Dosing & Uses
Dosage Forms & Strengths
tablet
- 100mg
- 400mg
- 500mg
Chronic Myelogenous Leukemia
Newly-diagnosed chronic phase Philadelphia chromosome positive
- Indicated for newly diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML)
- 400 mg PO qDay with food
- Continue until disease progression or unacceptable toxicity
Chronic, accelerated, or blast phase Philadelphia chromosome positive
- Indicated for chronic, accelerated, or blast phase Ph+ CML in patients resistant to or intolerant to other therapies, including imatinib
- 500 mg PO qDay with food
- Continue until disease progression or unacceptable toxicity
Dose escalation
- Consider escalating dose in patients with Ph+ CML who did not achieve or maintain a hematologic, cytogenetic, or molecular response and did not have Grade ≥3 adverse reactions at the initial dose
- May increase dose by 100-mg/day increments; not to exceed 600 mg/day
Dosage Modifications
Renal impairment
- Hemodialysis: Safety and efficacy not established
- For patients who have declining renal function while on bosutinib who cannot tolerate the starting dose, follow dose adjustment recommendations for toxicity
-
Newly diagnosed chronic phase Ph+ CML
- CrCl 30-50 mL/min: 300 mg PO qDay
- CrCl <30 mL/min: 200 mg PO qDay
-
Chronic, accelerated, or blast phase Ph+ CML
- CrCl 30-50 mL/min: 400 mg PO qDay
- CrCl <30 mL/min: 300 mg PO qDay
Hepatic impairment
- Mild to severe (Child-Pugh A to C): 200 mg PO qDay
- There are no clinical data for efficacy at 200-mg/day
Hepatotoxicity
- AST/ALT>5X ULN: Hold until recovery to ≤2.5X ULN; resume at 400 mg qDay thereafter; discontinue if recovery takes >4 weeks
- AST/ALT ≥3X ULN concurrently with bilirubin elevations >2X ULN and alkaline phosphatase <2X ULN (Hy’s law case definition): Discontinue treatment
Diarrhea
- Grade 3-4 (≥7 stools/day over baseline/pretreatment): Hold until recovery to Grade ≤1; may resume dose at 400 mg qDay
Other moderate or severe nonhematologic toxicities
- Withhold until toxicity resolved, and then consider reducing dose by 100 mg/day
- If clinically appropriate, consider re-escalating to the initial dose taken once daily
- Doses <300 mg/day have been used in patients; however, efficacy has not been established
Myelosuppression
- ANC <1000 x 106/L or platelets <50,000 x 106/L: Withhold until ANC ≥1000 x106/L and platelets ≥50,000 x106/L
- Resume at same dose if recovery occurs within 2 weeks
- If blood cell counts remain low for >2 weeks, reduce dose by 100 mg upon recovery and resume treatment
- If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment
- Doses <300 mg/day have been used in patients; however, efficacy has not been established
Dosing Considerations
Verify pregnancy status in females of reproductive potential prior to initiation
<18 years: Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (1)
- lefamulin
lefamulin will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.
Serious - Use Alternative (93)
- abametapir
abametapir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- abiraterone
abiraterone increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- amiodarone
amiodarone increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
amiodarone increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - apalutamide
apalutamide will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- aprepitant
aprepitant increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- atazanavir
atazanavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- atorvastatin
atorvastatin increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- bicalutamide
bicalutamide increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bosentan
bosentan decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .
- carbamazepine
carbamazepine decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .
- carvedilol
carvedilol increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- cimetidine
cimetidine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
clarithromycin increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - clotrimazole
clotrimazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clozapine
clozapine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- conivaptan
conivaptan increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- crizotinib
crizotinib increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cyclosporine
cyclosporine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
cyclosporine increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - darunavir
darunavir increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- desipramine
desipramine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dexamethasone
dexamethasone decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .
- diltiazem
diltiazem increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dipyridamole
dipyridamole increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- doxycycline
doxycycline increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dronedarone
dronedarone increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
dronedarone increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - efavirenz
efavirenz decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .
- enzalutamide
enzalutamide decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .
- erythromycin base
erythromycin base increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin base increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - erythromycin ethylsuccinate
erythromycin ethylsuccinate increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin ethylsuccinate increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - erythromycin lactobionate
erythromycin lactobionate increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
erythromycin stearate increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%
eslicarbazepine acetate decreases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%. - etravirine
etravirine decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- famotidine
famotidine will decrease the level or effect of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole and bosutinib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.
fexinidazole will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates. - fluconazole
fluconazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fosamprenavir
fosamprenavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- fosphenytoin
fosphenytoin decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- grapefruit
grapefruit increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
grapefruit increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - haloperidol
haloperidol increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ibuprofen/famotidine
ibuprofen/famotidine will decrease the level or effect of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- imatinib
imatinib increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- indinavir
indinavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- isoniazid
isoniazid increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- itraconazole
itraconazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
itraconazole increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - ivosidenib
ivosidenib will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
ketoconazole increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - lapatinib
lapatinib increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
lapatinib increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - lidocaine
lidocaine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lonafarnib
lonafarnib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
lopinavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
lopinavir increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - lorlatinib
lorlatinib will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mefloquine
mefloquine increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- metronidazole
metronidazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- nefazodone
nefazodone increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- nelfinavir
nelfinavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
nelfinavir increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - nevirapine
nevirapine decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- nicardipine
nicardipine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
nicardipine increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - nilotinib
nilotinib increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- nizatidine
nizatidine will decrease the level or effect of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- oxcarbazepine
oxcarbazepine decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- palifermin
palifermin increases toxicity of bosutinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- pentobarbital
pentobarbital decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- phenobarbital
phenobarbital decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- phenytoin
phenytoin decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- posaconazole
posaconazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- primidone
primidone decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- progesterone, natural
progesterone, natural increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- propafenone
propafenone increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- propranolol
propranolol increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- quinidine
quinidine increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
quinidine increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - ranolazine
ranolazine increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- ribociclib
ribociclib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rifabutin
rifabutin decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- rifampin
rifampin decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- rifapentine
rifapentine decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.
- ritonavir
ritonavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
ritonavir increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - saquinavir
saquinavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
saquinavir increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - sertraline
sertraline increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- simvastatin
simvastatin increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- sunitinib
sunitinib increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- tacrolimus
tacrolimus increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- tamoxifen
tamoxifen increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- tetracycline
tetracycline increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tipranavir
tipranavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- tolvaptan
tolvaptan increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- tucatinib
tucatinib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- verapamil
verapamil increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
verapamil increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. - voriconazole
voriconazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- voxelotor
voxelotor will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (108)
- aliskiren
bosutinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- aluminum hydroxide
aluminum hydroxide decreases levels of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Bosutinib displays pH-dependent solubility; may use short-acting antacids with administration separated by 2 hr.
- amiodarone
bosutinib increases levels of amiodarone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- arsenic trioxide
bosutinib and arsenic trioxide both increase QTc interval. Use Caution/Monitor.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate decreases levels of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Bosutinib displays pH-dependent solubility; may use short-acting antacids with administration separated by 2 hr.
- atorvastatin
bosutinib increases levels of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bedaquiline
bosutinib and bedaquiline both increase QTc interval. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- betrixaban
bosutinib increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.
- cabazitaxel
bosutinib increases levels of cabazitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- calcium carbonate
calcium carbonate decreases levels of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Bosutinib displays pH-dependent solubility; may use short-acting antacids with administration separated by 2 hr.
- carvedilol
bosutinib increases levels of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- cetirizine
bosutinib increases levels of cetirizine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- chlorpromazine
bosutinib and chlorpromazine both increase QTc interval. Use Caution/Monitor.
