Data from FDA - Curated by EPG Health - Last updated 21 December 2016
CONTRAINDICATIONS Tramadol hydrochloride tablets should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids.
Tramadol hydrochloride tablets are contraindicated in any situation where opioids are contraindicated, including
Use in Renal and Hepatic Disease
In patients with creatinine clearances of less than 30 mL/min,
In cirrhotic patients,
Information for Patients Patients should be informed that tramadol hydrochloride may cause seizures and/or serotonin syndrome with concomitant use of serotonergic agents (including
SSRIs, SNRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol.
Tramadol hydrochloride should not be taken with alcohol containing beverages.
Tramadol hydrochloride should be used with
The patient should be instructed to inform the physician if they are pregnant, think they might become pregnant, or are trying to become pregnant (see PRECAUTIONS, Labor and Delivery).
The patient should understand the single-dose and
Drug Interactions CYP2D6 and CYP3A4 Inhibitors Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors (see
PHARMACOLOGY, Pharmacokinetics), such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors), and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce
Serotonergic Drugs There have been postmarketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and?2-adrenergic blockers.
If concomitant treatment of tramadol hydrochloride with a drug affecting the serotonergic neurotransmitter system is clinically warranted,
Triptans Based on the mechanism of action of tramadol and the
If concomitant treatment of tramadol hydrochloride with a triptan is clinically warranted,
Use With Carbamazepine Patients taking
Use With Quinidine Tramadol is metabolized to M1 by CYP2D6.
Quinidine is a selective inhibitor of that isoenzyme, so that concomitant administration of quinidine and tramadol hydrochloride results in
The clinical consequences of these findings are unknown.
In vitro drug interaction studies in human liver microsomes indicate that
Potential for Other Drugs to Affect Tramadol In vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine, paroxetine, and amitriptyline could result in some
Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampin and St. John 's Wort, with tramadol hydrochloride may affect the metabolism of tramadol leading to altered tramadol exposure.
Potential for Tramadol to Affect Other Drugs In vitro studies indicate that
Tramadol does not appear to induce its own metabolism in humans, since observed
Use With Cimetidine Concomitant administration of tramadol hydrochloride with cimetidine does not result in clinically
Use With Digoxin and Warfarin Postmarketing surveillance has revealed
Mice were dosed orally up to 30 mg/kg (90 mg/m2 or 0.36 times the maximum daily human dosage of 246 mg/m2) for approximately two years, although the study was not done with the Maximum Tolerated Dose.
This finding is not believed to suggest risk in humans.
Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the
Overall, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans.
These dosages are 1.2 and 1.8 times the maximum daily human dosage of 246 mg/m2, respectively.
Pregnancy Teratogenic Effects: Pregnancy Category C Tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg or 360 mg/m2),
These dosages on a mg/ m2 basis are 1.4,?0.6, and?3.6 times the maximum daily human dosage (246 mg/m2) for mouse,
Embryo and fetal toxicity consisted primarily of decreased fetal weights, skeletal ossification and
Embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg (3600 mg/m2), a dose that would cause extreme maternal toxicity in the rabbit.
The dosages listed for mouse,
Nonteratogenic Effects Tramadol was evaluated in peri - and post-natal studies in
Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/m2 or 1.2 times the maximum daily human tramadol dosage) or
Tramadol hydrochloride should be used during pregnancy only if the potential
Neonatal seizures, neonatal withdrawal syndrome, fetal
Labor and Delivery Tramadol hydrochloride should not be used in pregnant women prior to or during labor unless
Tramadol has been shown to cross the placenta.
The effect of tramadol hydrochloride, if any, on the later
Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours postdose was 100 mcg of tramadol (0.1 % of the maternal dose) and 27 mcg of M1.
Pediatric Use The
Geriatric Use In general,
In patients over 75 years of age, daily doses in
A total of 455 elderly (65 years of age or older)
Of those, 145 subjects were 75 years of age and older.
In studies including geriatric patients, treatment-limiting
Specifically, 30 % of those over
Constipation resulted in discontinuation of treatment in 10 % of those over 75.
Of these patients, 375 were 65 years old or
Table 2 reports the cumulative incidence rate of
The most frequently
Although the reactions listed in the table are felt to be probably related to tramadol hydrochloride administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication.
The overall incidence rates of
Table 2: Cumulative Incidence of
and for which the possibility of a causal relationship with tramadol hydrochloride exists. Body as a Whole:
Urogenital:Menopausal symptoms, Urinary frequency, Urinary retention.
Incidence less than 1 %, possibly causally related: the following lists
Body as a Whole:
Cardiovascular: Orthostatic hypotension, Syncope, Tachycardia.
Skin: Stevens-Johnson syndrome/
Urogenital: Dysuria, Menstrual
A causal relationship between tramadol hydrochloride and these events has not been determined.
Sensory: Cataracts, Deafness, Tinnitus.
DOSAGE AND ADMINISTRATION Adults (17 years of age and over) For
After titration, tramadol hydrochloride 50 to 100 mg can be administered as
For the subset of patients for whom
Individualization of Dose
Studies with tramadol in adults have shown that starting at the
In all patients with creatinine clearance less than 30 mL/min,
Since only 7 % of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis.
In general, dose selection for an elderly patient over 65 years old should be
For elderly patients over 75 years old,
|Date Last Revised||30-09-2014|
|Type||HUMAN PRESCRIPTION DRUG|
|Marketing authorisation holder||Accord Healthcare, Inc.|