Tramadol
/api/v1/drug/tramadolBoxed 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)] .
Mechanism of action
Sourced from openFDATramadol hydrochloride extended-release tablets contain tramadol, an opioid agonist and an inhibitor of reuptake of norepinephrine and serotonin. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to μ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.
Indications
Sourced from openFDA- Tramadol hydrochloride extended-release tablets are 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 dosages or duration, and persist over the course of therapy, [see Warnings and Precautions (5.1)], reserve opioid analgesics, including tramadol hydrochloride extended-release tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.
Contraindications
Sourced from openFDA- Tramadol hydrochloride extended-release tablets are contraindicated for: all children younger than 12 years of age [see Warnings and Precautions (5.4)] post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.4)] . Tramadol hydrochloride extended-release tablets are also contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.3)] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.12)] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.15)] Hypersensitivity to tramadol (e.g., anaphylaxis) [see Warnings and Precautions (5.17), Adverse Reactions (6.2)] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7)] .contraindicated
Dosage & administration
Sourced from openFDATramadol hydrochloride extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. (2.1) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of tramadol hydrochloride extended-release tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. (2.1, 5) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. (2.1, 5.1) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tramadol hydrochloride extended-release tablets. Consider this risk when selecting an initial dose and when making dose adjustments. (2.1, 5.2) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with tramadol hydrochloride extended-release tablets, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. (2.2, 5.1, 5.2, 5.3) Tramadol hydrochloride extended-release tablets should be taken once daily, at approximately the same time every day.
Warnings & precautions
Sourced from openFDAOpioid Induced Hyperalgesia (OIH) and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation (5.8) Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue tramadol hydrochloride extended-release tablets if serotonin syndrome is suspected. (5.9) Increased Risk of Seizures : Present within recommended dosage range. Risk is increased with higher than recommended doses and concomitant use of SSRIs, SNRIs, anorectics, tricyclic antidepressants and other tricyclic compounds, other opioids, MAOIs, neuroleptics, other drugs that reduce seizure threshold, in patients with epilepsy or at risk for seizures. (5.10, 7) Risk of Suicide : Do not use tramadol hydrochloride extended-release tablets in suicidal or addiction-prone patients. Use with caution in those taking tranquilizers, antidepressants or abuse alcohol. (5.11) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Regularly evaluate closely, particularly during initiation and titration. (5.12) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.13) Severe Hypotension : Regularly evaluate during dosage initiation and titration.
Adverse reactions
Sourced from openFDAThe following serious or otherwise important adverse reactions are described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see Warnings and Precautions (5.6)] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)] Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions (5.3)] Opioid-Induced Hyperalgesia and Allodynia [See Warnings and Precautions (5.8)] Serotonin Syndrome [see Warnings and Precautions (5.9)] Seizures [see Warnings and Precautions (5.10)] Suicide [see Warnings and Precautions (5.11)] Adrenal Insufficiency [see Warnings and Precautions (5.13)] Severe Hypotension [see Warnings and Precautions (5.14)] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.16)] Hypersensitivity Reactions [see Warnings and Precautions (5.17)] Withdrawal [see Warnings and Precautions (5.18)] Most common adverse reactions (≥10% and ≥2 x placebo rate): Dizziness, constipation, nausea, headache, somnolence, flushing, pruritus, vomiting, insomnia, dry mouth. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Use in specific populations
Sourced from openFDAPregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) Severe Hepatic or Renal Impairment: Use not recommended. ( 8.6 , 8.7 ) 8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4)] . Available data with tramadol hydrochloride extended-release tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, tramadol administration during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD). Tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the MRHD [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Pharmacokinetics
Sourced from openFDA- Metabolism
- The analgesic activity of tramadol is due to both parent drug and the M1 metabolite. Tramadol hydrochloride extended-release tablet is administered as a racemate and both the [-] and [+] forms of both tramadol and M1 are detected in the circulation.