- cimetidine
bosutinib increases levels of cimetidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ciprofloxacin
bosutinib increases levels of ciprofloxacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cisapride
bosutinib and cisapride both increase QTc interval. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- dabrafenib
dabrafenib will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- darunavir
darunavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.
- daunorubicin
bosutinib increases levels of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- desloratadine
bosutinib increases levels of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dexamethasone
bosutinib increases levels of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dexlansoprazole
dexlansoprazole decreases levels of bosutinib by Other (see comment). Use Caution/Monitor. Comment: PPIs may decrease bosutinib concentration by ~45%; bosutinib displays pH-dependent solubility.
- digoxin
bosutinib increases levels of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- disopyramide
bosutinib and disopyramide both increase QTc interval. Use Caution/Monitor.
- docetaxel
bosutinib increases levels of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dofetilide
bosutinib and dofetilide both increase QTc interval. Use Caution/Monitor.
- doxorubicin
bosutinib increases levels of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- duvelisib
duvelisib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of
- elagolix
elagolix will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- encorafenib
encorafenib, bosutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- erythromycin base
bosutinib increases levels of erythromycin base by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin ethylsuccinate
bosutinib increases levels of erythromycin ethylsuccinate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- esomeprazole
esomeprazole will decrease the level or effect of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Bosutinib displays pH dependent solubility
- estradiol
bosutinib increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- etoposide
bosutinib increases levels of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fedratinib
fedratinib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fexofenadine
bosutinib increases levels of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fosamprenavir
bosutinib increases levels of fosamprenavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fostemsavir
bosutinib and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- goserelin
bosutinib and goserelin both increase QTc interval. Use Caution/Monitor.
- haloperidol
bosutinib and haloperidol both increase QTc interval. Use Caution/Monitor.
- histrelin
bosutinib and histrelin both increase QTc interval. Use Caution/Monitor.
- hydrocortisone
bosutinib increases levels of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ibutilide
bosutinib and ibutilide both increase QTc interval. Use Caution/Monitor.
- idarubicin
bosutinib increases levels of idarubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- iloperidone
iloperidone increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
- indinavir
bosutinib increases levels of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- irinotecan
bosutinib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- irinotecan liposomal
bosutinib increases levels of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- ivermectin
bosutinib increases levels of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lansoprazole
lansoprazole decreases levels of bosutinib by Other (see comment). Use Caution/Monitor. Comment: PPIs may decrease bosutinib concentration by ~45%; bosutinib displays pH-dependent solubility.
- lenvatinib
bosutinib and lenvatinib both increase QTc interval. Use Caution/Monitor.
- lidocaine
bosutinib increases levels of lidocaine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loperamide
bosutinib increases levels of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loratadine
bosutinib increases levels of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lovastatin
bosutinib increases levels of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- magnesium oxide
magnesium oxide decreases levels of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Bosutinib displays pH-dependent solubility; may use short-acting antacids with administration separated by 2 hr.
- methadone
bosutinib and methadone both increase QTc interval. Use Caution/Monitor.
- methotrexate
bosutinib increases levels of methotrexate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mitomycin
bosutinib increases levels of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mitotane
mitotane decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- nadolol
bosutinib increases levels of nadolol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nelfinavir
bosutinib increases levels of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nicardipine
bosutinib increases levels of nicardipine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- olodaterol inhaled
bosutinib and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.
- omeprazole
omeprazole decreases levels of bosutinib by Other (see comment). Use Caution/Monitor. Comment: PPIs may decrease bosutinib concentration by ~45%; bosutinib displays pH-dependent solubility.
- ondansetron
bosutinib increases levels of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- osilodrostat
osilodrostat and bosutinib both increase QTc interval. Use Caution/Monitor.
- oxaliplatin
oxaliplatin and bosutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Use of oxaliplatin with concomitant immunosuppressants or with impaired immune systems may increased risk for serious infections.
