Tramadol Hydrochloride
Pronouncation: (TRA-ma-dol HYE-droe-KLOR-ide)Class: Opioid analgesic
Trade Names:
Ultram
- Tablets 50 mg
Trade Names:
Ultram ER
- Tablets, extended-release 100 mg
- Tablets, extended-release 200 mg
- Tablets, extended-release 300 mg
Tridural (Canada)
Zytram XL (Canada)
Pharmacology
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Binds to certain opioid receptors and inhibits reuptake of norepinephrine and serotonin; exact mechanism of action unknown.
Pharmacokinetics
Absorption
Mean absolute bioavailability of tramadol is 75%. High-fat meals increased T max 3 h and decreased C max and AUC 28% and 16%, respectively (ER). T max is 2 to 3 h (immediate-release) and 12 to 15 h for (ER). Steady-state plasma concentrations of both tramadol and the metabolite are achieved within 2 days (immediate-release) and within 4 days (ER).
Distribution
Tramadol is 20% protein bound and is independent of concentrations up to 10 mcg/mL. Vd is approximately 2.7 L/kg. Tramadol follows linear kinetics.
Metabolism
There is no evidence of self-induction. Production of M1 (metabolite) is dependent on CYP-450 2D6. The O-demethylated metabolite is M1. Tramadol is extensively metabolized after administration. The major metabolic pathway is N- and O-demethylation, and glucuronidation or sulfation in liver.
Elimination
30% of a dose is excreted unchanged in urine; 60% is excreted as metabolites. The t ½ is 6.3 h for tramadol immediate-release and 7.4 h for the metabolite. The t ½ is 7.9 h for tramadol ER and 8.8 h for the metabolite.
Onset
The onset of action is 1 h (immediate-release).
Peak
Time to peak effect is 2 to 3 h (immediate-release) and 12 to 15 h (ER).
Special Populations
Renal Function ImpairmentIn patients with renal function impairment, there is a decreased rate and extent of excretion of tramadol and M1. In patients with CrCl less than 30 mL/min, dose adjustment is recommended.
Hepatic Function ImpairmentMetabolism of tramadol and M1 is reduced in patients with advanced cirrhosis. In cirrhotic patients, dose adjustment is recommended.
ElderlyIn patients older than 75 yr of age, dose adjustment is recommended.
GenderAbsolute bioavailability, AUC, and C max are higher in women than in men. The clinical importance of these differences in unknown.
Indications and Usage
Relief of moderate to moderately severe pain (immediate-release); relief of moderate to moderately severe chronic pain for patients who require around-the-clock treatment for an extended period of time (ER).
Unlabeled Uses
Premature ejaculation; restless leg syndrome.
Contraindications
Acute intoxication with alcohol, hypnotics, centrally acting analgesics, narcotics, opioids, or psychotropic agents; hypersensitivity.
Dosage and Administration
Immediate-Release TabletsAdults and Children 17 yr of age and older
PO Start with 25 mg/day in the morning and titrate in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg 4 times daily). Thereafter, increase the dose by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg 4 times daily). After titration, administer 50 to 100 mg every 4 to 6 h as needed for pain relief (max, 400 mg/day).
Elderly (65 yr of age and older)PO Start with low end of dosing (max, 300 mg/day in patients 75 yr of age and older).
Renal Function Impairment (CrCl less than 30 mL/min)PO Increase the dosing interval to 12 h (max, 200 mg/day).
Hepatic Function Impairment (cirrhosis)PO 50 mg every 12 h.
ER TabletsAdults
PO Patients not currently on tramadol immediate-release: Start with 100 mg once daily and titrate as needed in 100 mg increments every 5 days to relief of pain, depending upon tolerability (max, 300 mg/day). Patients currently on tramadol immediate-release: Calculate the tramadol immediate-release dose and start a total dose of tramadol ER rounded down to the next lowest 100 mg increment. Subsequently, individualize the dose as needed. Because of limitations in flexibility of the tramadol ER dosage form, some patients maintained on tramadol immediate-release may not be able to convert to tramadol ER (max, 300 mg/day).
Elderly (65 yr of age and older)PO Use with caution, starting at the low end of the dosing range.
Renal Function Impairmentߙ(CrCl less than 30 mL/min)Do not administer.
Severe Hepatic Function Impairment (Child-Pugh class C)Do not administer.
Storage/Stability
Store at 59° to 86°F in a tightly closed container.
Drug Interactions
Alpha-2 adrenergic blockers, lithium, St. John's wortIncreased the risk of serotonin syndrome.
Amitriptyline, erythromycin, ketoconazole, linezolid, MAOIs, selective 5-HT 1 receptor agonists (eg, sumatriptan), SSRIs (eg, fluoxetine), tricyclic antidepressantsIncreased risk of serotonin syndrome and increased risk of seizures.
CarbamazepineMay reduce serum tramadol levels, leading to decreased efficacy.
