METHADONE HYDROCHLORIDE
Methadone Hydrochloride Injection is indicated for the management of severe and persistent pain requiring continuous, around-the-clock opioid therapy when alternative treatments are inadequate or not tolerated. It is not indicated for use as an as-needed (PRN) analgesic. Additionally, it is indicated for the temporary treatment of opioid dependence in patients unable to take oral medication, such as those who are hospitalized. Due to significant risks of addiction, abuse, and respiratory depression, its use is strictly reserved for cases where other options are insufficient, and its use for addiction is subject to specific federal regulatory requirements (42 CFR 8).
How METHADONE HYDROCHLORIDE Works
Methadone hydrochloride is a synthetic opioid that acts primarily as a mu-receptor agonist. Its therapeutic effects, including analgesia and suppression of opioid withdrawal, are qualitatively similar to morphine and involve the central nervous system and smooth muscle. Methadone also functions as an antagonist at the N-methyl-D-aspartate (NMDA) receptor, although the specific clinical contribution of this antagonism to its efficacy is not fully defined. Compared to morphine, the methadone abstinence syndrome is characterized by a slower onset, a more prolonged duration, and less severe symptoms.
Development Insights
Details
- Status
- Prescription
- First Approved
- 1947-08-13
- Routes
- ORAL, INJECTION, FOR RX COMPOUNDING
- Dosage Forms
- SOLUTION, TABLET, CONCENTRATE, INJECTABLE, TABLET, FOR SUSPENSION, POWDER
METHADONE HYDROCHLORIDE Approval History
What METHADONE HYDROCHLORIDE Treats
28 FDA approvalsOriginally approved for its first indication in 1947 . Covers 28 distinct patient populations.
- Other (28)
Other
(28 approvals)- • Approved indication (Aug 1947)
- • Approved indication (Dec 1947)
- • Approved indication (Mar 1973)
- • Approved indication (May 1981)
- • Approved indication (Aug 1982)
- • Approved indication (Mar 1983)
- • Approved indication (Nov 1994)
- • Approved indication (Apr 1995)
- • Approved indication (Mar 1998)
- • Approved indication (Apr 1998)Letter
- • Approved indication (May 1998)Letter
- • Approved indication (Apr 2004)
- • Approved indication (Jul 2005)
- • Approved indication (Nov 2009)
- • Approved indication (Jun 2010)
- • Approved indication (Aug 2015)
- • Approved indication (Aug 2015)
- • Approved indication (Oct 2017)Letter
- • Approved indication (Mar 2018)Letter
- • Approved indication (Aug 2018)
- • Approved indication (Jan 2019)
- • Approved indication (Aug 2019)
- • Approved indication (Oct 2019)
- • Approved indication (Mar 2020)
- • Approved indication (Nov 2020)
- • Approved indication (Mar 2021)
- • Approved indication (Dec 2024)
- • Approved indication (May 2025)
METHADONE HYDROCHLORIDE Boxed Warning
SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE INJECTION Addiction, Abuse, and Misuse Because the use of Methadone Hydrochloride Injection 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 and reassess all patients regularly for the development of these behaviors and conditions (see WARNINGS ). Life-Threatening Respiratory Depression Serious, life-thre...
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE INJECTION Addiction, Abuse, and Misuse Because the use of Methadone Hydrochloride Injection 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 and reassess all patients regularly for the development of these behaviors and conditions (see WARNINGS ). Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Methadone Hydrochloride Injection, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of Methadone Hydrochloride Injection are essential (see WARNINGS ). Neonatal Opioid Withdrawal Syndrome (NOWS) Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of Methadone Hydrochloride Injection during pregnancy. NOWS may be life-threatening if not recognized and treated in the neonate. The balance between the risks of NOWS and the benefits of maternal Methadone Hydrochloride Injection use may differ based on the risks associated with the mother’s underlying condition, pain, or addiction. Advise the patient of the risk of NOWS so that appropriate planning for management of the neonate can occur (see WARNINGS ). Managing Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of Methadone Hydrochloride Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate (see WARNINGS , PRECAUTIONS ). Life-Threatening QT Prolongation QT interval prolongation and serious arrhythmia (torsades de pointes) hav