- paclitaxel
bosutinib increases levels of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paclitaxel protein bound
bosutinib increases levels of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paliperidone
bosutinib increases levels of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pantoprazole
pantoprazole decreases levels of bosutinib by Other (see comment). Use Caution/Monitor. Comment: PPIs may decrease bosutinib concentration by ~45%; bosutinib displays pH-dependent solubility.
- pazopanib
bosutinib increases levels of pazopanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ponesimod
ponesimod and bosutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- pravastatin
bosutinib increases levels of pravastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- procainamide
bosutinib and procainamide both increase QTc interval. Use Caution/Monitor.
- quinidine
bosutinib increases levels of quinidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
bosutinib and quinidine both increase QTc interval. Use Caution/Monitor. - quinine
bosutinib and quinine both increase QTc interval. Use Caution/Monitor.
- rabeprazole
rabeprazole decreases levels of bosutinib by Other (see comment). Use Caution/Monitor. Comment: PPIs may decrease bosutinib concentration by ~45%; bosutinib displays pH-dependent solubility.
- ranolazine
bosutinib increases levels of ranolazine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifampin
bosutinib increases levels of rifampin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ritonavir
bosutinib increases levels of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
bosutinib increases levels of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- saxagliptin
bosutinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- selpercatinib
bosutinib and selpercatinib both increase QTc interval. Use Caution/Monitor.
- siponimod
siponimod and bosutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sirolimus
bosutinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sitagliptin
bosutinib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sodium zirconium cyclosilicate
sodium zirconium cyclosilicate will decrease the level or effect of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.
- stiripentol
stiripentol, bosutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- tacrolimus
bosutinib increases levels of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temsirolimus
bosutinib increases levels of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- teniposide
bosutinib increases levels of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tolvaptan
bosutinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vandetanib
bosutinib and vandetanib both increase QTc interval. Use Caution/Monitor.
- verapamil
bosutinib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vinblastine
bosutinib increases levels of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine
bosutinib increases levels of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- voclosporin
bosutinib and voclosporin both increase QTc interval. Use Caution/Monitor.
- ziprasidone
bosutinib and ziprasidone both increase QTc interval. Use Caution/Monitor.
Minor (0)
Adverse Effects
>10%
Newly diagnosed CP CML
-
All grades
- Creatinine increased (94%)
- Hemoglobin decreased (89%)
- Lymphocyte count decreased (84%)
- Diarrhea (75%)
- Platelet count decreased (68%)
- Serum glutamic-pyruvic transaminase (SGPT)/ALT increased (68%)
- Glucose increased (57%)
- Serum glutamic-oxaloacetic transaminase (SGOT)/AST increased (56%)
- Calcium decreased (55%)
- Phosphorus decreased (54%)
- Lipase increased (53%)
- WBC decreased (50%)
- Hepatic dysfunction (45%)
- ANC decreased (42%)
- Alkaline phosphatase increased (41%)
- Rash (40%)
- Abdominal pain (39%)
- Nausea (37%)
- Creatine kinase increased (36%)
- Fatigue (33%)
- Amylase increased (32%)
- Respiratory tract infection (27%)
- Headache (22%)
- Vomiting (21%)
- Arthralgia (18%)
- Pyrexia (17%)
- Edema (15%)
- Constipation (13%)
- Back pain (12%)
- Pruritus (11%)
- Cough (11%)
- Dyspnea (11%)
- Decreased appetite (11%)
-
Grade 3 or 4
- SGPT/ALT increased (26%)
- Hepatic dysfunction (27%)
