Last reviewed 2026-04-20 · How we verify

Ultram (tramadol)

At a glance

Approved indications

• Chronic pain
• Osteoarthritis
• Pain

Boxed warnings

• 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, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions (5.4)] . Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions (5.5)] . Ultra-Rapid Metabolism Of Tramadol And Other Risk Factors For Life-Threatening Respiratory Depression In Children Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy, and in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism [ see Warnings and Precautions (5.6) ]. Tramadol hydrochloride extended-release tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [ see Contraindications (4) ] . Avoid the use of tramadol hydrochloride extended-release tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol. [see Warnings and Precautions (5.6)] Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride extended-release tablets requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 [see Warnings and Precautions (5.7), Drug Interactions (7)] . WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS See full prescribing information for complete boxed warning . Tramadol hydrochloride extended-release tablets expose users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and reassess regularly for these behaviors and conditions. (5.1) Serious, life-threatening, or fatal respiratory depression may occur, especially upon initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration are essential. Instruct patients to swallow tramadol hydrochloride extended-release tablets whole to avoid exposure to a potentially fatal dose of tramadol. (5.2) Accidental ingestion of tramadol hydrochloride extended-release tablets, especially by children, can result in a fatal overdose of tramadol. (5.2) 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 for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.3, 7) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be lifethreatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. (5.4) • Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription (5.5). Tramadol hydrochloride extended-release tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. (4) Avoid the use of Tramadol hydrochloride extended-release tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol. (5.6) The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride extended-release tablets requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 (5.7, 7)

Common side effects

• Dizziness/Vertigo
• Nausea
• Constipation
• Headache
• Somnolence
• Vomiting
• Pruritus

Serious adverse events

• Serotonin syndrome
• Seizure
• Anaphylaxis
• Stevens-Johnson syndrome/Toxic epidermal necrolysis
• Suicidal tendency
• Death
• Syncope
• Hallucinations
• Dyspnea
• Orthostatic hypotension

Key clinical trials

• Comparison of Magnesium Sulphate vs Tramadol as Adjuvants in Intrathecal Bupivacaine for Postoperative Pain in TURP Patients (Phase 4)
• Comparative Study of Ultrasound-guided Paravertebral Block Versus Intravenous Tramadol for Postoperative Pain Control in Percutaneous Nephrolithotomy (Phase 4)
• NCT02801968 (NA)
• Effect of Tramadol or Magnesium in Local Anesthetic Solution on Ultrasound-guided Bilateral TAP Block During Robotic Radical Prostatectomy on Acute Perioperative Pain and Chronic Postoperative Pain. (NA)
• Comparative Study of Conventional and Topical Heparin Treatments in Second Degree Burn Patients for Burn Analgesia and Duration of Wound Healing (NA)
• Erector Spinae Plane Block Versus Thoracic Paravertebral Block in Laparoscopic Cholecystectomy: A Randomized Controlled Trial on Opioid Consumption (NA)
• Cognitive Function and Addiction in Patients With Chronic Pain Under Opioid Tapering in a Multidisciplinary Pain Treatment (Phase 3)
• Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes (NA)

Primary sources

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