|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(TRA ma dole)
Generic Available (U.S.)
Yes: Extended release tablet, immediate release tablet
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Relief of moderate to moderately-severe pain
Extended release formulations are indicated for patients requiring around-the-clock management of moderate to moderately-severe pain for an extended period of time
Use: Dental
Relief of moderate to moderately-severe dental pain
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal studies. Tramadol has been shown to cross the human placenta when administered during labor. Postmarketing reports following tramadol use during pregnancy include neonatal seizures, withdrawal syndrome, fetal death, and stillbirth. Not recommended for use during labor and delivery.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Sixteen hours following a single 100 mg I.V. dose, the amount of tramadol found in breast milk was 0.1% of the maternal dose. Use is not recommended by the manufacturer for postdelivery analgesia in nursing mothers.
Contraindications
Hypersensitivity to tramadol, opioids, or any component of the formulation
Additional contraindications for Ultram®, Rybix™ ODT, and Ultram® ER: Any situation where opioids are contraindicated, including acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugs
Additional contraindications for ConZip™, Ryzolt™: Severe/acute bronchial asthma, hypercapnia, or significant respiratory depression in the absence of appropriately monitored setting and/or resuscitative equipment
Canadian product labeling:
Tramadol is contraindicated during or within 14 days following MAO inhibitor therapy
Extended release formulations (Ralivia™ ER [CAN], Tridural™[CAN], and Zytram® XL [CAN]): Additional contraindications: Severe (Clcr <30 mL/minute) renal dysfunction, severe (Child-Pugh class C) hepatic dysfunction
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylactoid reactions: Rare but serious anaphylactoid reactions (including fatalities) often following initial dosing have been reported. Pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome also have been reported with use. Previous anaphylactoid reactions to opioids may increase risks for similar reactions to tramadol.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Seizures: Even when taken within the recommended dosage seizures may occur; risk is increased in patients receiving serotonin reuptake inhibitors (SSRIs or anorectics), other opioids, tricyclic antidepressants or other cyclic compounds (including cyclobenzaprine, promethazine), neuroleptics, MAO inhibitors, drugs which may lower seizure threshold, or drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors). Patients with a history of seizures, or with a risk of seizures (head trauma, metabolic disorders, CNS infection, malignancy, or during alcohol/drug withdrawal) are also at increased risk.
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists.
• Ethanol use: Use with caution in heavy alcohol users.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution and reduce dosage in patients with mild-to-moderate hepatic impairment; extended release formulations should not be used in severe hepatic impairment (Child-Pugh class C); Ryzolt™ (extended release tablet) should not be used in any degree of hepatic impairment.
• Renal impairment: Use with caution and reduce dosage in patients with mild-to-moderate renal impairment; extended release formulations should not be used in severe renal impairment Clcr <30 mL/minute.
• Respiratory disease: Patients with respiratory disorders (eg, significant chronic obstructive pulmonary disease (COPD), cor pulmonale, hypoxia, hypercapnia) may be at greater risk of respiratory depression.
• Suicide risk: Suicide risk: Avoid use in patients who are suicidal; use with caution in patients taking tranquilizers and/or antidepressants, or those with an emotional disturbance including depression.
Concurrent drug therapy issues:
• CNS depressants: Use with caution and reduce dosage when administering to patients receiving other CNS depressants; may cause CNS depression and/or respiratory depression.
• Serotonin syndrome: Avoid, if possible, use with serotonergic agents such as TCAs, MAO inhibitors (use with extreme caution; contraindicated in Canadian product labeling), triptans, venlafaxine, trazodone, lithium, sibutramine, meperidine, dextromethorphan, St John's wort, SNRIs, and SSRIs; use caution with drugs which impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors); concomitant use may increase the risk of serotonin syndrome.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Extended-release formulation should be used with extreme caution in the elderly (particularly >75 years of age); may be more sensitive to adverse effects. Reduce initial dose.
Dosage form specific issues:
• Extended release tablets: Caution patients to swallow tablets whole. Rapid release absorption of tramadol from tablets that are broken, crushed, or chewed may lead to a potentially-lethal overdose.
• Phenylalanine: Some products may contain phenylalanine.
Other warnings/precautions:
• Abuse/misuse/diversion: Healthcare provider should be alert to problems of abuse, misuse, and diversion.
