WARNING: ADDICTION, ABUSE AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; LIFE-THREATENING QT PROLONGATION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and TREATMENT FOR OPIOID ADDICTION
Addiction, Abuse, and Misuse
DOLOPHINE exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can
lead to overdose and death. Assess each patient’s risk prior to prescribing DOLOPHINE, and monitor all patients regularly for the development of these behaviors or conditions
[see Warnings and Precautions]
Life-threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of DOLOPHINE. Monitor for
respiratory depression, especially during initiation of DOLOPHINE or following a dose increase [see Warnings
Accidental ingestion of even one dose of DOLOPHINE, especially by children, can result in a fatal overdose of
[see Warnings and Precautions]
Life-threatening QT Prolongation
QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred 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. Closely monitor patients for changes in cardiac rhythm during initiation and titration of
[see Warnings and Precautions]
Neonatal Opioid Withdrawal Syndrome
Prolonged use of DOLOPHINE during pregnancy can result in neonatal opioid withdrawal syndrome, which
may be life-threatening if not recognized and treated, and requires management according to protocols
developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise
the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be
[see Warnings and Precautions]
Conditions For Distribution And Use Of Methadone Products For The Treatment Of Opioid Addiction
For detoxification and maintenance of opioid dependence, methadone should be administered in accordance
with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration
[see Indications and Usage]
DOLOPHINE® 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.
Media Articles Related to Dolophine (Methadone)
Methadone provides pain relief for kids with sickle cell
Source: Pain / Anesthetics News From Medical News Today [2016.10.11]
Relieves pain more quickly, lasts longer than other drugs.Many children with sickle cell disease experience frequent and severe pain episodes, requiring emergency room visits or hospitalization.
Published Studies Related to Dolophine (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 Dolophine (Methadone)
Methadone in Pediatric Anesthesiology II [Recruiting]
Methadone Pharmacokinetics and Cardiac Effects in Newborns [Active, not 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.
The Use of Methadone in Newborn Infants [Active, not 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.
Methadone and Ketamine for Neuropathic Pain Treatment [Completed]
Methadone and ketamine are effective for neuropathic pain management. However, the benefits
of the association of both drugs are uncertain. Here, the investigators conducted a
randomized, double-blind, in parallel, active controlled clinical trial to test the
hypothesis that methadone combined ketamine (methadone/ketamine) is more effective than
methadone or ketamine alone in reducing neuropathic pain.
Pharmacogenomics of Methadone in Spine Fusion Surgery [Withdrawn]
The overall objective is to develop a patient oriented research program to efficiently
evaluate the effects of pharmacogenetic variants on the dose-response relationships and
safety of opioids and non-opioid analgesics. If an opioid regimen can be created that
produces excellent opioid analgesia with minimal toxicity related to supratherapeutic opioid
concentrations (i. e., ventilatory depression), other non-opioid analgesics (i. e.,
gabapentin/pregabalin, ketamine, lidocaine, cyclooxygenase inhibitors, etc.) that may
decrease preoperative opioid requirements can be more efficiently and safely evaluated.
These interventions may limit the opioid related toxicities related to effect site
concentrations that are below those required when opioids are the predominant analgesic,
such as opioid related ileus. Methadone's slow elimination clearance and limited
pharmacokinetic drug-drug interactions make it an attractive perioperative opioid. The
first step towards personalized opioid analgesia is to determine the effect of common
pharmacogenetic variants that affect either methadone metabolism (CYP2B6) or opioid
Page last updated: 2016-10-11