Interactions : אינטראקציות

4.5    Interaction with other medicinal products and other forms of interaction
Potential for other medicinal products to influence the pharmacokinetics (PK) of tofacitinib 
Since tofacitinib is metabolised by CYP3A4, interaction with medicinal products that inhibit or induce CYP3A4 is likely. Tofacitinib exposure is increased when coadministered with potent inhibitors of CYP3A4 (e.g., ketoconazole) or when administration of one or more concomitant medicinal products results in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole) (see section 4.2).

Tofacitinib exposure is decreased when coadministered with potent CYP inducers (e.g., rifampicin).
Inhibitors of CYP2C19 alone or P-glycoprotein are unlikely to significantly alter the PK of tofacitinib.

Coadministration with ketoconazole (strong CYP3A4 inhibitor), fluconazole (moderate CYP3A4 and potent CYP2C19 inhibitor), tacrolimus (mild CYP3A4 inhibitor) and ciclosporin (moderate CYP3A4 inhibitor) increased tofacitinib AUC, while rifampicin (potent CYP inducer) decreased tofacitinib AUC. Coadministration of tofacitinib with potent CYP inducers (e.g., rifampicin) may result in a loss of or reduced clinical response (see Figure 1). Coadministration of potent inducers of CYP3A4 with tofacitinib is not recommended. Coadministration with ketoconazole and fluconazole increased tofacitinib Cmax, while tacrolimus, ciclosporin and rifampicin decreased tofacitinib Cmax. Concomitant administration with MTX 15-25 mg once weekly had no effect on the PK of tofacitinib in RA patients (see Figure 1).

Figure 1. Impact of other medicinal products on PK of tofacitinib

Coadministered            PK         Ratio and 90% CI                   Recommendation Medicinal Product

CYP3A Inhibitor
Ketoconazole           AUC                                               Tofacitinib dose should be reduced a Cmax

CYP3A & CYP2C19 Inhibitor
Fluconazole            AUC                                               Tofacitinib dose should be reduced a Cmax

CYP Inducer
Rifampicin          AUC                                               Efficacy may be decreased Cmax

Methotrexate          AUC                                               No dose adjustment Cmax

Tacrolimus         AUC                                               Combined use of tofacitinib with Cmax                                               tacrolimus should be avoided 

Ciclosporin          AUC                                               Combined use of tofacitinib with Cmax                                               ciclosporin should be avoided 

0      0.5      1      1.5      2      2.5
Ratio relative to reference
Note: Reference group is administration of tofacitinib alone.
a Tofacitinib dose should be reduced to 5 mg film-coated tablet once daily or oral solution weight-based equivalent in  patients receiving 5 mg or weight-based equivalent twice daily (see section 4.2).

Potential for tofacitinib to influence the PK of other medicinal products 
Coadministration of tofacitinib did not have an effect on the PK of oral contraceptives, levonorgestrel and ethinyl estradiol, in healthy female volunteers.


In RA patients, coadministration of tofacitinib with MTX 15-25 mg once weekly decreased the AUC and Cmax of MTX by 10% and 13%, respectively. The extent of decrease in MTX exposure does not warrant modifications to the individualised dosing of MTX.

Paediatric population

Interaction studies have only been performed in adults.