Overdosage
Sourced from openFDAClinical Presentation Acute overdosage with tramadol hydrochloride extended-release tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, QT prolongation, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures.
Approval history
Sourced from openFDA- Jun 19, 2002ANDAANDA075977Teva
- Jun 20, 2002ANDAANDA076003Amneal Pharms
- Jun 25, 2002ANDAANDA075968Graviti Pharms
- Dec 9, 2009ANDAANDA090485Amneal Pharms
- May 7, 2010NDANDA022370Cipher Pharms Inc
- Aug 29, 2011ANDAANDA200503Lupin Ltd
- Nov 28, 2011ANDAANDA202075Strides Pharma
- Sep 1, 2020NDANDA214044Rosemont
FAERS reports
- 1Dependence7,82321%
- 2Overdose3,88910%
- 3Vomiting3,3298.9%
- 4Pain3,0278.0%
- 5Nausea2,8657.6%
- 6Drug Ineffective2,6377.0%
- 7Headache2,3836.3%
- 8Dyspnoea2,3696.3%
- 9Fatigue2,3516.3%
- 10Off Label Use2,3476.2%
- 11Drug Hypersensitivity2,1845.8%
- 12Drug Dependence2,1795.8%
- 13Dizziness2,0525.5%
- 14Arthralgia2,0115.3%
- 15Malaise1,9975.3%
Literature
Recent PubMed references pinned to Tramadol as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.
- Tramadol Eye Drop Reduces Ocular Nocifensive Behavior Not Primarily Mediated by μ-Opioid Receptor Activation in a Rat Dry Eye Model.Biological & pharmaceutical bulletin · 2026 · Nagaoka S, Takai Y, Kiyoi T, et al.PMID 42128871DOI 10.1248/bpb.b26-00041
- Activation of TGF-β/ALK5/SMAD signaling alleviates behavioral and neurochemical deficits in tramadol withdrawal.Toxicology and applied pharmacology · 2026 · Wani SN, Grewal AK, Sharma O, et al.PMID 42097514DOI 10.1016/j.taap.2026.117849
- Comparative risk of psychiatric comorbidities associated with codeine and tramadol in patients with hip osteoarthritis: a nationwide population-based cohort study.Journal of global health · 2026 · Kim Y, Choo E, Shin S, et al.PMID 42024864DOI 10.7189/jogh.16.04121
- Development and validation of ratio spectra manipulation methods for the determination of etoricoxib and tramadol in binary mixtures.Scientific reports · 2026 · Al Kamaly O, Sayedahmed M, Abdelzaher AM, et al.PMID 42010288DOI 10.1038/s41598-026-49144-4
- Chrysin attenuates tramadol-driven renal dysfunction via regulation of RNA networks, antioxidant pathways, and ketogenic metabolism.European journal of pharmacology · 2026 · Öz MA, Kandemir Ö, Özdemir S, et al.PMID 42002091DOI 10.1016/j.ejphar.2026.178882
- Review of Structural Modification and Development of Novel Tramadol Derivatives.Molecules (Basel, Switzerland) · 2026 · Wang N, Zhou X, Wang J, et al.PMID 41976217DOI 10.3390/molecules31071177
- Behavioral and cardiorespiratory effects of a medetomidine and tramadol combination in horses.Journal of veterinary science · 2026 · Kim A, Lee I, Lee K, et al.PMID 41947678DOI 10.4142/jvs.25252
- Long-term tramadol use increases the risk of depression in patients with musculoskeletal pain: A retrospective cohort study.Journal of affective disorders · 2026 · Lee JE, Kim HJ, Park SJ, et al.PMID 41921874DOI 10.1016/j.jad.2026.121715
Clinical trials
The 10 most recently updated of 660 ClinicalTrials.gov registrations naming Tramadol as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- Ultrasound-Guided Regional Blocks for Postoperative Analgesia After Laparoscopic CholecystectomyRecruiting · Interventional · 90 enrolled · Istanbul Medipol University HospitalNCT07321639updated 2026-06-11
- KinesioTaping for Thoracic Drain SupportCompleted · Phase 2 · Phase 3 · Interventional · 100 enrolled · Kastamonu UniversityNCT07098962updated 2026-06-09
- Comparison of IV Analgesia Protocols After the Regional Block's Effect Diminishes in Thoracic SurgeryRecruiting · Interventional · 135 enrolled · Ankara Etlik City HospitalNCT07610408updated 2026-06-09