• Withdrawal: Tolerance or drug dependence may result from extended use (withdrawal symptoms have been reported); abrupt discontinuation should be avoided. Tapering of dose at the time of discontinuation limits the risk of withdrawal symptoms.
Adverse Reactions
>10%:
Cardiovascular: Flushing (8% to 16%)
Central nervous system: Dizziness (10% to 33%), headache (4% to 32%), somnolence (7% to 25%), insomnia (2% to 11%)
Dermatologic: Pruritus (3% to 12%)
Gastrointestinal: Constipation (9% to 46%), nausea (15% to 40%), vomiting (5% to 17%), dyspepsia (1% to 13%)
Neuromuscular & skeletal: Weakness (4% to 12%)
1% to 10%:
Cardiovascular: Postural hypotension (2% to 5%), chest pain (1% to <5%), hypertension (1% to <5%), peripheral edema (1% to <5%), vasodilation (1% to <5%)
Central nervous system: Agitation (1% to <5%), anxiety (1% to <5%), apathy (1% to <5%), chills (1% to <5%), confusion (1% to <5%), coordination impaired (1% to <5%), depersonalization (1% to <5%), depression (1% to <5%), euphoria (1% to <5%), fever (1% to <5%), hypoesthesia (1% to <5%), lethargy (1% to <5%), nervousness (1% to <5%), pain (1% to <5%), pyrexia (1% to <5%), restlessness (1% to <5%), malaise (<1% to <5%), fatigue (2%), vertigo (2%)
Dermatologic: Dermatitis (1% to <5%), rash (1% to <5%)
Endocrine & metabolic: Hot flashes (2% to 9%), hyperglycemia (1% to <5%), menopausal symptoms (1% to <5%)
Gastrointestinal: Diarrhea (5% to 10%), xerostomia (3% to 13%), anorexia (1% to 6%), abdominal pain (1% to <5%), appetite decreased (1% to <5%), weight loss (1% to <5%), flatulence (<1% to <5%)
Genitourinary: Pelvic pain (1% to <5%), prostatic disorder (1% to <5%), urine abnormalities (1% to <5%), urinary tract infection (1% to <5%), urinary frequency (<1% to <5%), urinary retention (<1% to <5%)
Neuromuscular & skeletal: Arthralgia (1% to 5%), back pain (1% to <5%), creatine phosphokinase increased (1% to <5%), myalgia (1% to <5%), hypertonia (1% to <5%), neck pain (1% to <5%), rigors (1% to <5%), paresthesia (1% to <5%), tremor (1% to <5%)
Ocular: Blurred vision (1% to <5%), miosis (1% to <5%)
Respiratory: Bronchitis (1% to <5%), congestion (nasal/sinus) (1% to <5%), cough (1% to <5%), dyspnea (1% to <5%), nasopharyngitis (1% to <5%), pharyngitis (1% to <5%), rhinitis (1% to <5%), rhinorrhea (1% to <5%), sinusitis (1% to <5%), sneezing (1% to <5%), sore throat (1% to <5%), upper respiratory infection (1% to <5%)
Miscellaneous: Diaphoresis (2% to 9%), flu-like syndrome (1% to < 5%), withdrawal syndrome (1% to <5%), shivering (<1% to <5%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Abnormal gait, allergic reaction, amnesia, anaphylactoid reactions, anaphylaxis, anemia, angioedema, appendicitis, ALT increased/decreased, AST increased/decreased, bradycardia, bronchospasm, BUN increased, cataracts, cellulitis, cholecystitis, cholelithiasis, clamminess, cognitive dysfunction, concentration difficulty, creatinine increased, deafness, disorientation, diverticulitis, dreams abnormal, dysphagia, dysuria, ear infection, ECG abnormalities, edema, fecal impaction, gastroenteritis, gastrointestinal bleeding, GGT increased, gout, hallucination, hematuria, hemoglobin decreased, hepatitis, hypotension, hypersensitivity, irritability, joint stiffness, libido decreased, liver enzymes increased, liver failure, menstrual disorder, MI, migraine, muscle cramps, muscle spasms, muscle twitching, myocardial ischemia, night sweats, orthostatic hypotension, palpitation, pancreatitis, peripheral edema, peripheral ischemia, pneumonia, proteinuria, pulmonary edema, pulmonary embolism, sedation, seizure, serotonin syndrome, sleep disorder, speech disorder, Stevens-Johnson syndrome, stomatitis, suicidal tendency, syncope, taste perversion, tachycardia, thrombocytopenia, tinnitus, toxic epidermal necrolysis, urticaria, vesicles, visual disturbance
A withdrawal syndrome may include anxiety, diarrhea, hallucinations (rare), nausea, pain, piloerection, rigors, sweating, and tremor. Uncommon discontinuation symptoms may include severe anxiety, panic attacks, or paresthesia.
