Tramicet Drug Interactions

Use with inhibitors of CYP3A4: The concomitant use of Tramicet and an inhibitor of CYP3A4 can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1.
Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir).
Use with CYP3A4 Inducers: The concomitant use of Tramicet and an inducer of CYP3A4 can decrease the plasma concentration of tramadol, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol. Examples: Rifampin, carbamazepine, phenytoin.
Use with Benzodiazepines and Other Central Nervous System (CNS) Depressants including alcohol: The concomitant use of tramadol with central nervous system depressants, such as benzodiazepines and other sedatives/hypnotics, anesthetic agents, phenothiazines, tranquilizers, opioids or alcohol, may produce additive CNS depressant effects, such as profound sedation and respiratory depression. If concomitant use of Tramicet with a CNS depressant is clinically necessary, prescribe the lowest effective dosages and minimum duration for both drugs, and follow patients closely for signs of respiratory depression.
Use with Serotonergic Drugs: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Examples: Examples of serotonergic drugs are selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g. mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Use with Monoamine Oxidase Inhibitors (MAOIs): The concomitant use of Tramicet with MAOIs, or use within 14 days of their discontinuation, is contraindicated due to the increased risk of seizures and serotonin syndrome. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity. Examples: Phenelzine, tranylcypromine, linezolid.
Use with Flucloxacillin: High anion gap metabolic acidosis (HAGMA) from pyroglutamic acid (5-oxoprolinemia) has been reported with concomitant use of therapeutic doses of acetaminophen and flucloxacillin.
Use with Warfarin: As medically appropriate, periodic evaluation of prothrombin time should be performed when Tramicet and these agents are administered concurrently due to reports of increased International Normalized Ratio (INR) in some patients.
Use with Inhibitors of CYP2D6: Concomitant administration with inhibitors of CYP2D6 could result in some inhibition of the metabolism of tramadol. Examples: Quinidine, fluoxetine, paroxetine, amitriptyline and bupropion.
Use with Cimetidine: Concomitant administration of tramadol and cimetidine does not result in clinically significant changes in tramadol pharmacokinetics.