Duocetz Drug Interactions

CYP2D6 and CYP3A4 Inhibitors: Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors) and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome.
Serotonergic Drugs: There have been postmarketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and alpha2 adrenergic blockers. Caution is advised when DUOCETZ are coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as SSRIs, MAOIs, triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, or St. John's Wort. If concomitant treatment of DUOCETZ with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
Triptans: Based on the mechanism of action of tramadol and the potential for serotonin syndrome, caution is advised when DUOCETZ are coadministered with triptan. If concomitant treatment of tramadol hydrochloride and paracetamol tablets with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
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 DUOCETZ and carbamazepine is not recommended.
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 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.
Potential for Tramadol to Affect Other Drugs: 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. Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampicin and St. John's Wort, with DUOCETZ may affect the metabolism of tramadol leading to altered tramadol exposure.
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 of Cimetidine: Concomitant administration of DUOCETZ and cimetidine has not been studied. Concomitant administration of tramadol and cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. Therefore, no alteration of the DUOCETZ dosage regimen is recommended.
Use with Digoxin: Tramadol has revealed rare reports of digoxin toxicity.
Use with Warfarin Like Compounds: Both tramadol and paracetamol individual products have revealed rare alterations of warfarin effect, including elevation of prothrombin times.
While such changes have been generally of limited clinical significance for the individual products, periodic evaluation of prothrombin time should be performed when DUPCETZ and warfarin-like compounds are administered concurrently.
Carcinogenesis, Mutagenesis, Impairment of Fertility: There are no animal or laboratory studies on the combination product (tramadol and paracetamol) to elevate carcinogenesis, mutagenesis, or impairment of fertility.