Tramadol hydrochloride tablets are indicated for the management of pain in adults that is severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses (SEE WARNINGS), reserve tramadol hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]:
Have not been tolerated, or are not expected to be tolerated.
Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Contraindications
Tramadol hydrochloride tablets contraindicated in patients with:
Significant respiratory depression ( SEE WARNINGS).
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment ( SEE WARNINGS).
Known or suspected gastrointestinal obstruction, including paralytic ileus ( SEE WARNINGS).
Hypersensitivity to tramadol, any other component of this product or opioids ( SEE WARNINGS).
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (SEE PRECAUTIONS; DRUG INTERACTIONS).
Warnings and precautions
Addiction, Abuse, and Misuse Tramadol hydrochloride tablets contain tramadol, a Schedule IV controlled substance. As an opioid, tramadol hydrochloride tablets expose users to the risks of addiction, abuse, and misuse (SEE DRUG ABUSE AND DEPENDENCE). 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.
Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing tramadol hydrochloride tablets, and monitor all patients receiving tramadol hydrochloride tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., 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 intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing tramadol hydrochloride tablets.
Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug (SEE PRECAUTIONS; INFORMATION FOR PATIENTS). 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. 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 antagonists, depending on the patient's clinical status (SEE OVERDOSAGE). Carbon dioxide (CO2 ) 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.
Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of tramadol hydrochloride tablets. To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride tablets are essential (SEE DOSAGE AND ADMINISTRATION). 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. Neonatal Opioid Withdrawal Syndrome Prolonged use of tramadol hydrochloride tablets 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. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (SEE PRECAUTIONS; INFORMATION FOR PATIENTS, PREGNANCY). 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 PRECAUTIONS; DRUG INTERACTIONS). Risks of Concomitant Use or Discontinuation of Cytochrome P450 2D6 Inhibitors The concomitant use of tramadol hydrochloride tablets with all cytochrome P450 2D6 inhibitors (e.g., 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.
Follow patients receiving tramadol hydrochloride tablets and any CYP2D6 inhibitor 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 PRECAUTIONS; DRUG INTERACTIONS). Cytochrome P450 3A4 Interaction The concomitant use of tramadol hydrochloride tablets with cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., 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. Follow patients receiving tramadol hydrochloride tablets and any CYP3A4 inhibitor or inducer 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 PRECAUTIONS; DRUG INTERACTIONS).
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of tramadol hydrochloride tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). 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 compare
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Adverse reactions
The following serious adverse reactions are described, or described in greater detail, in other sections:
Addiction, Abuse, and Misuse ( SEE WARNINGS)
Life-Threatening Respiratory Depression ( SEE WARNINGS)
Neonatal Opioid Withdrawal Syndrome ( SEE WARNINGS)
Interactions with Benzodiazepines or Other CNS Depressants ( SEE WARNINGS)
Serotonin Syndrome ( SEE WARNINGS)
Seizures ( SEE WARNINGS)
Suicide ( SEE WARNINGS)
Adrenal Insufficiency ( SEE WARNINGS)
Severe Hypotension ( SEE WARNINGS)
Gastrointestinal Adverse Reactions ( SEE WARNINGS)
Hypersensitivity Reactions ( SEE WARNINGS)
Withdrawal ( SEE WARNINGS) 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. Tramadol hydrochloride tablets were administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. Table 2 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 2: 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 1 “CNS Stimulation” is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinations 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% 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. Body as a Whole: Malaise. Cardiovascular: Vasodilation. Central Nervous System: Anxiety, Confusion, Coordination disturbance, Euphoria, Miosis, Nervousness, Sleep disorder. Gastrointestinal: Abdominal pain, Anorexia, Flatulence. Musculoskeletal: Hypertonia. Skin: Rash. Special Senses: Visual disturbance. Urogenital: 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. Body as a Whole: Accidental injury, Allergic reaction, Anaphylaxis, Death, Suicidal tendency, Weight loss, Serotonin syndrome (mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma). Cardiovascular: Orthostatic hypotension, Syncope, Tachycardia. Central Nervous System: Abnormal gait, Amnesia, Cognitive dysfunction, Delirium, Depression, Difficulty in concentration, Hallucinations, Movement disorder, Paresthesia, Seizure, Speech disorder, Tremor. Metabolism and Nutrition Disorders: Cases of hypoglycemia have been reported very rarely in patients taking tramadol. Most reports were in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients. Respiratory: Dyspnea. Skin: Stevens-Johnson syndrome/Toxic epidermal necrolysis, Urticaria, Vesicles. Special Senses: Dysgeusia, Mydriasis. Urogenital: 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. Cardiovascular: Abnormal ECG, Hypertension, Hypotension, Myocardial ischemia, Palpitations, Pulmonary edema, Pulmonary embolism. Central Nervous System: Migraine. Gastrointestinal: Gastrointestinal bleeding, Hepatitis, Stomatitis, Liver failure. Laboratory Abnormalities: Creatinine increase, Elevated liver enzymes, Hemoglobin decrease, Proteinuria. Sensory: Cataracts, Deafness, Tinnitus. Postmarketing Experience 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. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids (SEE CLINICAL PHARMACOLOGY).
Composition
Active ingredients
TRAMADOL HYDROCHLORIDE 50MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
