Comprehensive Guide to Ultram (Tramadol): Uses and Side Effects
School
Brandeis University**We aren't endorsed by this school
Course
BIOL 149B
Subject
Nursing
Date
Dec 11, 2024
Pages
44
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2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description1/45Drug SummaryWhat Is Ultram?Ultram (tramadol) is a pain reliever (analgesic) used to treat moderate to moderately severepain in adults. Ultram is available as 50 mg oral tablets. Ultram is available in generic form.What Are Side E±ects of Ultram?Side e±ects of Ultram include:agitation,nervousness,anxiety,seizures (convulsions),skin rash,dizziness,spinning sensation,hallucinations,fever,fast heart rate,overactive re²exes,ULTRAMGeneric Name: tramadol hclBrand Name: UltramDrug Class: Opioid AnalgesicsLast updated on RxList: 7/11/2022HOMEDRUGS A-Z LISTULTRAM (TRAMADOL HCL) DRUGRelated DrugsHealth ResourcesRelated SupplementsDrug ComparisonUltram User Reviews
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description2/45nausea,vomiting,upset stomach,diarrhea,constipation,loss of coordination,headache,drowsiness, andfainting.Seek medical care or call 911 at once if you have the following serious side e±ects:Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eyepain or swelling, or seeing halos around lights;Serious heart symptoms such as fast, irregular, or pounding heartbeats; ²uttering inyour chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, lossof coordination, feeling unsteady, very sti± muscles, high fever, profuse sweating, ortremors.This document does not contain all possible side e±ects and others may occur. Check withyour physician for additional information about side e±ects.Dosage for UltramGood pain management practice dictates that the dose of Ultram be individualizedaccording to patient need using the lowest bene³cial dose.What Drugs, Substances, or Supplements Interact with Ultram?Ultram may interact with other drugs including monoamine oxidase inhibitors (MAOIs) andother antidepressant medications.Ultram During Pregnancy and BreastfeedingThere are no adequate and well-controlled studies of Ultram in pregnant women. Ultramshould be used during pregnancy only if the potential bene³t justi³es the potential risk tothe fetus. Ultram passes into breast milk and may harm a nursing baby. Breastfeeding whiletaking Ultram is not recommended.Additional Information
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description3/45Our Ultram Side E±ects Drug Center provides a comprehensive view of available druginformation on the potential side e±ects when taking this medication.Description for UltramDrug SubstanceProper name: tramadol hydrochlorideChemical name: (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanolhydrochlorideMolecular formula and molecular mass: CHNO•HCl and 299.84Structural formula:Physicochemical properties: Tramadol hydrochloride is a white to o±-white, crystalline, odourlesspowder with a melting point between 180-184°C.Uses for UltramULTRAM is indicated in adults for the management of pain severe enough to require an opioidanalgesic and for which alternative treatments are inadequate.Limitations Of UseBecause of the risks of addiction, abuse, and misuse with opioids, even at recommended doses[see WARNINGS AND PRECAUTIONS], reserve ULTRAM for use in patients for whom alternativetreatment options [e.g., non-opioid analgesics]:®*Average annual per household savings based on a 2022 national survey by State Farmof new policyholders who reported savings by switching to State Farm.16252®*Average annual per household savings based on a 2022 national survey by State Farmof new policyholders who reported savings by switching to State Farm.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description4/45Have not been tolerated or are not expected to be tolerated.Have not provided adequate analgesia or are not expected to provide adequate analgesia.Dosage for UltramImportant Dosage And Administration InstructionsDo not use ULTRAM concomitantly with other tramadol-containing products.Do not administer ULTRAM at a dose exceeding 400 mg per day.Use the lowest e±ective dosage for the shortest duration consistent with individual patienttreatment goals [seeWARNINGS AND PRECAUTIONS].Initiate the dosing regimen for each patient individually, taking into account the patient's severityof pain, patient response, prior analgesic treatment experience, and risk factors for addiction,abuse, and misuse [seeWARNINGS AND PRECAUTIONS].Monitor patients closely for respiratory depression, especially within the ³rst 24–72 hours ofinitiating therapy and following dosage increases with ULTRAM and adjust the dosage accordingly[seeWARNINGS AND PRECAUTIONS].Patient Access To Naloxone For The Emergency Treatment Of Opioid OverdoseDiscuss the availability of naloxone for the emergency treatment of opioid overdose with thepatient and caregiver and assess the potential need for access to naloxone, both when initiatingand renewing treatment with ULTRAM [see WARNINGS AND PRECAUTIONS, Patient CounselingInformation].Inform patients and caregivers about the various ways to obtain naloxone as permitted byindividual state naloxone dispensing and prescribing requirements or guidelines (e.g., byprescription, directly from a pharmacist, or as part of a community-based program).Consider prescribing naloxone, based on the patient's risk factors for overdose, such asconcomitant use of CNS depressants,a history of opioid use disorder, or prior opioid overdose.However, the presence of risk factors for overdose should notprevent the proper managementof pain in any given patient [seeWARNINGS AND PRECAUTIONS].Consider prescribing naloxone if the patient has household members (including children) orother close contacts at risk for accidental exposure or overdose.Initial DosageInitiating Treatment With ULTRAM
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description5/45For patients not requiring rapid onset of analgesic e±ect, the tolerability of ULTRAM can beimproved by initiating therapy with the following titration regimen: Start ULTRAM at 25 mg/dayand titrated in 25 mg increments as separate doses every 3days to reach 100 mg/day (25 mgfour times a day). Thereafter the total daily dose may be increased by 50 mg as tolerated every 3days to reach 200 mg/day (50 mg four times a day). After titration, ULTRAM 50 to 100 mg can beadministered 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 e±ect is required and for whom thebene³ts outweigh the risk of discontinuation due to adverse events associated with higher initialdoses, ULTRAM 50 mg to 100 mg can be administered as needed for pain relief every four to sixhours, not to exceed 400 mg per day.Conversion From ULTRAM To Extended-Release TramadolThe relative bioavailability of ULTRAM compared to extended-release tramadol is unknown, soconversion to extended-release formulations must be accompanied by close observation forsigns of excessive sedation and respiratory depression.Dosage Modi²cation In Patients With Hepatic ImpairmentThe recommended dose for adult patients with severe hepatic impairment is 50 mg every 12hours.Dosage Modi²cation In Patients With Renal ImpairmentIn all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosinginterval of ULTRAM beincreased to 12 hours, with a maximum daily dose of 200 mg. Since only7% of an administered dose is removed by hemodialysis, dialysis patients can receive theirregular dose on the day of dialysis.Dosage Modi²cation In Geriatric PatientsDo not exceed a total dose of 300 mg/day in patients over 75 years old.Titration And Maintenance Of TherapyIndividually titrate ULTRAM to a dose that provides adequate analgesia and minimizes adversereactions. Continually reevaluate patients receiving ULTRAM to assess the maintenance of paincontrol and the relative incidence of adverse reactions, as well as to monitor for thedevelopment of addiction, abuse, or misuse [see WARNINGS AND PRECAUTIONS].Frequentcommunication is important among the prescriber, other members of the healthcare team, thepatient, and the caregiver/family during periods of changing analgesic requirements, includinginitial titration.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description6/45If the level of pain increases after dosage stabilization, attempt to identify the source ofincreased pain before increasing the ULTRAM dosage. If unacceptable opioid-related adversereactions are observed, consider reducing the dosage. Adjust the dosage to obtain anappropriate balance between management of pain and opioid-related adverse reactions.Safe Reduction Or Discontinuation Of ULTRAMDo not abruptly discontinue ULTRAM in patients who may be physically dependent on opioids.Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioidshas resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapiddiscontinuation has also been associated with attempts to ³nd other sources ofopioidanalgesics, which may be confused with drug-seeking for abuse. Patients may also attemptto treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and othersubstances.When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking ULTRAM, there are a variety of factors that should be considered,including the dose of ULTRAM the patient has been taking, the duration of treatment, the type ofpain being treated, and the physical and psychological attributes of the patient. It is important toensure 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 opioidanalgesics are being discontinued due to a suspected substance use disorder, evaluate and treatthe patient, or refer for evaluation and treatment of the substance use disorder. Treatmentshould include evidence-based approaches, such as medication assisted treatment of opioid usedisorder. Complex patients with comorbid pain and substance use disorders may bene³t fromreferral to a specialist.There are no standard opioid tapering schedules that are suitable for all patients. Good clinicalpractice dictates a patient-speci³c plan to taper the dose of the opioid gradually. For patients onULTRAM who are physically opioid-dependent, initiate the taper by a small enough increment,(e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, andproceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been takingopioids 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 asuccessful 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 alsomay develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps,insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, orheart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period oftime or raise the dose of the opioid analgesic to the previous dose, and then proceed with aslower taper. In addition, monitor patients for any changes in mood, emergence of suicidalthoughts, or use of other substances.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description7/45When managing patients taking opioid analgesics, particularly those who have been treated for along duration and/or with high doses for chronic pain, ensure that a multimodal approach topain management, including mental health support (if needed), is in place prior to initiating anopioid analgesic taper. A multimodal approach to pain management may optimize the treatmentof chronic pain, as well as assist with the successful tapering of the opioid analgesic [seeWARNINGS AND PRECAUTIONS, Drug Abuse And Dependence].HOW SUPPLIEDDosage Forms And StrengthsULTRAM (tramadol hydrochloride) 50 mg (equivalent to 43.9 mg of tramadol) tablets are white,capsule-shaped, coated, with a functional score. The tablets are imprinted “ULTRAM” on one sideand “06 59” on the scored side.Storage And HandlingULTRAM ®(tramadol hydrochloride) 50 mg tablets are white, capsule-shaped, coated, with afunctional score. The tablets are imprinted “ULTRAM” on one side and “06 59” on the scored side.Bottle of 100 tablets: NDC 50458-659-60Dispense in a tight container. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°Cto 30°C (59°F to 86°F).[see USP Controlled Room Temperature].Store ULTRAM securely and dispose of properly [see Patient Counseling Information].Manufactured by: Janssen Ortho LLCGurabo, Puerto Rico 00778. Manufactured for: Janssen Pharmaceuticals, Inc. Titusville, New Jersey08560. Revised: Sep 2021Side E±ects for UltramThe following serious adverse reactions are described, or described in greater detail, in othersections:Addiction, Abuse, and Misuse [seeWARNINGS AND PRECAUTIONS]Life-Threatening Respiratory Depression [seeWARNINGS AND PRECAUTIONS]Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening RespiratoryDepression in Children[seeWARNINGS AND PRECAUTIONS]
