TRAMADOL HYDROCHLORIDE
Tramadol hydrochloride extended-release tablets are indicated for the management of severe and persistent pain that requires daily, around-the-clock, long-term opioid treatment for which alternative options—such as non-opioid analgesics or immediate-release opioids—are inadequate or not tolerated. Due to the significant risks of addiction, abuse, misuse, and overdose, this medication is reserved for cases where other treatments provide insufficient pain management. It is intended for continuous administration and is not indicated for use as an as-needed (PRN) analgesic.
How TRAMADOL HYDROCHLORIDE Works
Tramadol hydrochloride is a centrally acting synthetic analgesic with a dual mechanism of action. It acts as a $\mu$-opioid receptor agonist and simultaneously inhibits the neuronal reuptake of norepinephrine and serotonin. The drug's opioid activity is derived from both the parent compound and its active O-desmethyl metabolite (M1); M1 has a significantly higher affinity for $\mu$-opioid receptors and is more potent in producing analgesia than the parent drug. These dual pathways—opioid receptor activation and monoamine reuptake inhibition—contribute independently to the medication's overall analgesic profile.
Development Insights
Details
- Status
- Discontinued
- First Approved
- 2002-06-19
- Routes
- ORAL
- Dosage Forms
- TABLET, EXTENDED RELEASE, TABLET
Companies
TRAMADOL HYDROCHLORIDE Approval History
What TRAMADOL HYDROCHLORIDE Treats
1 indicationsTRAMADOL HYDROCHLORIDE is approved for 1 conditions since its original approval in 2002. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Pain
TRAMADOL HYDROCHLORIDE Boxed Warning
SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride extended-release tablets 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 and Precautions (5.1)] . Life-Thr...
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride extended-release tablets 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 and Precautions (5.1)] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of tramadol hydrochloride extended-release tablets , especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride extended-release tablets are essential [see Warnings and Precautions (5.2)]. Instruct patients to swallow tramadol hydrochloride extended-release tablets whole to avoid exposure to a potentially fatal dose of tramadol [see Warnings and Precautions (5.2)]. Accidental Ingestion Accidental ingestion of even one dose of tramadol hydrochloride extended-release tablets , especially by children, can result in a fatal overdose of tramadol [see Warnings and Precautions (5.2)] . 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 tramadol hydrochloride extended-release tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3), Drug Interactions (7)] . Neonatal Opioid Withdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, wh
TRAMADOL HYDROCHLORIDE Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Direct competitors
Same target(s) AND same indication — head-to-head.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
Drugs Similar to TRAMADOL HYDROCHLORIDE
3 of 20FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.
Clinical Trial Registry
90 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT07064993 KATD-PAIN | 19.11.2024 | Ph 4 | not yet recruiting | Effects of Intraarticular Tramadol and Tramadol-Dexamethasone on Postoperative Pain After Knee Arthroscopy |
| NCT07469826 | F.2-81/22-GENL/275/JPMC | Ph 3 | completed | Bupivacaine Alone vs Bupivacaine With Tramadol in Local Anesthesia Procedures |
