Simultaneous use of duloxetine (in a dose of 60 mg 2 times / day) did not significantly affect the pharmacokinetics of theophylline metabolized by CYP1A2. Duloxetine is unlikely to have a clinically significant effect on the metabolism of other drugs - CYP1A2 substrates.
Simultaneous administration of duloxetine with potential inhibitors of CYP1A2 (eg, fluoroquinolones) may increase the concentration of duloxetine because CYP1A2 is involved in the metabolism of duloxetine (the appointment of such a combination requires caution and reduced duloxetine doses).
The potent inhibitor of CYP1A2 fluvoxamine (when administered at a dose of 100 mg 1 time / day) reduced the average plasma clearance of duloxetine by approximately 77%.
When prescribing duloxetine with drugs metabolized by CYP2D6 and having a narrow therapeutic index, caution should be exercised (because duloxetine is a mild inhibitor of CYP2D6). With simultaneous application with duloxetine at a dose of 60 mg 2 times / day, the AUC of desipramine (substrate CYP2D6) is increased 3-fold. Simultaneous application with duloxetine (40 mg twice daily) increased the stable portion of the AUC of tolterodine (used at a dose of 2 mg 2 times / day) by 71%, but did not affect the pharmacokinetics of the 5-hydroxyl metabolite. The simultaneous use of duloxetine with potential inhibitors of CYP2D6 can lead to an increase in the concentrations of duloxetine. Paroxetine (when applied at a dose of 20 mg 1 time / day) reduced the average clearance of duloxetine by about 37%. Care should be taken when using duloxetine with CYP2D6 inhibitors (for example, with selective serotonin reuptake inhibitors).
With the simultaneous use of duloxetine and other drugs that affect the central nervous system and have a similar mechanism of action (including ethanol and ethanol-containing drugs), there may be a mutual enhancement of effects (this combination requires caution).
Duloxetine is largely associated with plasma proteins, so simultaneous use with other drugs, highly binding to plasma proteins, can lead to an increase in the concentration of free fractions of both drugs.