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description8/45Neonatal Opioid Withdrawal Syndrome [seeWARNINGS AND PRECAUTIONS]Interactions with Benzodiazepines or Other CNS Depressants [seeWARNINGS ANDPRECAUTIONS]Serotonin Syndrome [seeWARNINGS AND PRECAUTIONS]Seizures [seeWARNINGS AND PRECAUTIONS]Suicide [seeWARNINGS AND PRECAUTIONS]Adrenal Insu´ciency [see WARNINGS AND PRECAUTIONS]Severe Hypotension [seeWARNINGS AND PRECAUTIONS]Gastrointestinal Adverse Reactions [seeWARNINGS AND PRECAUTIONS]Hypersensitivity Reactions [seeWARNINGS AND PRECAUTIONS]Withdrawal [seeWARNINGS AND PRECAUTIONS]Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another drug and may not re²ect the rates observed in practice.ULTRAM was administered to 550 patients during the double-blind or open-label extensionperiods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old orolder. Table 1 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days forthe most frequent reactions (5% or more by 7 days). The most frequently reported events werein the central nervous system and gastrointestinal system. Although the reactions listed in thetable are felt to be probably related to ULTRAM administration, the reported rates also includesome events that may have been due to underlying disease or concomitant medication. Theoverall incidence rates of adverse experiences in these trials were similar for ULTRAM and theactive control groups, TYLENOL with Codeine #3 (acetaminophen 300 mg with codeinephosphate 30mg), and aspirin 325 mg with codeine phosphate 30 mg, however, the rates ofwithdrawals due to adverse events appeared tobe higher in the ULTRAM groups.Table 1: Cumulative Incidence of Adverse Reactions for ULTRAM in Chronic Trials ofNonmalignant Pain (N=427)Up to 7 DaysUp to 30 DaysUp to 90 DaysDizziness/Vertigo26%31%33%Nausea24%34%40%Constipation24%38%46%Headache18%26%32%Somnolence16%23%25%Vomiting9%13%17%
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description9/45Pruritus8%10%11%“CNS Stimulation”*7%11%14%Asthenia6%11%12%Sweating6%7%9%Dyspepsia5%9%13%Dry Mouth5%9%10%Diarrhea5%6%10%* “CNS Stimulation” is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinationsIncidence 1% to Less Than 5% Possibly Causally RelatedThe following lists adverse reactions that occurred with an incidence of 1% to less than 5% inclinical trials, and for which the possibility of a causal relationship with ULTRAM 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 RelatedThe following lists adverse reactions that occurred with an incidence of less than 1% in clinicaltrials of tramadol and/orreported in postmarketing experience with tramadol-containingproducts.Body as a Whole:Accidental injury, Allergic reaction, Anaphylaxis, Death, Suicidal tendency,Weight loss, Serotoninsyndrome (mental status change, hyperre²exia, fever, shivering, tremor,agitation, diaphoresis, seizures and coma).Cardiovascular:Orthostatic hypotension, Syncope, Tachycardia.Central Nervous System: Abnormal gait, Amnesia, Cognitive dysfunction, Depression, Di´cultyin concentration, Hallucinations, Paresthesia, Seizure, Tremor.Respiratory:Dyspnea.Skin:Stevens-Johnson syndrome/Toxic epidermal necrolysis, Urticaria, Vesicles.Special Senses:Dysgeusia.Urogenital:Dysuria, Menstrual disorder.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description10/45Other Adverse Experiences, Causal Relationship UnknownA variety of other adverse events were reported infrequently in patients taking ULTRAM duringclinical trials and/or reported in postmarketing experience. A causal relationship betweenULTRAM and these events has not been determined. However, the most signi³cant events arelisted 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 ExperienceThe following adverse reactions have been identi³ed during post-approval use of ULTRAM.Because these reactions arereported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to drugexposure.Serotonin syndrome:Cases of serotonin syndrome, a potentially life-threatening condition, havebeen reported during concomitant use of opioids with serotonergic drugs.Adrenal insu³ciency:Cases of adrenal insu´ciency have been reported with opioid use, moreoften following greater than one month of use.Androgen de²ciency:Cases of androgen de³ciency have occurred with chronic use of opioids[see CLINICAL PHARMACOLOGY].QT prolongation/torsade de pointes:Cases of QT prolongation and/or torsade de pointes havebeen reported with tramadoluse. Many of these cases were reported in patients taking anotherdrug labeled for QT prolongation, in patients with a risk factor for QT prolongation (e.g.,hypokalemia), or in the overdose setting.Eye disorders - mydriasisMetabolism and nutrition disorders -Hyponatremia: Cases of severe hyponatremia and/orSIADH have been reported inpatients taking tramadol, most often in females over the age of 65,and within the ³rst week of therapy [seeWARNINGS AND PRECAUTIONS].Hypoglycemia:Cases of hypoglycemia have been reported in patients taking tramadol. Mostreports were in patients with predisposing risk factors, including diabetes or renal insu´ciency,or in elderly patients [seeWARNINGS AND PRECAUTIONS].Nervous system disorders -movement disorder, speech disorderPsychiatric disorders -delirium
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description11/45Drug Interactions for UltramTable 2: Clinically Signi²cant Drug Interactions with ULTRAMCYP2D6 Clinical Impact:Clinical ImpactThe concomitant use of ULTRAM and CYP2D6 inhibitors may result in an increase in theplasma concentration of tramadol and a decrease in the plasma concentration of Ml,particularly when an inhibitor is added after a stable dose of ULTRAM is achieved. Since Ml isa more potent (i-opioid agonist, decreased Ml exposure could result in decreased therapeutice±ects, and may result in signs and symptoms of opioid withdrawal in patients who haddeveloped physical dependence to tramadol. Increased tramadol exposure can result inincreased or prolonged therapeutic e±ects and increased risk for serious adverse eventsincluding seizures and serotonin syndrome. After stopping a CYP2D6 inhibitor, as the e±ectsof the inhibitor decline, the tramadol plasma concentration will decrease and the Ml plasmaconcentration will increase. This could increase or prolong therapeutic e±ects but alsoincrease adverse reactions related to opioid toxicity, such as potentially fatal respiratorydepression [see CLINICAL PHARMACOLOGY].Intervention:If concomitant use of a CYP2D6 inhibitor is necessary, follow patients closely for adversereactions including opioid withdrawal, seizures and serotonin syndrome. If a CYP2D6 inhibitoris discontinued, consider lowering ULTRAM dosage until stable drug e±ects are achieved.Follow patients closely for adverse events including respiratory depression and sedation.ExamplesQuinidine, ²uoxetine, paroxetine and bupropionInhibitors of CYP3A4Clinical Impact:The concomitant use of ULTRAM and CYP3A4 inhibitors can increase the plasmaconcentration of tramadol and may result in a greater amount of metabolism via CYP2D6 andgreater levels of Ml. Follow patients closely for increased risk of serious adverse eventsincluding seizures and serotonin syndrome, and adverse reactions related to opioid toxicityincluding potentially fatal respiratory depression, particularly when an inhibitor is added aftera stable dose of ULTRAM is achieved. After stopping a CYP3A4 inhibitor, as the e±ects of theinhibitor decline, the tramadol plasma concentration will decrease [see CLINICALPHARMACOLOGY], resulting in decreased opioid e´cacy or a withdrawal syndrome inpatients who had developed physical dependence to tramadol.Intervention:If concomitant use is necessary, consider dosage reduction of ULTRAM until stable druge±ects are achieved. Follow patients closely for seizures and serotonin syndrome, and signsof respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor isdiscontinued, consider increasing the ULTRAM dosage until stable drug e±ects are achievedand follow patients for signs and symptoms of opioid withdrawal.ExamplesMacrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole),protease inhibitors (e.g., ritonavir)CYP3A4 InducersClinical Impact:The concomitant use of ULTRAM and CYP3A4 inducers can decrease the plasmaconcentration of tramadol [see CLINICAL PHARMACOLOGY], resulting in decreased e´cacyor onset of a withdrawal syndrome in patients who have developed physical dependence totramadol.After stopping a CYP3A4 inducer, as the e±ects of the inducer decline, the tramadol plasmaconcentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolongboth the therapeutic e±ects and adverse reactions, and may cause seizures, serotoninsyndrome, and/or potentially fatal respiratory depression. If concomitant use is necessary,consider increasing the ULTRAM dosage until stable drug e±ects are achieved. Follow patientsfor signs of opioid withdrawal.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description12/45Intervention:If a CYP3A4 inducer is discontinued, consider ULTRAM dosage reduction and monitor forseizures and serotonin syndrome, and signs of sedation and respiratory depression.Patients taking carbamazepine, a CYP3A4 inducer, may have a signi³cantly reduced analgesice±ect of tramadol. Because carbamazepine increases tramadol metabolism and because ofthe seizure risk associated with tramadol, concomitant administration of ULTRAM andcarbamazepine is not recommended.Examples:Rifampin, carbamazepine, phenytoinBenzodiazepines and Other Central Nervous System (CNS) DepressantsClinical Impact:Due to additive pharmacologic e±ect, the concomitant use of benzodiazepines or other CNSdepressants, including alcohol, increases the risk of respiratory depression, profoundsedation, coma, and death.Intervention:Reserve concomitant prescribing of these drugs for use in patients for whom alternativetreatment options are inadequate. Limit dosages and durations to the minimum required.Follow patients closely for signs of respiratory depression and sedation [see WARNINGS ANDPRECAUTIONS]. If concomitant use is warranted, consider prescribing naloxone for theemergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION, WARNINGSAND PRECAUTIONS].Examples:Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants,general anesthetics, antipsychotics, other opioids, and alcohol.Serotonergic DrugsClinical Impact:The concomitant use of opioids with other drugs that a±ect the serotonergicneurotransmitter system has resulted in serotonin syndrome.Intervention:If concomitant use is warranted, carefully observe the patient, particularly during treatmentinitiation and dose adjustment. Discontinue ULTRAM immediately if serotonin syndrome issuspected.Examples:Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptakeinhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugsthat a±ect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol),certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO)inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid andintravenous methylene blue).Monoamine Oxidase Inhibitors (MAOIs)Clinical Impact:MAOI interactions with opioids may manifest as serotonin syndrome [see WARNINGS ANDPRECAUTIONS] or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS ANDPRECAUTIONS].Intervention:Do not use ULTRAM in patients taking MAOIs or within 14 days of stopping such treatment.Examples:phenelzine, tranylcypromine, linezolidMixed Agonist/Antagonist and Partial Agonist Opioid AnalgesicsClinical Impact:May reduce the analgesic e±ect of ULTRAM and/or precipitate withdrawal symptoms.Intervention:Avoid concomitant use.Examples:butorphanol, nalbuphine, pentazocine, buprenorphineMuscle RelaxantsClinical Impact:Tramadol may enhance the neuromuscular blocking action of skeletal muscle relaxants andproduce an increased degree of respiratory depression.Intervention:Monitor patients for signs of respiratory depression that may be greater than otherwiseexpected and decrease the dosage of ULTRAM and/or the muscle relaxant as necessary. Dueto the risk of respiratory depression with concomitant use of skeletal muscle relaxants andopioids, consider prescribing naloxone for the emergency treatment of opioid overdose [seeDOSAGE AND ADMINISTRATION,WARNINGS AND PRECAUTIONS].DiureticsClinical Impact:Opioids can reduce the e´cacy of diuretics by inducing the release of antidiuretic hormone.Intervention:Monitor patients for signs of diminished diuresis and/or e±ects on blood pressure andincrease the dosage of the diuretic as needed.Anticholinergic DrugClinical Impact:The concomitant use of anticholinergic drugs may increase risk of urinary retention and/orsevere constipation, which may lead to paralytic ileus.