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Journal of Pain and Symptom Management Mar 2019Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into...
Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. The American Pain Society, College on Problems of Drug Dependence, and the Heart Rhythm Society collaborated to issue guidelines on best practices to maximize methadone safety and efficacy, but guidelines for the end-of-life scenario have not yet been developed. A panel of 15 interprofessional hospice and palliative care experts from the U.S. and Canada convened in February 2015 to evaluate the American Pain Society methadone recommendations for applicability in the hospice and palliative care setting. The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care. This article represents the consensus opinion of the hospice and palliative care experts for methadone use at end of life, including guidance on appropriate candidates for methadone, detail in dosing, titration, and monitoring of patients' response to methadone therapy.
Topics: Analgesics, Opioid; Hospice Care; Humans; Methadone; Pain; Palliative Care
PubMed: 30578934
DOI: 10.1016/j.jpainsymman.2018.12.001 -
Molecules (Basel, Switzerland) Apr 2022In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage...
In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5-7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95-105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.
Topics: Amber; Chromatography, High Pressure Liquid; Drug Compounding; Drug Stability; Drug Storage; Methadone; Solutions
PubMed: 35566167
DOI: 10.3390/molecules27092812 -
BMC Palliative Care Nov 2022Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone...
BACKGROUND
Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone in the treatment of refractory cancer pain.
METHODS
A retrospective study was conducted in patients who used methadone for refractory cancer pain from April 2016 to December 2020 at a cancer specialized hospital. Pain control, evaluated via pain score and breakthrough pain frequency, and adverse events of methadone were compared with analgesic regimens prior to methadone administration. The factors potentially affecting the switching outcome were analyzed via multivariate analysis. Moreover, the cost of pain control was estimated.
RESULTS
Ninety patients received methadone for poor pain control (74.4%), intolerable adverse events (10.0%), or both (15.6%) after prior opioid treatments. Sixty-four patients (71.1%) were successfully switched to methadone with median pain score significantly decreased from 4.0 to 2.0 (p < 0.001) and median daily frequency of breakthrough pain from 3.0 to 0.0 (p < 0.001) at a maintained median conversion ratio of 6.3 [interquartile range (IQR): 4.0-10.0] to prior opioid treatment. Similar adverse event profiles of constipation, nausea, vomiting, and dizziness were observed between methadone and prior opioid regimens. The median daily cost of analgesic regimens was significantly reduced from $19.5 (IQR: 12.3-46.2) to $10.8 (IQR: 7.1-18.7) (p < 0.01) after switching to methadone. The 3-day switch method significantly improved the rate of successful switching compared with the stop and go method (odds ratio = 3.37, 95% CI: 1.30-8.76, p = 0.013).
CONCLUSION
Methadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain.
Topics: Humans; Methadone; Cancer Pain; Analgesics, Opioid; Retrospective Studies; Breakthrough Pain; Neoplasms
PubMed: 36324113
DOI: 10.1186/s12904-022-01076-2 -
Pharmacogenomics Aug 2020Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to... (Review)
Review
Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.
Topics: Analgesics, Opioid; Animals; Genetic Variation; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacogenetics
PubMed: 32705966
DOI: 10.2217/pgs-2020-0040 -
Canadian Family Physician Medecin de... Feb 2021
Topics: British Columbia; Humans; Methadone
PubMed: 33608353
DOI: 10.46747/cfp.670281_3 -
American Journal of Public Health Apr 2022
Topics: Humans; Methadone; Opioid-Related Disorders; Policy
PubMed: 35349312
DOI: 10.2105/AJPH.2021.306665 -
Canadian Medical Association Journal Oct 1973Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more... (Comparative Study)
Comparative Study Review
Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more gradual and less intense withdrawal syndrome, and blockade of euphoric effect of other opiates in addicts. A high percentage of patients maintained on methadone are better able to hold employment or to be otherwise socially productive than when dependent on heroin or morphine.A review of published results and procedures used in methadone maintenance treatment programs for heroin dependence is presented. Former heroin addicts are usually maintained on 80 to 120 mg. (high dose) or 20 to 60 mg. (low dose) oral methadone daily. Some programs are reported to have produced 80% success (patients employed or otherwise socially productive). Selection of patients, availability of allied therapeutic and rehabilitative facilities, strict control of supply, record keeping and periodic evaluation are considered essential.Different criteria ("drug-free" vs. "socially productive") for judging "success" of treatment of heroin-dependent persons by methadone maintenance and administrative problems in large-scale treatment programs constitute the principal aspects of controversy.
