 8% dermal patch, is a localized treatment that can provide patients with significant pain relief for up to 3 months following a single 60-minute application. The NGX-4010 application can be associated with application-site pain and in previous clinical trials pretreatment with a topical 4% lidocaine anesthetic was used to enhance tolerability.

Opioid titration and conversion in patients receiving morphine sulfate and naltrexone hydrochloride extended release capsules.

Objective: To determine the number of steps and identify characteristics associated with attaining a stable dose of morphine sulfate and sequestered naltrexone extended release capsules (MS-sNT).

Patients And Methods: Data from an open-label, long-term multicenter study designed to assess the safety of MS-sNT for managing chronic (≥ 3 m), moderate-to-severe pain were analyzed post hoc. Initial MS-sNT dose was 20 mg twice daily (BID) for opioid-naïve patients and 50% to 75% of current daily opioid dose for opioid-experienced patients.

Impact of intravenous naltrexone on intravenous morphine-induced high, drug liking, and euphoric effects in experienced, nondependent male opioid users.

Background: Opioid analgesics can be abused by crushing followed by solubilization and intravenous injection to attain rapid absorption. Morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA, MS-sNT), indicated for management of chronic, moderate to severe pain, contain pellets of morphine sulfate with a sequestered naltrexone core. Should product tampering by crushing occur, the sequestered naltrexone is intended for release to reduce morphine-induced subjective effects.

Oxycodone extended-release using gel-cap technology to resist alteration and abuse for the treatment of moderate-to-severe pain.

SUMMARY Abuse of commercial oxycodone extended-release is common, fueling motivation by drug developers to investigate new formulations intended to resist alteration and abuse without compromising effective around-the-clock analgesia. An oral formulation of oxycodone extended-release that uses gel-cap technology as a tamper-resistant barrier is currently in development. Gel-cap oxycodone extended-release met the primary end point of significantly improved mean pain intensity scores compared with placebo in a Phase III, placebo-controlled trial.

Current status and evolving role of abuse-deterrent opioids in managing patients with chronic pain.

Opioids are widely used for the treatment of patients with chronic pain; yet, the increase in their abuse, misuse, and diversion is an ongoing focus of regulatory, governmental, and legal scrutiny. As a consequence, clinicians are faced with numerous challenges in an effort to use opioids in appropriate patients with pain while minimizing the potential for opioid abuse, misuse, and diversion. Policies and programs such as state prescription monitoring programs, which have been in existence for decades, are but one attempt to address some of the issues regarding the prescribing of opioids.

An analysis of the root causes for opioid-related overdose deaths in the United States.

Objective: A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths and to propose recommendations to reduce death rates.

Methods: Panelists reviewed results from a search of PubMed and state and federal government sources to assess frequency, demographics, and risk factors for opioid-related overdose deaths over the past decade. They also reviewed results from a Utah Department of Health study and a summary of malpractice lawsuits involving opioid-related deaths.

Obtaining adequate data to determine causes of opioid-related overdose deaths.

Current data collected by medical examiners and coroners are incomplete and inadequate to evaluate the factors that lead to fatalities involving prescription opioids. Determining cause of death is critically important. Two methods are proposed to improve consistency and accuracy in the collection and analysis of decedent data in opioid-related poisoning deaths.

Efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in an open-label study of patients with peripheral neuropathic pain.

Aims: To assess efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in patients with peripheral neuropathic pain.

Methods: This open-label, uncontrolled, 12-week study enrolled 25 patients with postherpetic neuralgia (PHN), one with HIV-distal sensory polyneuropathy, and 91 with painful diabetic neuropathy (PDN). Patients received pre-treatment with one of three 4% lidocaine topical anesthetics (L.

Long-term safety and efficacy of morphine sulfate and naltrexone hydrochloride extended release capsules, a novel formulation containing morphine and sequestered naltrexone, in patients with chronic, moderate to severe pain.

Context: Morphine sulfate and naltrexone hydrochloride extended release capsules contain extended-release pellets of morphine with a sequestered naltrexone core (MS-sNT). Taken whole, as intended, morphine is released to provide pain relief; if tampered with by crushing, naltrexone is released to mitigate subjective effects of morphine.

Objectives: This open-label study assessed long-term (12-month) safety of MS-sNT in patients with chronic, moderate to severe pain.

A double-blind, placebo-controlled study of dual-opioid treatment with the combination of morphine plus oxycodone in patients with acute postoperative pain.

Objective: animal and human studies suggest that coadministration of two opioids with different receptor binding properties may result in enhanced analgesia and fewer opioid-related adverse events (AEs). Q8003 (MoxDuo), an oral dual-opioid formulation with a fixed ratio (3:2) of morphine and oxycodone, was evaluated for analgesic effects and safety in the management of acute moderate to severe pain.

Design: randomized, double-blind, placebo-controlled, ascending-dose cohort, dose-response study with flexible dosing.

Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia.

Background: Postherpetic neuralgia (PHN) is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN.