Label: TRAMADOL HYDROCHLORIDE Tablet, Film Coated - DailyMed

These highlights do not include all the information needed to use TRAMADOL HYDROCHLORIDE TABLETS safely and effectively. See full prescribing information for TRAMADOL HYDROCHLORIDE TABLETS. TRAMADOL HYDROCHLORIDE tablets, for oral use, C-IVInitial U.S. Approval: 1995. WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE TABLETS See full prescribing information for complete boxed warning.

• Tramadol hydrochloride tablets expose users to the risks of addiction, abuse and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing tramadol hydrochloride tablets, and monitor regularly for these behaviors or conditions. (5.1)
• Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially during initiation or following a dose increase. (5.3)
• Accidental ingestion of tramadol hydrochloridetablets, especially by children, can result in a fatal overdose of tramadol. (5.3)
• 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. (5.7, 7)
• 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. (5.4)
• To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. (5.2)
• Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism (5.4).
• Tramadol hydrochloridetablets 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 hydrochloridetablets 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. (5.4)
• 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 hydrochloridetablets requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.(5.6, 7)

RECENT MAJOR CHANGES

Boxed Warning	10/2025
Indications and Usage (1)	10/2025
Dosage and Administration (2.2, 2.5)	10/2025
Warnings and Precaution (5.1, 5.2, 5.3, 5.16, 5.18)	10/2025

INDICATIONS AND USAGE

Tramadol hydrochloride tablets are opioid agonist indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Limitations of Use

Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions (5.1)], reserve opioid analgesics, including tramadol hydrochloride, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

DOSAGE AND ADMINISTRATION

• Periodically reassess patients receiving tramadol hydrochloride to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. (2.4).
• Tramadol hydrochloride tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. (2.1)
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals (2.1). Reserve titration to higher doses of tramadol hydrochloride 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 severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse (2.1, 5.1).
• Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. (2.1)
• 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 tablets. Consider this risk when selecting an initial dose and when making dose adjustments. (2.1, 5.2)
• Start at 25 mg/day and titrate in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg four times a day). Thereafter the total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg four times a day). After titration, tramadol hydrochloride, tablets 50 mg to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day (2.3, 2.4).
• Severe Renal Impairment: increase the tramadol hydrochloride tablets, dosing interval to 12 hours, and limit maximum daily dose to 200 mg (2.3).
• Severe hepatic impairment: Recommended dose is 50 mg every 12 hours.
• 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 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).
• Do not rapidly reduce or abruptly discontinue tramadol hydrochloride, in a physically-dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide (2.3, 5.18).

DOSAGE FORMS AND STRENGTHS

•   Tablets: tramadol hydrochloride 50 mg (3).

CONTRAINDICATIONS

• Children younger than 12 years of age (4).
• Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (4).
• Significant respiratory depression (4).
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (4).
• Known or suspected gastrointestinal obstruction, including paralytic ileus (4).
• Hypersensitivity to tramadol, any other component of this product or opioids (4).
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (4).

WARNINGS AND PRECAUTIONS

•   Opioid-Induced Hyperalgesia 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: May be life-threatening. Can occur with use of tramadol alone, with concomitant use of serotonergic drugs, with drugs that impair metabolism of serotonin or tramadol (5.9).
•   Risk of Seizure: Can occur at the recommended dose of tramadol.
•   Concomitant use with other drugs may increase seizure risk. Risk may increase in patients with epilepsy, a history of seizures, and in patients with a recognized risk for seizures (5.10).
•   Risk of Suicide: Do not prescribe for suicidal or addiction-prone patients (5.11).
•   Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off the opioid (5.13).
•   Life-Threatening Respiratory Depression in Patients with ChronicPulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Regularly evaluate, particularly during initiation and titration (5.12).
•   Severe Hypotension: Regularly evaluate during dosage initiation and titration. Avoid use of tramadol hydrochloride tablets in patients with circulatory shock (5.14).
•   Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Regularly evaluate for sedation and respiratory depression. Avoid use of tramadol hydrochloride tablets in patients with impaired consciousness or coma (5.15).

ADVERSE REACTIONS

The most common incidence of treatment-emergent adverse events (≥15.0%) in patients from clinical trials were dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting and pruritus. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Unichem Pharmaceuticals (USA) Inc. at 1-866-562-4616 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch  (6)

DRUG INTERACTIONS

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with tramadol hydrochloride tablets because they may reduce analgesic effect of tramadol hydrochloride or precipitate withdrawal symptoms. (7)

USE IN SPECIFIC POPULATIONS

• Pregnancy : May cause fetal harm (8.1).
• Lactation : Breastfeeding not recommended (8.2).

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 2/2026