| NCT07440069 TRAMPA | PO-UNAH-49-7-2026 | Ph 4 | recruiting | Analgesic Efficacy and Obstetric Effects of Tramadol, Paracetamol and Placebo in Active Labor |
| NCT06373978 | 24-307 | Ph 4 | recruiting | NonNarcotic Pain Control in Percutaneous Needle Tenotomy of Elbow |
| NCT06215859 | MR-107A-02-TFZ-3002 | Ph 3 | completed | Study of MR-107A-02 for the Treatment of Acute Postoperative Pain Following Herniorrhaphy |
| NCT05488847 results posted | 15592 | Ph 4 | active not recruiting | Opioid-Free Pain Protocol After Shoulder Arthroplasty |
| NCT06232577 | 2023-0818 NCI-2024-00632 | Ph 2 | active not recruiting | 5x-Multiplier vs 3-Tier Model for Discharge Opioid Prescriptions After Intra-abdominal Cancer Surgery: A Randomized Clinical Trial |
| NCT02851394 ATLAS | Bethenod Ellouze 2014 | Ph 4 | completed | Advantage of Tramadol in Local Analgesia Post-Sternotomy |
| NCT07332572 | LNH | Ph 4 | completed | COMPARISON OF INTRAVENOUS DEXMEDETOMEDINE AND TRAMADOL FOR POST OPERATIVE SHIVERING AFTER SPINAL ANESTHESIA FOR CAESAREAN SECTION |
| NCT04110665 Shoulder1 | Local/2017/PC-03 2017-A01316-47 | Ph 4 | completed | Multimodal Analgesia Strategies After Major Shoulder Ambulatory Surgery |
| NCT06215820 | MR-107A-02-TFZ-3001 | Ph 3 | completed | Study of MR-107A-02 for the Treatment of Acute Postoperative Pain Following Bunionectomy |
| NCT07066111 | KY 20250527-02 | Ph 4 | not yet recruiting | The Effect of Bupivacaine Liposome Preemptive Analgesia on Postoperative Pain and Delirium in Elderly Patients Undergoing Hip Fracture Surgery |
| NCT07043049 KETRA4PSAS | SIUT-ERC-2021/A-326 SIUT-ERC-2021/A-326 | Ph 3 | completed | Comparison of Prophylactic Use of Tramadol Versus Ketamine for Prevention of Post Spinal Anesthesia Shivering |
| NCT04752384 results posted | PRO00040100 | Ph 2 | completed | Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients |
| NCT06742554 | BUT002/2024 | Ph 4 | active not recruiting | Comparative Efficacy of Buprenorphine Transdermal Patch Versus Tramadol in Postoperative Analgesia for Shoulder Arthroscopy |
| NCT06722742 | #882-2023-LNH-ERC | Ph 3 | recruiting | Use of Iv Tramadol and Ketamine for Prevention of Post Spinal Anesthesia Shivering |
| NCT05995912 | LT-04-20 LT-04-20 | Ph 2 | completed | Efficacy and Safety of Etoricoxib-tramadol Tablet in Acute Postoperative Pain |
| NCT06612996 | AZAST/19/14-May-2024 | Ph 4 | not yet recruiting | Intravenous Tramadol and Magnesium Sulphate for Prevention of Shivering |
| NCT06601530 | 367860 | Ph 4 | completed | Effect of Transversus Thoracic Muscle Plane Block (TTMP) on Analgesia |
| NCT05982392 | 2889 | Ph 2, Ph 3 | completed | Effect of Preoperative Tramadol and Naproxen Sodium on Post Operative Pain |
| NCT03781544 OPIOVASC | OPIOVASC | Ph 4 | recruiting | Effects of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function |
| NCT04694300 results posted | 844440 IIR | Ph 4 | completed | OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients |
| NCT06269770 | Tapentadol | Ph 4 | recruiting | Tapentadol vs Tramadol in Total Knee Arthroplasty |
| NCT04991493 | QPOST | Ph 4 | recruiting | Effect of Tramadol on Postoperative Sore Throat After General Anesthesia |
| NCT06385561 | Tramadol_OIBD 2022-500108-23-00 | Ph 2 | completed | The Influence of Tramadol on Opioid-induced Bowel Dysfunction |
| NCT06237231 ALIV | DIT112-III-0123 | Ph 3 | not yet recruiting | Efficacy and Safety of DIT112 in the Treatment of Moderate to Severe Pain After Dental Surgery for the Extraction of Impacted Third Molars |
| NCT05237492 | 1 | Ph 4 | completed | The Influence of Tramadol on Platelet Function |
