avapritinib (Rx)

Brand and Other Names:Ayvakit
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 25mg
  • 50mg
  • 100mg
  • 200mg
  • 300mg

Gastrointestinal Stromal Tumors

Indicated for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutation

300 mg PO qDay

Continue until disease progression or unacceptable toxicity

Systemic Mastocytosis

Indicated for advanced systemic mastocytosis (AdvSM)

AdvSM includes patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SMAHN), and mast cell leukemia (MCL)

200 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reductions for adverse reactions

  • GIST
    • First dose reduction: 200 mg qDay
    • Second dose reduction: 100 mg qDay
    • Unable to tolerate a 100-mg dose: Permanently discontinue
  • AdvSM
    • First dose reduction: 100 mg qDay
    • Second dose reduction: 50 mg qDay
    • Third dose reduction: 25 mg qDay
    • Unable to tolerate a 25-mg dose: Permanently discontinue

Intracranial hemorrhage

  • First occurrence of Grade 1 or 2: Withhold until resolution; resume at reduced dose
  • Subsequent occurrence of Grade 1 or 2: Permanently discontinue
  • Grade 3 or 4: Permanently discontinue

CNS effects

  • Grade 1: Continue dose at the same dose or withhold until improvement to baseline or resolution; resume at same dose or reduced dose
  • Grade 2 or 3: Withhold until improvement to baseline, Grade 1, or resolution; resume at same dose or reduced dose
  • Grade 4: Permanently discontinue

Other adverse reactions

Grade 3 or 4: Withhold until improvement to Grade ≤2, or resolution; resume at same dose or reduced dose, as clinically appropriate

Thrombocytopenia

  • Platelet counts <50 x 109/L: Interrupt until platelet count ≥50 x 109/L, then resume at reduced dose
  • If platelet counts do not recover above 50 x 109/L, consider platelet support

Strong or moderate CYP3A4 inhibitors

  • Avoid coadministration
  • If use is unavoidable, reduce starting dose as follows
    • GIST: 100 mg PO qDay
    • AdvSM: 50 mg PO qDay

Renal impairment

  • Mild-to-moderate (CrCl 30-90 mL/mL): No dosage adjustment necessary
  • Severe or end-stage renal disease (CrCl <30 mL/min): Effect on pharmacokinetics unknown

Hepatic impairment

  • Mild-to-moderate (total bilirubin ≤3x ULN and any AST): No dosage adjustment necessary
  • Severe (total bilirubin >3x ULN and any AST): Effect on pharmacokinetics unknown

Dosing Considerations

Verify pregnancy status in females of reproductive potential

Patient selection (GIST)

  • Select patients based on presence of a PDGFRA exon 18 mutation
  • No FDA-approved test available

Limitations of use

  • Not recommended for AdvSM with platelet counts <50 X 109/L

Safety and efficacy not established

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Interactions

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              Serious - Use Alternative (91)

              • abametapir

                abametapir will increase the level or effect of avapritinib 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.

              • amiodarone

                amiodarone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • apalutamide

                apalutamide will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • aprepitant

                aprepitant will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • armodafinil

                armodafinil will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • atazanavir

                atazanavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • bexarotene

                bexarotene will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • bicalutamide

                bicalutamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • bosentan

                bosentan will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • brigatinib

                brigatinib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • butabarbital

                butabarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • butalbital

                butalbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • carbamazepine

                carbamazepine will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • ceritinib

                ceritinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • chloramphenicol

                chloramphenicol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • clarithromycin

                clarithromycin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • clobazam

                clobazam will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • clozapine

                clozapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • cobicistat

                cobicistat will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • conivaptan

                conivaptan will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • crizotinib

                crizotinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • cyclosporine

                cyclosporine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • darunavir

                darunavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • desipramine

                desipramine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • diltiazem

                diltiazem will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • doxycycline

                doxycycline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • dronedarone

                dronedarone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • elagolix

                elagolix will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • encorafenib

                encorafenib, avapritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate or strong CYP3A4 inhibitors. If coadministration of avapritinib with a moderate inhibitor cannot be avoided, reduce avapritinib starting dose (see drug monograph Dosage Modifications).