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description13/45Intervention:Monitor patients for signs of urinary retention or reduced gastric motility when ULTRAM isused concomitantly with anticholinergic drugs.DigoxinClinical Impact:Postmarketing surveillance of tramadol has revealed rare reports of digoxin toxicity.Intervention:Follow patients for signs of digoxin toxicity and adjust dosage of digoxin as needed.WarfarinClinical Impact:Postmarketing surveillance of tramadol has revealed rare reports of alteration of warfarine±ect, including elevation of prothrombin times.Intervention:Monitor the prothrombin time of patients on warfarin for signs of an interaction and adjustthe dosage of warfarin as needed.Drug Abuse And DependenceControlled SubstanceULTRAM (tramadol hydrochloride) contain tramadol, a Schedule IV controlled substance.AbuseULTRAM contains tramadol, a substance with a high potential for abuse similar to other opioids.ULTRAM can be abusedand is subject to misuse, addiction, and criminal diversion [seeWARNINGS AND PRECAUTIONS].All patients treated with opioids require careful monitoring for signs of abuse and addiction,because use of opioid analgesic products carries the risk of addiction even under appropriatemedical use.Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once,for its rewarding psychological or physiological e±ects.Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that developafter repeated substance useand includes: a strong desire to take the drug, di´culties incontrolling its use, persisting in its use despite harmful, orpotentially harmful, consequences, ahigher priority given to drug use than to other activities and obligations, increased tolerance, andsometimes a physical withdrawal.“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seekingtactics include emergency calls or visits near the end of o´ce hours, refusal to undergoappropriate examination, testing or referral, repeated “loss” of prescriptions, tampering withprescriptions and reluctance to provide prior medical records or contact information for othertreating physician(s). “Doctor shopping” (visiting multiple prescribers to obtain additionalprescriptions) is common amongdrug abusers and people su±ering from untreated addiction.Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient withpoor pain control.Abuse and addiction are separate and distinct from physical dependence and tolerance.Healthcare providers should be aware that addiction may not be accompanied by concurrenttolerance and symptoms of physical dependence in all addicts. Inaddition, abuse of opioids can
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description14/45occur in the absence of true addiction.ULTRAM, like other opioids, can be diverted for non-medical use into illicit channels ofdistribution. Careful record-keeping of prescribing information, including quantity, frequency,and renewal requests, as required by state and federal law, is strongly advised.Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy,and proper dispensing and storage are appropriate measures that help to limit abuse of opioiddrugs.Risks Speci³c To Abuse Of ULTRAMULTRAM is intended for oral use only. Abuse of ULTRAM poses a risk of overdose and death. Therisk is increased with concurrent abuse of ULTRAM with alcohol and other central nervoussystem depressants.Parenteral drug abuse is commonly associated with transmission of infectious diseases such ashepatitis and HIV.DependenceBoth tolerance and physical dependence can develop during chronic opioid therapy. Tolerance isthe need for increasing doses of drugs to maintain a de³ned e±ect such as analgesia (in theabsence of disease progression or other external factors).Tolerance may occur to both thedesired and undesired e±ects of drugs, and may develop at di±erent rates for di±erent e±ects.Physical dependence is a physiological state in which the body adapts to the drug after a periodof regular exposure, resultingin withdrawal symptoms after abrupt discontinuation or asigni³cant dosage reduction of a drug. Withdrawal also may beprecipitated through theadministration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixedagonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists(buprenorphine). Physicaldependence may not occur to a clinically signi³cant degree until afterseveral days to weeks of continued opioid usage.Do not abruptly discontinue ULTRAM in a patient physically dependent on opioids. Rapidtapering of ULTRAM in a patient physically dependent on opioids may lead to serious withdrawalsymptoms, uncontrolled pain and suicide. Rapid discontinuation has also been associated withattempts to ³nd other sources of opioid analgesics, which may be confused with drug-seekingfor abuse.When discontinuing ULTRAM, gradually taper the dosage using a patient-speci³c plan thatconsiders the following: the dose of ULTRAM the patient has been taking, the duration oftreatment, and the physical and psychological attributes of the patient. To improve the likelihoodof a successful taper and minimize withdrawal symptoms, it is important that the opioid taperingschedule is agreed upon by the patient. In patients taking opioids for a long duration at highdoses, ensure that amultimodal approach to pain management, including mental health support(if needed), is in place prior to initiating anopioid analgesic taper [see DOSAGE ANDADMINISTRATION, WARNINGS AND PRECAUTIONS].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description15/45Infants born to mothers physically dependent on opioids will also be physically dependent andmay exhibit respiratory di´culties and withdrawal signs [see Use In Speci²c Populations].Warnings for UltramIncluded as part of the PRECAUTIONSsection.Precautions for UltramAddiction, Abuse And MisuseULTRAM contains tramadol, a Schedule IV controlled substance. As an opioid, ULTRAM exposesusers to the risks of addiction, abuse, and misuse [seeDrug Abuse And Dependence].Although the risk of addiction in any individual is unknown, it can occur in patients appropriatelyprescribed ULTRAM. Addiction can occur at recommended dosages and if the drug is misused orabused.Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing ULTRAM,and monitor all patients receiving ULTRAM for the development of these behaviors andconditions. 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).Thepotential for these risks should not, however, prevent the proper management of pain in anygiven patient. Patients at increased risk may be prescribed opioids such as ULTRAM, but use insuch patients necessitates intensive counseling about the risks and proper use of ULTRAM alongwith intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribingnaloxone for the emergency treatment of opioid overdose [seeDOSAGE AND ADMINISTRATION,WARNINGS AND PRECAUTIONS].Opioids are sought by drug abusers and people with addiction disorders and are subject tocriminal diversion. Consider the serisks when prescribing or dispensing ULTRAM. Strategies toreduce these risks include prescribing the drug in the smallest appropriate quantity and advisingthe patient on the proper disposal of unused drug [see Patient Counselling Information].Contact local state professional licensing board or state controlled substances authority forinformation on how toprevent and detect abuse or diversion of this product.Opioid Analgesic Risk Evaluation And Mitigation Strategy (REMS)
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description16/45To ensure that the bene³ts of opioid analgesics outweigh the risks of addiction, abuse, andmisuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and MitigationStrategy (REMS) for these products. Under the requirements of the REMS, drug companies withapproved opioid analgesic products must make REMS-compliant education programs availableto healthcare providers. Healthcare providers are strongly encouraged to do all of the following:Complete a REMS-compliant education program o±ered by an accredited provider of continuingeducation (CE) or another education program that includes all the elements of the FDA EducationBlueprint 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 withpatients and/or their caregivers every time these medicines are prescribed. The PatientCounseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.Emphasize to patients and their caregivers the importance of reading the Medication Guide thatthey 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.To obtain further information on the opioid analgesic REMS and for a list of accredited REMSCME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. FDA Blueprint can befound atwww.fda.gov/OpioidAnalgesic REMSBlueprint.Life-Threatening Respiratory DepressionSerious, life-threatening, or fatal respiratory depression has been reported with the use ofopioids, even when used as recommended. Respiratory depression, if not immediatelyrecognized and treated, may lead to respiratory arrest and death. Management of respiratorydepression may include close observation, supportive measures, and use of opioid antagonists,depending on the patient's clinical status [seeOVERDOSAGE]. Carbon dioxide (CO2) retentionfrom opioid-induced respiratory depression can exacerbate the sedating e±ects of opioids.While serious, life-threatening, or fatal respiratory depression can occur at any time during theuse of ULTRAM, the risk is greatest during the initiation of therapy or following a dosageincrease. Monitor patients closely for respiratory depression, especially within the ³rst 24–72hours of initiating therapy with and following dosage increases of ULTRAM.To reduce the risk of respiratory depression, proper dosing and titration of ULTRAM are essential[seeDOSAGE AND ADMINISTRATION]. Overestimating the ULTRAM dosage when convertingpatients from another opioid product can resultin a fatal overdose with the ³rst dose.Accidental ingestion of even one dose of ULTRAM, especially by children, can result in respiratorydepression and deathdue to an overdose of tramadol.Educate patients and caregivers on how to recognize respiratory depression and emphasize theimportance of calling 911 or getting emergency medical help right away in the event of a knownor suspected overdose [seePATIENT INFORMATION].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description17/45Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) andsleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. Inpatients who present with CSA, consider decreasing the opioid dosage using best practices foropioid taper [seeDOSAGE AND ADMINISTRATION].Patient Access To Naloxone For The Emergency Treatment Of Opioid OverdoseDiscuss the availability of naloxone for the emergency treatment of opioid overdose with thepatient and caregiver and assess the potential need for access to naloxone, both when initiatingand renewing treatment with ULTRAM. Inform patients and caregivers about the various ways toobtain naloxone as permitted by individual state naloxone dispensing and prescribingrequirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of acommunity-based program).Educate patients and caregivers on how to recognize respiratorydepression and emphasize the importance of calling 911 or getting emergency medical help,even if naloxone is administered [seePatient Counseling Information].Consider prescribing naloxone, based on the patient's risk factors for overdose, such asconcomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose.However, the presence of risk factors for overdose should not prevent the proper managementof pain in any given patient. Also consider prescribing naloxone if the patient has householdmembers (including children) or other close contacts at risk for accidental exposure or overdose.If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone. [seeWARNINGS AND PRECAUTIONS, Patient Counseling Information].Ultra-Rapid Metabolism Of Tramadol And Other Risk Factors For Life-threatening Respiratory Depression In ChildrenLife-threatening respiratory depression and death have occurred in children who receivedtramadol. Tramadol and codeineare subject to variability in metabolism based upon CYP2D6genotype (described below), which can lead to increased exposure to an active metabolite. Basedupon postmarketing reports with tramadol or with codeine, children younger than 12years ofage may be more susceptible to the respiratory depressant e±ects of tramadol. Furthermore,children with obstructive sleep apnea who are treated with opioids for post-tonsillectomy and/oradenoidectomy pain may be particularly sensitive to their respiratory depressant e±ect. Becauseof the risk of life-threatening respiratory depression and death:ULTRAM is contraindicated for all children younger than 12 years of age [seeCONTRAINDICATIONS].ULTRAM is contraindicated for postoperative management in pediatric patients younger than 18years of age following tonsillectomy and/or adenoidectomy [seeCONTRAINDICATIONS].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description18/45Avoid the use of ULTRAM in adolescents 12 to 18 years of age who have other risk factors thatmay increase their sensitivity to the respiratory depressant e±ects of tramadol unless thebene³ts outweigh the risks. Risk factors include conditions associated with hypoventilation suchas postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease,neuromuscular disease, and concomitant use of other medications that cause respiratorydepression.As with adults, when prescribing opioids for adolescents, healthcare providers should choose thelowest e±ective dosefor the shortest period of time and inform patients and caregivers aboutthese risks and the signs of opioid overdose [see Use In Speci²c Populations, OVERDOSAGE].Nursing MothersTramadol is subject to the same polymorphic metabolism as codeine, with ultra-rapidmetabolizers of CYP2D6 substratesbeing potentially exposed to life-threatening levels of theactive metabolite O-desmethyltramadol (M1). At least one death was reported in a nursing infantwho 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 takingULTRAM could potentially be exposed to high levels of M1, and experience life-threateningrespiratory depression. For this reason, breastfeeding is notrecommended during treatmentwith ULTRAM [seeUse In Speci²c Populations].CYP2D6 Genetic Variability: Ultra-rapid MetabolizerSome individuals may be ultra-rapid metabolizers because of a speci³c CYP2D6 genotype (e.g.,gene duplications denotedas *1/*1×N or *1/*2×N). The prevalence of this CYP2D6phenotype varies widely and has been estimated at 1 to 10% forWhites (European, NorthAmerican), 3 to 4% for Blacks (African Americans), 1 to 2% for East Asians (Chinese,Japanese,Korean), and may be greater than 10% in certain racial/ethnic groups (i.e., Oceanian,Northern African, Middle Eastern,Ashkenazi Jews, Puerto Rican). These individuals converttramadol into its active metabolite, O-desmethyltramadol (M1),more rapidly and completely thanother people. This rapid conversion results in higher than expected serum M1 levels. Evenatlabeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threateningor fatal respiratory depression or experience signs of overdose (such as extreme sleepiness,confusion, or shallow breathing) [seeOVERDOSAGE]. Therefore, individuals who are ultra-rapidmetabolizers should not use ULTRAM.Neonatal Opioid Withdrawal SyndromeProlonged use of ULTRAM during pregnancy can result in withdrawal in the neonate. Neonatalopioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocolsdeveloped by neonatology experts. Observe newborns for signs of neonatal opioid withdrawalsyndrome and manage accordingly. Advise pregnant women using opioids for a prolonged
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description19/45period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriatetreatment will be available [seeUse In Speci²c Populations and Patient CounselingInformation].Risks Of Interactions With Drugs A±ecting Cytochrome P450 IsoenzymesThe e±ects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4inhibitors, or 2D6 inhibitors onlevels of tramadol and M1 from ULTRAM are complex. Use ofcytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6inhibitors with ULTRAM requires carefulconsideration of the e±ects on the parent drug, tramadol which is a weak serotoninandnorepinephrine reuptake inhibitor and μ-opioid agonist, and the active metabolite, M1, which ismore potent than tramadol in μ-opioid receptor binding [seeDRUG INTERACTIONS].Risks Of Concomitant Use Or Discontinuation Of Cytochrome P450 2D6 InhibitorsThe concomitant use of ULTRAM 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 theactive metabolite, M1. A decrease in M1 exposure inpatients who have developed physicaldependence to tramadol, may result in signs and symptoms of opioid withdrawal andreducede´cacy. The e±ect of increased tramadol levels may be an increased risk for serious adverseevents including seizures and serotonin syndrome.Discontinuation of a concomitantly used cytochrome P450 2D6 inhibitor may result in a decreasein tramadol plasma levels and an increase in active metabolite M1 levels, which could increase orprolong adverse reactions related to opioid toxicityand may cause potentially fatal respiratorydepression.Follow patients receiving ULTRAM and any CYP2D6 inhibitor for the risk of serious adverseevents including seizures and serotonin syndrome, signs and symptoms that may re²ect opioidtoxicity, and opioid withdrawal when ULTRAM is used in conjunction with inhibitors of CYP2D6[seeDRUG INTERACTIONS].Cytochrome P450 3A4 InteractionThe concomitant use of ULTRAM with cytochrome P450 3A4 inhibitors, such as macrolideantibiotics (e.g., erythromycin),azole-antifungal agents (e.g., ketoconazole), and proteaseinhibitors (e.g., ritonavir) or discontinuation of a cytochrome P4503A4 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 eventsincluding seizures and serotonin syndrome, and may cause potentially fatal respiratorydepression.The concomitant use of ULTRAM with all cytochrome P450 3A4 inducers or discontinuation of acytochrome P450 3A4inhibitor may result in lower tramadol levels. This may be associated with adecrease in e´cacy, and in some patients, mayresult in signs and symptoms of opioidwithdrawal.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description20/45Follow patients receiving ULTRAM and any CYP3A4 inhibitor or inducer for the risk for seriousadverse events including seizures and serotonin syndrome, signs and symptoms that may re²ectopioid toxicity and opioid withdrawal when ULTRAM is used in conjunction with inhibitors andinducers of CYP3A4 [seeDRUG INTERACTIONS].Risks From Concomitant Use With Benzodiazepines Or Other CNS DepressantsProfound sedation, respiratory depression, coma, and death may result from the concomitantuse of ULTRAM with benzodiazepines or other CNS depressants (e.g., non-benzodiazepinesedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics,antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing ofthese drugs for use in patients for whom alternative treatment options are inadequate.Observational studies have demonstrated that concomitant use of opioid analgesics andbenzodiazepines increases the risk of drug-related mortality compared to use of opioidanalgesics alone. Because of similar pharmacological properties, it is reasonable to expectsimilar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [seeDRUG INTERACTIONS].If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantlywith an opioid analgesic, prescribe the lowest e±ective dosages and minimum durations ofconcomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial doseof the benzodiazepine or other CNS depressant than indicated in the absence of anopioid, andtitrate based on clinical response. If an opioid analgesic is initiated in a patient already taking abenzodiazepineor other CNS depressant, prescribe a lower initial dose of the opioid analgesic,and titrate based on clinical response. Follow patients closely for signs and symptoms ofrespiratory depression and sedation.If concomitant use is warranted, consider prescribing naloxone for the emergency treatment ofopioid overdose [seeDOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].Advise both patients and caregivers about the risks of respiratory depression and sedation whenULTRAM is used with benzodiazepines or other CNS depressants (including alcohol and illicitdrugs). Advise patients not to drive or operate heavy machinery until the e±ects of concomitantuse of the benzodiazepine or other CNS depressant have been determined. Screen patients forrisk of substance use disorders, including opioid abuse and misuse, and warn them of the riskfor overdose and death associated with the use of additional CNS depressants including alcoholand illicit drugs [seeDRUG INTERACTIONS; and Patient Counseling Information].Serotonin Syndrome RiskCases of serotonin syndrome, a potentially life-threatening condition, have been reported withthe use of tramadol, particularly during concomitant use with serotonergic drugs. Serotonergicdrugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrinereuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists,drugs that a±ect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone,tramadol),certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description21/45metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatricdisorders and also others, such as linezolid and intravenous methyleneblue) [seeDRUGINTERACTIONS]. This may occur within the recommended dosage range.Serotonin syndrome symptoms may include mental status changes (e.g., agitation,hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure,hyperthermia), neuromuscular aberrations (e.g., hyperre²exia, incoordination, rigidity), and/orgastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptomsgenerallyoccurs within several hours to a few days of concomitant use, but may occur later than that.Discontinue ULTRAM if serotonin syndrome is suspected.Increased Risk Of SeizureSeizures have been reported in patients receiving ULTRAM within the recommended dosagerange. Spontaneouspostmarketing reports indicate that seizure risk is increased with doses ofULTRAM above the recommended range.Concomitant use of ULTRAM increases the seizure risk in patients taking [seeDRUGINTERACTIONS]:Selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics),Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine,promethazine, etc.),Other opioids,MAO inhibitors [seeWARNINGS AND PRECAUTIONS; DRUG INTERACTIONS].Neuroleptics, orOther drugs that reduce the seizure threshold.Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or inpatients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcoholand drug withdrawal, CNS infections). In ULTRA Moverdose, naloxone administration mayincrease the risk of seizure.Suicide RiskDo not prescribe ULTRAM for patients who are suicidal or addiction-prone. Consideration shouldbe given to the use of non-narcotic analgesics in patients who are suicidal or depressed [seeDrugAbuse And Dependence].Prescribe ULTRAM with caution for patients with a history of misuse and/or are currently takingCNS-active drugs including tranquilizers or antidepressant drugs, alcohol in excess, and patientswho su±er from emotional disturbance or depression [seeDRUG INTERACTIONS].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description22/45Inform patients not to exceed the recommended dose and to limit their intake of alcohol [seeDOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].Adrenal Insu³ciencyCases of adrenal insu´ciency have been reported with opioid use, more often following greaterthan one month of use. Presentation of adrenal insu´ciency may include non-speci³c symptomsand signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low bloodpressure. If adrenal insu´ciency is suspected, con³rm the diagnosis with diagnostic testing assoon as possible. If adrenal insu´ciency is diagnosed, treat with physiologic replacement dosesof corticosteroids. Wean the patient o± of the opioid to allow adrenal function to recover andcontinue corticosteroid treatment until adrenal function recovers. Other opioids may be tried assome cases reported use of a di±erent opioid without recurrence of adrenal insu´ciency. Theinformation available does not identify any particular opioids as being more likely to beassociated with adrenal insu´ciency.Life-Threatening Respiratory Depression In Patients With Chronic PulmonaryDisease Or In Elderly, Cachectic, Or Debilitated PatientsThe use of ULTRAM in patients with acute or severe bronchial asthma in an unmonitored settingor in the absence of resuscitative equipment is contraindicated.Patients With Chronic Pulmonary DiseaseULTRAM -treated patients with signi³cant chronic obstructive pulmonary disease or corpulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia,or pre-existing respiratory depression are at increased risk of decreased respiratory driveincluding apnea, even at recommended dosages of ULTRAM [see WARNINGS ANDPRECAUTIONS].Elderly, Cachectic, Or Debilitated PatientsLife-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitatedpatients because they mayhave altered pharmacokinetics or altered clearance compared toyounger, healthier patients [seeWARNINGS AND PRECAUTIONS].Monitor such patients closely, particularly when initiating and titrating ULTRAM and whenULTRAM is given concomitantly with other drugs that depress respiration [seeWARNINGS ANDPRECAUTIONS; DRUG INTERACTIONS].Alternatively, consider the use of non-opioid analgesics inthese patients.Severe HypotensionULTRAM may cause severe hypotension including orthostatic hypotension and syncope inambulatory patients. There is increased risk in patients whose ability to maintain blood pressurehas already been compromised by a reduced blood volumeor concurrent administration of
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description23/45certain CNS depressant drugs (e.g. phenothiazines or general anesthetics) [seeDRUGINTERACTIONS]. Monitor these patients for signs of hypotension after initiating or titrating thedosage of ULTRAM. Inpatients with circulatory shock, ULTRAM may cause vasodilation that canfurther reduce cardiac output and blood pressure. Avoid the use of ULTRAM in patients withcirculatory shock.Risks Of Use In Patients With Increased Intracranial Pressure, Brain Tumors,Head Injury, Or Impaired ConsciousnessIn patients who may be susceptible to the intracranial e±ects of COretention (e.g., those withevidence of increased intracranial pressure or brain tumors), ULTRAM may reduce respiratorydrive, and the resultant COretention can further increase intracranial pressure. Monitor suchpatients for signs of sedation and respiratory depression, particularly wheninitiating therapy withULTRAM.Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use ofULTRAM in patients with impaired consciousness or coma.Risks Of Use In Patients With Gastrointestinal ConditionsULTRAM is contraindicated in patients with known or suspected gastrointestinal obstruction,including paralytic ileus [seeCONTRAINDICATIONS].The tramadol in ULTRAM may cause spasm of the sphincter of Oddi. Opioids may causeincreases in serum amylase. Monitor patients with biliary tract disease, including acutepancreatitis for worsening symptoms.Anaphylaxis And Other Hypersensitivity ReactionsSerious and rarely fatal anaphylactic reactions have been reported in patients receiving therapywith ULTRAM. When the seevents do occur it is often following the ³rst dose. Other reportedallergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysisand Stevens-Johnson syndrome. Patients with a history of hypersensitivity reactionsto tramadoland other opioids may be at increased risk and therefore should not receive ULTRAM [seeCONTRAINDICATIONS]. If anaphylaxis or other hypersensitivity occurs, stop administration ofULTRAM immediately, discontinue ULTRAM permanently, and do not rechallenge with anyformulation of tramadol. Advise patients to seek immediate medical attention if they experienceany symptoms of a hypersensitivity reaction. [see CONTRAINDICATIONS; Patient CounsellingInformation].WithdrawalDo not abruptly discontinue ULTRAM in a patient physically dependent on opioids. Whendiscontinuing ULTRAM in aphysically dependent patient, gradually taper the dosage. Rapidtapering of tramadol in a patient physically dependent onopioids may lead to a withdrawalsyndrome and return of pain [seeDOSAGE AND ADMINISTRATION, Drug Abuse AndDependence].22
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description24/45Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, andbutorphanol) or partial agonist(e.g., buprenorphine) analgesics in patients who are receiving afull opioid agonist analgesic, including ULTRAM. In thesepatients, mixed agonist/antagonist andpartial agonist analgesics may reduce the analgesic e±ect and/or precipitatewithdrawalsymptoms [seeDRUG INTERACTIONS].Driving And Operating MachineryULTRAM may impair the mental or physical abilities needed to perform potentially hazardousactivities such as driving a caror operating machinery. Warn patients not to drive or operatedangerous machinery unless they are tolerant to the e±ects ofULTRAM and know how they willreact to the medication [seePatient Counselling Information].HyponatremiaHyponatremia (serum sodium < 135 mmol/L) has been reported with the use of tramadol, andmany cases are severe (sodiumlevel < 120 mmol/L). Most cases of hyponatremia occurred infemales over the age of 65 and within the ³rst week oftherapy. In some reports, hyponatremiaresulted from the syndrome of inappropriate antidiuretic hormone secretion(SIADH). Monitor forsigns and symptoms of hyponatremia (e.g., confusion, disorientation), during treatmentwithULTRAM, especially during initiation of therapy. If signs and symptoms of hyponatremia arepresent, initiate appropriatetreatment (e.g., ²uid restriction) and discontinue ULTRAM [seeDOSAGE AND ADMINISTRATION: Safe Reduction or Discontinuation Of ULTRAM].HypoglycemiaCases of tramadol-associated hypoglycemia have been reported, some resulting inhospitalization. In most cases, patients hadpredisposing risk factors (e.g. diabetes). Ifhypoglycemia is suspected, monitor blood glucose levels and consider drugdiscontinuation asappropriate [see DOSAGE AND ADMINISTRATION: Safe Reduction Or Discontinuation OfULTRAM].Patient Counseling InformationAdvise the patient to read the FDA-approved patient labeling (Medication Guide).Storage And DisposalBecause of the risks associated with accidental ingestion, misuse, and abuse, advise patients tostore ULTRAM securely, out of sight and reach of children, and in a location not accessible byothers, including visitors to the home [see WARNINGS AND PRECAUTIONS, Drug Abuse AndDependence]. Inform patients that leaving ULTRAM unsecured can pose a deadly risk to othersin the home.Advise patients and caregivers that when medicines are no longer needed, they should bedisposed of promptly. Inform patients that medicine take-back options are the preferred way tosafely dispose of most types of unneeded medicines. If notake back programs or Drug
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description25/45Enforcement Administration (DEA)-registered collectors are available, instruct patients to disposeof ULTRAM by following these four steps:Mix ULTRAM (do not crush) with an unpalatable substance such as dirt, cat litter, or used co±eegrounds;Place the mixture in a container such as a sealed plastic bag;Throw the container in the household trash;Delete all personal information on the prescription label of the empty bottle.Inform patients that they can visit www.fda.gov/drugdisposal for additional information ondisposal of unused medicines.Addiction, Abuse, And MisuseInform patients that the use of ULTRAM, even when taken as recommended, can result inaddiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS ANDPRECAUTIONS]. Instruct patients not to share ULTRAM with others and to take steps to protectULTRAM from theft or misuse.Life-Threatening Respiratory DepressionInform patients of the risk of life-threatening respiratory depression, including information thatthe risk is greatest when starting ULTRAM or when the dosage is increased, and that it can occureven at recommended dosages.Educate patients and caregivers on how to recognize respiratory depression and emphasize theimportance of calling 911 or getting emergency medical help right away in the event of a knownor suspected overdose [seeWARNINGS AND PRECAUTIONS].Patient Access To Naloxone For The Emergency Treatment Of Opioid OverdoseDiscuss with the patient and caregiver the availability of naloxone for the emergency treatmentof opioid overdose, both when initiating and renewing treatment with ULTRAM. Inform patientsand caregivers about the various ways to obtainnaloxone as permitted by individual statenaloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directlyfrom a pharmacist, or as part of a community-based program) [see DOSAGE ANDADMINISTRATION, WARNINGS AND PRECAUTIONS].Educate patients and caregivers on how to recognize the signs and symptoms of an overdose.Explain to patients and caregivers that naloxone's e±ects are temporary, and that they must call911 or get emergency medical help right away in all cases of known or suspected opioidoverdose, even if naloxone is administered [seeOVERDOSAGE].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description26/45If naloxone is prescribed, also advise patients and caregivers:How to treat with naloxone in the event of an opioid overdoseTo tell family and friends about their naloxone and to keep it in a place where family and friendscan access it in an emergencyTo read the Patient Information (or other educational material) that will come with theirnaloxone. Emphasize the importance of doing this before an opioid emergency happens, so thepatient and caregiver will know what to do.Accidental IngestionInform patients that accidental ingestion, especially by children, may result in respiratorydepression or death [see WARNINGS AND PRECAUTIONS].Ultra-Rapid Metabolism Of Tramadol And Other Risk Factors For Life-threatening Respiratory DepressionIn ChildrenAdvise caregivers that ULTRAM is contraindicated in children younger than 12 years of age and inchildren younger than 18years of age following tonsillectomy and/or adenoidectomy. Advisecaregivers of children ages 12 to 18 years of age receiving ULTRAM to monitor for signs ofrespiratory depression [seeWARNINGS AND PRECAUTIONS].Interactions With Benzodiazepines And Other CNS DepressantsInform patients and caregivers that potentially fatal additive e±ects may occur if ULTRAM is usedwith benzodiazepines, CNS depressants, including alcohol, or some illicit drugs and not to usethese concomitantly unless supervised by a healthcare provider [see WARNINGS ANDPRECAUTIONS; DRUG INTERACTIONS].Serotonin SyndromeInform patients that opioids could cause a rare but potentially life-threatening conditionresulting from concomitant administration of serotonergic drugs. Warn patients of thesymptoms of serotonin syndrome, and to seek medical attention right away if symptomsdevelop. Instruct patients to inform their healthcare provider if they are taking, or plan to takeserotonergic medications [seeWARNINGS AND PRECAUTIONS].SeizuresInform patients that ULTRAM may cause seizures with concomitant use of serotonergic agents(including SSRIs, SNRIs, and triptans) or drugs that signi³cantly reduce the metabolic clearance oftramadol [seeWARNINGS AND PRECAUTIONS].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description27/45MAOI InteractionInform patients not to take ULTRAM while using any drugs that inhibit monoamine oxidase.Patients should not start MAOIs while taking ULTRAM [see DRUG INTERACTIONS].Adrenal Insu³ciencyInform patients that opioids could cause adrenal insu´ciency, a potentially life-threateningcondition. Adrenal insu´ciency may present with non-speci³c symptoms and signs such asnausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patientsto seek medical attention if they experience a constellation of these symptoms [see WARNINGSAND PRECAUTIONS].Important Administration InstructionsInstruct patients how to properly take ULTRAM. [see DOSAGE AND ADMINISTRATION].Advise patients not to adjust the dose of ULTRAM without consulting with a physician or otherhealthcare professional.Important Discontinuation InstructionsIn order to avoid developing withdrawal symptoms, instruct patients not to discontinue ULTRAMwithout ³rst discussing a tapering plan with the prescriber [seeDOSAGE AND ADMINISTRATION].HypotensionInform patients that ULTRAM may cause orthostatic hypotension and syncope. Instruct patientshow to recognize symptoms of low blood pressure and how to reduce the risk of seriousconsequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lyingposition) [seeWARNINGS AND PRECAUTIONS].AnaphylaxisInform patients that anaphylaxis has been reported with ingredients contained in ULTRAM.Advise patients how torecognize such a reaction and when to seek medical attention [seeCONTRAINDICATIONS; WARNINGS AND PRECAUTIONS; ADVERSE REACTIONS].PregnancyNeonatal Opioid Withdrawal Syndrome