Metabolism/Transport Effects
Substrate of CYP2B6 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Antipsychotics: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP2D6 Inhibitors (Moderate): May diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
MAO Inhibitors: TraMADol may enhance the neuroexcitatory and/or seizure-potentiating effect of MAO Inhibitors. TraMADol may enhance the serotonergic effect of MAO Inhibitors. Management: Consider alternatives to combined treatment with tramadol and monoamine oxidase inhibitors due to an increased risk of serotonin syndrome and seizures. Avoid transdermal selegiline. Risk D: Consider therapy modification
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk D: Consider therapy modification
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. TraMADol may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): TraMADol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food:
Immediate release tablet: Rate and extent of absorption were not significantly affected.
Extended release:
ConZip™: Rate and extent of absorption were unaffected.
Ryzolt™: Increased Cmax; no effect on AUC.
Ultram® ER: High-fat meal reduced Cmax and AUC, and increased Tmax by 3 hours.
Orally disintegrating tablet: Food delays the time to peak serum concentration by 30 minutes; extent of absorption was not significantly affected.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Tramadol and its active metabolite (M1) binds to μ-opiate receptors in the CNS causing inhibition of ascending pain pathways, altering the perception of and response to pain; also inhibits the reuptake of norepinephrine and serotonin, which also modifies the ascending pain pathway
Pharmacodynamics/Kinetics
Onset of action: Immediate release: ~1 hour
Duration: 9 hours
Absorption: Immediate release formulation: Rapid and complete; Extended release formulation: Delayed
Distribution: Vd: 2.5-3 L/kg
Protein binding, plasma: ~20%
Metabolism: Extensively hepatic via demethylation (mediated by CYP3A4 and CYP2B6), glucuronidation, and sulfation; has pharmacologically active metabolite formed by CYP2D6 (M1; O-desmethyl tramadol)
Bioavailability: Immediate release: 75%; Extended release: Ultram® ER: 85% to 90% (as compared to immediate release), Zytram® XL, Tridural™: 70%, Ryzolt™: ~95% (as compared to immediate release)
Half-life elimination: Tramadol: ~6-8 hours; Active metabolite: 7-9 hours; prolonged in elderly, hepatic or renal impairment; Zytram® XL: ~16 hours; Ralivia™ ER, Ryzolt™, Tridural™: ~5-9 hours
Time to peak: Immediate release: ~2 hours; Extended release: ConZip™: ~10-12 hours, Ryzolt™: ~4 hours, Tridural™: ~4 hours, Ultram® ER: ~12 hours
Excretion: Urine (30% as unchanged drug; 60% as metabolites)
Dosage
Oral: Moderate-to-severe pain:
Children ≥17 years and Adults:
Immediate release: 50-100 mg every 4-6 hours (not to exceed 400 mg/day).For patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 25 mg/day and titrating dose by 25 mg every 3 days, until reaching 25 mg 4 times/day. The total daily dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.
Orally-disintegrating tablet (Rybix™ ODT): 50-100 mg every 4-6 hours (not to exceed 400 mg/day); for patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 50 mg/day and titrating dose by 50 mg every 3 days, until reaching 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.
