avapritinib (Rx)

Brand and Other Names:Ayvakit

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

Indolent Systemic Mastocytosis

Indicated for indolent systemic mastocytosis (ISM)

25 mg PO qDay

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
    • ISM: Avoid coadministration

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 [total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin > 1 to 1.5 times ULN and any AST or moderate [total bilirubin >1.5 to 3 times ULN and any AST] hepatic impairment: No dosage adjustment necessary
  • Severe (Child-Pugh C)
    • Reduce starting dose
    • GIST: 200 mg PO qDay
    • AdvSM: 100 mg PO qDay
    • SIM: 25 mg PO every other day

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 or ISM with platelet counts <50 X 109/L

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and avapritinib

No Results

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    Interactions Found

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      Serious - Use Alternative

        Significant - Monitor Closely

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             activity indicator 

            Contraindicated (1)

            • thalidomide

              avapritinib and thalidomide both increase sedation. Contraindicated.

            Serious - Use Alternative (109)

            • alfentanil

              avapritinib and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • amobarbital

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

            • 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.

            • benzhydrocodone/acetaminophen

              avapritinib and benzhydrocodone/acetaminophen both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • buprenorphine

              avapritinib and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine buccal

              avapritinib and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine subdermal implant

              avapritinib and buprenorphine subdermal implant both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine transdermal

              avapritinib and buprenorphine transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine, long-acting injection

              avapritinib and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • 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.

            • codeine

              avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • 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.

            • fentanyl

              avapritinib and fentanyl both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl intranasal

              avapritinib and fentanyl intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl iontophoretic transdermal system

              avapritinib and fentanyl iontophoretic transdermal system both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transdermal

              avapritinib and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transmucosal

              avapritinib and fentanyl transmucosal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • fosaprepitant

              fosaprepitant 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.

            • hydrocodone

              avapritinib and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • hydromorphone

              avapritinib and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • 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.

            • levoketoconazole

              levoketoconazole 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.

            • 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.

            • methadone

              avapritinib and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • morphine

              avapritinib and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • oxycodone

              avapritinib and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • oxymorphone

              avapritinib and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • remifentanil

              avapritinib and remifentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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 (257)

            • 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.

            • acetaminophen/phenyltoloxamine

              avapritinib and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

            • acrivastine

              acrivastine and avapritinib both increase sedation. Use Caution/Monitor.

            • alprazolam

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

              avapritinib and alprazolam both increase sedation. Use Caution/Monitor.

            • amisulpride

              amisulpride and avapritinib both increase sedation. Use Caution/Monitor.

            • amitriptyline

              avapritinib and amitriptyline both increase sedation. Use Caution/Monitor.

            • amlodipine

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

            • amobarbital

              avapritinib and amobarbital both increase sedation. Use Caution/Monitor.

            • amoxapine

              avapritinib and amoxapine both increase sedation. Use Caution/Monitor.

            • aripiprazole

              avapritinib and aripiprazole both increase sedation. Use Caution/Monitor.

            • asenapine

              asenapine and avapritinib both increase sedation. Use Caution/Monitor.

            • asenapine transdermal

              asenapine transdermal and avapritinib both increase sedation. 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.

            • baclofen

              avapritinib and baclofen both increase sedation. 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.

            • brexanolone

              avapritinib and brexanolone both increase sedation. Use Caution/Monitor.

            • brexpiprazole

              avapritinib and brexpiprazole both increase sedation. Use Caution/Monitor.

            • brimonidine

              avapritinib and brimonidine both increase sedation. Use Caution/Monitor.

              brimonidine and avapritinib both increase sedation. Use Caution/Monitor.

            • brivaracetam

              avapritinib and brivaracetam both increase sedation. Use Caution/Monitor.

            • bromocriptine

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

            • brompheniramine

              avapritinib and brompheniramine both increase sedation. Use Caution/Monitor.

            • butabarbital

              avapritinib and butabarbital both increase sedation. Use Caution/Monitor.

            • butalbital

              avapritinib and butalbital both increase sedation. Use Caution/Monitor.

            • butorphanol

              avapritinib and butorphanol both increase sedation. Use Caution/Monitor.

            • carbinoxamine

              avapritinib and carbinoxamine both increase sedation. Use Caution/Monitor.

            • cariprazine

              avapritinib and cariprazine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              avapritinib and carisoprodol both increase sedation. Use Caution/Monitor.

            • cenobamate

              avapritinib and cenobamate both increase sedation. Use Caution/Monitor.

            • cetirizine

              avapritinib and cetirizine both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              avapritinib and chlordiazepoxide both increase sedation. Use Caution/Monitor.

            • chlorpheniramine

              avapritinib and chlorpheniramine both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              avapritinib and chlorpromazine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

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

              avapritinib and chlorzoxazone both increase sedation. 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.

              avapritinib and clemastine both increase sedation. Use Caution/Monitor.

            • clobazam

              avapritinib and clobazam both increase sedation. Use Caution/Monitor.

            • clomipramine

              avapritinib and clomipramine both increase sedation. Use Caution/Monitor.

            • clonazepam

              avapritinib and clonazepam both increase sedation. Use Caution/Monitor.

            • clonidine

              avapritinib and clonidine both increase sedation. Use Caution/Monitor.

            • clorazepate

              avapritinib and clorazepate both increase sedation. Use Caution/Monitor.

            • clozapine

              avapritinib and clozapine both increase sedation. Use Caution/Monitor.

            • cocaine topical

              cocaine topical 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.

            • cyclobenzaprine

              avapritinib and cyclobenzaprine both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              avapritinib and cyproheptadine both increase sedation. 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.

            • dantrolene

              avapritinib and dantrolene both increase sedation. Use Caution/Monitor.

            • daridorexant

              avapritinib and daridorexant both increase sedation. 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.

            • desflurane

              avapritinib and desflurane both increase sedation. Use Caution/Monitor.

            • desipramine

              avapritinib and desipramine both increase sedation. Use Caution/Monitor.

            • desvenlafaxine

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

            • deutetrabenazine

              avapritinib and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dexbrompheniramine

              avapritinib and dexbrompheniramine both increase sedation. Use Caution/Monitor.

            • dexchlorpheniramine

              avapritinib and dexchlorpheniramine both increase sedation. 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.

              avapritinib and diazepam both increase sedation. Use Caution/Monitor.

            • diclofenac

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

            • difenoxin hcl

              avapritinib and difenoxin hcl both increase sedation. Use Caution/Monitor.

            • dihydroergotamine

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

            • dimenhydrinate

              avapritinib and dimenhydrinate both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              avapritinib and diphenhydramine both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              avapritinib and diphenoxylate hcl both increase sedation. 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.

            • doxepin

              avapritinib and doxepin both increase sedation. 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.

            • doxylamine

              avapritinib and doxylamine both increase sedation. Use Caution/Monitor.

            • droperidol

              avapritinib and droperidol both increase sedation. 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.

              avapritinib and efavirenz both increase sedation. Use Caution/Monitor.

            • entacapone

              avapritinib and entacapone both increase sedation. 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.

            • esketamine intranasal

              avapritinib and esketamine intranasal both increase sedation. Use Caution/Monitor.

            • estazolam

              avapritinib and estazolam both increase sedation. Use Caution/Monitor.

            • eszopiclone

              avapritinib and eszopiclone both increase sedation. Use Caution/Monitor.

            • ethanol

              avapritinib and ethanol both increase sedation. Use Caution/Monitor.

            • ethosuximide

              avapritinib and ethosuximide both increase sedation. Use Caution/Monitor.

            • ethotoin

              avapritinib and ethotoin both increase sedation. 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.

            • felbamate

              avapritinib and felbamate both increase sedation. Use Caution/Monitor.

            • felodipine

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

            • fenfluramine

              avapritinib and fenfluramine both increase sedation. 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.

            • fexofenadine

              avapritinib and fexofenadine both increase sedation. Use Caution/Monitor.

            • flibanserin

              avapritinib and flibanserin both increase sedation. Use Caution/Monitor.

            • fluoxetine

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

            • fluphenazine

              avapritinib and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              avapritinib and flurazepam both increase sedation. Use Caution/Monitor.

            • gabapentin

              avapritinib and gabapentin both increase sedation. Use Caution/Monitor.

            • ganaxolone

              avapritinib and ganaxolone both increase sedation. Use Caution/Monitor.

            • guanfacine

              avapritinib and guanfacine both increase sedation. Use Caution/Monitor.

            • haloperidol

              avapritinib and haloperidol both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              avapritinib and hydroxyzine both increase sedation. Use Caution/Monitor.

            • iloperidone

              avapritinib and iloperidone both increase sedation. Use Caution/Monitor.

            • imipramine

              avapritinib and imipramine both increase sedation. Use Caution/Monitor.

            • isoflurane

              avapritinib and isoflurane both increase sedation. 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.

            • ketamine

              avapritinib and ketamine both increase sedation. Use Caution/Monitor.

            • ketotifen, drug-eluting contact lens

              avapritinib and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

            • lamotrigine

              avapritinib and lamotrigine both increase sedation. Use Caution/Monitor.

            • lansoprazole

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

            • lasmiditan

              avapritinib and lasmiditan both increase sedation. Use Caution/Monitor.

            • lemborexant

              avapritinib and lemborexant both increase sedation. Use Caution/Monitor.

