Plain-language summary, compiled from the cited regulatory records
Tramadol hydrochloride is an opioid analgesic [1]. It belongs to the drug class of other opioids (N02AX) [1].
Tramadol hydrochloride extended-release tablets are approved for managing severe and persistent pain that requires an opioid analgesic and cannot be adequately treated with alternative options, including immediate-release opioids [1]. However, due to the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist throughout therapy, its use should be carefully considered [1].
In the last 12 months, there have been 2,310 adverse event reports associated with tramadol [2]. The most frequently reported adverse events include vomiting, off-label use, pneumonia, pain, and wheezing [2].
This is not medical advice. Consult a qualified healthcare professional.
GBOfficial regulatory label· revised June 2, 2026[1]
Treatment of moderate to severe pain
How to take
GBOfficial regulatory label
USUnited States· FDA
25 products
Uses
USOfficial regulatory label· revised April 10, 2026[2]
1 INDICATIONS AND USAGE Tramadol hydrochloride tablets are indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate ( 1 ). 1 ). 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.
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.
How to take
Drug interactions
Known interactions involving Tramadol. Select one for details. This list is informational and not a complete interaction checker.
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Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[2]FDA DailyMed · 007bf37f-0e46-42… · revised April 10, 2026 [PDF]
[3]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
4). Posology The dose should be adjusted to the intensity of the pain and the sensitivity of the individual patient. The lowest effective dose for analgesia should generally be selected. The total daily dose of 400 mg active substance should not be exceeded, except in special circumstances.
Unless otherwise prescribed, tramadol should be administered as follows:
Adults and adolescents above the age of 12 years: The usual initial dose is 50-100 mg tramadol hydrochloride SUN twice daily, morning and evening. 1). Children Tramadol is not suitable for children below the age of 12 years. Geriatric patients A dose adjustment is not usually necessary in patients up to 75 years without clinically manifest hepatic or renal insufficiency.
In elderly patients over 75 years elimination may be prolonged. Therefore, if necessary the dosage interval is to be extended according to the patient's requirements. Renal insufficiency/dialysis and hepatic insufficiency In patients with renal and/or hepatic insufficiency the elimination of tramadol is delayed.
In these patients prolongation of the dosage interval should be carefully considered according to the patients requirements. In cases of severe renal and/or severe hepatic insufficiency tramadol tablets are not recommended. Method of administration The tablets are to be taken whole, not divided or chewed, with sufficient liquid, independent of meals.
Treatment goals and discontinuation Before initiating treatment with tramadol, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.
During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with tramadol, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
4).
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised June 2, 2026[1]
The most commonly reported adverse reactions are nausea and dizziness, both occurring in more than 10 % of patients.
The frequencies are defined as follows:
Very common: ≥1/10 Common: ≥1/100, <1/10 Uncommon: ≥1/1000, <1/100 Rare: ≥1/10 000, <1/1000 Very rare: <1/10 000 Not known: cannot be estimated from the available data Cardiac disorders: Uncommon: cardiovascular regulation (palpitation, tachycardia).
These adverse reactions may occur especially on intravenous administration and in patients who are physically stressed.
Rare: bradycardia Investigations:
Rare: increase in blood pressure Vascular disorders: Uncommon: cardiovascular regulation (postural hypotension or cardiovascular collapse). These adverse reactions may occur especially on intravenous administration and in patients who are physically stressed.
5), respiratory depression may occur. Worsening of asthma has been reported, though a causal relationship has not been established.
Rare: hallucinations, confusion, sleep disturbance, delirium, anxiety and nightmares. Psychic adverse reactions may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of treatment).
g. decision behaviour, perception disorders). g. pruritus, rash, urticaria) Musculoskeletal and connective tissue disorders: Rare: motorial weakness Hepatobiliary disorders: In a few isolated cases an increase in liver enzyme values has been reported in a temporal connection with the therapeutic use of tramadol.
g. dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis Metabolism and nutrition disorders: Not known: hypoglycaemia General disorders and administration site conditions: Common: fatigue Uncommon: drug withdrawal syndrome.
Symptoms of drug withdrawal syndrome, similar to those occurring during opiate withdrawal, may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms. e. confusion, delusions, depersonalisation, derealisation, paranoia).
Drug dependence:
Repeated use of tramadol can lead to drug dependence, even at therapeutic doses. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised June 2, 2026[1]
Tramadol may only be used with particular caution in opioid-dependent patients, patients with head injury, shock, a reduced level of consciousness of uncertain origin, disorders of the respiratory centre or function, increased intracranial pressure.
In patients sensitive to opiates tramadol should only be used with caution. Concomitant use of tramadol and sedating medicinal products such as benzodiazepines or related substances, may result in sedation, respiratory depression, coma and death.
Because of these risks, concomitant prescribing with these sedating medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe tramadol concomitantly with sedating medicinal products, the lowest effective dose of tramadol should be used, and the duration of the concomitant treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). 9) as the possibility of respiratory depression cannot be excluded in these situations. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia.
Opioid use increases the risk of CSA in a dose- dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. Convulsions have been reported in patients receiving tramadol at the recommended dose levels.
The risk may be increased when doses of tramadol exceed the recommended upper daily dose limit (400 mg). 5). Patients with epilepsy or those susceptible to seizures should be only treated with tramadol if there are compelling circumstances.
9). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose escalations. Symptoms of serotonin syndrome may include mental status changes, autonomic instability, neuromuscular abnormalities and/or gastrointestinal symptoms.
Serotonin syndrome is likely when one of the following is observed: - Spontaneous clonus - Inducible or ocular clonus with agitation or diaphoresis - Tremor and hyperreflexia - Hypertonia and body temperature > 38 °C and inducible or ocular clonus If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised June 2, 2026[1]
5), - in patients with epilepsy not adequately controlled by treatment, - for use in narcotic withdrawal treatment.
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised April 10, 2026[2]
2 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.
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. 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.
1 ). , 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.
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. 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 ) 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).
4 ). 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.
3 ). 18 ). 1 Important Dosage and Administration Instructions Do not use tramadol hydrochloride tablets concomitantly with other tramadol-containing products. Do not administer tramadol hydrochloride tablets at a dose exceeding 400 mg per day.
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. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions ( 5 )] .
Because the risk of overdose increases as opioid doses increase, 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.
, 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.
There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. 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 [see Warnings and Precautions ( 5 )] . ,naloxone, nalmefene). , concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.
3 )] . 2 )] . There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.
3 Initial Dosage Initiating Treatment with tramadol hydrochloride tablets Initiate treatment with tramadol hydrochloride tablets in a dosing range of 50 mg to 100 mg every 4 to 6 hours as needed for pain, and at the lowest dose necessary to achieve adequate analgesia.
Titrate the dose based upon the individual patient's response to their initial dose of tramadol hydrochloride tablets. For patients not requiring rapid onset of analgesic effect, the tolerability of tramadol hydrochloride tablets can be improved by initiating therapy with the following titration regimen: Start tramadol hydrochloride tablets at 25 mg/day and titrated 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 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day.
For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, tramadol hydrochloride tablets 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day.
Conversion from Tramadol to Extended-Release Tramadol The relative bioavailability of tramadol compared to extended-release tramadol is unknown, so conversion to extended-release formulations may lead to increased risk of excessive sedation and respiratory depression.
Dosage Modification in Patients with Hepatic Impairment The recommended dose for adult patients with severe hepatic impairment is 50 mg every 12 hours. Dosage Modification in Patients with Renal Impairment In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200 mg.
Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis. Dosage Modification in Geriatric Patients Do not exceed a total dose of 300 mg/day in patients over 75 years old.
4 Titration and Maintenance of Therapy Individually titrate tramadol hydrochloride tablets to a dose that provides adequate analgesia and minimizes adverse reactions. 18) ] . Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.
If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the tramadol hydrochloride tablets dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage [see Warnings and Precautions (5) ] .
Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. 5 Safe Reduction or Discontinuation of tramadol hydrochloride Do not rapidly reduce or abruptly discontinue tramadol hydrochloride in patients who may be physically dependent on opioids.
Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking tramadol hydrochloride tablets, there are a variety of factors that should be considered, including the total daily dose of opioid (including tramadol hydrochloride tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.
It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder.
Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients.
Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. , no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks.
Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with a lower dosage strength to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge.
Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper.
3 )] .
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 2,310 reports total. [3]
Vomiting 565
Off Label Use 485
Pneumonia 452
Pain 449
Wheezing 446
Drug Hypersensitivity 432
Dyspnoea 421
Oedema 382
Rash 371
Wound 354
Drug Ineffective 345
Asthma 344
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised April 10, 2026[2]
0%) in patients from clinical trials were dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting and pruritus. To report SUSPECTED ADVERSE REACTIONS, contact Unichem Pharmaceuticals (USA) Inc. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. Table 1 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days).
The most frequently reported events were in the central nervous system and gastrointestinal system. Although the reactions listed in the table are felt to be probably related to tramadol hydrochloride tablets administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication.