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description28/45Inform female patients of reproductive potential that prolonged use of ULTRAM duringpregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening ifnot recognized and treated and that the patient should inform their healthcare provider if theyhave used opioids at any time during their pregnancy, especially near the time of birth. [seeWARNINGS AND PRECAUTIONS; Use In Speci²c Populations].Embryo-Fetal ToxicityInform female patients of reproductive potential that ULTRAM may cause fetal harm and toinform the healthcare providerof a known or suspected pregnancy [see Use In Speci²cPopulations].LactationAdvise women that breastfeeding is not recommended during treatment with ULTRAM [seeWARNINGS AND PRECAUTIONS; Use In Speci²c Populations].InfertilityInform patients that chronic use of opioids may cause reduced fertility. It is not known whetherthese e±ects on fertility are reversible [seeUse In Speci²c Populations].Driving Or Operating Heavy MachineryInform patients that ULTRAM may impair the ability to perform potentially hazardous activitiessuch as driving a car or operating heavy machinery. Advise patients not to perform such tasksuntil they know how they will react to the medication[seeWARNINGS AND PRECAUTIONS].ConstipationAdvise patients of the potential for severe constipation, including management instructions andwhen to seek medical attention [see ADVERSE REACTIONS].Maximum Single-Dose And 24-Hour DoseAdvise patients not to exceed the single-dose and 24-hour dose limit and the time intervalbetween doses, since exceeding these recommendations can result in respiratory depression,seizures and death [see DOSAGE AND ADMINISTRATION; WARNINGS AND PRECAUTIONS].Nonclinical ToxicologyCarcinogenesis, Mutagenesis, Impairment Of FertilityCarcinogenesis
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description29/45A slight, but statistically signi³cant, increase in two common murine tumors, pulmonary andhepatic, was observed in an NMRI mouse carcinogenicity study, particularly in aged mice. Micewere dosed orally up to 30 mg/kg in the drinking water(0.36 times the MRHD) for approximatelytwo years, although the study was not done with the Maximum Tolerated Dose. This ³nding isnot believed to suggest risk in humans. No evidence of carcinogenicity was noted in a rat 2-yearcarcinogenicity study testing oral doses of up to 30 mg/kg in the drinking water, 0.73 timesthe MRHD.MutagenesisTramadol was mutagenic in the presence of metabolic activation in the mouse lymphoma assay.Tramadol was not mutagenicin the in vitro bacterial reverse mutation assay using Salmonellaand E. coli (Ames), the mouse lymphoma assay in the absence of metabolic activation, the in vitrochromosomal aberration assay, or the in vivo micronucleus assay in bonemarrow.Impairment Of FertilityNo e±ects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg in male ratsand 75 mg/kg in femalerats. These dosages are 1.2 and 1.8 times the maximum recommendedhuman daily dose based on body surface area, respectively.Use In Speci²c PopulationsPregnancyRisk SummaryProlonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawalsyndrome. Available data with ULTRAM in pregnant women are insu´cient to inform a drug-associated risk for major birth defects and miscarriage.In animal reproduction studies, tramadol administration during organogenesis decreased fetalweights and reduced ossi³cation in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times themaximum recommended human daily dosage (MRHD).Tramadol decreased pup body weightand increased pup mortality at 1.2 and 1.9 times the MRHD [see Data]. Based onanimal data,advise pregnant women of the potential risk to a fetus.The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. Allpregnancies have a background risk of birth defect, loss, or otheradverse outcomes. In the U.S. general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is 2–4% and15–20%,respectively.Clinical ConsiderationsFetal/Neonatal Adverse Reactions
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description30/45Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes canresult in respiratory depressionand physical dependence in the neonate and neonatal opioidwithdrawal syndrome shortly after birth.Neonatal opioid withdrawal syndrome can present as irritability, hyperactivity and abnormalsleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset,duration, and severity of neonatal opioid withdrawal syndrome vary based on the speci³c opioidused, duration of use, timing and amount of last maternal use, and rate of elimination of thedrug by the newborn. Observe newborns for symptoms and signs of neonatal opioid withdrawalsyndromeand manage accordingly [see WARNINGS AND PRECAUTIONS].Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reportedduring postmarketing.Labor Or DeliveryOpioids cross the placenta and may produce respiratory depression and psycho-physiologice±ects in neonates. An opioidantagonist, such as naloxone, must be available for reversal ofopioid-induced respiratory depression in the neonate. ULTRAM is not recommended for use inpregnant women during or immediately prior to labor, when other analgesic techniques aremore appropriate. Opioid analgesics, including ULTRAM, can prolong labor through actionswhich temporarily reduce the strength, duration, and frequency of uterine contractions.However, this e±ect is not consistent andmay be o±set by an increased rate of cervical dilation,which tends to shorten labor. Monitor neonates exposed to opioidanalgesics during labor forsigns of excess sedation and respiratory depression.Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in theumbilical veins compared tomaternal veins was 0.83 for 40 women given tramadol during labor.The e±ect of ULTRAM, if any, on the later growth, development, and functional maturation of thechild is unknown.DataAnimal DataTramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg)and rabbits (75 mg/kg) atmaternally toxic dosages, but was not teratogenic at these dose levels.These doses on a mg/m 2basis are 1.4, 0.6, and 3.6times the maximum recommended humandaily dosage (MRHD) for mouse, rat and rabbit, respectively.No drug-related teratogenic e±ects were observed in progeny of mice (up to 140 mg/kg), rats (upto 80 mg/kg) or rabbits (upto 300 mg/kg) treated with tramadol by various routes. Embryo andfetal toxicity consisted primarily of decreased fetal weights, decreased skeletal ossi³cation andincreased supernumerary ribs at maternally toxic dose levels. Transient delays in developmentalor behavioral parameters were also seen in pups from rat dams allowed to deliver. Embryo and
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description31/45fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would causeextreme maternal toxicity in the rabbit. Thedosages listed for mouse, rat and rabbit are 1.7, 1.9and 14.6 times the MRHD, respectively.Tramadol was evaluated in pre- and post-natal studies in rats. Progeny of dams receiving oral(gavage) dose levels of 50mg/kg 1.2 times the MRHD) or greater had decreased weights, and pupsurvival was decreased early in lactation at 80 mg/kg(1.9 times the MRHD).LactationRisk SummaryULTRAM is not recommended for obstetrical preoperative medication or for post-deliveryanalgesia in nursing mothers because its safety in infants and newborns has not been studied.Tramadol and its metabolite, O-desmethyltramadol (M1), are present in human milk. There is noinformation on the e±ects of the drug on the breastfed infant or the e±ects of the drug on milkproduction. The M1 metabolite is more potent than tramadol in mu opioid receptor binding [seeCLINICAL PHARMACOLOGY]. Published studies have reported tramadol and M1in colostrumwith administration of tramadol to nursing mothers in the early post-partum period. Womenwho are ultra-rapidmetabolizers of tramadol may have higher than expected serum levels of M1,potentially leading to higher levels of M1 inbreast milk that can be dangerous in their breastfedinfants. In women with normal tramadol metabolism, the amount of tramadol secreted intohuman milk is low and dose-dependent. Because of the potential for serious adverse reactions,including excess sedation and respiratory depression in a breastfed infant, advise patients thatbreastfeeding is not recommended during treatment with ULTRAM [seeWARNINGS ANDPRECAUTIONS].Clinical ConsiderationsIf infants are exposed to ULTRAM through breast milk, they should be monitored for excesssedation and respiratorydepression. Withdrawal symptoms can occur in breastfed infants whenmaternal administration of an opioid analgesic isstopped, or when breast-feeding is stopped.DataFollowing a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16hours post dose was 100mcg of tramadol (0.1% of the maternal dose) and 27 mcg of M1.Females And Males Of Reproductive PotentialInfertilityChronic use of opioids may cause reduced fertility in females and males of reproductivepotential. It is not known whether these e±ects on fertility are reversible [see ADVERSEREACTIONS].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description32/45Pediatric UseThe safety and e±ectiveness of ULTRAM in pediatric patients have not been established.Life-threatening respiratory depression and death have occurred in children who receivedtramadol [seeWARNINGS AND PRECAUTIONS]. In some of the reported cases, these eventsfollowed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being anultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochromeP450isoenzyme 2D6). Children with sleep apnea may be particularly sensitive to the respiratorydepressant e±ects of tramadol.Because of the risk of life-threatening respiratory depression anddeath:ULTRAM is contraindicated for all children younger than 12 years of age [seeCONTRAINDICATIONS].ULTRAM is contraindicated for postoperative management in pediatric patients younger than 18years of age following tonsillectomy and/or adenoidectomy [seeCONTRAINDICATIONS].Avoid the use of ULTRAM in adolescents 12 to 18 years of age who have other risk factors thatmay increase their sensitivity to the respiratory depressant e±ects of tramadol unless thebene³ts outweigh the risks. Risk factors include conditions associated with hypoventilation suchas postoperative status, obstructive sleep apnea, obesity, severe pulmonarydisease,neuromuscular disease, and concomitant use of other medications that cause respiratorydepression.Geriatric UseA total of 455 elderly (65 years of age or older) subjects were exposed to ULTRAM in controlledclinical trials. Of those,145 subjects were 75 years of age and older.In studies including geriatric patients, treatment-limiting adverse events were higher in subjectsover 75 years of agecompared to those under 65 years of age. Speci³cally, 30% of those over 75years of age had gastrointestinal treatment-limiting adverse events compared to 17% of thoseunder 65 years of age. Constipation resulted in discontinuation of treatment in 10% of thoseover 75.Respiratory depression is the chief risk for elderly patients treated with opioids, and hasoccurred after large initial doses were administered to patients who were not opioid-tolerant orwhen opioids were co-administered with other agents that depress respiration. Titrate thedosage of ULTRAM slowly in geriatric patients starting at the low end of the dosing range andmonitor closely for signs of central nervous system and respiratory depression [see WARNINGSAND PRECAUTIONS].Tramadol is known to be substantially excreted by the kidney, and the risk of adverse reactionsto this drug may be greater inpatients with impaired renal function. Because elderly patients aremore likely to have decreased renal function, care should be taken in dose selection, and it maybe useful to monitor renal function.