            • lenacapavir

              lenacapavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lenvatinib

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

            • levetiracetam

              avapritinib and levetiracetam both increase sedation. Use Caution/Monitor.

            • levocetirizine

              avapritinib and levocetirizine both increase sedation. Use Caution/Monitor.

            • levorphanol

              avapritinib and levorphanol both increase sedation. 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.

            • loratadine

              avapritinib and loratadine both increase sedation. Use Caution/Monitor.

            • lorazepam

              avapritinib and lorazepam both increase sedation. 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.

            • loxapine

              avapritinib and loxapine both increase sedation. Use Caution/Monitor.

            • lumateperone

              avapritinib and lumateperone both increase sedation. Use Caution/Monitor.

            • lurasidone

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

              avapritinib and lurasidone both increase sedation. Use Caution/Monitor.

            • maprotiline

              avapritinib and maprotiline both increase sedation. Use Caution/Monitor.

            • meclizine

              avapritinib and meclizine both increase sedation. Use Caution/Monitor.

            • mefloquine

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

            • meperidine

              avapritinib and meperidine both increase sedation. Use Caution/Monitor.

            • meprobamate

              avapritinib and meprobamate both increase sedation. Use Caution/Monitor.

            • mestranol

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

            • metaxalone

              avapritinib and metaxalone both increase sedation. 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.

            • methocarbamol

              avapritinib and methocarbamol both increase sedation. Use Caution/Monitor.

            • methohexital

              avapritinib and methohexital both increase sedation. Use Caution/Monitor.

            • methoxsalen

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

            • methsuximide

              avapritinib and methsuximide both increase sedation. Use Caution/Monitor.

            • 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.

              avapritinib and midazolam both increase sedation. Use Caution/Monitor.

            • mirtazapine

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

              avapritinib and mirtazapine both increase sedation. Use Caution/Monitor.

            • mitoxantrone

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

            • molindone

              avapritinib and molindone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              avapritinib and nalbuphine both increase sedation. 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.

            • nitrous oxide

              avapritinib and nitrous oxide both increase sedation. Use Caution/Monitor.

            • nizatidine

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

            • nortriptyline

              avapritinib and nortriptyline both increase sedation. Use Caution/Monitor.

            • olanzapine

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

              avapritinib and olanzapine both increase sedation. Use Caution/Monitor.

            • oliceridine

              avapritinib and oliceridine both increase sedation. Use Caution/Monitor.

            • olopatadine intranasal

              avapritinib and olopatadine intranasal both increase sedation. Use Caution/Monitor.

            • omeprazole

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

            • opicapone

              avapritinib and opicapone both increase sedation. Use Caution/Monitor.

            • opium tincture

              avapritinib and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

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

              avapritinib and orphenadrine both increase sedation. Use Caution/Monitor.

            • oxazepam

              avapritinib and oxazepam both increase sedation. 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.

            • paliperidone

              avapritinib and paliperidone both increase sedation. 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.

            • pentazocine

              avapritinib and pentazocine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              avapritinib and pentobarbital both increase sedation. Use Caution/Monitor.

            • perampanel

              avapritinib and perampanel both increase sedation. Use Caution/Monitor.

            • perphenazine

              avapritinib and perphenazine both increase sedation. Use Caution/Monitor.

            • pheniramine

              avapritinib and pheniramine both increase sedation. Use Caution/Monitor.

            • phenobarbital

              avapritinib and phenobarbital both increase sedation. 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.

              avapritinib and pimozide both increase sedation. Use Caution/Monitor.

            • pitolisant

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

            • pomalidomide

              avapritinib and pomalidomide both increase sedation. Use Caution/Monitor.

            • pravastatin

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

            • pregabalin

              avapritinib and pregabalin both increase sedation. Use Caution/Monitor.

            • primaquine

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

            • primidone

              avapritinib and primidone both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              avapritinib and prochlorperazine both increase sedation. 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.

            • promethazine

              avapritinib and promethazine both increase sedation. Use Caution/Monitor.

            • propofol

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

              avapritinib and propofol both increase sedation. Use Caution/Monitor.

            • protriptyline

              avapritinib and protriptyline both increase sedation. Use Caution/Monitor.

            • pyrilamine

              avapritinib and pyrilamine both increase sedation. Use Caution/Monitor.

            • quazepam

              avapritinib and quazepam both increase sedation. Use Caution/Monitor.

            • quetiapine

              avapritinib and quetiapine both increase sedation. 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.

            • ramelteon

              avapritinib and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

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

            • remimazolam

              avapritinib and remimazolam both increase sedation. Use Caution/Monitor.

            • reserpine

              avapritinib and reserpine both increase sedation. Use Caution/Monitor.

            • risperidone

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

              avapritinib and risperidone both increase sedation. 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.

