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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 -
International Journal of Cancer Oct 2018Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In... (Review)
Review
Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use d,l-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of d,l-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting. Finally, the receptors mostly responsible for induction of apoptosis by d,l-methadone remain unclear as contributions of both µ-opioid receptors, Fas cell death receptors, toll-like receptors, N-Methyl-d-aspartate receptors and opioid growth factor receptors were suggested. Such ambiguity prevents rational application of d,l-methadone or patient stratification to enhance beneficial antineoplastic effects. From a clinical point of view, d,l-methadone and other opioids might in fact prolong survival, but such effects likely originate from their analgesic and neuro-psychotropic properties and, thus, improvements of quality of life. Crucial obstacles to the administration of d,l-methadone are incomplete knowledge about its systemic disposition, highly variable pharmacokinetics, profound drug-drug- or drug-disease interaction and QT-prolongation potential. This article summarizes and rates the pharmacological basis of d,l-methadone as an antineoplastic agent and puts its administration in clinical oncology into perspective. Despite enthralling experimental findings about d,l-methadone-mediated apoptosis in cancerous cells or tissues, clinicians should realize the current lack of evidence for the use of d,l-methadone as an antineoplastic agent. Its administration against cancer pain is, however, tenable, albeit restricted to certain clinical situations.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Methadone; Neoplasms
PubMed: 29516505
DOI: 10.1002/ijc.31356 -
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 -
Drug and Alcohol Dependence Feb 2023Starting in 2008, Vietnam's national MMT program expanded quickly, but it is struggling with increasing attrition rates and poor adherence among patients. Several... (Review)
Review
BACKGROUND
Starting in 2008, Vietnam's national MMT program expanded quickly, but it is struggling with increasing attrition rates and poor adherence among patients. Several studies have reported on MMT retention and adherence, but no overview has yet been published. The objective of this study is to fill that gap and to review factors associated with retention and adherence in MMT in Vietnam.
METHODS
A systematic search was conducted using databases of literature - Pubmed, Cochrane, Scopus, Academic search premiere, and SoINDEX. Peer-reviewed empirical studies with full text in English discussing retention attrition and adherence regarding MMT in Vietnam were selected. The results were synthesized using qualitative methods.
RESULTS
Adherence and retention rates varied among the 11 included studies. In general, patients in mountainous provinces had lower adherence and retention rates than those in big cities. Retention rates decreased with the studies' follow-up period and had a downward trend over time. Factors associated with adherence and retention can be classified into three groups: individual, community, and institutional factors. Important individual factors areage, education, awareness of MMT and HIV, and co-occurring disorders and comorbidities. Stigma is the major community risk factor, and methadone daily dose, the distance between home and clinic, and clinic's service hours are the three most important institutional factors.
CONCLUSIONS
The literature reviewed identifies important factors associated with MMT adherence and retention in Vietnam. The findings suggest further research exploring both subjective and objective factors and more policies to remove social and structural barriers to enhance treatment outcomes.
Topics: Humans; Vietnam; Opiate Substitution Treatment; Methadone; Risk Factors; Treatment Adherence and Compliance
PubMed: 36603363
DOI: 10.1016/j.drugalcdep.2022.109699 -
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