Tyrosine Kinase Inhibitors

Question 1

Imatinib

Answer 1

1. First generation TKI
2. Recommended initial dose = 400 mg once daily for CP-CML
3. Recommended initial dose = 600 mg once daily for AP-CML and BP- CML

Question 2

Imatinib DDI w/ Antidepressants

Answer 2

Minor increase in exposure; Monitor QTc monitoring

Question 3

Imatinib DDI w/ Cardiovascular Meds

Answer 3

Increase in exposure; strongly consider alternative cardiac medication or TKI dose adjustment

Question 4

Imatinib DDI w/ Anti-infectives

Answer 4

Increase in exposure

Question 5

Imatinib Side Effects

Answer 5

~ fluid retention
~ GI upset
~ Muscle cramps
~ rash

Question 6

Nilotinib Dosing : newly diagnosed CP-CML

Answer 6

300 mg twice daily

Question 7

Nilotinib Dosing: resistant or intolerant CP-CML and AP-CML

Answer 7

400 mg twice daily

Question 8

Nilotinib Dosing: BP-CML

Answer 8

400 mg twice daily

Question 9

Nilotinib prolongs the…

Answer 9

QT interval
ECGs should be obtained at baseline, 7 days after initiation, and periodically thereafter, as well as following any dose adjustments

Question 10

Nilotinib DDI w/ PPIs

Answer 10

decrease in exposure

Question 11

Nilotinib DDI w/ H2RAs

Answer 11

decrease in exposure; AVOID; if absolutely necessary consider once daily H2RA greater than or equal to 2 hours after or greater than 10 hours before taking nilotinib

Question 12

Nilotinib DDI w/ Antacids

Answer 12

decrease in exposure if concomitant; use antacids at least 2 hours before or at least 2 hours after taking

Question 13

Nilotinib DDI w/ antidepressants

Answer 13

AVOID d/t cumulative QTc prolongation risk

Question 14

Nilotinib DDI w/ CV Medications

Answer 14

increase in exposure and arrhythmia risk; AVOID

Question 15

Nilotinib DDI w/ anti-infectives (azole antifungals, clarithromycin, telithromycin, ritonavir)

Answer 15

increase in exposure

Question 16

Nilotinib Dosing Considerations

Answer 16

avoid food 2 hours before and 1 hour after taking

Question 17

Omacetaxine Dosing: Resistant or Intolerant CP- CML and AP-CML

Answer 17

Induction: 1.25 mg/m2 twice daily for 14 days of a 28 day cycle
Maintenance: 1.25 mg/m2 twice daily for 7 days of a 28 day cycle

Question 18

Omacetaxine Non Hematologic Toxicity

Answer 18

grade 3 or 4 hyperglycemia

Question 19

Ponatinib Dosing: CP -CML

Answer 19

45 mg once daily with a reduction to 15 mg once daily upon achievement of BCR::ABL1 less than 1%

Question 20

Ponatinib Adverse Reactions

Answer 20

~ arterial occlusive events and venous thromboembolic events
~ heart failure
~ hepatotoxicity
~ CV risk
~ skin rash
~ pancreatitis

Question 21

Ponatinib DDI w/ PPIs

Answer 21

minor decrease in exposure

Question 22

Ponatinib DDI w/ antidepressants

Answer 22

minor increase in exposure; monitor QTc monitoring

Question 23

Ponatinib DDI w/ CV Medications

Answer 23

increase in exposure

Question 24

Ponatinib DDI w/ anti-infectives (azole antifungals, clarithromycin, telithromycin, ritonavir)

Answer 24

increase in exposure

Question 25

Asciminib Dosing: CP- CML (previously treated with more than 2 TKIs)

Answer 25

80 mg once daily or 40 mg twice daily

Question 26

Asciminib Dosing: CP-CML with T315I mutation

Answer 26

200 mg twice daily

Question 27

Asciminib Administration Pearls

Answer 27

should be taken orally without food. Avoid food 2 hours before and 1 hour after taking

Question 28

Asciminib DDI w/ anti-infectives (azole antifungals, clarithromycin, telithromycin, ritonavir)

Answer 28

Increase in exposure

Question 29

Asciminib Drug Interactions

Answer 29

~ strong CYP3A4 inhibitors ~ CYP3A4 substrates ~ CYP2C9 substrates ~ P-glycoprotein substrates

Question 30

Dasatinib Dosing: CP-CML

Answer 30

100 mg once daily

Question 31

Dasatinib Dosing: AP-CML and BP-CML

Answer 31

140 mg once daily

Question 32

Dasatinib Rare but Serious Toxicity

Answer 32

Pulmonary arterial hypertension

Question 33

Dasatinib Adverse Events

Answer 33

fluid retention pleural/pericardial effusion GI upset rash

Question 34

Dasatinib DDI w/ PPIs

Answer 34

decrease in exposure

Question 35

Dasatinib DDI w/ H2RAs

Answer 35

decrease in exposure; AVOID; if absolutely necessary consider once daily H2RA greater than 2 hours after taking

Question 36

Dasatinib DDI w/ antacids

Answer 36

decrease in exposure; use antacids at least 2 hours before or at least 2 hours after taking dasatinib

Question 37

Dasatinib DDI w/ antidepressants

Answer 37

minor increase in exposure; monitor QTc

Question 38

Dasatinib DDI w/ CV Medications

Answer 38

increase in exposure

Question 39

Dasatinib DDI w/ anti-infectives (azole antifungals, clarithromycin, telithromycin, ritonavir)

Answer 39

increase in exposure

Question 40

Dasatinib DDI w/ fluoroquinolones

Answer 40

QTc monitoring