Adults: Extended release:
ConZip™, Ultram® ER:
Patients not currently on immediate-release: 100 mg once daily; titrate every 5 days (maximum: 300 mg/day)
Patients currently on immediate-release: Calculate 24-hour immediate release total dose and initiate total extended release daily dose (round dose to the next lowest 100 mg increment); titrate as tolerated to desired effect (maximum: 300 mg/day)
Ryzolt™:
Patients not currently on immediate-release: 100 mg once daily; titrate every 2-3 days by 100 mg/day increments; usual daily dose: 200-300 mg/day (maximum: 300 mg/day)
Patients currently on immediate-release: Calculate 24 hour immediate release total dose and initiate total extended release daily dose (round dose to the next lowest 100 mg increment); titrate as tolerated to desired effect (maximum: 300 mg/day)
Ralivia™ ER (Canadian labeling, not available in U.S.): 100 mg once daily; titrate every 5 days as needed based on clinical response and severity of pain (maximum: 300 mg/day)
Tridural™ (Canadian labeling, not available in U.S.): 100 mg once daily; titrate by 100 mg/day every 2 days as needed based on clinical response and severity of pain (maximum: 300 mg/day)
Zytram® XL (Canadian labeling, not available in U.S.): 150 mg once daily; if pain relief is not achieved may titrate by increasing dosage incrementally, with sufficient time to evaluate effect of increased dosage; generally not more often than every 7 days (maximum: 400 mg/day)
Elderly >65 years: Use caution and initiate at the lower end of the dosing range
Elderly >75 years:
Immediate release: Do not exceed 300 mg/day; see dosing adjustments for renal and hepatic impairment.
Extended release: Use with great caution. See adult, renal, and hepatic dosing.
Dosing adjustment in renal impairment:
Immediate release: Clcr <30 mL/minute: Administer 50-100 mg dose every 12 hours (maximum: 200 mg/day)
Extended release: Should not be used in patients with Clcr <30 mL/minute
Dosing adjustment in hepatic impairment:
Immediate release: Cirrhosis: Recommended dose: 50 mg every 12 hours
Extended release: Should not be used in patients with severe (Child-Pugh class C) hepatic dysfunction; Ryzolt™ should not be used in any degree of hepatic impairment
Dental Usual Dosing
Moderate-to-severe chronic pain: Oral:
Adults:
Immediate release formulation: 50-100 mg every 4-6 hours (not to exceed 400 mg/day)
For patients not requiring rapid onset of effect, tolerability may be improved by starting dose at 25 mg/day and titrating dose by 25 mg every 3 days, until reaching 25 mg 4 times/day. The total daily dose may then be increased by 50 mg every 3 days as tolerated, to reach dose of 50 mg 4 times/day. After titration, 50-100 mg may be given every 4-6 hours as needed up to a maximum 400 mg/day.
Extended release formulations:
Ultram® ER:
Patients not currently on immediate-release: 100 mg once daily; titrate every 5 days (maximum: 300 mg/day)
Patients currently on immediate-release: Calculate 24-hour immediate release total and initiate total daily dose (round dose to the next lowest 100 mg increment); titrate (maximum: 300 mg/day)
Ralivia™ ER (Canadian labeling, not available in U.S.): 100 mg once daily; titrate every 5 days as needed based on clinical response and severity of pain (maximum: 300 mg/day)
Ryzolt™:
Patients not currently on immediate-release: 100 mg once daily; titrate every 2-3 days by 100 mg/day increments; usual daily dose: 200-300 mg/day (maximum: 300 mg/day)
Patients currently on immediate-release: Calculate 24 hour immediate release total dose and initiate total extended release daily dose (round dose to the next lowest 100 mg increment); titrate (maximum: 300 mg/day)
Tridural™ (Canadian labeling, not available in U.S.): 100 mg once daily; titrate by 100 mg/day every 2 days as needed based on clinical response and severity of pain (maximum: 300 mg/day)
Zytram® XL (Canadian labeling, not available in U.S.): 150 mg once daily; if pain relief is not achieved may titrate by increasing dosage incrementally, with sufficient time to evaluate effect of increased dosage; generally not more often than every 7 days (maximum: 400 mg/day)
Elderly >75 years:
Immediate release: 50 mg every 6 hours (not to exceed 300 mg/day); see dosing adjustments for renal and hepatic impairment.
Extended release formulation: Use with great caution. See adult dosing.
Administration: Oral
Immediate release: Administer without regard to meals.
Extended release: Swallow whole; do not crush, chew, or split.
ConZip™, Zytram® XL (Canadian labeling, not available in U.S.): May administer without regard to meals.
Ultram® ER, Ralivia™ ER (Canadian labeling, not available in U.S.), Tridural™ (Canadian labeling, not available in U.S.): May administer without regard to meals, but administer in a consistent manner of either with or without meals.
Orally-disintegrating tablet: Remove from foil blister by peeling back (do not push tablet through the foil). Place tablet on tongue and allow to dissolve (may take ~1 minute); water is not needed, but may be administered with water. Do not chew, break, or split tablet.
