Clinical drug investigation
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Review
Abuse-Deterrent Opioid Formulations: A Key Ingredient in the Recipe to Prevent Opioid Disasters?
The US Food and Drug Administration (FDA) is encouraging the innovation of long-acting opioid formulations that are manipulation-resistant. The purpose of this commentary is to assess the benefits and limitations of abuse-deterrent opioid formulations (ADFs) and discuss their role in mitigating the current opioid epidemic. ADFs have been created with chemical properties that make it difficult for people who non-medically use prescription drugs to crush and dissolve opioid tablets, as well as by combining opioids with antagonists such as naloxone or naltrexone, which are released only when the dosage form has been manipulated or the drug is taken by a non-intended route. ⋯ Researchers also question if the creation of abuse-deterrent drugs will have a positive effect on those struggling with a severe opioid-use disorder, fearing that current opioid users will simply find a new - perhaps more dangerous - drug of choice. Abuse-deterrent opioids are still opioids, and although they may make manipulation more difficult than non-ADF formulations, they are not "abuse proof." The introduction of ADFs could provide a false sense of security among prescribers and dispensers, and we fear that ADFs may have a minimal impact on non-medical use of prescription opioids. Further epidemiological studies will be required to determine the large-scale impact of abuse-deterrent opioids in preventing opioid use disorder and its downstream consequences.
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Oral oxycodone/naloxone prolonged release (PR) [Targin®, Targinact®, Targiniq®] is a 12-hourly opioid receptor agonist and opioid receptor antagonist fixed-dose combination product that is approved in countries in the EU for the management of severe pain (adequately manageable only with opioid analgesics) in adults. Oral naloxone prevents oxycodone from binding to μ-receptors in the gastrointestinal (GI) tract, thereby counteracting opioid-induced constipation (OIC). In short-term (5- to 12-week) clinical trials of adults with moderate to severe, chronic pain and OIC (OXN3001, OXN3006, OXN3506), oxycodone/naloxone PR significantly improved OIC while providing noninferior analgesia relative to oxycodone PR; results were consistent between cancer and non-cancer patients in OXN3506. ⋯ Results in real-world studies were consistent with those in clinical trials. Oxycodone/naloxone PR was generally well tolerated, with nausea, hyperhidrosis, and diarrhoea (generally transient) reported as the most commonly occurring adverse events. Thus, oxycodone/naloxone PR is a useful treatment option to consider in adults with severe chronic pain that can be adequately managed only with opioid analgesics, particularly in those with OIC.
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Metformin has been associated with lactic acidosis. Lactate levels are not commonly tested in clinical practice, and it is unclear to what extent metformin would typically increase lactate levels with chronic use. The aim of this review was to determine whether regular monitoring of the plasma lactate level would be beneficial in avoiding lactate accumulation and, ultimately, minimising the incidence of lactic acidosis in metformin-treated patients. ⋯ However, most results showed that the lactate level remained in the normal range. No definitive conclusions on the benefits of regular lactate monitoring in patients taking metformin can be made. Future research on larger populations focusing on the measurement of lactate levels with continuous metformin use is warranted.
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Review Meta Analysis
Interventions for Refractory Trigeminal Neuralgia: A Bayesian Mixed Treatment Comparison Network Meta-Analysis of Randomized Controlled Clinical Trials.
Patients with trigeminal neuralgia (TN) are often refractory to recommended first-line agents. Due to the absence of a systematic review, we undertook a network meta-analysis to assess various interventions that can be used to manage refractory TN. ⋯ We found that drug-related interventions that include sumatriptan, intranasal lidocaine, intravenous lidocaine, and botulinum toxin and combined continuous and pulsed radiofrequency thermocoagulation had significant effects in reducing pain in patients with refractory TN. However, the quality of evidence was graded as very low for all except botulinum toxin.
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Review Meta Analysis
Interventions for Refractory Trigeminal Neuralgia: A Bayesian Mixed Treatment Comparison Network Meta-Analysis of Randomized Controlled Clinical Trials.
Patients with trigeminal neuralgia (TN) are often refractory to recommended first-line agents. Due to the absence of a systematic review, we undertook a network meta-analysis to assess various interventions that can be used to manage refractory TN. ⋯ We found that drug-related interventions that include sumatriptan, intranasal lidocaine, intravenous lidocaine, and botulinum toxin and combined continuous and pulsed radiofrequency thermocoagulation had significant effects in reducing pain in patients with refractory TN. However, the quality of evidence was graded as very low for all except botulinum toxin.