midostaurin (Rx)

Brand and Other Names:Rydapt
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Dosing & Uses

AdultPediatric

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

Safety and efficacy not established

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Interactions

Interaction Checker

and midostaurin

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            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 (81)

            • abametapir

              abametapir will increase the level or effect of midostaurin 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.

            • alfuzosin

              alfuzosin and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • deutetrabenazine

              deutetrabenazine 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 (17)

            • 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.

            • 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.

            • 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.

            Minor (0)

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              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%)

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              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
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              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.

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              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

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              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

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

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              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.