The overall incidence rates of adverse experiences in these trials were similar for tramadol hydrochloride tablets and the active control groups, TYLENOL with Codeine #3 (acetaminophen 300 mg with codeine phosphate 30 mg), and aspirin 325 mg with codeine phosphate 30 mg, however, the rates of withdrawals due to adverse events appeared to be higher in the tramadol hydrochloride tablets groups.
Table 1:
Cumulative Incidence of Adverse Reactions for tramadol hydrochloride tablets in Chronic Trials of Nonmalignant Pain (N=427) Up to 7 days Up to 30 days Up to 90 days Dizziness/Vertigo 26% 31% 33% Nausea 24% 34% 40% Constipation 24% 38% 46% Headache 18% 26% 32% Somnolence 16% 23% 25% Vomiting 9% 13% 17% Pruritus 8% 10% 11% "CNS Stimulation" 1 7% 11% 14% Asthenia 6% 11% 12% Sweating 6% 7% 9% Dyspepsia 5% 9% 13% Dry Mouth 5% 9% 10% Diarrhea 5% 6% 10% 1 "CNS Stimulation" is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinations Incidence 1% to Less than 5% Possibly Causally Related The following lists adverse reactions that occurred with an incidence of 1% to less than 5% in clinical trials, and for which the possibility of a causal relationship with tramadol hydrochloride tablets exists.
Menopausal symptoms, Urinary frequency, Urinary retention. Incidence Less than 1%, Possibly Causally Related The following lists adverse reactions that occurred with an incidence of less than 1% in clinical trials of tramadol and/or reported in post-marketing experience with tramadol-containing products.
Dysuria, Menstrual disorder. Other Adverse Experiences, Causal Relationship Unknown A variety of other adverse events were reported infrequently in patients taking tramadol hydrochloride tablets during clinical trials and/or reported in post-marketing experience.
A causal relationship between tramadol hydrochloride tablets and these events has not been determined. However, the most significant events are listed below as alerting information to the physician.
Cataracts, Deafness, Tinnitus. 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of tramadol hydrochloride tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Serotonin syndrome :
Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency :
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. 2) ] . 8 )] QT prolongation/torsade de pointes : Cases of QT prolongation and/or torsade de pointes have been reported with tramadol use.
, hypokalemia), or in the overdose setting. 20 )] .
Hypoglycemia:
Cases of hypoglycemia have been reported in patients taking tramadol. 21 )] . 16 )] . Adverse Reactions from Observational Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021.
Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90- day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244).
Those included also had no dispensing of the qualifying opioids in the previous 6 months. 2 )] , respectively, as measured with a validated self-reported instrument. A retrospective, observational cohort study estimated the risk of opioid involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249).
Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days' supply over the 3 months prior to study entry and none during the preceding 6 months.
Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. 5% to 4% across study sites, counting only the first event during follow-up.
Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involved overdose or opioid overdose-related death.
Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates. The risk estimates from the studies described above may not be generalizable to all patients receiving opioid analgesics, such as those with exposures shorter or longer than the duration evaluated in the studies.
USOfficial regulatory label· Warnings and precautions· revised April 10, 2026[2]
5 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.
8 ) Serotonin Syndrome : May be life-threatening. 9 ).
Risk of Seizure :
Can occur at the recommended dose of tramadol. Concomitant use with other drugs may increase seizure risk. 10 ). 11 ). 13 ). 12 ).
Severe Hypotension :
Regularly evaluate during dosage initiation and titration. 14 ). Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Regularly evaluate for sedation and respiratory depression.
15 ). 1 Addiction, Abuse and Misuse Tramadol hydrochloride tablet contains tramadol, a Schedule IV controlled substance. As an opioid, tramadol hydrochloride tablets exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9) ] .
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed tramadol hydrochloride tablets. Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy.
2 )] . Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing tramadol hydrochloride tablets, and reassess all patients receiving tramadol hydrochloride tablets for the development of these behaviors and conditions.
, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as tramadol hydrochloride tablets, but use in such patients necessitates intensive counseling about the risks and proper use of tramadol hydrochloride tablets along with frequent reevaluation for signs of addiction, abuse, and misuse.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised April 10, 2026[2]
4 )]. 4 )] . 3 )]. 12) ] . 15 )]. 16 )]. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7) ]. 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 ).
This is not medical advice. Consult a qualified healthcare professional.
Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as tramadol PR.
Repeated use of tramadol can lead to opioid use disorder (OUD). A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of tramadol may result in overdose and/or death.
g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should be advised to contact their physician.
g. too early requests for refills). This includes the review of concomitant opioids and psychoactive drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.
Drug withdrawal syndrome Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with tramadol. Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction.
When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months. The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations.
Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome. Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms.