METHADONE HYDROCHLORIDE Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
Clinical Trial Registry
93 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT06323824 | 2000033271 CTN-0131, 5UG1DA015831-21 | Ph 4 | recruiting | Office-based Methadone Versus Buprenorphine to Address Retention in Medication for Opioid Use Disorder Treatment. |
| NCT06784999 | 21583 | Ph 4 | recruiting | Sufentanil Infusion vs Intravenous Methadone for Postoperative Analgesia Following Head and Neck Dissection With Free Flap or Rotational Reconstruction |
| NCT07546396 | H25-03989 | Ph 4 | not yet recruiting | Methadone Rapid Restart |
| NCT03574792 results posted | I 61117 NCI-2018-01055, I 61117 | Ph 2 | completed | Gabapentin, Methadone, and Oxycodone With or Without Venlafaxine Hydrochloride in Managing Pain in Participants With Stage II-IV Squamous Cell Head and Neck Cancer Undergoing Chemoradiation Therapy |
| NCT06962306 OPAL-Cleft | Pro00117598 | Ph 4 | recruiting | Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery |
| NCT07528508 | 8527-020 MK-8527-020 | Ph 1 | not yet recruiting | A Clinical Trial in Healthy Participants to Study the Effect of a Single Dose of MK-8527 on Levels of Methadone (MK-8527-020) |
| NCT07517679 | 111197 | Ph 4 | not yet recruiting | Methadone for Post-operative Spine Surgery |
| NCT04480554 AMOHI-1 results posted | R01DA048728 | Ph 2 | terminated | Anti-retroviral Therapy, Medications for Opioid Use Disorder, Opioids and HIV Infection - Study 1 |
| NCT06868589 RELIEF-LT | 20243140 | Ph 4 | active not recruiting | Reducing Pain With Methadone and Ketamine in Liver Transplant |
| NCT07485803 | 2387801 | Ph 4 | not yet recruiting | A RCT Using Methadone in the Management of Post-Operative Pain in Total Knee Replacement |
| NCT05905367 SIFI | H23-00111 | Ph 4 | completed | Symptom-inhibited Fentanyl Induction |
| NCT06525740 | 24-001383 NCI-2024-06145, 24-001383 | Ph 4 | recruiting | Methadone Versus Intrathecal Hydromorphone for Postoperative Pain Relief in Gynecologic Cancer Undergoing Surgery |
| NCT07227064 | Pro00147100 | Ph 3 | recruiting | Methadone in THA for Post-op Pain and Opioid Reduction |
| NCT07226076 | Pro00147447 | Ph 3 | recruiting | Methadone in TKA for Post-op Pain and Opioid Reduction |
| NCT05417100 | 22-015 | Ph 3 | active not recruiting | Understanding How Methadone Treatment During Surgery Affects Pain Levels and the Need for Pain Medications After Surgery |
| NCT06536517 | IRB00459067 | Ph 2 | recruiting | The Effects of One-time Intraoperative Methadone During Laparoscopic Hysterectomy in Reducing Opioid Prescription. |
| NCT07222072 MEND | The MEND Study pilot | Ph 4 | recruiting | Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study |
| NCT02025855 results posted | Smoot_8503 | Ph 4 | terminated | Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit |
| NCT06576830 OPTIMAL | Pro00114677 1R01HD114678-01 | Ph 4 | recruiting | Optimization of Pediatric Tonsillectomy to IMprove AnaLgesia |
| NCT03726268 OSPREy results posted | Pro00089977 1R01DA042985-01 | Ph 4 | completed | Optimizing Outpatient Anesthesia (OSPREy-Outpatient Surgery Pain Relief Enhancement) |
| NCT06877858 | 857972 | Ph 1 | recruiting | MethaLoad Dose-Finding Study |
| NCT05786599 METACIN | H22-01702 | Ph 2, Ph 3 | recruiting | Methadone to Treat Painful Chemotherapy Induced Peripheral Neuropathy |
| NCT05913284 | 2022.636-T | Ph 3 | active not recruiting | Intravenous Methadone in Perioperative Acute and Chronic Management in Chinese Adult Cardiac Surgical Patients |
| NCT06086171 | SHS-An-4-2023 | Ph 4 | completed | Perioperative Methadone Compared to Placebo in Elderly Hip Fracture Patients |
| NCT04214834 results posted | ACTNOW-02 | Ph 3 | active not recruiting | Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS) |
| NCT05831345 | CHUB-Methadone | Ph 3 | recruiting | Intraoperative Methadone for the Prevention of Postoperative Pain |
| NCT06728371 MethadoneRCT | CUHK_PWH | Ph 3 | recruiting | Intravenous Methadone for Sternotomy Pain Control in Cardiac Surgery |
| NCT04764825 METASPINE | 89456049 2020-004826-47 | Ph 4 | terminated | Methadone for Spinal Fusion Surgery. |
| NCT01793480 EQUIMETH2 | 2011-004609-26 | Ph 3 | completed | Evaluation of the Efficacy and Safety of Two Methadone Titration Methods for the Treatment of Cancer-related Pain With Inadequate Pain Relief or Intolerable Side Effects When Treated With Level 3 Opioids. |
