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In vitro studies indicate that tramadol is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when tramadol is administered concomitantly at therapeutic doses. Tramadol does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals.
Use With Carbamazepine
Patients taking carbamazepine may have a significantly reduced analgesic effect of tramadol. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of Tramadol Hydrochloride and carbamazepine is not recommended.
Use With Quinidine
Tramadol is metabolized to M1 by CYP2D6. Quinidine is a selective inhibitor of the isoenzyme, so that concomitant administration of quinidine and tramadol results in increased concentrations of tramadol and reduced concentrations of M1. The clinical consequences of these findings are unknown. In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism.
Use With Inhibitors of CYP2D6
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 inhibition of the metabolism of tramadol.
Use With Cimetidine
Concomitant administration with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. Therefore, no alteration of the Tramadol Hydrochloride dosage regimen is recommended.
Use With MAO Inhibitors
Interactions with MAO Inhibitors , due to interference with detoxification mechanisms, have been reported for some centrally acting drugs (see WARNINGS , Use With MAO Inhibitors).
Use With Digoxin and Warfarin
Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity and alteration of warfarin effect, including elevation of prothrombin times.
Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.
This drug should not be used with the following medications because very serious (possibly fatal) interactions may occur: MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine).
Avoid taking MAO inhibitors within 2 weeks before, during, and after treatment with tramadol.
If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting tramadol.
Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other narcotic medications.
Before using tramadol, report the use of other drugs that increase serotonin, such as dextromethorphan, lithium, St. John's wort, sibutramine, street drugs such as MDMA/”ecstasy”, tryptophan, certain antidepressants including SSRIs (such as citalopram, paroxetine) and SNRIs (such as duloxetine, venlafaxine), “triptans” used to treat migraine headaches (such as eletriptan, sumatriptan), among others. The risk of serotonin syndrome may be more likely when you start or increase the dose of these medications.
Also report the use of drugs that might increase seizure risk when combined with tramadol such as isoniazid (INH), phenothiazines (e.g., thioridazine, chlorpromazine, promethazine), theophylline, or tricyclic antidepressants (e.g., amitriptyline), among others. Consult your doctor or pharmacist for details.
Other medications can affect the removal of tramadol from your body, which may affect how tramadol works or increase the risk of side effects. These drugs include quinidine, azole antifungals (such as ketoconazole), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), drugs used to treat seizures (such as carbamazepine, phenytoin), and St. John's wort. This is not a complete list.
Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as certain antihistamines (e.g., diphenhydramine), anti-anxiety drugs (e.g., diazepam), anti-seizure drugs (e.g., phenytoin), medicine for sleep (e.g., zolpidem), muscle relaxants (e.g., cyclobenzaprine).
Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.
This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
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