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description33/45Renal And Hepatic ImpairmentImpaired renal function results in a decreased rate and extent of excretion of tramadol and itsactive metabolite, M1. Inpatients with creatinine clearances of less than 30 mL/min, dosingreduction is recommended [see DOSAGE AND ADMINISTRATION]. Metabolism of tramadol andM1 is reduced in patients with severe hepatic impairment based on as tudy in patients withadvanced cirrhosis of the liver. In patients with severe hepatic impairment, dosing reduction isrecommended [seeDOSAGE AND ADMINISTRATION].With the prolonged half-life in these conditions, achievement of steady-state is delayed, so that itmay take several days for elevated plasma concentrations to develop.Overdose Information for UltramClinical PresentationAcute overdosage with ULTRAM can be manifested by respiratory depression, somnolenceprogressing to stupor or coma, skeletal muscle ²accidity, cold and clammy skin, constrictedpupils, and, in some cases, pulmonary edema, brady cardia, QTprolongation, hypotension,partial or complete airway obstruction, atypical snoring, seizures, and death. Marked mydriasisrather than miosis may be seen with hypoxia in overdose situations.Deaths due to overdose have been reported with abuse and misuse of tramadol [see WARNINGSAND PRECAUTIONS; Drug Abuse And Dependence]. Review of case reports has indicated thatthe risk of fatal overdose is further increased when tramadol is abused concurrently with alcoholor other CNS depressants, including other opioids.Treatment Of OverdoseIn case of overdose, priorities are the re-establishment of a patent and protected airway andinstitution of assisted or controlled ventilation, if needed. Employ other supportive measures(including oxygen and vasopressors) in the management of circulatory shock and pulmonaryedema as indicated. Cardiac arrest or serious arrhythmias will require advanced life-supportingmeasures.Opioid antagonists, such as naloxone, are speci³c antidotes to respiratory depression resultingfrom opioid overdose. Forclinically signi³cant respiratory or circulatory depression secondary toopioid overdose, administer an opioid antagonist.While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol,the risk of seizures is also increased with naloxone administration. In animals, convulsionsfollowing the administration of toxic doses of ULTRAMcould be suppressed with barbiturates or
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description34/45benzodiazepines but were increased with naloxone. Naloxone administration did not change thelethality of an overdose in mice. Hemodialysis is not expected to be helpful in an overdosebecause it removes less than 7% of the administered dose in a 4-hour dialysis period.Because the duration of opioid reversal is expected to be less than the duration of action oftramadol in ULTRAM, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist issuboptimal or only brief in nature,administer additional antagonist as directed by the product's prescribing information.In an individual physically dependent on opioids, administration of the recommended usualdosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of thewithdrawal symptoms experienced will depend on the degree of physical dependence and thedose of the antagonist administered. If a decision is made to treat serious respiratory depressionin the physically dependent patient, administration of the antagonist should be begun with careand by titration with smaller than usual doses of the antagonist.Contraindications for UltramULTRAM is contraindicated for:all children younger than 12 years of age [see WARNINGS AND PRECAUTIONS].postoperative management in children younger than 18 years of age following tonsillectomyand/or adenoidectomy [seeWARNINGS AND PRECAUTIONS].ULTRAM is also contraindicated in patients with:Signi³cant respiratory depression [seeWARNINGS AND PRECAUTIONS].Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitativeequipment [seeWARNINGS AND PRECAUTIONS].Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ANDPRECAUTIONS].Hypersensitivity to tramadol, any other component of this product or opioids [seeWARNINGSAND PRECAUTIONS].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description35/45Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [seeDRUG INTERACTIONS].Clinical Pharmacology for UltramMechanism Of ActionULTRAM contains tramadol, an opioid agonist and inhibitor of norepinephrine and serotonin re-uptake. Although the mode of action is not completely understood, the analgesic e±ect oftramadol is believed to be due to both binding to μ-opioidreceptors and weak inhibition of re-uptake of norepinephrine and serotonin.Opioid activity is due to both low a´nity binding of the parent compound and higher a´nitybinding of the O-demethylated metabolite M1 to μ-opioid receptors. In animal models, M1 is upto 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opioidantagonist naloxone in several animal tests. The relative contribution of both tramadol and M1to human analgesia is dependent upon the plasma concentrations of each compound [seeCLINICAL PHARMACOLOGY].Analgesia in humans begins approximately within one hour after administration and reaches apeak in approximately two tothree hours.PharmacodynamicsE±ects On The Central Nervous SystemTramadol produces respiratory depression by direct action on brain stem respiratory centers.The respiratory depression involves a reduction in the responsiveness of the brain stemrespiratory centers to both increases in carbon dioxide tensionand electrical stimulation.Tramadol administration may produce a constellation of symptoms including nausea andvomiting, dizziness, and somnolence.Tramadol causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose butare not pathognomonic(e.g., pontine lesions of hemorrhagic or ischemic origins may producesimilar ³ndings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdosesituations.E±ects On The Gastrointestinal Tract And Other Smooth Muscle
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description36/45Tramadol causes a reduction in motility associated with an increase in smooth muscle tone inthe antrum of the stomach and duodenum. Digestion of food in the small intestine is delayedand propulsive contractions are decreased. Propulsive peristaltic waves in the colon aredecreased, while tone may be increased to the point of spasm resulting in constipation. Otheropioid-induced e±ects may include a reduction in biliary and pancreatic secretions, spasm ofsphincter of Oddi, and transient elevations in serum amylase.E±ects On The Cardiovascular SystemTramadol produces peripheral vasodilation, which may result in orthostatic hypotension orsyncope. Manifestations of peripheral vasodilation may include pruritus, ²ushing, red eyes,sweating and/or orthostatic hypotension.The e±ect of oral tramadol on the QTcF interval was evaluated in a double-blind, randomized,four-way crossover, placebo-and positive- (moxi²oxacin) controlled study in 68 adult male andfemale healthy subjects. At a 600 mg/day dose (1.5-foldthe maximum immediate-release dailydose), the study demonstrated no signi³cant e±ect on the QTcF interval.E±ects On The Endocrine SystemOpioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizinghormone (LH) in humans.They also stimulate prolactin, growth hormone (GH) secretion, andpancreatic secretion of insulin and glucagon [see WARNINGS AND PRECAUTIONS; ADVERSEREACTIONS].Chronic use of opioids may in²uence the hypothalamic-pituitary-gonadal axis, leading toandrogen de³ciency that may manifest as low libido, impotence, erectile dysfunction,amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism isunknown because the various medical, physical, lifestyle, and psychological stressors that mayin²uence gonadal hormone levels have not been adequately controlled for in studies conductedto date [seeADVERSE REACTIONS].E±ects On The Immune SystemOpioids have been shown to have a variety of e±ects on components of the immune system in invitro and animal models. The clinical signi³cance of these ³ndings is unknown. Overall, thee±ects of opioids appear to be modestly immunosuppressive.Concentration–E³cacy RelationshipsThe minimum e±ective analgesic concentration will vary widely among patients, especiallyamong patients who have been previously treated with potent opioid agonists. The minimume±ective analgesic concentration of tramadol for any individual patient may increase over timedue to an increase in pain, the development of a new pain syndrome and/or the development ofanalgesic tolerance [see DOSAGE AND ADMINISTRATION].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description37/45Concentration–Adverse Reaction RelationshipsThere is a relationship between increasing tramadol plasma concentration and increasingfrequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS e±ects, andrespiratory depression. In opioid-tolerant patients, the situation may be altered by thedevelopment of tolerance to opioid-related adverse reactions [seeDOSAGE ANDADMINISTRATION].PharmacokineticsThe analgesic activity of ULTRAM is due to both parent drug and the M1 metabolite [seeCLINICAL PHARMACOLOGY]. Tramadol is administered as a racemate and both the [-] and [+]forms of both tramadol and M1 are detected in the circulation. Linear pharmacokinetics havebeen observed following multiple doses of 50 and 100 mg to steady-state.AbsorptionThe mean absolute bioavailability of a 100 mg oral dose is approximately 75%. The mean peakplasma concentration of racemic tramadol and M1 occurs at two and three hours, respectively,after administration in healthy adults. In general, both enantiomers of tramadol and M1 follow aparallel time course in the body following single and multiple doses although smalldi±erences (~10%) exist in the absolute amount of each enantiomer present.Steady-state plasma concentrations of both tramadol and M1 are achieved within two days withfour times per day dosing. There is no evidence of self-induction (see Figure 1 and Table 3below).Figure 1: Mean Tramadol and M1 Plasma Concentration Pro²les after a Single 100 mg OralDose and after Twenty-Nine 100 mg Oral Doses of Tramadol HCl given four times per day.Table 3: Mean (%CV) Pharmacokinetic Parameters for Racemic Tramadol and M1MetabolitePopulation/Dosage Regimen*Parent Drug/MetabolitePeak Cone.(ng/mL)Time to Peak (hrs)Clearance/ F†(mL/min/Kg)t½ (hrs)Healthy Adults, 100 mg qid, MDp.o.Tramadol592 (30)2.3(61)5.90 (25)‡6.7(15)Ml110(29)2.4(46)7.0(14)Healthy Adults, 100 mg SD p.o.Tramadol308 (25)1.6(63)8.50 (31)‡5.6 (20)M155.0 (36)3.0(51)6.7(16)Geriatric, (>75 yrs) 50 mg SDp.o.Tramadol208 (31)§2.1 (19)§6.89 (25)‡M17.0 (23)§
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description38/45Hepatic Impaired, 50 mg SDp.o.Tramadol217(11)1.9(16)4.23 (56)‡13.3 (11)M119.4(12)9.8 (20)18.5 (15)Renal Impaired, CLcr 10-30mL/min 100 mg SD i.v.Tramadol‡‡4.23 (54)‡10.6(31)M1‡‡11.5 (40)Renal Impaired, CLcr<5 mL/min100 mg SD i.v.Tramadol‡‡3.73 (17)‡11.0(29)M1‡‡16.9(18)*SD = Single dose, MD = Multiple dose, p.o.= Oral administration, i.v.= Intravenous administration,q.i.d. = Four times daily†F represents the oral bioavailability of tramadol‡Not applicable§Not measuredFood E±ectsOral administration of ULTRAM with food does not signi³cantly a±ect its rate or extent ofabsorption, therefore, ULTRAM can be administered without regard to food.DistributionThe volume of distribution of tramadol was 2.6 and 2.9 liters/kg in male and female subjects,respectively, following a 100mg intravenous dose. The binding of tramadol to human plasmaproteins is approximately 20% and binding also appears tobe independent of concentration upto 10 mcg/mL. Saturation of plasma protein binding occurs only at concentrations outside theclinically relevant range.EliminationTramadol is eliminated primarily through metabolism by the liver and the metabolites areeliminated primarily by the kidneys. The mean (%CV) apparent total clearance of tramadol after asingle 100 mg oral dose is 8.50 (31) mL/min/kg. The mean terminal plasma elimination half-livesof racemic tramadol and racemic M1 are 6.3 ± 1.4 and 7.4 ± 1.4 hours, respectively. The plasmaelimination half-life of racemic tramadol increased from approximately six hours to sevenhoursupon multiple dosing.MetabolismTramadol is extensively metabolized after oral administration by a number of pathways,including CYP2D6 and CYP3A4, as well as by conjugation of parent and metabolites.Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of thedose is excreted as metabolites. The remainder is excreted either as unidenti³ed or asunextractable metabolites. The major metabolic pathways appear to be N- and O-demethylationand glucuronidation or sulfation in theliver. One metabolite (O-desmethyltramadol, denoted M1)is pharmacologically active in animal models. Formation of M1 isdependent on CYP2D6 and assuch is subject to inhibition, which may a±ect the therapeutic response [Warnings andPrecautions (5.4); Drug Interactions (7)].
