Deaths have been reported during initiation of methadone treatment for opioid dependence. In some cases, drug interactions with other drugs, both licit and illicit, have been suspected. However, in other cases, deaths appear to have occurred due to the respiratory or cardiac effects of methadone and too-rapid titration without appreciation for the accumulation of methadone over time. It is critical to understand the pharmacokinetics of methadone and to exercise vigilance during treatment initiation and dose titration (see
DOSAGE AND ADMINISTRATION). Patients must also be strongly cautioned against self-medicating with CNS depressants during initiation of methadone treatment.
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.
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.
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.
Methadone Hydrochloride Oral Concentrate, USP, is supplied in two formulations. The first is supplied as a cherry flavored liquid concentrate. The second is a dye-free, sugar-free, unflavored liquid concentrate. Each liquid concentrate contains 10 mg of methadone hydrochloride per mL.
METHADONE (Methadone) is indicated for the following:
- For detoxification treatment of opioid addiction (heroin or other morphine-like drugs).
- For maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.
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 Methadone
Topiramate for cocaine dependence during methadone maintenance treatment: a
randomized controlled trial. 
CONCLUSION: Topiramate is not efficacious for increasing cocaine abstinence in
Effectiveness of naltrexone in the prevention of delayed respiratory arrest in
opioid-naive methadone-intoxicated patients. 
Acute methadone toxicity is a major public health concern in Iran... Further studies are warranted before the generalization of this approach to other
The effects of gabapentin on methadone based addiction treatment: a randomized
controlled trial. 
Gabapentin is a potentially useful drug in alleviating the hyperexcitatory
painful states in the control of opiate dependence in acute detoxification and
the stabilization phase. This study aim was to evaluate the effectiveness of
gabapentin adds-on methadone therapy on lowering the methadone... This drug leads to
relief of withdrawal symptoms and lower methadone consumption.
Effects of disulfiram on QTc interval in non-opioid-dependent and
methadone-treated cocaine-dependent patients. 
clinical trial of disulfiram were prospectively determined... CONCLUSIONS: These results suggest that cocaine use and possibly MT status, but
A randomized investigation of methadone doses at or over 100 mg/day, combined
with contingency management. 
provide such evidence... CONCLUSIONS: Under double-blind conditions, dosages of methadone over 100mg/day,
Clinical Trials Related to 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
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.
Reports of Suspected Methadone Side Effects
Respiratory Arrest (10),
Cardiac Arrest (10),
Drug Abuse (7),
Completed Suicide (6),
Drug Ineffective (3),
Toxicity TO Various Agents (3),
Escherichia Sepsis (2), more >>
PATIENT REVIEWS / RATINGS / COMMENTS
Based on a total of 8 ratings/reviews, Methadone has an overall score of 8.25. The effectiveness score is 10 and the side effect score is 6.75. The scores are on ten point scale: 10 - best, 1 - worst. Below are selected reviews: the highest, the median and the lowest rated.
Methadone review by 35 year old male patient
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || No Side Effects|
|Condition / reason:|| || OPIATE ADDICTION|
|Dosage & duration:|| || 10MG taken daily for the period of ONE YEAR|
|Other conditions:|| || NONE|
|Other drugs taken:|| || NONE|
|Benefits:|| || I had tesiticular cancer, and I became addicted to OxyContin. Try as I did, I simply could not kick the habit. Methadone really worked for me, and after a while, I tapered at a slow rate.|
|Side effects:|| || None.|
|Comments:|| || Ten Miligrams daily. Of course, at first you have to deal wiht the clinic, but take-home doses are easy to earn as long as you're doing what you're supposed to be doing.|
Methadone review by 40 year old female patient
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || Moderate Side Effects|
|Condition / reason:|| || drug addiction|
|Dosage & duration:|| || 130 mg taken daily for the period of 7 yrs|
|Other conditions:|| || asthma, high blood pressure, diabetes|
|Other drugs taken:|| || metfromin, inhalers, |
|Benefits:|| || I was able to control my addiction and not have to depend on pills to get through the day|
|Side effects:|| || falling asleep anywhere |
|Comments:|| || i started off taking approx 130mg in about 7 yrs and have now reached 65mg in my 8th yr off taking methadone. it has helped me to be a normal person again and no spend my day trying to find the next pill.|
Methadone review by 26 year old female patient
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || Mild Side Effects|
|Condition / reason:|| || opiod addiction|
|Dosage & duration:|| || 60mg/day taken daily for the period of monthly|
|Other conditions:|| || back pain|
|Other drugs taken:|| || none|
|Benefits:|| || It worked but then I became addicted to methadone so basically it just traded one addiction for another. I don't take as many Methedone a day as I did pain pills because Methadone is long lasting so I guess it did help me.|
|Side effects:|| || At first I got painful headaches but that subsided after continued use. I do still have horrible constipation and I have sexual dsyfuntion.|
|Comments:|| || I began recieving Methadone when I was 21 years old. I started seeing a pschiatrist because I needed help for pain pill addiction. I began getting prescriptions for hydrocodone when I was 19. I have an abnormality in my lower back which causes me severe pain. I began taking more than I was supposed to for the pain and was taking anywhere from 20 to 30 pain pills a day. So I knew I needed help. That's when my doctor gave me Methadone. He gave me 60mg a day but I usually only took 40mg depending on what I needed. Over the years I have weaned myself down to 20mg a day and everyone even my doctor says to me that I should be able to come off of these pills easily but no one understands the physical and psychological symptoms I go through. It's so hard to just stop taking them when I have became so depended on them in my daily life. I have four kids and with out them I feel like a different person and it takes everything in me to get out of bed and take care of my kids. Is it in my head? I don't know but either way, in a lot of ways it helped me but in a lot of ways it ruined my life. I don't want to be addicted to a pill for the rest of my life. Now my doctor has stopped giving them to me because he feels that I can come off them easily at such a low dose but what does he know he does not understand what it feels like. I am at such a downfall in my life, I have to buy them now just to feel normal every day. I feel like if these doctors give them to me then they should help me with the withdrawals ao I can get off them. I still need help after all these yesrs. I don't have a car to drive to a methadone clinic everyday and no one to help me. So what are people like me to do?|
Page last updated: 2015-08-10