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
Dosage Modifications
Dose reductions for adverse reactions
-
GIST
- First dose reduction: 200 mg qDay
- Second dose reduction: 100 mg qDay
- Unable to tolerate a 100-mg dose: Permanently discontinue
-
AdvSM
- First dose reduction: 100 mg qDay
- Second dose reduction: 50 mg qDay
- Third dose reduction: 25 mg qDay
- Unable to tolerate a 25-mg dose: Permanently discontinue
Intracranial hemorrhage
- First occurrence of Grade 1 or 2: Withhold until resolution; resume at reduced dose
- Subsequent occurrence of Grade 1 or 2: Permanently discontinue
- Grade 3 or 4: Permanently discontinue
CNS effects
- Grade 1: Continue dose at the same dose or withhold until improvement to baseline or resolution; resume at same dose or reduced dose
- Grade 2 or 3: Withhold until improvement to baseline, Grade 1, or resolution; resume at same dose or reduced dose
- Grade 4: Permanently discontinue
Other adverse reactions
Grade 3 or 4: Withhold until improvement to Grade ≤2, or resolution; resume at same dose or reduced dose, as clinically appropriate
Thrombocytopenia
- Platelet counts <50 x 109/L: Interrupt until platelet count ≥50 x 109/L, then resume at reduced dose
- If platelet counts do not recover above 50 x 109/L, consider platelet support
Strong or moderate CYP3A4 inhibitors
- Avoid coadministration
-
If use is unavoidable, reduce starting dose as follows
- GIST: 100 mg PO qDay
- AdvSM: 50 mg PO qDay
Renal impairment
- Mild-to-moderate (CrCl 30-90 mL/mL): No dosage adjustment necessary
- Severe or end-stage renal disease (CrCl <30 mL/min): Effect on pharmacokinetics unknown
Hepatic impairment
- Mild-to-moderate (total bilirubin ≤3x ULN and any AST): No dosage adjustment necessary
- Severe (total bilirubin >3x ULN and any AST): Effect on pharmacokinetics unknown
Dosing Considerations
Verify pregnancy status in females of reproductive potential
Patient selection (GIST)
- Select patients based on presence of a PDGFRA exon 18 mutation
- No FDA-approved test available
Limitations of use
- Not recommended for AdvSM with platelet counts <50 X 109/L
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (90)
- abametapir
abametapir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- amiodarone
amiodarone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- 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.
- bexarotene
bexarotene will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bicalutamide
bicalutamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- bosentan
bosentan will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- brigatinib
brigatinib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butalbital
butalbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- chloramphenicol
chloramphenicol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- clarithromycin
clarithromycin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- clobazam
clobazam will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- conivaptan
conivaptan will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- crizotinib
crizotinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- cyclosporine
cyclosporine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- darunavir
darunavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- desipramine
desipramine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- diltiazem
diltiazem will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- doxycycline
doxycycline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- dronedarone
dronedarone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- elagolix
elagolix will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- encorafenib
encorafenib, avapritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate or strong CYP3A4 inhibitors. If coadministration of avapritinib with a moderate inhibitor cannot be avoided, reduce avapritinib starting dose (see drug monograph Dosage Modifications).
- erythromycin base
erythromycin base will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- erythromycin stearate
erythromycin stearate will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fedratinib
fedratinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- fexinidazole
fexinidazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fluconazole
fluconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- fluvoxamine
fluvoxamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications
- fosamprenavir
fosamprenavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- fosphenytoin
fosphenytoin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fostamatinib
fostamatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- grapefruit
grapefruit will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- haloperidol
haloperidol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- idelalisib
idelalisib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- iloperidone
iloperidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- imatinib
imatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- indinavir
indinavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- isoniazid
isoniazid will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- itraconazole
itraconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- ivacaftor
ivacaftor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- ivosidenib
ivosidenib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ketoconazole
ketoconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- lapatinib
lapatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- 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.
- 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.