| NCT02484859 results posted | 2015/14 | Ph 4 | completed | Comparison of Metoprolol and Tramadol With Remifentanil in Endoscopic Sinus Surgery |
| NCT04593329 | EMS1519 - TIRADENTES 500/50 | Ph 2 | withdrawn | Efficacy and Safety of Tiradentes Association in the Treatment of Acute Pain |
| NCT05125978 CANADÁ | EMS1120 - CANADÁ | Ph 2 | withdrawn | Efficacy and Safety of Canadá Association in the Treatment of Chronic Pain |
| NCT05956275 | AIBU-TF-AR-AE-001 | Ph 4 | completed | USG-Guided Infiltration Popliteal Artery Capsule Knee Block Versus Adductor Canal Block Application as Postoperative Analgesia |
| NCT04766996 results posted | STUDY00002021 | Ph 4 | terminated | PROUD Study - Preventing Opioid Use Disorders |
| NCT02291705 | USG12 | Ph 4 | completed | Ultrasound-guided Rectus Sheath Block In Children |
| NCT05390905 | HSK21542-303 | Ph 3 | completed | A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in Patients for Postoperative Pain Treatment |
| NCT04613830 | 515 | Ph 3 | completed | Continuous Erector Spinae Block for Post Analgesia in Pediatric Patients |
| NCT04939987 | IRB00074034 | Ph 2, Ph 3 | withdrawn | Opioid-Free Pain Control Regiment Following Robotic Radical Prostatectomy |
| NCT01517711 results posted | INTRuST-Tramadol | Ph 4 | completed | Tramadol Extended-Release (ER) for Posttraumatic Stress Disorder (PTSD) |
| NCT05488925 | BDC/ERB/2021/016 | Ph 4 | completed | Comparison of Preoperative Analgesics on the Efficacy of Inferior Alveolar Nerve Block. |
| NCT03775629 | CG100650-1-01 | Ph 1 | completed | Drug-Drug Interaction Study of "CG100650" in Healthy Volunteers |
| NCT03477851 TramIsch | WNOZA/1/2017 | Ph 4 | completed | Tramadol Simultaneously With Sciatic Nerve Block for Calcaneus Fracture Osteosynthesis |
| NCT03586934 | ORA 17071004 | Ph 3 | withdrawn | Multimodal Analgesia in Shoulder Arthroplasty |
| NCT03472469 MAST results posted | HSC-MS-18-0036 KL2TR000370, UL1TR000371 | Ph 4 | completed | MAST Trial: Multi-modal Analgesic Strategies in Trauma |
| NCT03469310 | 1177315 | Ph 4 | completed | Minimizing Narcotic Analgesics After Endocrine Surgery |
| NCT03380533 | 2960 | Ph 2, Ph 3 | completed | Buprenorphine Transdermal Patches in Arthroscopic Rotator Cuff Repair |
| NCT03395808 results posted | AVE-901-104 | Ph 3 | completed | Evaluate Safety of Tramadol in the Management of Postoperative Pain Following Surgery |
| NCT03454217 TROXAT | CER 2017-01976 | Ph 4 | completed | Impact of Tramadol and Oxycodone on Sleep Apnea |
| NCT02247648 | unique Protocol ID | Ph 2 | terminated | Efficacy of Extended-release, Once Daily Tramadol for Post Operative Analgesia in Shoulder Arthroscopy |
| NCT03509740 | dysmenorrhea | Ph 4 | completed | Intravenous Tramadol Versus Intravenous Paracetamol in Patients With Dysmenorrhea |
| NCT03290378 results posted | AVE-901-102 | Ph 3 | completed | Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy |
| NCT04178109 | 17200 | Ph 2 | completed | Oral Use of Dexketoprofen/Tramadol for Acute Postoperative Pain in Total Hip Replacement With a Direct Anterior Approach. |
Showing 50 of 90 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.
TRAMADOL HYDROCHLORIDE FDA Label Details
Indications & Usage
FDA Label (PDF)TRAMADOL HYDROCHLORIDE is indicated for the treatment of Pain.
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride extended-release tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead...
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ULTRAM
Full clinical data, patents, trials, and competitive landscape for tramadol 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