Monitoring Parameters
Pain relief, respiratory rate, blood pressure, and pulse; signs of tolerance, abuse, or suicidal ideation
Reference Range
100-300 ng/mL; however, serum level monitoring is not required
Test Interactions
May interfere with urine detection of PCP (false-positive).
Dietary Considerations
Some products may contain phenylalanine.
Patient Education
Extended release tablet must be swallowed whole; do not break, chew, or crush. May cause physical and/or psychological dependence. While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or cough preparations) without consulting prescriber. Maintain adequate hydration, unless instructed to restrict fluid intake. You may experience headache, drowsiness, dizziness, dry mouth, or blurred vision; nausea, vomiting, or loss of appetite; insomnia; or constipation. Report severe unresolved constipation, respiratory difficulty or shortness of breath, excessive sedation or increased insomnia and restlessness, rash or hives, seizures, muscle weakness or tremors, or chest pain or palpitations.
Geriatric Considerations
One study in the elderly found that tramadol 50 mg was similar in efficacy as acetaminophen 300 mg with codeine 30 mg. In Ultram® ER trials, elderly patients experienced more adverse effects than younger adults, particularly constipation, fatigue, weakness, postural hypotension, and dyspepsia. In Conzip™ trials, elderly patients also experienced more side effects than younger adults. For this reason, the extended release formulations should probably be avoided in the elderly, or only used with great caution.
Anesthesia and Critical Care Concerns/Other Considerations
Tramadol 50 mg is comparable to codeine 60 mg; tramadol 100 mg is comparable to aspirin 650 mg/codeine 60 mg. Tramadol is 5-10 times less potent than morphine and reported to cause less respiratory depression.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation). See Dental Health Professional Considerations.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
Literature reports suggest that the efficacy of tramadol in oral surgery pain is equivalent to the combination of aspirin and codeine. One study (Olson, 1990) showed acetaminophen and dextropropoxyphene combination to be superior to tramadol and another study showed tramadol to be superior to acetaminophen and dextropropoxyphene combination. Tramadol appears to be at least equal to if not better than codeine alone. Seizures have been reported with the use of tramadol.
Mental Health: Effects on Mental Status
May cause dizziness, drowsiness, or restlessness
Mental Health: Effects on Psychiatric Treatment
Avoid if possible, the use of tramadol with serotonergic agents such as TCAs, MAO inhibitors (contraindicated during or within 14 days of MAO inhibitor therapy in Canadian product labeling), triptans, venlafaxine, trazodone, lithium, sibutramine, meperidine, dextromethorphan, St John's wort, SNRIs, and SSRIs. Use caution with drugs which may impair metabolism of tramadol (ie, CYP2D6 and 3A4 inhibitors); concomitant use may increase the risk of serotonin syndrome. Symptoms of serotonin syndrome include diaphoresis, myoclonus, shivering, sialorrhea, mydriasis, and agitation. Changes in vital signs include hypertension, tachycardia, tachypnea, and hyperthermia. If the combination of tramadol and a psychotropic agent cannot be avoided, document patient counseling and concurrence of risk:benefit profile; monitor for serotonin syndrome.
Tramadol is also contraindicated during acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugs. In addition, the manufacturer of tramadol notes that concomitant therapy with an SSRI may increase the risk of seizures.
Nursing: Physical Assessment/Monitoring
Assess patient's physical and/or psychological dependence. Discontinue slowly after prolonged use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, variable release, oral, as hydrochloride:
ConZip™: 100 mg [25 mg (immediate release) and 75 mg (extended release)]
ConZip™: 200 mg [50 mg (immediate release) and 150 mg (extended release)]
ConZip™: 300 mg [50 mg (immediate release) and 250 mg (extended release)]
Tablet, oral, as hydrochloride: 50 mg
Ultram®: 50 mg [scored]
Tablet, extended release, oral, as hydrochloride: 100 mg, 200 mg, 300 mg
Ryzolt™: 100 mg, 200 mg, 300 mg
Ultram® ER: 100 mg, 200 mg, 300 mg
Tablet, orally disintegrating, oral, as hydrochloride:
Rybix™ ODT: 50 mg [contains aspartame; mint flavor]
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Ryzolt)
200 mg (30): $213.98
Tablet, 24-hour (TraMADol HCl)
100 mg (30): $109.99
200 mg (30): $145.99
Tablet, 24-hour (Ultram ER)
100 mg (30): $132.96
200 mg (30): $224.99
300 mg (30): $298.00
Tablets (TraMADol HCl)
50 mg (30): $16.99
Tablets (Ultram)
50 mg (30): $57.99
Extemporaneously Prepared
A 5 mg/mL oral suspension may be made with tablets and either Ora-Sweet® SF or a mixture of 30 mL Ora-Plus® and 30 mL strawberry syrup. Crush six 50 mg tramadol tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well before use". Stable for 90 days refrigerated or at room temperature.