- Lipase increased (19%)
- Platelet count (14%)
- SGOT/AST increased (13%)
- Lymphocyte count (12%)
- Pruritus (11%)
- Hypertension (11%)
Imatinib-resistant or -intolerant Ph+ CP, AP, and BP CML
-
All grades
- Hemoglobin decreased (89-97%)
- Creatinine increased (87-95%)
- Diarrhea (76-85%)
- Lymphocyte decreased (79-82%)
- Platelet count decreased (66-80%)
- ANC decreased (50-66%)
- SGPT/ALT increased (39-58%)
- WBC decreased (51-57%)
- Calcium decreased (45-55%)
- SGOT/AST increased (37-50%)
- Abdominal pain (36-49%)
- Urate increased (43-46%)
- Rash (42-48%)
- Nausea (47-48%)
- Vomiting (38-43%)
- Glucose increased (39-42%)
- Phosphorus decreased (33-41%)
- Alkaline phosphatase increased (39%)
- Fatigue (27-35%)
- Lipase increased (19-32%)
- Hepatic dysfunction (21-29%)
- Potassium decreased (22-29%)
- Magnesium increased (18-27%)
- Respiratory tract infection (17-27%)
- Potassium increased (19-25%)
- Pyrexia (25-37%)
- Cough (224%)
- Sodium decreased (18-27%)
- Sodium increased (11-23%)
- Total bilirubin increased (16-22%)
- Headache (18-21%)
- Dyspnea (12-20%)
- Edema (17-19%)
- Arthralgia (15-19%)
- Pneumonia (10-18%)
- Constipation (15-17%)
- Decreased appetite (14%)
- Pleural effusion (9-14%)
- Dizziness (11-14%)
- Back pain (8-14%)
- Chest pain (8-12%)
- Pruritis (7-12%)
- Hypertension (8-11%)
- Influenza (3-11%)
-
Grade 3 or 4
- Platelet count decreased (26-57%)
- ANC decreased (16-39%)
- Hemoglobin decreased (13-38%)
- WBC decreased (7-27%)
- Lymphocyte (14-21%)
- Lipase increased (6-12%)
- Pneumonia (4-12%)
- Hepatic dysfunction (10-11%)
- SGPT/ALT increased (6-11%)
1-10%
Pulmonary hypertension
Acute kidney injury
Renal impairment
Renal failure
Dysgeusia
Myalgia
Dehydration
Electrocardiogram QT prolonged
Bronchitis
Drug hypersensitivity
Pain
Gastritis
Pancreatitis
Gastrointestinal hemorrhage
Hypothyroidism
Tinnitus
Pericardial effusion
Newly diagnosed CP CML
-
Grade 3 or 4
- Diarrhea (9%)
- ANC decreased (9%)
- Hemoglobin decreased (9%)
- Phosphorus decreased (9%)
- WBC decreased (6%)
- Hypertension (5%)
- Amylase increased (3.4%)
- Glucose increased (3%)
- Creatinine kinase increased (3%)
- Rash (2%)
- Abdominal pain (2%)
- Calcium decreased (1.5%)
- Creatinine increased (1.1%)
- Vomiting (1%)
- Dyspnea (1%)
- Arthralgia (1%)
- Headache (1%)
- Respiratory tract infection (1%)
- Pyrexia (1%)
- Fatigue (1%)
Imatinib-resistant or -intolerant Ph+ CP, AP, and BP CML
-
All grades
- Chest pain (8%)
-
Grade 3 or 4
- Diarrhea (4-10%)
- Rash (5-9%)
- Phosphorus decreased (7-8%)
- Abdominal pain (2-7%)
- Fatigue (3-6%)
- SGOT/AST increased (3.5-5%)
- Pleural effusion (4%)
- Vomiting (3%)
- Hypertension (3%)
- Pyrexia (1-3%)
- Total bilirubin increased (0.7-2.8%)
- Dyspnea (2%)
- Nausea (1-2%)
- Chest pain (1%)
- Headache (1%)
- Back pain (1%)
- Decreased appetite (<1%)
- Constipation (<1%)
- Edema (<1%)
- Influenza (<1%)
- Pruritis (<1%)
- Respiratory tract infection (<1%)
- Arthralgia (<1%)
<1%
Febrile neutropenia
Pericarditis
Hyperthyroidism
Acute pulmonary edema (eg, acute pulmonary edema, pulmonary edema)
Erythema multiforme
Newly diagnosed CP CML
-
Grade 3 or 4
- Decreased appetite
- Back pain
- Pruritis
Postmarketing Reports
Thrombotic microangiopathy
Stevens Johnson syndrome
Warnings
Contraindications
Hypersensitivity
Cautions
Diarrhea, nausea, vomiting, and abdominal pain may occur; monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement
Thrombocytopenia, anemia, and neutropenia occur with treatment; perform CBC weekly for first month and then monthly thereafter, or as clinically indicated
Fluid retention may occur and manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema
Cardiac failure and left ventricular dysfunction have been reported in patients taking; monitor for signs and symptoms consistent with cardiac failure and treat as clinically indicated; interrupt, dose reduce, or discontinue as necessary
Decline in glomerular filtration rate reported in patients receiving therapy, which in turn increases bosutinib exposure in patients; use caution in patients with moderate renal impairment; dosage adjustment recommended
Fetal harm may occur when administered to pregnant females
Hepatic toxicity