Hyperalgesia Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be […]
3 )]. Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing DEMEROL Tablets and Oral Solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug.
Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient's clinical status [see Overdosage( 10 )] .
Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of tramadol hydrochloride tablets, the risk is greatest during the initiation of therapy or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride tablets are essential [see Dosage and Administration ( 2 )] . Overestimating the tramadol hydrochloride tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of tramadol hydrochloride tablets, especially by children, can result in respiratory depression and death due to an overdose of tramadol. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information ( 17 )].
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. 5 )]. , naloxone, nalmefene). , concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.
3 )] . , prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.
Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Educate patients and caregivers on how to recognize respiratory depression, and how to use an opioid overdose reversal agent for the emergency treatment of opioid overdose.
3 ), Overdosage ( 10 )]. , non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7) ] .
If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.
If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation).
3 ), Overdosage ( 10 )]. Advise both patients and caregivers about the risks of respiratory depression and sedation when tramadol hydrochloride tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).
Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [ see Drug Interactions (7) ; and Patient Counseling Information (17) ] .
4 Neonatal Opioid Withdrawal Syndrome Use of tramadol hydrochloride tablets for an extended period of time during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. 1) and Patient Counseling Information (17) ] . 5 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) 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.
Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.
Healthcare providers are strongly encouraged to do all of the following:
Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. gov/OpioidAnalgesicREMSPC G . Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities. com . gov/OpioidAnalgesicREMSBlueprint . 6 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.
Tramadol and codeine are subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to increased exposure to an active metabolite. Based upon post-marketing reports with tramadol or with codeine, children younger than 12 years of age may be more susceptible to the respiratory depressant effects of tramadol.
Furthermore, children with obstructive sleep apnea who are treated with opioids for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to their respiratory depressant effect.
Because of the risk of life-threatening respiratory depression and death:
Tramadol hydrochloride tablets are contraindicated for all children younger than 12 years of age [see Contraindications (4) ]. Tramadol hydrochloride tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4) ].
Avoid the use of tramadol hydrochloride 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 unless the benefits outweigh the risks.
Risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.
4) , Overdosage (10) ]. Nursing Mothers Tramadol is subject to the same polymorphic metabolism as codeine, with ultra-rapid metabolizers of CYP2D6 substrates being potentially exposed to life-threatening levels of the active metabolite O -desmethyltramadol (M1).
At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra- rapid metabolizer of codeine. A baby nursing from an ultra-rapid metabolizer mother taking tramadol hydrochloride tablets could potentially be exposed to high levels of M1, and experience life-threatening respiratory depression.
2) ] . , gene duplications denoted as *1/*1xN or *1/*2xN). , Oceanian, Northern African, Middle Eastern, Ashkenazi Jews, Puerto Rican). These individuals convert tramadol into its active metabolite, O -desmethyltramadol (M1), more rapidly and completely than other people.
This rapid conversion results in higher than expected serum M1 levels. Even at labeled dosage regimens, individuals who are ultra- rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing) [see Overdosage (10) ] .
Therefore, individuals who are ultra-rapid metabolizers should not use tramadol hydrochloride tablets. 7 Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors on levels of tramadol and M1 from tramadol hydrochloride tablets are complex.
Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride tablets requires careful consideration of the effects on the parent drug, tramadol which is a weak serotonin and norepinephrine reuptake inhibitor and µ-opioid agonist, and the active metabolite, M1, which is more potent than tramadol in µ-opioid receptor binding [see Drug Interactions (7) ] .
, amiodarone, quinidine) may result in an increase in tramadol plasma levels and a decrease in the levels of the active metabolite, M1. A decrease in M1 exposure in patients who have developed physical dependence to tramadol, may result in signs and symptoms of opioid withdrawal and reduced efficacy.
The effect of increased tramadol levels may be an increased risk for serious adverse events including seizures and serotonin syndrome. Discontinuation of a concomitantly used cytochrome P450 2D6 inhibitor may result in a decrease in tramadol plasma levels and an increase in active metabolite M1 levels, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression.
Evaluate patients receiving tramadol hydrochloride tablets and any CYP2D6 inhibitor at frequent intervals for the risk of serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity, and opioid withdrawal when tramadol hydrochloride tablets are used in conjunction with inhibitors of CYP2D6 [see Drug Interactions (7) ] .
, ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in tramadol plasma concentrations, which could increase or prolong adverse reactions, increase the risk for serious adverse events including seizures and serotonin syndrome, and may cause potentially fatal respiratory depression.
The concomitant use of tramadol hydrochloride tablets with all cytochrome P450 3A4 inducers or discontinuation of a cytochrome P450 3A4 inhibitor may result in lower tramadol levels. This may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal.