- nafcillin
nafcillin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nefazodone
nefazodone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- nelfinavir
nelfinavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- pentobarbital
pentobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- posaconazole
posaconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- primidone
primidone will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- ribociclib
ribociclib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- rifabutin
rifabutin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ritonavir
ritonavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- saquinavir
saquinavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- schisandra
schisandra will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- secobarbital
secobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sertraline
sertraline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- St John's Wort
St John's Wort will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- stiripentol
stiripentol, avapritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate or strong CYP3A4 inhibitors. If coadministration of avapritinib with a moderate inhibitor cannot be avoided, reduce avapritinib starting dose (see drug monograph Dosage Modifications).
- telotristat ethyl
telotristat ethyl will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tetracycline
tetracycline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
- tipranavir
tipranavir will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- tucatinib
tucatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- verapamil
verapamil will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- voriconazole
voriconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.
- voxelotor
voxelotor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.
Monitor Closely (112)
- 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.
- alprazolam
alprazolam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- amlodipine
amlodipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
atorvastatin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- azelastine
azelastine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- betamethasone
betamethasone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bortezomib
bortezomib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bromocriptine
bromocriptine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- chlorzoxazone
chlorzoxazone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cimetidine
cimetidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ciprofloxacin
ciprofloxacin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clemastine
clemastine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cocaine 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.
- dabrafenib
dabrafenib will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- danazol
danazol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- darifenacin
darifenacin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dasatinib
dasatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- desvenlafaxine
desvenlafaxine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dexlansoprazole
dexlansoprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dexmedetomidine
dexmedetomidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- diazepam
diazepam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- diclofenac
diclofenac will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dihydroergotamine
dihydroergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- disulfiram
disulfiram will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- docetaxel
docetaxel will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- doxorubicin
doxorubicin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- doxorubicin liposomal
doxorubicin liposomal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- drospirenone
drospirenone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- efavirenz
efavirenz will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- enzalutamide
enzalutamide will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ergotamine
ergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etoposide
etoposide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- felodipine
felodipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fentanyl
fentanyl will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fentanyl transdermal
fentanyl transdermal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluoxetine
fluoxetine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isradipine
isradipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lansoprazole
lansoprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lenvatinib
lenvatinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lidocaine
lidocaine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lomustine
lomustine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- losartan
losartan will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lovastatin
lovastatin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lurasidone
lurasidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mefloquine
mefloquine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mestranol
mestranol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- methadone
methadone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- methimazole
methimazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- methoxsalen
methoxsalen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- methylprednisolone
methylprednisolone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- micafungin
micafungin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- midazolam
midazolam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mirtazapine
mirtazapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mitoxantrone
mitoxantrone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nevirapine
nevirapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nifedipine
nifedipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nilotinib
nilotinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nisoldipine
nisoldipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nizatidine
nizatidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- olanzapine
olanzapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- omeprazole
omeprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- orphenadrine
orphenadrine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- oxybutynin
oxybutynin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- oxybutynin topical
oxybutynin topical will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- oxybutynin transdermal
oxybutynin transdermal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- palbociclib
palbociclib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- paroxetine
paroxetine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pazopanib
pazopanib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pentamidine
pentamidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pilocarpine
pilocarpine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pimozide
pimozide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pitolisant
pitolisant will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pravastatin
pravastatin will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- primaquine
primaquine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- progesterone micronized
progesterone micronized will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- progesterone, natural
progesterone, natural will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- propofol
propofol will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- quinidine
quinidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- quinine
quinine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rabeprazole
rabeprazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ranolazine
ranolazine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- risperidone
risperidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of avapritinib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.