              • erythromycin base

                erythromycin base will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • erythromycin ethylsuccinate

                erythromycin ethylsuccinate will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • erythromycin lactobionate

                erythromycin lactobionate will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • erythromycin stearate

                erythromycin stearate will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • eslicarbazepine acetate

                eslicarbazepine acetate will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • fedratinib

                fedratinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • fexinidazole

                fexinidazole will increase the level or effect of avapritinib 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 will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • fluvoxamine

                fluvoxamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications

              • fosamprenavir

                fosamprenavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • fostamatinib

                fostamatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • grapefruit

                grapefruit will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • haloperidol

                haloperidol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • idelalisib

                idelalisib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • iloperidone

                iloperidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • imatinib

                imatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • indinavir

                indinavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • isoniazid

                isoniazid will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • itraconazole

                itraconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • ivacaftor

                ivacaftor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • ivosidenib

                ivosidenib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • ketoconazole

                ketoconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • lapatinib

                lapatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • larotrectinib

                larotrectinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • letermovir

                letermovir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • lonafarnib

                lonafarnib will increase the level or effect of avapritinib 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 will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • lorlatinib

                lorlatinib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • metronidazole

                metronidazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • mifepristone

                mifepristone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • mitotane

                mitotane will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • modafinil

                modafinil will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • nafcillin

                nafcillin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • nefazodone

                nefazodone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • nelfinavir

                nelfinavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • netupitant/palonosetron

                netupitant/palonosetron will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • pentobarbital

                pentobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • phenobarbital

                phenobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • phenytoin

                phenytoin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • posaconazole

                posaconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • primidone

                primidone will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • quinupristin/dalfopristin

                quinupristin/dalfopristin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • ribociclib

                ribociclib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • rifabutin

                rifabutin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifampin

                rifampin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifapentine

                rifapentine will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • ritonavir

                ritonavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • saquinavir

                saquinavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • schisandra

                schisandra will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • secobarbital

                secobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • sertraline

                sertraline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • St John's Wort

                St John's Wort will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • stiripentol

                stiripentol, avapritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate or strong CYP3A4 inhibitors. If coadministration of avapritinib with a moderate inhibitor cannot be avoided, reduce avapritinib starting dose (see drug monograph Dosage Modifications).

              • telotristat ethyl

                telotristat ethyl will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • tetracycline

                tetracycline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              • tipranavir

                tipranavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • tucatinib

                tucatinib will increase the level or effect of avapritinib 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 will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • voriconazole

                voriconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

              • voxelotor

                voxelotor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              Monitor Closely (116)

              • acetaminophen

                acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • acetaminophen IV

                acetaminophen IV will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • acetaminophen rectal

                acetaminophen rectal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • acetazolamide

                acetazolamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • alprazolam

                alprazolam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • amlodipine

                amlodipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • amobarbital

                amobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • anastrozole

                anastrozole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • atorvastatin

                atorvastatin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • azelastine

                azelastine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • belzutifan

                belzutifan will decrease the level or effect of avapritinib 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.

              • betamethasone

                betamethasone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • bortezomib

                bortezomib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • bromocriptine

                bromocriptine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • chlorzoxazone

                chlorzoxazone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • cimetidine

                cimetidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ciprofloxacin

                ciprofloxacin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • clemastine

                clemastine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • cocaine

                cocaine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • crofelemer

                crofelemer will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • cyclophosphamide

                cyclophosphamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dabrafenib

                dabrafenib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • danazol

                danazol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • darifenacin

                darifenacin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dasatinib

                dasatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • desvenlafaxine

                desvenlafaxine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dexlansoprazole

                dexlansoprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dexmedetomidine

                dexmedetomidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • diazepam

                diazepam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • diclofenac

                diclofenac will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • dihydroergotamine

                dihydroergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • disulfiram

                disulfiram will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • docetaxel

                docetaxel will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • doxorubicin

                doxorubicin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • doxorubicin liposomal

                doxorubicin liposomal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • drospirenone

                drospirenone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • efavirenz

                efavirenz will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • enzalutamide

                enzalutamide will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ergotamine

                ergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • etoposide

                etoposide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • etravirine

                etravirine will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • felodipine

                felodipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fentanyl

                fentanyl will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fentanyl transdermal

                fentanyl transdermal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fluoxetine

                fluoxetine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • isradipine

                isradipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • istradefylline

                istradefylline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lansoprazole

                lansoprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lenvatinib

                lenvatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lidocaine

                lidocaine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lomustine

                lomustine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • losartan

                losartan will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lovastatin

                lovastatin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lurasidone

                lurasidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • mefloquine

                mefloquine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • mestranol

                mestranol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • methadone

                methadone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • methimazole

                methimazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • methoxsalen

                methoxsalen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • methylprednisolone