- Elevated ALT, AST, and/or bilirubin may occur; perform monthly hepatic enzyme tests for first 3 months during treatment, and then as clinically indicated
- Median time to onset of increased ALT and AST was 35 and 33 days; median duration for each was 21 days
- Perform hepatic enzyme tests monthly for the first 3 months of treatment and as clinically indicated; in patients with transaminase elevations, monitor liver enzymes more frequently
Drug interaction overview
- CYP3A4 substrate
-
Strong or moderate CYP3A4 inhibitors
- Avoid coadministration
- Strong or moderate CYP3A4 inhibitors increase bosutinib Cmax and AUC, which may increase the risk of toxicities
-
Strong CYP3A4 inducers
- Avoid coadministration
- Strong CYP3A4 inducers decrease bosutinib Cmax and AUC, which may reduce efficacy
-
Proton pump inhibitors (PPI)
- Use short-acting antacids or H2-blockers as an alternant; separate dosing by >2 hr from bosutinib dosing
- PPIs decrease bosutinib Cmax and AUC, which may reduce efficacy
Pregnancy & Lactation
Pregnancy
No data are available in pregnant women to inform the drug-associated risk; however, fetal harm may occur when administered to pregnant women based on mechanism of action and findings from animal studies
Verify pregnancy status in females of reproductive potential prior to starting treatment
Animal data
- In rats and rabbits, oral administration of bosutinib during organogenesis caused adverse developmental outcomes, including structural abnormalities, embryofetal mortality, and alterations to growth at maternal exposures (AUC) as low as 1.2 times the human exposure at a 500-mg/day dose
- Advise pregnant women of the potential risk to a fetus
Contraception
- Based on findings from animal studies, fetal harm may occur when administered to pregnant females
- Females of reproductive potential: Use effective contraception during treatment and for at least 2 weeks after the last dose
Infertility
- Risk of infertility in females or males of reproductive potential has not been studied in humans
- Based on findings from animal studies, reduced fertility may occur in females and males of reproductive potential
Lactation
No data are available regarding presence of bosutinib or its metabolites in human milk or its effects on a breastfed child or on milk production
Bosutinib is present in the milk of lactating rats
Owing to the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Tyrosine kinase inhibitor; Inhibits Bcr-Abl kinase that promotes CML; also inhibits SRc-family kinases including Src, Lyn, and Hck
Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines, but did not inhibit T315I and V299L mutant cells
Absorption
Absolute bioavailability: 34% (healthy volunteers with food)
Peak plasma time (500-mg dose with food): 6 hr
Peak plasma concentration
- Multiple 400-mg doses: 146 ng/mL
- Multiple 500-mg doses: 200 ng/mL
AUC
- Multiple 400-mg doses: 2720 ng•hr/mL
- Multiple 500-mg doses: 3650 ng•hr/mL
Effect of food
- Bosutinib administered with a high-fat meal (800-1000 total calories) increased Cmax by 1.8-fold and increased AUC by 1.7-fold
Distribution
Protein bound: 94% (in vivo); 96% (ex vivo)
Vd: 6,080 L
P-gp substrate and inhibitor
Metabolism
Metabolized by in liver primarily by CYP3A4
Metabolites (inactive): Oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite
Elimination
Half-life
- Single 120-mg IV: 33.5 hr
- Single oral dose: 22.5 hr
Clearance
- Single 120-mg IV: 63.6 L/hr
- Single oral dose: 189 L/hr
Excretion: Feces (91.3%); urine (3%)
Administration
Oral Administration
Take with food
Swallow tablet whole; do not chew, crush, or cut
Consider procedures for proper disposal of drug
Avoid touching or handling crushed or broken tablets
Take antacids or H2-blockers at least 2 hr before or 2 hr after bosutinib
Missed dose
- Missed dose >12 hr: Skip dose and take the usual prescribed dose on the following day: do not take 2 doses at one time
Storage
Tablets: Store at 20-25ºC (68-7ºF)
Discard any unused products or waste materials in accordance with local requirements, or drug take back programs
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Bosulif oral - | 500 mg tablet |  | |
