Table 3 Recommended dose adjustments in the setting of drug-drug interactions

Nilotinib

*

Should interrupt TKI therapy. If cannot interrupt TKI therapy, consider reducing TKI dose to:

300 mg QD (Resistant/intolerant Ph + CML)

200 mg QD (Newly diagnosed Chronic Phase Ph + CML, with careful monitoring, especially of QT interval)

If 3A4 inhibitor discontinued, allow washout period prior to uptitrating dose.

Pazopanib

*

Reduce TKI dose to 400 mg QD (careful monitoring). Further dose reductions may be necessary if toxicity occurs.

Ponatinib

*

Reduce TKI dose to 30 mg QD

Ruxolitinib

*

Dose of TKI:

Myelofibrosis

-Platelets ≥ 100,000/mm³: 10 mg BID

-Platelets 50,000/mm³ - 100,000/mm³: 5 mg QD

Polycythemia Vera: 5 mg BID

Patients on already stable TKI doses of:

-5 mg QD: AVOID or interrupt TKI therapy

-5 mg BID: Reduce TKI dose to 5 mg QD

- ≥ 10 mg BID: Reduce TKI dose by 50% (rounded to closest available tablet strength)

D

(Canadian Labeling)

Reduce TKI dose by 50% (rounded to closest available tablet strength).

Monitor hematologic parameters more frequently (i.e. twice weekly).

-If platelets < 100,000/mm3: AVOID

-Titrate dose based on safety & efficacy

Sunitinib

*

Consider TKI dose reduction to minimum of:

GIST, RCC: 37.5 mg/day

PNET: 25 mg/day