Jakavi Drug Interactions

Agents that may alter plasma concentration of ruxolitinib: Strong CYP3A4 inhibitors: In healthy subjects receiving ketoconazole, a strong CYP3A4 inhibitor, at 200 mg twice daily for four days, the AUC of ruxoltinib increased by 91% and the half-life was prolonged from 3.7 to 6.0 hours.
When administering Jakavi with strong CYP3A4 inhibitors the total daily dose of Jakavi should be reduced by approximately 50%, except in GvHD patients. The effect of strong CYP3A4 inhibitors in patients with GvHD was not found to have a significant impact on any parameter in the Population PK model.
Patients should be closely monitored for cytopenias and dose titrated based on safety and efficacy (see Dosage & Administration).
Mild or moderate CYP3A4 inhibitors: In healthy subjects receiving erythromycin, a moderate CYP3A4 inhibitor, at 500 mg twice daily for four days, there was a 27% increase in the AUC of ruxolitinib.
No dose adjustment is recommended when Jakavi is co-administered with mild or moderate CYP3A4 inhibitors (e.g. erythromycin). Patients should be closely monitored for cytopenias when initiating therapy with a moderate CYP3A4 inhibitor.
Dual moderate CYP2C9 and CYP3A4 inhibitors (e.g Fluconazole): In healthy subjects receiving fluconazole, a dual CYP2C9 and CYP3A4 inhibitor, as a single 400 mg dose followed by 200 mg once daily for seven days, there was a 232% increase in the AUC of ruxolitinib. A 50% dose reduction should be considered when using medicinal products which are dual inhibitors of CYP2C9 and CYP3A4 enzymes. The concomitant use of Jakavi with fluconazole doses of greater than 200 mg daily should be avoided.
CYP3A4 inducers: Upon initiation of a CYP3A4 inducer, no dose adjustment is recommended. Gradual dose increases of Jakavi may be considered if the effectiveness of therapy is diminished during treatment with a CYP3A4 inducer.
In healthy subjects receiving rifampin, a potent CYP3A4 inducer, at 600 mg once daily for ten days, the AUC of Jakavi following a single dose decreased by 71% and the half-life decreased from 3.3 to 1.7 hours. The relative amount of active metabolites increased in relation to parent compound.
P-glycoprotein and other transporters: No dose adjustment is recommended when Jakavi is co-administered with substances that interact with P-gp and other transporters.
Other drug interactions studied: CYP3A4 substrates: A study in healthy subjects indicated that Jakavi had no clinically significant pharmacokinetic interaction with midazolam (CYP3A4 substrate).
Oral contraceptives: A study in healthy subjects indicated that Jakavi does not affect the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel. Therefore it is not anticipated that contraceptive efficacy of this combination will be compromised by co-administration of ruxolitinib.