Dosing & Uses
Dosage Forms & Strengths
capsule
- 25mg
Acute Myeloid Leukemia (AML)
Indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA-approved test
50 mg PO BID (~q12hr) on Days 8-21 of each cycle of induction with cytarabine and daunorubicin and on Days 8-21 of each cycle of consolidation with high-dose cytarabine
Take dose with food
Also see Administration
Systemic Mastocytosis (SM)
Indicated for adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL)
100 mg PO BID (~q12hr) with food
Continue treatment until disease progression or unacceptable toxicity
Also see Administration
Dosage Modifications (ASM, SM-AHN, MCL)
ANC <1 x 10^9/L (without MCL) or ANC < 0.5 x 10^9/L with baseline ANC of 0.5-1.5 x 10^9/L
- Interrupt dosing until ANC ≥1 x 10^9/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
- Discontinue if low ANC persists for >21 days and is suspected to be related to midostaurin
Platelet count <50 x 10^9/L (without MCL) or <25 x 10^9/L with baseline of 25-75 x 10^9/L
- Interrupt dosing until platelet count ≥50 x 10^9/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
- Discontinue if low platelet count persists for >21 days and is suspected to be related to midostaurin
Hemoglobin <8 g/L (without MCL) or life-threatening anemia with baseline of 8-10 g/L
- Interrupt dosing until hemoglobin ≥8 g/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
- Discontinue if low platelet count persists for >21 days and is suspected to be related to midostaurin
Grade 3 to 4 nausea and/or vomiting despite optimal antiemetic therapy
- Interrupt dosing for 3 days (6 doses), then resume at 50 mg BID; if tolerated, increase to 100 mg BID
Other grade 3 to 4 nonhematological toxicities
- Interrupt dosing until event has resolved to ≤grade 2, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
Dosing Considerations
Administer prophylactic antiemetics before treatment to decrease risk of nausea and vomiting
AML
- Limitations of use: Not indicated as a single-agent induction therapy for AML
- Select patients for the treatment of AML based on the presence of FLT3 mutation positivity
- Information on FDA-approved tests for the detection of FLT3 mutation in AML is available at: http://www.fda.gov/CompanionDiagnostics
ASM, SM-AHN, and MCL
- Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment
Patient selection
- Select patients based on presence of FLT3 mutation in blood or bone marrow by LeukoStrat CDx FLT3 Mutation Assay
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 midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.
Serious - Use Alternative (110)
- alfuzosin
alfuzosin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- amisulpride
amisulpride and midostaurin both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.
- amobarbital
amobarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- anagrelide
anagrelide and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of midostaurin 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.
- apomorphine
apomorphine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- aripiprazole
aripiprazole and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- artemether
artemether and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- artemether/lumefantrine
artemether/lumefantrine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine
asenapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine transdermal
asenapine transdermal and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- atazanavir
atazanavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- atomoxetine
atomoxetine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- bedaquiline
bedaquiline and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- bosentan
bosentan will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- buprenorphine
buprenorphine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine buccal
buprenorphine buccal and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine subdermal implant
buprenorphine subdermal implant and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine transdermal
buprenorphine transdermal and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- butalbital
butalbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- carbamazepine
carbamazepine will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- ceritinib
ceritinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
ceritinib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - chloramphenicol
chloramphenicol will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloroquine
chloroquine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- citalopram
citalopram and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
clarithromycin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug. - clozapine
clozapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- conivaptan
conivaptan will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- crizotinib
crizotinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- dabrafenib
dabrafenib will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- darunavir
darunavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- dasatinib
dasatinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- degarelix
degarelix and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- desflurane
desflurane and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- dexamethasone
dexamethasone will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- diltiazem
diltiazem will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- dolasetron
dolasetron and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- donepezil
donepezil and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- doxepin
doxepin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- efavirenz
efavirenz will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
efavirenz and midostaurin both increase QTc interval. Avoid or Use Alternate Drug. - eliglustat
eliglustat and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- encorafenib
encorafenib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- entrectinib
entrectinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- enzalutamide
enzalutamide will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- eribulin
eribulin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- etravirine
etravirine will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- fexinidazole
fexinidazole will increase the level or effect of midostaurin 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.