- rufinamide
rufinamide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- selegiline
selegiline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- sirolimus
sirolimus will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- sulconazole
sulconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tamoxifen
tamoxifen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- temsirolimus
temsirolimus will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- teniposide
teniposide will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- testosterone
testosterone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- testosterone buccal system
testosterone buccal system will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- testosterone topical
testosterone topical will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ticagrelor
ticagrelor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ticlopidine
ticlopidine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tranylcypromine
tranylcypromine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- trazodone
trazodone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- valproic acid
valproic acid will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- vinblastine
vinblastine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- vincristine
vincristine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- vinorelbine
vinorelbine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- zafirlukast
zafirlukast will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- zileuton
zileuton will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ziprasidone
ziprasidone will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (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%)
Grade ≥3
-
GIST
- Decreased hemoglobin (28%)
- Decreased phosphate (13%)
-
AdvSM
- Decreased neutrophils (25%)
- Decreased hemoglobin (23%)
- Decreased platelets (21%)
- Decreased lymphocytes (11%)
1-10%
All grades
-
GIST
- Hypertension (8%)
- Thyroid disorders (hyperthyroid, hypothyroid) (3%)
- Palmar-plantar erythrodysesthesia (1%)
-
AdvSM
- Arthralgia (10%)
- Increased lymphocytes (10%)
- Dyspnea (9%)
- Alopecia (9%)
- Lacrimation increased (9%)
- Decreased phosphate (9%)
- Rash (8%)
- Pruritus (8%)
- Decreased appetite (8%)
- Upper respiratory tract infection (6%)
- Urinary tract infection (6%)
- Insomnia (6%)
- Pain in extremity (6%)
- Hair color changes (6%)
- Ascites (5%)
- Anemia (5%)
- Subdural hematoma (4%)
- Flushing (3.8%)
- Hypertension (3.8%)
- Hypotension (3.8%)
- Pleural effusion (3%)
- Pneumonia (3%)
- Herpes zoster (2.5%)
- Cardiac failure (2.5%)
- Hot flush (2.5%)
- Cough (2.5%)
- Acute kidney injury (2%)
- Gastrointestinal hemorrhage (2%)
- Intracranial hemorrhage (2%)
- Encephalopathy (2%)
- Gastric hemorrhage (2%)
- Pyrexia (2%)
- Cardiac failure congestive (1.3%)
- Gastrointestinal hemorrhage (1.3%)
- Large intestine perforation (1.3%)
- Cholelithiasis (1.3%)
Grade ≥3
GIST
- Fatigue (9%)
- Increased bilirubin (9%)
- Abdominal pain (6%)
- Decreased neutrophils (6%)
- Decreased potassium (6%)
- Decreased sodium (7%)
- Decreased leukocytes (5%)
- Diarrhea (4.9%)
- Cognitive impairment (4.9%)
- Decreased appetite (2.9%)
- Nausea (2.5%)
- Dyspnea (2.5%)
- Rash (2.1%)
- Vomiting (2%)
- Edema (2%)
- Pleural effusion (2%)
- Decreased albumin (2%)
- Constipation (1.5%)
- Increased AST (1.5%)
- Mood disorders (1%)
- Decreased weight (1%)
- Decreased magnesium (1%)
- Increased alkaline phosphatase (1%)
AdvSM
- Edema (5%)
- Increased alkaline phosphatase (5%)
- Fatigue/asthenia (4%)
- Decreased potassium (4%)
- Vomiting (3%)
- Decreased calcium (3%)
- Increased bilirubin (3%)
- Diarrhea (1%)
- Nausea (1%)
- Abdominal pain (1%)
- Cognitive effects (1%)
- Arthralgia (1%)
- Increased aPTT (1%)
- Increased AST (1%)
- Increased ALT (1%)
- Decreased sodium (1%)
- Decreased albumin (1%)
- Decreased magnesium (1%)
<1%
Grade ≥3
-
GIST
- Increased INR (0.6%)
- Pyrexia (0.5%)
- Dizziness (0.5%)
- Headache (0.5%)
- Hair color changes (0.5%)
- Decreased platelets (0.5%)
- Increased ALT (0.5%)
Warnings
Contraindications
None
Cautions
A broad spectrum of CNS adverse reactions reported; these include, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations
Cognitive adverse reactions reported; depending on severity, withhold treatment and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue treatment