- Effect of Abdominal Ice Pack After vNOTES HysterectomyEnrolling by invitation · Interventional · 122 enrolled · Erzincan Military HospitalNCT07626684updated 2026-06-04
- An Efficacy and Safety Study of Tramadol/Acetaminophen Versus Diclofenac in the Treatment of Pain in Participants With Ankylosing Spondylitis Receiving Stable Treatment of Disease Modifying Anti-rheumatic Drugs (DMARDs)Terminated · Phase 4 · Interventional · 8 enrolled · Johnson & Johnson Taiwan LtdNCT00766402updated 2026-06-04
- Efficacy of Transversus Abdominis Plane Block in Alleviating Acute AppendicitisCompleted · Interventional · 105 enrolled · Ankara City Hospital BilkentNCT06808737updated 2026-06-04
- Interscalene Brachial Plexus Block and Early Wound-Related Symptoms After Open Rotator Cuff RepairCompleted · Interventional · 34 enrolled · Yuzuncu Yil UniversityNCT05499897updated 2026-06-04
- Dexmedetomidine vs Tramadol for Anxiety, Pain, and Hemodynamics in HemorrhoidectomyActive not recruiting · Interventional · 90 enrolled · Yuzuncu Yil UniversityNCT06860100updated 2026-06-03
- Suzetrigine for Opioid-Sparing Postoperative Analgesia Following Transvaginal Pelvic Reconstructive SurgeryNot yet recruiting · Phase 4 · Interventional · 120 enrolled · University of California, Los AngelesNCT07600697updated 2026-06-02
- Clinical Study of HRS-2129 for Postoperative Analgesia in OrthopaedicsCompleted · Phase 1 · Phase 2 · Interventional · 199 enrolled · Shandong Suncadia Medicine Co., Ltd.NCT06780267updated 2026-06-02
Pharmacogenomics
CPIC-curated drug–gene pairs for Tramadol. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.
- COMTCPIC CClinPGx 3
- CYP2D6CPIC AClinPGx 1AFDA label: Actionable PGx
- OPRM1CPIC CClinPGx 3
Frequently asked questions
- How does Tramadol work?
- Tramadol hydrochloride extended-release tablets contain tramadol, an opioid agonist and an inhibitor of reuptake of norepinephrine and serotonin. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to μ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.
- What is Tramadol used for?
- According to FDA labeling, Tramadol carries indications including: Tramadol hydrochloride extended-release tablets are 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 dosages or duration, and persist over the course of therapy, [see Warnings and Precautions (5.1)], reserve opioid analgesics, including tramadol hydrochloride extended-release tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Tramadol?
- Tramadol is classified as Other opioids, Opioid Agonist, Full Opioid Agonists, Analgesia, Decreased Organized Electrical Activity, Increased Norepinephrine Activity, Increased Serotonin Activity.
- What are the brand names for Tramadol?
- Tramadol is marketed under brand names including ConZip, Qdolo, Seglentis, Ultracet, Ultram.
- What are the contraindications for Tramadol?
- Tramadol labeling lists contraindications including: Tramadol hydrochloride extended-release tablets are contraindicated for: all children younger than 12 years of age [see Warnings and Precautions (5.4)] post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.4)] . Tramadol hydrochloride extended-release tablets are also contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.3)] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.12)] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.15)] Hypersensitivity to tramadol (e.g., anaphylaxis) [see Warnings and Precautions (5.17), Adverse Reactions (6.2)] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7)] .. Always consult the full prescribing information and a clinician.
tramadol is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.