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Deaths, cardiac and respiratory, have been reported during initiation and conversion of pain patients to methadone treatment from treatment with other opioid agonists. It is critical to understand the pharmacokinetics of methadone when converting patients from other opioids ( see DOSAGE AND ADMINISTRATION). Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose titration.
Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration.
In addition, cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methadone treatment for analgesic therapy in patients with acute or chronic pain should only be initiated if the potential analgesic or palliative care benefit of treatment with methadone is considered and outweighs the risks.
Conditions for Distribution and Use of Methadone Products for the Treatment of Opioid Addiction
Code of Federal Regulations, Title 42, Sec 8
Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by opioid treatment programs (and agencies, practitioners or institutions by formal agreement with the program sponsor) certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority. Certified treatment programs shall dispense and use methadone in oral form only and according to the treatment requirements stipulated in the Federal Opioid Treatment Standards (42 CFR 8.12). See below for important regulatory exceptions to the general requirement for certification to provide opioid agonist treatment.
Failure to abide by the requirements in these regulations may result in criminal prosecution, seizure of the drug supply, revocation of the program approval, and injunction precluding operation of the program.
Regulatory Exceptions to the General Requirement for Certification to Provide Opioid Agonist Treatment:
- During inpatient care, when the patient was admitted for any condition other than concurrent opioid addiction (pursuant to 21 CFR 1306.07(c)), to facilitate the treatment of the primary admitting diagnosis).
- During an emergency period of no longer than 3 days while definitive care for the addiction is being sought in an appropriately licensed facility (pursuant to 21 CFR 1306.07(b)).
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METHADOSE SUMMARY
METHADOSE® ORAL TABLETS
METHADONE HYDROCHLORIDE TABLETS USP
5 mg, 10 mg
Methadose® Oral Concentrate (methadone hydrochloride USP) is supplied as a cherry flavored liquid concentrate. Methadose® Sugar-Free Oral Concentrate (methadone hydrochloride USP) is a dye-free, sugar-free, unflavored liquid concentrate of methadone hydrochloride. Each liquid concentrate contains 10 mg of methadone hydrochloride per mL. Methadone hydrochloride (3-heptanone, 6-(dimethylamino)-4, 4-diphenyl-, hydrochloride) is a white, essentially odorless, bitter-tasting crystalline powder. It is very soluble in water, soluble in isopropranolol and in chloroform, and practically insoluble in ether and in glycerine. It is present in Methadose as the racemic mixture. Methadone hydrochloride has a melting point of 235ºC, a pKa of 8.25 in water at 20°C, a solution (1 in 100) pH between 4.5 and 6.5, a partition coefficient of 117 at pH 7.
Methadose (Methadone) is indicated for the following:
- Detoxification treatment of opioid addiction (heroin or other morphine-like drugs).
- Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.
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NEWS HIGHLIGHTSMedia Articles Related to Methadose (Methadone)
Hepatitis C Screening Of Mothers Using Methadone And Their Babies Is Inadequate, Australia
Source: Liver Disease / Hepatitis News From Medical News Today [2009.11.16]
Screening for Hepatitis C virus (HCV) infection among pregnant women on methadone maintenance treatment and their infants is inadequate, according to the authors of a study published in the Medical Journal of Australia. Dr Ralph Nanan, Professor of Paediatrics at the University of Sydney, and his co-authors undertook a retrospective review of medical records from two major hospitals in Sydney and a hospital in rural NSW.
Published Studies Related to Methadose (Methadone)
Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. [2009.10]
CONTEXT: Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration-approved pharmacotherapy. OBJECTIVES: To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence... CONCLUSIONS: Attaining high (>or=43 microg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters. Trial Registration clinicaltrials.gov Identifier: NCT00142857.
Rationale, design, and sample characteristics of a randomized controlled trial of directly observed antiretroviral therapy delivered in methadone clinics. [2009.09]
BACKGROUND: Directly observed therapy (DOT) programs for HIV treatment have demonstrated feasibility, acceptability, and improved viral suppression, but few have been rigorously tested. We describe a randomized controlled trial testing the efficacy of an antiretroviral DOT program in methadone maintenance clinics. Our objective was to determine if DOT is more efficacious than self-administered antiretroviral therapy for reducing HIV viral load, improving adherence, and reducing drug resistance among opioid dependent drug users receiving methadone treatment... CONCLUSIONS: Our trial will allow rigorous evaluation of the efficacy of directly observed antiretroviral therapy delivered in methadone clinics for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs and can guide protocols for studies among HIV-infected drug users receiving methadone for opioid dependence.
Diacetylmorphine versus methadone for the treatment of opioid addiction. [2009.08.20]
BACKGROUND: Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence... CONCLUSIONS: Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.) 2009 Massachusetts Medical Society
Interim methadone treatment: impact on arrests. [2009.08.01]
AIMS: This study examines the frequency and severity of arrest charges among heroin addicts randomly assigned to either interim methadone (IM) maintenance or to remain on a waiting list for methadone treatment. It was hypothesized that IM participants would have a: (1) lower number of arrests at 6 and 12 months and (2) lower mean crime severity scores at 6 and 12 months post-baseline... CONCLUSIONS: IM as compared to the waiting list condition, had a significant reduction in number of officially recorded arrests from baseline to 6 months post-baseline. Those who were enrolled in methadone treatment at the 4- and 10-month follow-up assessment, regardless of initial assignment, had fewer arrests at 12 and 24 months post-baseline.