Wagner DS, Johnson CE, Cichon-Hensley BK, et al, "Stability of Oral Liquid Preparations of Tramadol in Strawberry Syrup and a Sugar-Free Vehicle," Am J Health Syst Pharm, 2003, 60(12):1268-70.
References
Bril V, England J, Franklin GM, et al, "Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation," Neurology, 2011, 76(20):1758-65.
Collins M, Young I, Sweeney P, et al, “The Effect of Tramadol on Dento-Alveolar Surgical Pain,” Br J Oral Maxillofac Surg, 1997, 35(1):54-8.
Dayer P, Collart L, and Desmeules J, “The Pharmacology of Tramadol,” Drugs, 1994, 47(Suppl 1):3-7.
“Drugs for Pain,” Treat Guidel Med Lett, 2004, 2(23):47-54.
Finkel JC, Rose JB, Schmitz ML, et al, “An Evaluation of the Efficacy and Tolerability of Oral Tramadol Hydrochloride Tablets for the Treatment of Postsurgical Pain in Children,” Anesth Analg, 2002, 94(6):1469-73.
Hull MJ, Griggs D, Knoepp SM, et al, “Postmortem Urine Immunoassay Showing False-Positive Phencyclidine Reactivity in a Case of Fatal Tramadol Overdose,” Am J Forensic Med Pathol, 2006, 27(4):359-62.
Kahn LH, Alderfer RJ, and Graham DJ, “Seizures Reported With Tramadol,” JAMA, 1997, 278(20):1661
Lewis KS and Han NH, “Tramadol: A New Centrally Acting Analgesic,” Am J Health Syst Pharm, 1997, 54(6):643-52.
Mehlisch DR, Minn F, and Brown P, “Tramadol Hydrochloride: Efficacy Compared to Codeine Sulfate, Acetaminophen With Dextropropoxyphene and Placebo in Dental Extraction Pain,” Clin Pharmacol Ther, 1992.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Olson NZ, Sunshine A, O'Neill, et al, Tramadol Hydrochloride: Oral Efficacy in Postoperative Pain, American Pain Society 9th Annual Scientific Meeting, St Louis, MO, October, 1990.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Rauck RL, Ruoff GE, and McGillen, “Comparison of Tramadol and Acetaminophen With Codeine for Long-Term Pain Management in Elderly Patients,” Curr Ther Res, 1994, 556:1417-31.
Riedel F and von Stockhausen HB, “Severe Cerebral Depression After Intoxication With Tramadol in a 6-Month-Old Infant,” Eur J Clin Pharmacol, 1984, 26(5):631-2.
Rose JB, Finkel JC, Arquedas-Mohs A, et al, “Oral Tramadol for the Treatment of Pain of 7-30 Days' Duration in Children, Anesth Analg, 2003, 96(1):78-81.
Ruoff GE, “Slowing the Initial Titration Rate of Tramadol Improves Tolerability,” Pharmacotherapy, 1999, 19(1):88-93.
Sunshine A, Olson NZ, Zighelboim I, et al, “Analgesic Oral Efficacy of Tramadol Hydrochloride in Postoperative Pain,” Clin Pharmacol Ther, 1992; 51(6):740-6.
Sunshine A, “New Clinical Experience With Tramadol,” Drugs, 1994, 47(Suppl 1):8-18.
Voorhees F, Leibold DG, Stumpf, et al, “Tramadol Hydrochloride: Efficacy Compared to Codeine Sulfate, Aspirin With Codeine Phosphate, and Placebo in Dental Extraction Pain,” Clin Pharmacol Ther, 1992, 51:122.
Wynn RL, “Tramadol (Ultram) - A New Kind of Analgesic,” Gen Dent, 1996, 44(3):216-8,220.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
| 