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description39/45Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme ofcytochrome P-450. These individuals are “poor metabolizers” of debrisoquine,dextromethorphan, tricyclic antidepressants, among other drugs. Based on apopulation PKanalysis of Phase 1 studies in healthy subjects, concentrations of tramadol were approximately20% higher in“poor metabolizers” versus “extensive metabolizers”, while M1 concentrations were40% lower. Concomitant therapy withinhibitors of CYP2D6 such as ²uoxetine, paroxetine andquinidine could result in signi³cant drug interactions. In vitro druginteraction studies in humanliver microsomes indicate that inhibitors of CYP2D6 such as ²uoxetine and its metabolitenor²uoxetine, amitriptyline and quinidine inhibit the metabolism of tramadol to various degrees,suggesting that concomitant administration of these compounds could result in increases intramadol concentrations and decreased concentrations of M1.The full pharmacological impact ofthese alterations in terms of either e´cacy or safety is unknown. Concomitant use of serotoninre-uptake inhibitors and MAO inhibitors may enhance the risk of adverse events, includingseizure and serotonin syndrome [see WARNINGS AND PRECAUTIONSand DRUGINTERACTIONS].ExcretionTramadol metabolites are eliminated primarily by the kidneys. Approximately 30% of the dose isexcreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.The remainder is excreted either as unidenti³ed or as unextractable metabolites.Special PopulationsHepatic ImpairmentMetabolism of tramadol and M1 is reduced in patients with severe hepatic impairment based ona study in patients with advanced cirrhosis of the liver, resulting in both a larger area under theconcentration time curve for tramadol and longer tramadol and M1 elimination half-lives (13 hrs.for tramadol and 19 hrs. for M1). In patients with severe hepatic impairment, adjustment of thedosing regimen is recommended [seeDOSAGE AND ADMINISTRATION].Renal ImpairmentImpaired renal function results in a decreased rate and extent of excretion of tramadol and itsactive metabolite, M1. Inpatients with creatinine clearances of less than 30 mL/min, adjustmentof the dosing regimen is recommended [see DOSAGE AND ADMINISTRATION]. The total amountof tramadol and M1 removed during a 4-hour dialysis period is less than 7% of the administereddose.Age: GeriatricHealthy elderly subjects aged 65 to 75 years have plasma tramadol concentrations andelimination half-lives comparable to those observed in healthy subjects less than 65 years of age.In subjects over 75 years, maximum serum concentrations are elevated (208 vs. 162 ng/mL) and
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description40/45the elimination half-life is prolonged (7 vs. 6 hours) compared to subjects 65 to 75 years of age.Adjustment of the daily dose is recommended for patients older than 75 years [see DOSAGEAND ADMINISTRATION].SexThe absolute bioavailability of tramadol was 73% in males and 79% in females. The plasmaclearance was 6.4 mL/min/kg inmales and 5.7 mL/min/kg in females following a 100 mg IV doseof tramadol. Following a single oral dose, and after adjusting for body weight, females had a 12%higher peak tramadol concentration and a 35% higher area under the concentration-time curvecompared to males. The clinical signi³cance of this di±erence is unknown.Poor / Extensive Metabolizers, CYP2D6The formation of the active metabolite, M1, is mediated by CYP2D6, a polymorphic enzyme.Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme ofcytochrome P450 metabolizing enzyme system. These individuals are “poor metabolizers” ofdebrisoquine, dextromethorphan and tricyclic antidepressants, among other drugs.Based on apopulation PK analysis of Phase 1 studies with IR tablets in healthy subjects, concentrations oftramadol wereapproximately 20% higher in “poor metabolizers” versus “extensive metabolizers,”while M1 concentrations were 40%lower.Clinical StudiesULTRAM has been given in single oral doses of 50, 75 and 100 mg to patients with pain followingsurgical procedures and pain following oral surgery (extraction of impacted molars).In single-dose models of pain following oral surgery, pain relief was demonstrated in somepatients at doses of 50 mg and 75mg. A dose of 100 mg ULTRAM tended to provide analgesiasuperior to codeine sulfate 60 mg, but it was not as e±ective asthe combination of aspirin 650mg with codeine phosphate 60 mg.ULTRAM has been studied in three long-term controlled trials involving a total of 820 patients,with 530 patients receiving ULTRAM. Patients with a variety of chronic painful conditions werestudied in double-blind trials of one to three months duration. Average daily doses ofapproximately 250 mg of ULTRAM in divided doses were generally comparable to ³ve doses ofacetaminophen 300 mg with codeine phosphate 30 mg (TYLENOL with Codeine #3) daily, ³vedoses of aspirin325 mg with codeine phosphate 30 mg daily, or two to three doses ofacetaminophen 500 mg with oxycodone hydrochloride5 mg (TYLOX) daily.Titration TrialsIn a randomized, blinded clinical study with 129 to 132 patients per group, a 10-day titration to adaily ULTRAM dose of200 mg (50 mg four times per day), attained in 50 mg increments every 3days, was found to result in fewer discontinuations due to dizziness or vertigo than titration over
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description41/45only 4 days or no titration. In a second study with 54 to 59 patients per group, patients who hadnausea or vomiting when titrated over 4 days were randomized to re-initiate ULTRAM therapyusing slower titration rates.A 16-day titration schedule, starting with 25 mg every morning and using additional doses in 25mg increments every thirdday to 100 mg/day (25 mg four times per day), followed by 50 mgincrements in the total daily dose every third day to 200mg/day (50 mg four times per day),resulted in fewer discontinuations due to nausea or vomiting and fewer discontinuations due toany cause than did a 10-day titration schedule.Figure 2:Protocol CAPSS-047 Time to Discontinuation Due to Nauseal/VomitingPatient Information for UltramULTRAM®[UHL-tram](tramadol hydrochloride) TabletsULTRAM is
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description42/45A strong prescription pain medicine that contains an opioid (narcotic) that is used for themanagement pain in adults, when other pain treatments such as non-opioid pain medicines donot treat your pain well enough or you cannot toleratethem.An opioid pain medicine that can put you at risk for overdose and death. Even if you take yourdose correctly asprescribed you are at risk for opioid addiction, abuse, and misuse that can leadto death.Important information about ULTRAM:Get emergency help or call 911 right away if you take too much ULTRAM (overdose). When you³rst start taking ULTRAM, when your dose is changed, or if you take too much (overdose), seriousor life-threatening breathing problems that can lead to death may occur. Talk to your healthcareprovider about naloxone, a medicine for the emergency treatment of an opioid overdose.Taking ULTRAM with other opioid medicines, benzodiazepines, alcohol, or other central nervoussystem depressants(including street drugs) can cause severe drowsiness, decreased awareness,breathing problems, coma, and death.Never give anyone else your ULTRAM. They could die from taking it. Selling or giving awayULTRAM is against the law.Store ULTRAM securely, out of sight and reach of children, and in a location not accessible byothers, including visitors to the home.Important Information Guiding Use in Pediatric Patients:Do not give ULTRAM to a child younger than 12 years of age.Do not give ULTRAM to a child younger than 18 years of age after surgery to remove the tonsilsand/or adenoids.Avoid giving ULTRAM to children between 12 to 18 years of age who have risk factors forbreathing problems such as obstructive sleep apnea, obesity, or underlying lung problems.Do not take ULTRAM if you have:Severe asthma, trouble breathing, or other lung problems.A bowel blockage or have narrowing of the stomach or intestines.An allergy to tramadol.Taken a Monoamine Oxidase Inhibitor, MAOI, (medicine used for depression) within the last 14days.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description43/45Before taking ULTRAM, tell your healthcare provider if you have a history of:head injury, seizuresproblems urinatingliver, kidney, thyroid problemspancreas or gallbladder problemsabuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental healthproblems.Tell your healthcare provider if you are:pregnant or planning to become pregnant. Prolonged use of ULTRAM during pregnancy cancause withdrawal symptoms in your newborn baby that could be life-threatening if notrecognized and treated.breastfeeding. Not recommended; it may harm your baby.living in a household where there are small children or someone who has abused street orprescription drugs.taking prescription or over-the-counter medicines, vitamins, or herbal supplements. TakingULTRAM with certain other medicines can cause serious side e±ects that could lead to death.When taking ULTRAM:Do not change your dose. Take ULTRAM exactly as prescribed by your healthcare provider. Usethe lowest dosepossible for the shortest time needed.Take your prescribed dose as indicated by your healthcare provider. The maximum dosage is 1 or2 tablets every 4 to 6hours, as needed for pain relief. Do not take more than your prescribeddose and do not take more than 8 tablets per day. If you miss a dose, take your next dose at yourusual time.Call your healthcare provider if the dose you are taking does not control your pain.If you have been taking ULTRAM regularly, do not stop taking ULTRAM without talking to yourhealthcare provider.Dispose of expired, unwanted, or unused ULTRAM by taking your drug to an authorized DrugEnforcement Administration (DEA)-registered collector or drug take-back program. If one is notavailable, you can dispose of ULTRAM by mixing the product with dirt, cat litter, or co±eegrounds; placing the mixture in a sealed plastic bag, and throwing the bag in your trash.
2/22/24, 10:57 AMUltram (Tramadol Hcl): Side Effects, Uses, Dosage, Interactions, Warningshttps://www.rxlist.com/ultram-drug.htm#description44/45While taking ULTRAM DO NOT:Drive or operate heavy machinery, until you know how ULTRAM a±ects you. ULTRAM can makeyou sleepy, dizzy, orlightheaded.Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Usingproducts containing alcoholduring treatment with ULTRAM may cause you to overdose and die.The possible side e±ects of ULTRAM:constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Callyour healthcare provider if you have any of these symptoms and they are severe.Get emergency medical help or call 911 right away if you have:trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue,or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation,high body temperature, trouble walking, sti± muscles, or mental changes such as confusion.These are not all the possible side e±ects of ULTRAM. Call your doctor for medical advice aboutside e±ects. You may report side e±ects to FDA at 1-800-FDA-1088. For more information go todailymed.nlm.nih.gov.This Medication Guide has been approved by the U.S. Food and Drug Administration.