What are the Ingredients in DOLOPHINE?
Active Ingredient: methadone hydrochloride, USP
Inactive Ingredients: magnesium stearate, microcrystalline cellulose, and starch.
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.
DOLOPHINEŽ HYDROCHLORIDE (Methadone Hydrochloride Tablets, USP), for oral administration, each contain 5 mg or 10 mg of methadone hydrochloride.
DOLOPHINE is indicated for the following:
1. For the treatment of moderate to severe pain not responsive to non-narcotic analgesics.
2. For detoxification treatment of opioid addiction (heroin or other morphine-like drugs).
3. For maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.
NOTE: Outpatient maintenance and outpatient detoxification treatment may be provided only by Opioid Treatment Programs (OTPs) certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA). This does not preclude the maintenance treatment of a patient with concurrent opioid addiction who is hospitalized for conditions other than opioid addiction and who requires temporary maintenance during the critical period of his/her stay, or of a patient whose enrollment has been verified in a program which has been certified for maintenance treatment with methadone.
Published Studies Related to Dolophine (Methadone)
Tramadol versus methadone for treatment of opiate withdrawal: a double-blind,
randomized, clinical trial. 
The aim of this study was to compare the efficacy and safety of tramadol versus
methadone for treatment of opiate withdrawal. Seventy patients randomly were
assigned in two groups to receive either prescribed methadone (60 mg/day) or
tramadol (600 mg/day)... Tramadol may be as effective as methadone in the
control of withdrawal and could be considered as a potential substitute for
methadone to manage opioids withdrawal.
Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics. [2011.11.12]
ABSTRACT: BACKGROUND: Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment...
Randomized Trial of Standard Methadone Treatment Compared to Initiating Methadone without Counseling: 12-month Findings. [2011.10.26]
Aims: This study aimed to determine the relative effectiveness of 12-months of Interim Methadone (IM; supervised methadone with emergency counseling only for the first 4 months of treatment), Standard Methadone treatment (SM; with routine counseling) and Restored Methadone treatment (RM: routine counseling with smaller caseloads)...
Trazodone for sleep disturbance during methadone maintenance: A double-blind, placebo-controlled trial. [2011.07.26]
BACKGROUND: To test whether trazodone, one of the most commonly prescribed medications for treatment of insomnia, improves subjective and/or objective sleep among methadone-maintained persons with sleep complaints, we performed a randomized, double-blind, placebo-controlled trial with 6-month follow-up... CONCLUSIONS: Trazodone did not improve subjective or objective sleep in methadone-maintained persons with sleep disturbance. Other pharmacologic and non-pharmacologic treatments should be investigated for this population with high rates of insomnia. Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency. [2011.07.26]
BACKGROUND: Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST). In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes... CONCLUSIONS: The higher satisfaction among those receiving medically prescribed injectable diacetylmorphine (or hydromorphone) supports current evidence regarding the attractiveness of this treatment for long-term, opioid-dependent individuals not benefiting sufficiently from other treatments. In addition, the measurement of treatment satisfaction provides valuable information about participants at risk of relapse and in need of additional services. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00175357.
Clinical Trials Related to Dolophine (Methadone)
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 48 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
CYP3A4-3A7-3A5, CYP2B6, CYP2C8, CYP2C19, and CYP2D6 and PGO 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.
Drug Interaction Study Of Filibuvir With Methadone, Among Subjects On Chronic Methadone Maintenance [Not yet recruiting]
Filibuvir, a CYP3A4 inhibitor is being developed for the treatment of chronic Hepatitis C
infection. Given the likelihood of co administration of filibuvir and methadone, this study
will evaluate the effect of filibuvir on the pharmacokinetics of R/S 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-Dolutegravir (DTG - GSK1349572) Drug Interaction Study. [Not yet recruiting]
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3
clinical development for the treatment of HIV infection. As HIV-infected subjects may also
be receiving methadone for opioid dependence, an evaluation of the potential interaction
between DTG and methadone is warranted. The primary objective of this study is to determine
whether concomitant administration of DTG can affect the pharmacokinetics (PK) of methadone.
As a secondary endpoint, the PK of DTG will be compared to historical data. This study
will be open-label with subjects receiving DTG and stable doses of methadone. The study
will be conducted at one center in Canada in adult male and female subjects.
The Use of Methadone in Newborn Infants [Recruiting]
This proposed investigation will test the following hypotheses: 1) Enzymatic activity of
CYP2B6 characterized by the formation clearance of methadone to EDDP (CLf,EDDP), is directly
related to both gestational and postnatal age; 2) variations in the CYP2B6 gene (SNPs) are
associated with variable activity of the CYP2B6 enzyme (as measured by the formation
clearance, CLf,EDDP), and 3) the elimination rate of methadone and its major metabolite EDDP
in neonates is dependent on the glomerular filtration rate and therefore on the stage of
development (defined by both gestational and postnatal age). The investigators propose to
develop a PK model for methadone dosing in neonates that takes into account both
developmental stage and genetic variability. The long-term goal of the proposed
investigations is to improve dosing of methadone in neonates exposed to opioids in utero or
post-natally, leading to improved control of their withdrawal syndrome and decreased adverse
drug reactions associated with the current use of methadone in these vulnerable patients.
More immediately, the investigators will develop a PK model for methadone dosing based on
relevant developmental and genetic characteristics. The acquired knowledge based on the
proposed study will lead to a more efficacious treatment of pain or opiate withdrawal
syndrome in newborn infants with a decreased chance of adverse drug reactions.
Page last updated: 2013-02-10