| NCT05244226 results posted | Pro00109911 | Ph 2 | completed | Pediatric Pain Optimization After Tonsillectomy |
| NCT05730920 AIMS | NCA2205 | Ph 4 | completed | IV Methadone Vs EXPAREL Erector Spinae Plane Blockade in Pediatric Subjects Undergoing Idiopathic Scoliosis Correction |
| NCT02252432 results posted | Pro00030109 | Ph 4 | terminated | The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy |
| NCT04680286 METACEBO | 23956082 2020-002945-41 | Ph 3 | terminated | Intraoperative Methadone in Children Undergoing Surgery |
| NCT02396979 Harapan | 0908005646 R01DA025943 | Ph 4 | completed | Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia |
| NCT00930332 | SC22 CAN-NCIC-SC22, CDR0000641372 | Ph 1 | terminated | Methadone Hydrochloride as First-Line Therapy in Treating Patients With Chronic Neuropathic Cancer Pain |
| NCT05164549 EXPO | 255522 | Ph 3 | completed | Extended-release Pharmacotherapy for Opioid Use Disorder |
| NCT02558010 results posted | CHW-Methadone-001 | Ph 3 | completed | Perioperative Methadone Use to Decrease Opioid Requirement in Pediatric Spinal Fusion Patients |
| NCT05845359 | 2022-14040 | Ph 4 | withdrawn | Intraoperative Methadone for Postoperative Pain Control |
| NCT03134703 results posted | IRB00107690 | Ph 2 | terminated | Methadone Demonstration Project With Neonatal Intensive Care Unit Infants Diagnosed With Neonatal Abstinence Syndrome |
| NCT01082679 | H-2008-0242 | Ph 2, Ph 3 | completed | Treatment for Opioid Dependent Offenders |
| NCT02851303 results posted | 16-176 | Ph 4 | completed | Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome |
| NCT02989597 MAPS results posted | 2016-6985 | Ph 4 | terminated | Intraoperative Methadone Administration for Improved Pain Control in Spinal Fusion Patients |
| NCT05251376 | LYN-014-C-101 4UH3DA050310-02 | Ph 1 | withdrawn | Study of LYN-014 in Individuals With Opioid Use Disorder Who Are Stable on Methadone Therapy |
| NCT05325164 METHADOPT | 638423678 | Ph 3 | withdrawn | Methadone for 'Adenocarcinopathic' Pain Treatment |
| NCT02531906 | I 262314 NCI-2015-01338, I 262314 | Ph 1 | completed | Gabapentin, Methadone Hydrochloride, and Oxycodone Hydrochloride in Improving Quality of Life in Patients With Stage II-IV Head and Neck Cancer During Chemoradiation |
| NCT01733693 NEO | 2012-433 1R01DA032552-01A1 | Ph 4 | completed | Neurocognitive Effects of Opiate Agonist Treatment |
| NCT03948464 pRESTO | BCCSU-002 | Ph 3 | terminated | Slow-Release Oral Morphine for the Treatment of Opioid Use Disorder |
| NCT04525898 | EH19-031 | Ph 4 | terminated | Intraoperative Methadone for Postoperative Pain Control After Thoracic Surgery |
| NCT01546948 | EH11-232 | Ph 4 | completed | Intraoperative Opioids and Postoperative Recovery After Hepatobiliary or Foregut Surgery |
| NCT00838981 results posted | 0705002636 R01DA021264, DPMC | Ph 1, Ph 2 | completed | Pharmacotherapy & CM for Opioid and Cocaine Dependence |
Showing 50 of 93 trials
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
METHADONE HYDROCHLORIDE FDA Label Details
Indications & Usage
FDA Label (PDF)1. Methadone Hydrochloride Injection is indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use • Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration (see WARNINGS ), and persist over the course of therapy, reserve opioid analgesics, including Methadone Hydrochloride Injection, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be ...
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE INJECTION Addiction, Abuse, and Misuse Because the use of Methadone Hydrochloride Injection exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, asse...
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METHADOSE
Full clinical data, patents, trials, and competitive landscape for methadone hydrochloride.
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.
How We Calculate These Metrics
Trial Activity Stage
Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.
Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.
- Growth: High proportion of early-phase trials (Phase 1/2), active development
- Expansion: Significant Phase 3 activity, approaching or pursuing approvals
- Mature: Substantial Phase 4 post-marketing studies
- Stable: Mixed phase distribution, steady development
- Declining: Low active trial ratio, reduced R&D investment