Fetal harm can occur when administered to pregnant females
Intracranial hemorrhage
- Intracranial hemorrhage (eg, subdural hematoma, intracranial hemorrhage, cerebral hemorrhage) occurred; thrombocytopenia was generally reversible by dose reduction or interruption
- Monitor patients closely for the risk of intracranial hemorrhage including those with thrombocytopenia, vascular aneurysm or a history of intracranial hemorrhage or cerebrovascular accident within the prior year
- Permanently discontinue therapy if intracranial hemorrhage of any grade occurs
Advanced systemic mastocytosis
- Platelet count must be performed prior to initiating therapy; drug not recommended in patients with AdvSM with platelet counts < 50 X 109/L
- Following treatment initiation, platelet counts must be performed every 2 weeks for first 8 weeks regardless of baseline platelet count
- After 8 weeks of treatment, monitor platelet counts every 2 weeks (or more frequently as clinically indicated) if values are less than 75 X 109/L, every 4 weeks if values are between 75 and 100 X 109/L, and as clinically indicated if values are greater than 100 X 109/L
- Manage platelet counts of < 50 X 109/L by treatment interruption or dose-reduction; platelet support may be necessary
- Dose-interruptions and dose reductions for thrombocytopenia occurred in 20% and 22% of treated patients, respectively; thrombocytopenia was generally reversible by reducing or interrupting drug
Drug interaction overview
Substrate of CYP3A4 and CYP2C9
Strong and moderate CYP3A inhibitors
- Avoid coadministration; reduce dose if unable to avoid
- Strong or moderate CYP3A inhibitor increases avapritinib plasma concentrations and adverse reactions
Strong and moderate CYP3A inducers
- Avoid coadministration
- Strong or moderate CYP3A inducer decreases plasma concentrations and efficacy of avapritinib
Pregnancy & Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
No data available on use in pregnant women
Verify pregnancy status of females of reproductive potential before initiation
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose
- Males with female partners of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose
Infertility
- Based on findings from animal studies, may impair fertility for both males and females
Animal studies
- Oral administration of avapritinib to pregnant animals during organogenesis was teratogenic and embryotoxic in rats at exposure levels approximately 6.3 and 2.7 times the human exposure based on AUC at the 200 mg and 300 mg dose
- Advise pregnant women of the potential risk to a fetus
Lactation
There are no data on the presence of avapritinib or its metabolites in human milk or the effects of avapritinib on the breastfed child or milk production
Advise women not to breastfeed during treatment and for 2 weeks following the final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Tyrosine kinase inhibitor binds to and inhibits specific mutant forms of PDGFRα and c-Kit, including the PDGFRα D842V mutant and various KIT exon 17 mutants
This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants
Absorption
Peak plasma time: 2-4 hr
Steady-state reached by day 15
Peak plasma concentration
- AdvSM: 377 ng/mL
- GIST: 813 ng/mL
AUC
- AdvSM: 6,600 ng·hr/mL
- GIST: 15,400 ng·hr/mL
Accumulation ratio
- AdvSM: 6.41
- GIST: 3.82
Effects of food
- Peak plasma concentration increased by 59% and AUC increased by 29% when administered with a high-calorie, high-fat meal (~909 calories, 58 grams carbohydrate, 56 grams fat, and 43 grams protein) compared with the fasted state
Distribution
Blood-to-plasma ratio: 0.95
Protein bound: 98.8%
Vd
- GIST: 1,200 L
- AdvSM: 1,900 L
Metabolism
Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9 into unchanged drug and its metabolites M690 (hydroxy glucuronide) and M499 (oxidative deamination)
Following oral administration of 300-mg dose, the steady-state AUC of M499 is ~80% of the AUC of avapritinib
M499 is not likely to contribute to efficacy at the recommended dose of avapritinib
Elimination
Half-life
- GIST: 32-57 hr
- AdvSM: 20-39 hr
Clearance
- GIST: 21.8 L/hr
- AdvSM: 40.3 L/hr
Excretion
- Feces (70% [11% unchanged])
- Urine (18% [0.23% unchanged])
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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- View the formulary and any restrictions for each plan.
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