CNS depressants (eg, alcohol, anesthetics, narcotics, phenothiazines, sedative-hypnotics, tranquilizers)Risk of CNS and respiratory depression may be increased.
Cyclobenzaprine, drugs that reduce the seizure threshold, neuroleptics, other opioidsRisk of seizures may be increased.
DigoxinDigoxin toxicity has been reported.
QuinidineTramadol plasma levels may be increased; however, the clinical importance of this interaction is not known.
WarfarinAnticoagulant effect of warfarin may be increased.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Postural hypotension (5%); vasodilation (less than 5% to 1%).
CNS
Dizziness/vertigo (33%); headache (32%); somnolence (25%); stimulation (14%); asthenia (12%); insomnia (11%); anxiety, confusion, coordination disturbance, depression, euphoria, hypoesthesia, lethargy, malaise, miosis, nervousness, paresthesia, pyrexia, restlessness, sleep disorder, tremor, weakness (less than 5% to 1%).
Dermatologic
Flushing (16%); pruritus (12%); sweating (9%); dermatitis, skin rash (less than 5% to 1%).
EENT
Blurred vision, nasal congestion, nasopharyngitis, rhinorrhea, sneezing, sore throat, visual disturbance (less than 5% to 1%).
GI
Constipation (46%); nausea (40%); vomiting (17%); dyspepsia (13%); diarrhea, dry mouth (10%); anorexia (6%); abdominal pain, flatulence, viral gastroenteritis (less than 5% to 1%).
Genitourinary
Menopausal symptoms, urinary frequency, urinary retention, urinary tract infection (less than 5% to 1%).
Lab Tests
Increased blood CPK (less than 5% to 1%).
Metabolic-Nutritional
Decreased appetite, decreased weight (less than 5% to 1%).
Musculoskeletal
Arthralgia, back pain, hypertonia, limb pain, neck pain, rigors (less than 5% to 1%).
Respiratory
Bronchitis, cough, dyspnea, sinus congestion, sinusitis, upper respiratory tract infection (less than 5% to 1%).
Miscellaneous
Influenza, influenza-like symptoms (2%); chest pain, fall, feeling hot, fever, pain, (less than 5% to 1%).
Precautions
Pregnancy
Category C .
Lactation
Excreted in breast milk.
Children
Immediate-release: Safety and efficacy not established in children younger than 16 yr of age. ER: Safety and efficacy not established in children younger than 18 yr of age.
Elderly
Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of hepatic, renal, or cardiac function impairment, and concomitant diseases or other drug therapy. In patients older than 75 yr of age, daily doses in excess of 300 mg are not recommended.
Hypersensitivity
Serious and, rarely, fatal anaphylactoid reactions may occur.
Renal Function
Dosage adjustments may be required.
Hepatic Function
Dosage adjustments may be required in patients with cirrhosis.
Acute abdominal conditions
Tramadol may complicate the assessment of acute abdominal conditions.
CNS depressants
Use with caution and in reduced dosage when administering to patients receiving CNS depressants or SSRIs.
Drug abuse
May induce psychic and physical dependence of the morphine type. Do not use in opioid-dependent patients.
Head trauma
Use with caution in patients with increased intracranial pressure or head trauma.
MAOIs (eg, isocarboxazid)
Use with great caution in patients taking MAOIs.
Opioid dependence
Not recommended for patients who are opioid-dependent; use caution when administering to patients who have recently received substantial amounts of opioids.
Respiratory depression
Use with caution.
Serotonin syndrome
Potentially life-threatening serotonin syndrome may develop, particularly when combined with serotinergic agents (eg, SSRIs, SNRIs, triptans).
Seizures
Seizures may occur within the recommended dosage range. In addition, the risk of convulsions may be increased in patients with epilepsy, history of seizures, or risk of seizures (eg, head trauma).
Suicide risk
Do not use in patients who are suicidal or addiction prone (ER only).
Withdrawal
If tramadol is discontinued abruptly, withdrawal symptoms may occur.
Overdosage
Symptoms
Bradycardia, cardiac arrest, coma, constricted pupils, death, hypotension, lethargy, respiratory depression, seizure, skeletal or muscle flaccidity.
Patient Information
- Instruct patient to take the prescribed dose at the recommended intervals.
- Advise patient to swallow the ER tablet whole and not to break, cut, or crush the tablet.
- Instruct patient to report any serious adverse reactions to health care provider.
- Advise patient not to wait until pain level is high to self-medicate; drug will not be as effective.
- Advise patient to avoid using alcohol or other CNS depressants (eg, sleeping pills).
- Advise patient that this medication may cause drowsiness and to use caution while driving or using heavy equipment, or performing other tasks requiring mental alertness.
- Advise patient not to abruptly discontinue this medication; when discontinuing treatment, taper the dose.
- Advise patient to notify health care provider if pain is not relieved by the medication at prescribed dosage.
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More Tramadol Hydrochloride resources:
Tramadol - Includes detailed dosage instructions.
Tramadol Hydrochloride Drug Interactions