                methylprednisolone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • micafungin

                micafungin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • midazolam

                midazolam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • mirtazapine

                mirtazapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • mitoxantrone

                mitoxantrone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nevirapine

                nevirapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nicardipine

                nicardipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nifedipine

                nifedipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nilotinib

                nilotinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nisoldipine

                nisoldipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nizatidine

                nizatidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • olanzapine

                olanzapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • omeprazole

                omeprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • orphenadrine

                orphenadrine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • oxybutynin

                oxybutynin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • oxybutynin topical

                oxybutynin topical will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • oxybutynin transdermal

                oxybutynin transdermal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • palbociclib

                palbociclib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • paroxetine

                paroxetine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pazopanib

                pazopanib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pentamidine

                pentamidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pilocarpine

                pilocarpine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pimozide

                pimozide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pitolisant

                pitolisant will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pravastatin

                pravastatin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • primaquine

                primaquine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • progesterone micronized

                progesterone micronized will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • progesterone, natural

                progesterone, natural will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • propofol

                propofol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • quinidine

                quinidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • quinine

                quinine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rabeprazole

                rabeprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ranolazine

                ranolazine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • risperidone

                risperidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rucaparib

                rucaparib will increase the level or effect of avapritinib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

              • rufinamide

                rufinamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • selegiline

                selegiline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • sirolimus

                sirolimus will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • sulconazole

                sulconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tamoxifen

                tamoxifen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tazemetostat

                tazemetostat will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • temsirolimus

                temsirolimus will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • teniposide

                teniposide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • testosterone

                testosterone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • testosterone buccal system

                testosterone buccal system will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • testosterone topical

                testosterone topical will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ticagrelor

                ticagrelor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ticlopidine

                ticlopidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tranylcypromine

                tranylcypromine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • trazodone

                trazodone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • valproic acid

                valproic acid will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • vinblastine

                vinblastine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • vincristine

                vincristine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • vinorelbine

                vinorelbine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • zafirlukast

                zafirlukast will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • zileuton

                zileuton will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ziprasidone

                ziprasidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              Minor (0)

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                Adverse Effects

                >10%

                • All grades

                • GIST
                  • Decreased hemoglobin (81%)
                  • Edema (72%)
                  • Increased bilirubin (69%)
                  • Nausea (64%)
                  • Decreased leukocytes (62%)
                  • Fatigue (61%)
                  • Increased AST (51%)
                  • Decreased phosphate (49%)
                  • Cognitive impairment (48%)
                  • Decreased neutrophils (43%)
                  • Vomiting (38%)
                  • Decreased appetite (38%)
                  • Diarrhea (37%)
                  • Decreased potassium (34%)
                  • Increased lacrimation (33%)
                  • Abdominal pain (31%)
                  • Decreased albumin (31%)
                  • Decreased magnesium (29%)
                  • Increased creatinine (29%)
                  • Decreased sodium (28%)
                  • Decreased platelets (27%)
                  • Increased INR (24%)
                  • Constipation (23%)
                  • Rash (23%)
                  • Dizziness (22%)
                  • Hair color changes (21%)
                  • Increased ALT (19%)
                  • Headache (17%)
                  • Dyspnea (17%)
                  • Sleep disorders (16%)
                  • Taste effects (15%)
                  • Pyrexia (14%)
                  • Increased alkaline phosphatase (14%)
                  • Mood disorders (13%)
                  • Alopecia (13%)
                  • Decreased weight (13%)
                  • Increased activated partial thromboplastin time (aPTT) (13%)
                  • Pleural effusion (12%)
                • AdvSM
                  • Edema (79%)
                  • Decreased platelets (64%)
                  • Decreased hemoglobin (55%)
                  • Decreased neutrophils (54%)
                  • Decreased calcium (50%)
                  • Increased bilirubin (41%)
                  • Increased AST (38%)
                  • Decreased lymphocytes (34%)
                  • Diarrhea (28%)
                  • Decreased potassium (26%)
                  • Nausea (24%)
                  • Increased alkaline phosphatase (24%)
                  • Fatigue/asthenia (23%)
                  • Increased creatinine (20%)
                  • Vomiting (18%)
                  • Increased ALT (18%)
                  • Decreased sodium (18%)
                  • Headache (15%)
                  • Decreased albumin (15%)
                  • Cognitive effects (14%)
                  • Abdominal pain (14%)
                  • Increased aPTT (14%)
                  • Decreased magnesium (14%)
                  • Taste effects (13%)
                  • Dizziness (13%)
                  • Constipation (11%)
                  • Epistaxis (11%)
                  • Increased potassium (11%)