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Project Study: protocol for a randomised controlled trial comparing methadone and buprenorphine for opiate detoxification. [2009.07.14]
BACKGROUND: In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use... Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification.
Clinical Trials Related to Methadose (Methadone)
Co-Administration Of Fosamprenavir With Methadone: A Drug Interaction Study. [Completed]
To assess the combined effects of fosamprenavir 700mg BID + ritonavir 100mg BID +
standardized dose of methadone, on plasma total and unbound methadone enantiomer
pharmacokinetics (PK), opiate pharmacodynamic (PD) measures, and safety. The effect of
methadone on plasma amprenavir PK will also be assessed by comparison to historical control
data.
Methadone Pharmacokinetics and Cardiac Effects in Newborns [Recruiting]
The Primary objectives of this proposal are to determine the population kinetics for
methadone and its enantiomers in preterm newborns and infants at 29 weeks to 52 weeks post
menstrual age (PMA) who are 1 week old and older and establish any correlations of the
kinetics with PMA to determine the bioavailability for enterally administered methadone in
these newborns and young infants. The secondary objectives of this proposal are to explore
possible genotypic changes in CYP3A4, CYP2B6, CYP2C8, CYP2c19, and CYP2D6 on the kinetics of
methadone in neonates and young infants and to test the safety of methadone in this
population by correlating the plasma concentrations of the methadone enantiomers,
S-methadone and R-methadone, with changes in cardiac repolarization by measurement of
corrected QT, heart rate, and blood pressure.
Study of Methadone for Management of Iatrogenic Opioid Dependence in Critical Care Children [Not yet recruiting]
The purpose of this study is to examine the efficacy of a standardized methadone weaning
treatment protocol and whether it leads to a reduction in the total number of days needed to
wean opioids after prolonged exposure. The use of this protocol may also promote a reduction
in abstinence syndrome symptoms. Patients will be converted from continuous intravenous
opioid infusions to one of three methadone dosing schedules. Initial methadone dose
conversion will be equipotent to the previously administered continuous intravenous opioid
infusion. Subsequently, a methadone weaning schedule will follow according to the guidelines
set forth by the Methadone Wean Protocol Also, concurrent validity and reliability testing
will be performed on the Pediatric Abstinence Syndrome Scoring Sheet, which is a
pediatric-specific abstinence syndrome assessment tool.
To assure consistency and compliance to the protocol, a standardized physician's order form
for methadone wean was developed. This order form includes a step-by-step calculation
approach for conversion from continuous opioid to intermittent methadone.
Methadone Maintenance & HIV Risk in Ukraine [Recruiting]
Treatment of opioid dependence is an important way to reduce the spread of HIV and other
infectious diseases, particularly in Ukraine since intravenous opioid use is the major way
these infections are being spread. This proposal will be done at the Kiev City Narcology
Hospital and the City AIDS Center with collaborators from the University of Alabama and the
University of Colorado. It will study the acceptability and impact of a 3-month course of
methadone maintenance on 50 persons with opioid dependence, 25 who are HIV+ and 25 HIV-.
The proposed work will build on a relationship that was established with the Ukrainian
Co-Principal Investigator, Sergiy Dvoryak, M. D., during his Humphrey Fellowship at Johns
Hopkins in 1999-2000 when he spent time with Dr. Woody and Metzger at the Penn Addiction and
Treatment and Research Center. It will also extend studies of pharmacologic treatment for
opioid dependence and risk reduction behavioral interventions that are being done by Drs.
Woody, Schumacher and Booth in Russia and Ukraine. Primary aims are to: measure the
acceptability and compliance with a 3-month course of methadone maintenance in HIV+ and HIV-
patients; measure the impact of a 3-month course of methadone in reducing opioid use in HIV+
and HIV- patients; measure the impact of a 3-month course of methadone on reducing HIV risk
behavior in HIV+_and HIV- patients. Secondary aims are to: assess the degree to which a
3-month course of methadone maintenance reduces illegal activities and improves employment
and psychiatric symptoms; determine short-term outcome after completion of methadone
treatment; and obtain pilot data on the prevalence of hepatitis B and C among study
patients. This study will provide pilot data on the acceptability and efficacy of a
short-term course of methadone maintenance on HIV+ and HIV- persons in a setting where this
treatment has not been evaluated, on the feasibility of conducting the kind of work that is
proposed, and will enhance research capabilities of Kiev investigators for future HIV
prevention and treatment studies.
Methadone Effects on Zidovudine (ZDV, AZT) Disposition [Completed]
To determine whether methadone maintenance alters the pharmacokinetics of zidovudine (AZT).
To determine whether any such effect of methadone on disposition of AZT is time dependent and
whether a metabolic interaction between AZT and methadone exists.
Injection drug users represent an increasing proportion of HIV-infected persons. Since daily
methadone maintenance is the major chemical treatment for injection drug abuse, it is
important to determine the impact of methadone on AZT absorption, distribution, and
elimination.
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Page last updated: 2009-11-16
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