| Bosulif oral - | 100 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
bosutinib oral
BOSUTINIB - ORAL
(boe-SUE-ti-nib)
COMMON BRAND NAME(S): Bosulif
USES: Bosutinib is used to treat a certain type of blood cancer (chronic myelogenous leukemia-CML). It works by slowing or stopping the growth of cancer cells.
HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking bosutinib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with food as directed by your doctor, usually once daily. Swallow the medication whole. Do not crush, chew, or split the tablets. Avoid handling or touching crushed or broken tablets.The dosage is based on your medical condition and response to treatment. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of serious side effects will increase.Use this medication regularly to get the most benefit from it. Remember to use it at the same time each dayMedications which reduce or block stomach acid (such as proton pump inhibitors/PPIs, H2 blockers, antacids) may reduce the absorption of bosutinib, making it work less well. Do not take PPIs (such as omeprazole, lansoprazole) while using this medication. If you take antacids or H2 blockers (such as famotidine, ranitidine), take these medications at least 2 hours before or after bosutinib.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.
SIDE EFFECTS: Nausea, vomiting, stomach/abdominal pain, loss of appetite, cough, joint pain, headache, or dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Diarrhea is a common side effect. Drink plenty of fluids as directed by your doctor to reduce your risk of dehydration. Your doctor may prescribe anti-diarrhea medication (such as loperamide) to control your symptoms. Tell your doctor right away if you develop severe or persistent diarrhea, signs of dehydration (such as extreme thirst, dizziness, decreased urination).People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following unlikely symptoms: unusual tiredness, pale skin, signs of infection (such as fever, chills, persistent sore throat), easy bleeding/bruising.Tell your doctor right away if you have any serious side effects, including: severe stomach/abdominal pain, yellowing eyes/skin, dark urine, swelling hands/ankles/feet, sudden weight gain, signs of kidney problems (such as change in the amount of urine).Get medical help right away if you have any very serious side effects, including: chest pain, shortness of breath.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.Bosutinib can commonly cause a mild rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Get medical help right away if you develop any rash.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking bosutinib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). Alcohol may also increase the risk of serious liver problems.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose). Wash your hands well to prevent the spread of infection.To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while taking bosutinib. Bosutinib may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Ask about reliable forms of birth control while using this medication and for 2 weeks after stopping treatment. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for 2 weeks after stopping treatment. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: drugs that reduce stomach acid (for example, antacids, H2 blockers such as famotidine/ranitidine, proton pump inhibitors such as omeprazole).Other medications can affect the removal of bosutinib from your body, which may affect how bosutinib works. Examples include azole antifungals (such as ketoconazole, itraconazole), boceprevir, macrolide antibiotics (such as clarithromycin), nefazodone, HIV protease inhibitors (such as indinavir, nelfinavir, ritonavir), rifamycins (such as rifabutin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), telaprevir, telithromycin, among others.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as kidney/liver function, complete blood count) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember if it is within 12 hours of your scheduled dose. If it is more than 12 hours after your scheduled dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
