Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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.
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
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
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.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])
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)
Images
Formulary
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