- fingolimod
fingolimod and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- fosamprenavir
fosamprenavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- fosphenytoin
fosphenytoin will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- gadobenate
gadobenate and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- gemifloxacin
gemifloxacin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- gilteritinib
gilteritinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- granisetron
granisetron and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- grapefruit
grapefruit will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- hydroxyzine
hydroxyzine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- imatinib
imatinib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- indinavir
indinavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- isoflurane
isoflurane and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- isoniazid
isoniazid will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- itraconazole
itraconazole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
itraconazole and midostaurin both increase QTc interval. Avoid or Use Alternate Drug. - ivosidenib
ivosidenib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- levoketoconazole
levoketoconazole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- lithium
lithium and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- lopinavir
lopinavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- mifepristone
mifepristone will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mirtazapine
mirtazapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- mitotane
mitotane will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- nafcillin
nafcillin will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- nefazodone
nefazodone will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- nelfinavir
nelfinavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- nevirapine
nevirapine will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- nicardipine
nicardipine will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- olanzapine
olanzapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- oxaliplatin
oxaliplatin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- palifermin
palifermin increases toxicity of midostaurin 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 will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- phenobarbital
phenobarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- phenytoin
phenytoin will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- posaconazole
posaconazole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- primaquine
primaquine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- rifabutin
rifabutin will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- rifampin
rifampin will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- rifapentine
rifapentine will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- ritonavir
ritonavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- saquinavir
saquinavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- secobarbital
secobarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- sertraline
sertraline and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- sevoflurane
sevoflurane and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- siponimod
siponimod and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- solifenacin
solifenacin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- St John's Wort
St John's Wort will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.
- sunitinib
sunitinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- tacrolimus
tacrolimus and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- tetrabenazine
tetrabenazine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- tipranavir
tipranavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- tucatinib
tucatinib will increase the level or effect of midostaurin 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.
- voriconazole
voriconazole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.
- vorinostat
vorinostat and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- voxelotor
voxelotor will increase the level or effect of midostaurin 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 (20)
- arformoterol
arformoterol and midostaurin both increase QTc interval. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- deutetrabenazine
deutetrabenazine and midostaurin both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
- duvelisib
duvelisib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
- elagolix
elagolix decreases levels of midostaurin 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, midostaurin. 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.
- fedratinib
fedratinib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fostemsavir
midostaurin and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- istradefylline
istradefylline will increase the level or effect of midostaurin 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.
- lenacapavir
lenacapavir will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lorlatinib
lorlatinib will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- osilodrostat
osilodrostat and midostaurin both increase QTc interval. Use Caution/Monitor.
- ponesimod
ponesimod and midostaurin 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.
- ribociclib
ribociclib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- siponimod
siponimod and midostaurin 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.
- stiripentol
stiripentol, midostaurin. 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.
- tazemetostat
tazemetostat will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- valbenazine
valbenazine and midostaurin both increase QTc interval. Use Caution/Monitor.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10% (AML)
Nausea (83%)
Febrile neutropenia (83%)
Hypocalcemia (74%)
Increased ALT, all grades (71%)
Mucositis (66%)
Vomiting (61%)
Headache (46%)
Petechiae (36%)
Musculoskeletal pain (33%)
Epistaxis (28%)
Device-related infection (24%)
Hypernatremia (21%)
Upper respiratory tract infection (20%)
Hyperglycemia (20%)
Increased ALT, grades 3 and 4 (20%)
Hemorrhoids (15%)
Arthralgia (14%)
Hyperhidrosis (14%)
Prolonged aPTT (13%)
Renal insufficiency (12%)
Insomnia (12%)
>10% (SM)
Nausea (82%)
Hyperglycemia (80%)
Vomiting (68%)