                Grade ≥3

                • GIST
                  • Decreased hemoglobin (28%)
                  • Decreased phosphate (13%)
                • AdvSM
                  • Decreased neutrophils (25%)
                  • Decreased hemoglobin (23%)
                  • Decreased platelets (21%)
                  • Decreased lymphocytes (11%)

                1-10%

                All grades

                • GIST
                  • Hypertension (8%)
                  • Thyroid disorders (hyperthyroid, hypothyroid) (3%)
                  • Palmar-plantar erythrodysesthesia (1%)
                • AdvSM
                  • Arthralgia (10%)
                  • Increased lymphocytes (10%)
                  • Dyspnea (9%)
                  • Alopecia (9%)
                  • Lacrimation increased (9%)
                  • Decreased phosphate (9%)
                  • Rash (8%)
                  • Pruritus (8%)
                  • Decreased appetite (8%)
                  • Upper respiratory tract infection (6%)
                  • Urinary tract infection (6%)
                  • Insomnia (6%)
                  • Pain in extremity (6%)
                  • Hair color changes (6%)
                  • Ascites (5%)
                  • Anemia (5%)
                  • Subdural hematoma (4%)
                  • Flushing (3.8%)
                  • Hypertension (3.8%)
                  • Hypotension (3.8%)
                  • Pleural effusion (3%)
                  • Pneumonia (3%)
                  • Herpes zoster (2.5%)
                  • Cardiac failure (2.5%)
                  • Hot flush (2.5%)
                  • Cough (2.5%)
                  • Acute kidney injury (2%)
                  • Gastrointestinal hemorrhage (2%)
                  • Intracranial hemorrhage (2%)
                  • Encephalopathy (2%)
                  • Gastric hemorrhage (2%)
                  • Pyrexia (2%)
                  • Cardiac failure congestive (1.3%)
                  • Gastrointestinal hemorrhage (1.3%)
                  • Large intestine perforation (1.3%)
                  • Cholelithiasis (1.3%)

                Grade ≥3

                GIST
                • Fatigue (9%)
                • Increased bilirubin (9%)
                • Abdominal pain (6%)
                • Decreased neutrophils (6%)
                • Decreased potassium (6%)
                • Decreased sodium (7%)
                • Decreased leukocytes (5%)
                • Diarrhea (4.9%)
                • Cognitive impairment (4.9%)
                • Decreased appetite (2.9%)
                • Nausea (2.5%)
                • Dyspnea (2.5%)
                • Rash (2.1%)
                • Vomiting (2%)
                • Edema (2%)
                • Pleural effusion (2%)
                • Decreased albumin (2%)
                • Constipation (1.5%)
                • Increased AST (1.5%)
                • Mood disorders (1%)
                • Decreased weight (1%)
                • Decreased magnesium (1%)
                • Increased alkaline phosphatase (1%)
                AdvSM
                • Edema (5%)
                • Increased alkaline phosphatase (5%)
                • Fatigue/asthenia (4%)
                • Decreased potassium (4%)
                • Vomiting (3%)
                • Decreased calcium (3%)
                • Increased bilirubin (3%)
                • Diarrhea (1%)
                • Nausea (1%)
                • Abdominal pain (1%)
                • Cognitive effects (1%)
                • Arthralgia (1%)
                • Increased aPTT (1%)
                • Increased AST (1%)
                • Increased ALT (1%)
                • Decreased sodium (1%)
                • Decreased albumin (1%)
                • Decreased magnesium (1%)

                <1%

                Grade ≥3

                • GIST
                  • Increased INR (0.6%)
                  • Pyrexia (0.5%)
                  • Dizziness (0.5%)
                  • Headache (0.5%)
                  • Hair color changes (0.5%)
                  • Decreased platelets (0.5%)
                  • Increased ALT (0.5%)
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                Warnings

                Contraindications

                None

                Cautions

                A broad spectrum of CNS adverse reactions reported; these include, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations

                Cognitive adverse reactions reported; depending on severity, withhold treatment and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue treatment

                Fetal harm can occur when administered to pregnant females

                Intracranial hemorrhage

                • Intracranial hemorrhage (eg, subdural hematoma, intracranial hemorrhage, cerebral hemorrhage) occurred; thrombocytopenia was generally reversible by dose reduction or interruption
                • Monitor patients closely for the risk of intracranial hemorrhage including those with thrombocytopenia, vascular aneurysm or a history of intracranial hemorrhage or cerebrovascular accident within the prior year
                • Permanently discontinue therapy if intracranial hemorrhage of any grade occurs