            • scopolamine

              avapritinib and scopolamine both increase sedation. Use Caution/Monitor.

            • selegiline

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

            • sevoflurane

              avapritinib and sevoflurane both increase sedation. Use Caution/Monitor.

            • sirolimus

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

            • sodium oxybate

              avapritinib and sodium oxybate both increase sedation. Use Caution/Monitor.

            • sparsentan

              sparsentan will decrease the level or effect of avapritinib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

            • stiripentol

              avapritinib and stiripentol both increase sedation. Use Caution/Monitor.

            • sufentanil

              avapritinib and sufentanil both increase sedation. Use Caution/Monitor.

            • sufentanil SL

              avapritinib and sufentanil SL both increase sedation. Use Caution/Monitor.

            • sulconazole

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

            • suvorexant

              avapritinib and suvorexant both increase sedation. Use Caution/Monitor.

            • tamoxifen

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

            • tapentadol

              avapritinib and tapentadol both increase sedation. Use Caution/Monitor.

            • tasimelteon

              avapritinib and tasimelteon both increase sedation. Use Caution/Monitor.

            • tazemetostat

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

            • temazepam

              avapritinib and temazepam both increase sedation. 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.

            • tetrabenazine

              avapritinib and tetrabenazine both increase sedation. Use Caution/Monitor.

            • thioridazine

              avapritinib and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              avapritinib and thiothixene both increase sedation. Use Caution/Monitor.

            • tiagabine

              avapritinib and tiagabine both increase sedation. 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.

            • tizanidine

              avapritinib and tizanidine both increase sedation. Use Caution/Monitor.

            • tolcapone

              avapritinib and tolcapone both increase sedation. Use Caution/Monitor.

            • topiramate

              avapritinib and topiramate both increase sedation. Use Caution/Monitor.

            • tramadol

              avapritinib and tramadol both increase sedation. 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.

              avapritinib and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              avapritinib and triazolam both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              avapritinib and trifluoperazine both increase sedation. Use Caution/Monitor.

            • triprolidine

              avapritinib and triprolidine both increase sedation. 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.

              avapritinib and valproic acid both increase sedation. Use Caution/Monitor.

            • vigabatrin

              avapritinib and vigabatrin both increase sedation. 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.

            • zaleplon

              avapritinib and zaleplon both increase sedation. Use Caution/Monitor.

            • ziconotide

              avapritinib and ziconotide both increase sedation. 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.

              avapritinib and ziprasidone both increase sedation. Use Caution/Monitor.

            • zolpidem

              avapritinib and zolpidem both increase sedation. Use Caution/Monitor.

            • zonisamide

              avapritinib and zonisamide both increase sedation. Use Caution/Monitor.

            Minor (4)

            • acetazolamide

              acetazolamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • larotrectinib

              larotrectinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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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%)
            • ISM
              • Eye edema (13%)
              • Dizziness (13%)
              • Peripheral edema (12%)
              • Flushing (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%)
            • ISM
              • Respiratory tract infection (8%)
              • Face edema (7%)
              • Rash (6%)
              • Liver transaminase increased (6%)
              • Insomnia (6%)
              • Hematoma (6%)
              • Blood alkaline phosphatase increased (6%)
              • Hemorrhage (5%)
              • Photosensitivity (2.8%)

            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%)

            Postmarketing Reports

            Photosensitivity

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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

            Therapy may cause photosensitivity reactions; in all patients treated in clinical trials, photosensitivity reactions occurred in 2.5% of patients; advise patients to limit direct ultraviolet exposure during treatment and for one week after discontinuation of treatment

            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
            • Symptoms of intracranial hemorrhage may include headache, nausea, vomiting, vision changes, or altered mental status; advise patients to seek immediate medical attention for signs or symptoms of intracranial hemorrhage
            • 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 to pregnant rats during period of organogenesis was teratogenic and embryotoxic at exposure levels approximately 31.4, 6.3 and 2.7 times human exposure based on AUC at 25 mg, 200 mg and 300 mg dose, respectively
            • 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

            • GIST: 813 ng/mL (300 mg/day)
            • AdvSM: 377 ng/mL (200 mg/day)
            • ISM: 70.2 ng/mL (25 mg/day)

            AUC

            • GIST: 15,400 ng·hr/mL (300 mg/day)
            • AdvSM: 6,600 ng·hr/mL (200 mg/day)
            • ISM: 1,330 ng·hr/mL (25 mg/day)

            Accumulation ratio of AUC

            • GIST: 3.82
            • AdvSM: 6.41
            • ISM: 4.06

            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
            • ISM: 1,400 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
            • ISM: 38-45 hr

            Clearance

            • GIST: 21.8 L/hr
            • AdvSM: 40.3 L/hr
            • ISM: 21.6 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.