Lymphopenia (66%)
Leukopenia (61%)
Anemia (60%)
Diarrhea (54%)
Thrombocytopenia (50%)
Neutropenia (49%)
Edema (40%)
Increased alkaline phosphatase (39%)
Hypocalcemia (39%)
Lipase increased (37%)
Hyperuricemia (37%)
Increased GGT (35%)
Musculoskeletal pain (35%)
Hyponatremia (34%)
Increased AST (32%)
Increased ALT (31%)
Fatigue (34%)
Abdominal pain (34%)
Upper respiratory tract infection (30%)
Hyperbilirubinemia (29%)
Hypoalbuminemia (27%)
Pyrexia (27%)
Constipation (29%)
Headache (26%)
Hypokalemia (25%)
Increased creatinine (25%)
Hyperkalemia (23%)
Dyspnea (23%)
Hypophosphatemia (22%)
Increased amylase (20%)
Hypomagnesemia (20%)
Arthralgia (19%)
Cough (18%)
Urinary tract infection (16%)
GI hemorrhage (14%)
Rash (14%)
Dizziness (13%)
Pleural effusion (13%)
Epistaxis (12%)
QT prolonged (11%)
Insomnia (11%)
Renal insufficiency (11%)
1-10% (AML)
Hyperuricemia (8%)
Hypertension (8%)
Cellulitis (7%)
Fungal infection (7%)
Dry skin (7%)
Weight increased (7%)
Pleural effusion (6%)
Thrombosis (5%)
Tremor (4%)
Pericardial effusion (4%)
Hypercalcemia (3%)
Eyelid edema (3%)
1-10% (SM)
Pneumonia (10%)
Herpes virus infection (10%)
Sepsis (9%)
Hypotension (9%)
Febrile neutropenia (8%)
Disturbance in attention (7%)
Tremor (6%)
Hematoma (6%)
Cardiac failure (6%)
Bronchitis (6%)
Dyspepsia (6%)
Weight increased (6%)
Contusion (6%)
Cellulitis or erysipelas (5%)
Vertigo (5%)
Chills (5%)
Oropharyngeal pain (4%)
Myocardial infarction or ischemia (4%)
Hypersensitivity (4%)
Mental status changes (4%)
Pulmonary edema (3%)
Gastritis (3%)
Interstitial lung disease or pneumonitis (2%)
Postmarketing Reports
Skin and subcutaneous tissue disorders: Acute febrile neutrophilic dermatosis (Sweet syndrome)
Warnings
Contraindications
Hypersensitivity; reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema (eg, swelling of the airways or tongue, with or without respiratory impairment)
Cautions
Cases of interstitial lung disease and pneumonitis, some fatal, reported with monotherapy or in combination with chemotherapy; monitor for pulmonary symptoms; discontinue if signs or symptoms of interstitial lung disease or pneumonitis occur without an infectious etiology
Prolonged severe neutropenia and thrombocytopenia in pediatric patients with AML when coadministered with strong CYP3A4 inhibitor azole antifungal
Based on its mechanism of action and findings from animal reproduction studies, midostaurin may cause fetal harm when administered to pregnant women (see Pregnancy)
Drug interaction overview
- Primarily metabolized by CYP3A4
-
Strong CYP3A4 inhibitors
- Coadministration with strong CYP3A inhibitors may increase midostaurin concentrations and risk of toxicity Consider alternative therapies that do not strongly inhibit CYP3A activity
- Alternatively, if coadministered, monitor for increased risk of adverse reactions, especially during the first week of treatment
-
Strong CYP3A inducers
- Coadministration with strong CYP3A inducers may decrease midostaurin concentrations and reduce efficacy
- Avoid coadministration with strong CYP3A inducers
-
CYP2B6 substrates
- Therapy may decrease systemic exposure of sensitive CYP2B6 substrate; dose adjustments for coadministered CYP2B6 substrate may be necessary
-
Substrates transporters
- Coadministration of midostaurin may increase the exposure of a breast cancer resistance protein (BCRP) and organic anion transporter polypeptide (OATP)1B1 substrate; dose adjustments for the coadministered BCRP or OATP1B1 substrates may be necessary with midostaurin
Pregnancy
Pregnancy
A pregnancy exposure registry monitors pregnancy outcomes in women exposed to therapy during pregnancy; Females who may have been exposed to RYDAPT during pregnancy directly or through a male partner receiving RYDAPT therapy should contact the Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com /
Based on mechanism of action and findings in animal reproduction studies, may cause fetal harm when administered to pregnant women
Administration to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicities, including late embryo-fetal death and reduced fetal birth weight, with delays in fetal growth at doses lower than the recommended human dose
Pregnancy testing: Recommended for females of reproductive potential within 7 days before initiating midostaurin
Infertility: Based on findings in animals, midostaurin may impair fertility in females and males of reproductive potential
Contraception
- Females: Drug may cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose
- Males: Males with female sexual partners of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose
Lactation
Unknown if distributed in human breast milk
Orally administered midostaurin and its active metabolites pass into the milk of lactating rats within 1 hr of a 30-mg/kg/day dose, with approximately 5 times more in the milk of lactating rats compared with plasma
Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 4 months 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
Inhibits multiple receptor tyrosine kinases
In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFR-alpha/beta, VEGFR2, and members of the serine/threonine kinase PKC (protein kinase C) family
Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors
Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation, and histamine release and induce apoptosis in mast cells
Absorption
Peak plasma time: 1-3 hr (fasting); 2.5-3 hr (with food)
Distribution
Protein bound: >99.8% (including metabolites
Vd: 95.2 L
Metabolism
Primarily metabolized by CYP3A4
Metabolites: CGP62221 and CGP52421 account for ~28% and 38%, respectively, of the total circulating radioactivity of midostaurin and its metabolites
Elimination
Half-life: 21 hr (midostaurin); 32 hr (CGP62221); 482 hr (CGP52421)
Excretion: 95% feces (91% as metabolites and 4% as unchanged drug); 5% urine
Administration
Oral Administration
Take with food twice daily at ~12-hr intervals
Administer prophylactic antiemetics before treatment to reduce the risk of nausea and vomiting
Swallow capsules whole; do not open or crush capsules
Consider interval assessments of QT by ECG if coadministered with medications that can prolong the QT interval
Missed or vomited dose
- Do not make up the dose by taking another capsule
- Take the next dose at the usual scheduled time
Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Store in the original package to protect from moisture
Images
Formulary
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