                Advanced systemic mastocytosis

                • Platelet count must be performed prior to initiating therapy; drug not recommended in patients with AdvSM with platelet counts < 50 X 109/L
                • Following treatment initiation, platelet counts must be performed every 2 weeks for first 8 weeks regardless of baseline platelet count
                • After 8 weeks of treatment, monitor platelet counts every 2 weeks (or more frequently as clinically indicated) if values are less than 75 X 109/L, every 4 weeks if values are between 75 and 100 X 109/L, and as clinically indicated if values are greater than 100 X 109/L
                • Manage platelet counts of < 50 X 109/L by treatment interruption or dose-reduction; platelet support may be necessary
                • Dose-interruptions and dose­ reductions for thrombocytopenia occurred in 20% and 22% of treated patients, respectively; thrombocytopenia was generally reversible by reducing or interrupting drug

                Drug interaction overview

                Substrate of CYP3A4 and CYP2C9

                Strong and moderate CYP3A inhibitors
                • Avoid coadministration; reduce dose if unable to avoid
                • Strong or moderate CYP3A inhibitor increases avapritinib plasma concentrations and adverse reactions
                Strong and moderate CYP3A inducers
                • Avoid coadministration
                • Strong or moderate CYP3A inducer decreases plasma concentrations and efficacy of avapritinib
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                Pregnancy & Lactation

                Pregnancy

                Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman

                No data available on use in pregnant women

                Verify pregnancy status of females of reproductive potential before initiation

                Contraception

                • Females of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose
                • Males with female partners of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose

                Infertility

                • Based on findings from animal studies, may impair fertility for both males and females

                Animal studies

                • Oral administration of avapritinib to pregnant animals during organogenesis was teratogenic and embryotoxic in rats at exposure levels approximately 6.3 and 2.7 times the human exposure based on AUC at the 200 mg and 300 mg dose
                • Advise pregnant women of the potential risk to a fetus

                Lactation

                There are no data on the presence of avapritinib or its metabolites in human milk or the effects of avapritinib on the breastfed child or milk production

                Advise women not to breastfeed during treatment and for 2 weeks following the final 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

                Tyrosine kinase inhibitor binds to and inhibits specific mutant forms of PDGFRα and c-Kit, including the PDGFRα D842V mutant and various KIT exon 17 mutants

                This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants

                Absorption

                Peak plasma time: 2-4 hr

                Steady-state reached by day 15

                Peak plasma concentration

                • AdvSM: 377 ng/mL
                • GIST: 813 ng/mL

                AUC

                • AdvSM: 6,600 ng·hr/mL
                • GIST: 15,400 ng·hr/mL

                Accumulation ratio

                • AdvSM: 6.41
                • GIST: 3.82

                Effects of food

                • Peak plasma concentration increased by 59% and AUC increased by 29% when administered with a high-calorie, high-fat meal (~909 calories, 58 grams carbohydrate, 56 grams fat, and 43 grams protein) compared with the fasted state

                Distribution

                Blood-to-plasma ratio: 0.95

                Protein bound: 98.8%

                Vd

                • GIST: 1,200 L
                • AdvSM: 1,900 L

                Metabolism

                Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9 into unchanged drug and its metabolites M690 (hydroxy glucuronide) and M499 (oxidative deamination)

                Following oral administration of 300-mg dose, the steady-state AUC of M499 is ~80% of the AUC of avapritinib

                M499 is not likely to contribute to efficacy at the recommended dose of avapritinib

                Elimination

                Half-life

                • GIST: 32-57 hr
                • AdvSM: 20-39 hr

                Clearance

                • GIST: 21.8 L/hr
                • AdvSM: 40.3 L/hr

                Excretion

                • Feces (70% [11% unchanged])
                • Urine (18% [0.23% unchanged])
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                Administration

                Oral Administration

                Administer on an empty stomach, at least 1 hr before and 2 hr after a meal

                Missed dose

                • Do not make up for a missed dose within 8 hr of the next scheduled dose
                • Do not take an additional dose if vomiting occurs after administration; continue with the next scheduled dose

                Storage

                Store at 20-25ºC (68-77ºF); excursions are permitted to 15-30ºC (59-86ºF)

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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.

                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.

                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.