Evaluate patients receiving tramadol hydrochloride tablets and any CYP3A4 inhibitor or inducer at frequent intervals for the risk for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity and opioid withdrawal when tramadol hydrochloride tablets are used in conjunction with inhibitors and inducers of CYP3A4 [see Drug Interactions (7) ] .
8 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. 3 )] . Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia).
These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics.
Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. 18 )] . 9 Serotonin Syndrome Risk Cases of serotonin syndrome, a potentially life-threatening condition, have been reported with the use of tramadol, particularly during concomitant use with serotonergic drugs.
, cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7) ] .
This may occur within the recommended dosage range. , nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue tramadol hydrochloride tablets if serotonin syndrome is suspected.
10 Increased Risk of Seizure Seizures have been reported in patients receiving tramadol hydrochloride tablets within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol hydrochloride tablets above the recommended range.
8 ); Drug Interactions ( 7 )]. Neuroleptics, or Other drugs that reduce the seizure threshold. Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections).
, naloxone or nalmefene) may increase the risk of seizure. 11 Suicide Risk Do not prescribe tramadol hydrochloride tablets for patients who are suicidal or addiction-prone. Consideration should be given to the use of non-narcotic analgesics in patients who are suicidal or depressed [see Drug Abuse and Dependence (9) ].
Prescribe tramadol hydrochloride tablets with caution for patients with a history of misuse and/or are currently taking CNS-active drugs including tranquilizers or antidepressant drugs, alcohol in excess, and patients who suffer from emotional disturbance or depression [see Drug Interactions (7) ].
7 ) ]. 12 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of tramadol hydrochloride tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
3 )] . 3 )] . 7 ); Drug Interactions (7) ] . Alternatively, consider the use of non-opioid analgesics in these patients. 13 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible.
If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
14 Severe Hypotension Tramadol hydrochloride tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. g. phenothiazines or general anesthetics) [see Drug Interactions (7) ] . Regularly evaluate these patients for signs of hypotension after initiating or titrating the dosage of tramadol hydrochloride tablets.
In patients with circulatory shock, tramadol hydrochloride tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of tramadol hydrochloride tablets in patients with circulatory shock.
, those with evidence of increased intracranial pressure or brain tumors), tramadol hydrochloride tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with tramadol hydrochloride tablets.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of tramadol hydrochloride tablets in patients with impaired consciousness or coma. 16 Risk of Gastrointestinal Complication Tramadol hydrochloride tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus [ see Contraindications (4) ] .
The tramadol in tramadol hydrochloride may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
Cases of opioid-induced esophageal dysfunction (OIED) have been reported in patients taking opioids. The risk of OIED may increase as the dose and/or duration of opioids increases. 2 )] . 17 Anaphylaxis and Other Hypersensitivity Reactions Serious and rarely fatal anaphylactic reactions have been reported in patients receiving therapy with tramadol hydrochloride tablets.
When these events do occur it is often following the first dose. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis and Stevens-Johnson syndrome. Patients with a history of hypersensitivity reactions to tramadol and other opioids may be at increased risk and therefore should not receive tramadol hydrochloride tablets [see Contraindications (4) ] .
If anaphylaxis or other hypersensitivity occurs, stop administration of tramadol hydrochloride tablets immediately, discontinue tramadol hydrochloride tablets permanently, and do not rechallenge with any formulation of tramadol. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction.
[see Contraindications (4) ; Patient Counselling Information (17) ] . 18 Withdrawal Do not rapidly reduce or abruptly discontinue tramadol hydrochloride tablets in patient who may be physically dependent on opioids. When discontinuing tramadol hydrochloride tablets in a physically dependent patient, gradually taper the dosage.
3 )] . , buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including tramadol hydrochloride tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions ( 7) ] .
19 Driving and Operating Machinery Tramadol hydrochloride tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of tramadol hydrochloride tablets and know how they will react to the medication [see Patient Counselling Information (17) ] .
20 Hyponatremia Hyponatremia (serum sodium < 135 mmol/L) has been reported with the use of tramadol, and many cases are severe (sodium level < 120 mmol/L). Most cases of hyponatremia occurred in females over the age of 65 and within the first week of therapy.
In some reports, hyponatremia resulted from the syndrome of inappropriate antidiuretic hormone secretion (SIADH). , confusion, disorientation), during treatment with tramadol hydrochloride tablets, especially during initiation of therapy.
5 )]. 21 Hypoglycemia Cases of tramadol-associated hypoglycemia have been reported, some resulting in hospitalization. g. diabetes). 5 )].