Topics: Acetates; Administration, Oral; Adolescent; American Medical Association; Canada; Chemical Phenomena; Chemistry; Drug and Narcotic Control; Female; Heroin Dependence; Humans; Methadone; Pregnancy; Pregnancy Complications; Private Practice; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; United States
PubMed: 4599599
DOI: No ID Found -
Electrophoresis Sep 2021The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone...
The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l-methadone and d-methadone and their major metabolites, l- and d-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection from liquid/liquid extracts prepared at alkaline pH. In both trials, the d-methadone concentrations were lower than those of l-methadone and the d-EDDP levels were lower than those of L-EDDP. For the case of a single intravenous bolus injection, the plasma concentration versus time profile of methadone enantiomers was analyzed with a two-compartment pharmacokinetic model. l-methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady-state volume of distribution than d-methadone. d-methadone and d-EDDP were eliminated faster than their respective l-enantiomers. This is the first study that outlines that the disposition of racemic methadone administered to anesthetized equines is enantioselective.
Topics: Animals; Electrophoresis, Capillary; Horses; Methadone; Pyrrolidines; Stereoisomerism
PubMed: 33978252
DOI: 10.1002/elps.202100115 -
Clinical Pharmacology and Therapeutics Oct 2021Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de...
Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de pointes, a potentially fatal arrhythmia. Most methadone-related deaths occur during sleep. The objective of this study was to determine whether methadone's arrhythmogenic effects increase during sleep, with a focus on cardiac repolarization instability using QT variability index (QTVI), a measure shown to predict arrhythmias and mortality. Sleep study data of 24 patients on chronic methadone therapy referred to a tertiary clinic for overnight polysomnography were compared with two matched groups not on methadone: 24 patients referred for overnight polysomnography to the same clinic (clinic group), and 24 volunteers who had overnight polysomnography at home (community group). Despite similar values for heart rate, heart rate variability, corrected QT interval, QTVI, and oxygen saturation (SpO ) when awake, patients on methadone had larger QTVI (P = 0.015 vs. clinic, P < 0.001 vs. community) and lower SpO (P = 0.008 vs. clinic, P = 0.013 vs. community) during sleep, and the increase in their QTVI during sleep vs. wakefulness correlated with the decrease in SpO (r = -0.54, P = 0.013). QTVI positively correlated with methadone dose during sleep (r = 0.51, P = 0.012) and wakefulness (r = 0.73, P < 0.001). High-density ectopy (> 1,000 premature beats per median sleep period), a precursor for torsades de pointes, was uncommon but more frequent in patients on methadone (P = 0.039). This study demonstrates that chronic methadone use is associated with increased cardiac repolarization instability. Methadone's pro-arrhythmic impact may be mediated by sleep-related hypoxemia, which could explain the increased nocturnal mortality associated with this opioid.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Arrhythmias, Cardiac; Electrocardiography; Female; Heart Conduction System; Humans; Male; Methadone; Middle Aged; Polysomnography; Sleep
PubMed: 34287835
DOI: 10.1002/cpt.2368 -
American Family Physician Apr 2005Methadone is a synthetic opioid with potent analgesic effects. Although it is associated commonly with the treatment of opioid addiction, it may be prescribed by... (Review)
Review
Methadone is a synthetic opioid with potent analgesic effects. Although it is associated commonly with the treatment of opioid addiction, it may be prescribed by licensed family physicians for analgesia. Methadone's unique pharmacokinetics and pharmacodynamics make it a valuable option in the management of cancer pain and other chronic pain, including neuropathic pain states. It may be an appropriate replacement for opioids when side effects have limited further dosage escalation. Metabolism of and response to methadone varies with each patient. Transition to methadone and dosage titration should be completed slowly and with frequent monitoring. Conversion should be based on the current daily oral morphine equivalent dosage. After starting methadone therapy or increasing the dosage, systemic toxicity may not become apparent for several days. Some medications alter the absorption or metabolism of methadone, and their concurrent use may require dosing adjustments. Methadone is less expensive than other sustained-release opioid formulations.
Topics: Analgesics, Opioid; Chronic Disease; Drug Costs; Drug Interactions; Humans; Methadone; Pain; Therapeutic Equivalency
PubMed: 15832538
DOI: No ID Found