Dosing & Uses
Dosage Forms & Strengths
capsule
- 150mg
Acute Myeloid Leukemia
Indicated for relapsed and/or refractory acute myeloid leukemia with a confirmed IDH1 mutation (mIDH1+ R/R AML)
150 mg PO BID until disease progression or unacceptable toxicity
For patients without disease progression or toxicity, treat for a minimum of 6 months to allow time for clinical response
Dosage Modifications
Differentiation syndrome
- Withhold if differentiation syndrome is suspected until signs and symptoms improve
- Administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution for a minimum of 3 days
- After resolution, resume at 150 mg BID
-
Recurrence
- If recurrence suspected, withhold and institute treatment per above guidance
- After symptom resolution, may resume at reduced dose of 150 mg qDay for minimum of 7 days; may then increase to 150 mg BID
Noninfectious leukocytosis
- Initiate treatment with hydroxyurea, as per standard practices
- Taper hydroxyurea only after leukocytosis improves or resolves
Hepatotoxicity
-
Grade 3
- Withhold and monitor liver function tests, twice per week, until laboratory values return to baseline or Grade 1 toxicity
- Resume at reduced dose of 150 mg qDay and continue monitoring
- May increase to 150 mg BID if hepatotoxicity resolves to baseline for at least 28 days
- Discontinue if hepatotoxicity (Grade 3) recurs at 150 mg qDay
-
Grade 4
- Grade 4 hepatotoxicity OR AST/ALT >3x ULN and total bilirubin (TB) >2x ULN and alkaline phosphatase <2x ULN in absence of a clear alternative explanation: Permanently discontinue
Other adverse effects Grade ≥3
- Interrupt dosing until toxicity resolves to Grade ≤2
- Resume at 150 mg qDay; may increase to 150 mg BID if toxicities resolve to Grade ≤1 for at least 1 week
- Discontinue if Grade ≥3 recurs at 150 mg qDay
Renal impairment
- Mild-to-moderate (CrCl 30 to <90 mL/min): No dosage modification recommended
- Severe (CrCl 15-29 mL/min), kidney failure (CrCl <15 mL/min), or dialysis: Recommended dose not established
Hepatic impairment
- Mild-to-moderate (TB <3x ULN with any AST): No dosage modification recommended; closely monitor for increased probability of differentiation syndrome
- Severe (TB >3 x ULN with any AST): Recommended dose not established
Dosing Considerations
Patient selection
- Treatment based on presence of IDH1 mutations in blood or bone marrow as detected by FDA-approved tests
Monitoring
- Assess blood counts, and blood chemistries including liver function tests H5
- Before initiating drug
- First 2 months: At least once weekly
- Third month: q2weeks
- Fourth month: Once
- Month 5 and for duration of therapy: Once every other month
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (70)
- alfentanil
olutasidenib will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- amobarbital
amobarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- apalutamide
apalutamide will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- armodafinil
armodafinil will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- belzutifan
belzutifan will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- bexarotene
bexarotene will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- bosentan
bosentan will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- butabarbital
butabarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- butalbital
butalbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- carbamazepine
carbamazepine will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
olutasidenib will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates. - cenobamate
cenobamate will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- clonidine
olutasidenib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- colchicine
olutasidenib will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- cyclosporine
olutasidenib will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- dabrafenib
dabrafenib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- dihydroergotamine
olutasidenib will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- disopyramide
olutasidenib will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- efavirenz
efavirenz will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- elacestrant
olutasidenib will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- elagolix
elagolix will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- encorafenib
encorafenib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- enzalutamide
enzalutamide will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- ergotamine
olutasidenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- ethosuximide
olutasidenib will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- etravirine
etravirine will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- everolimus
olutasidenib will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- fentanyl
olutasidenib will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- fentanyl intranasal
olutasidenib will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- fentanyl iontophoretic transdermal system
olutasidenib will decrease the level or effect of fentanyl iontophoretic transdermal system by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- fentanyl transdermal
olutasidenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- fentanyl transmucosal
olutasidenib will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- fosphenytoin
fosphenytoin will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- ivosidenib
ivosidenib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- lenacapavir
olutasidenib will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.
- leniolisib
olutasidenib will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lorlatinib
lorlatinib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- mavacamten
mavacamten will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- midazolam
olutasidenib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- mitapivat
mitapivat will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- mitotane
mitotane will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- mobocertinib
mobocertinib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- modafinil
modafinil will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- nafcillin
nafcillin will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- omaveloxolone
olutasidenib will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pacritinib
olutasidenib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- palovarotene
olutasidenib will decrease the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pentobarbital
pentobarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- pexidartinib
pexidartinib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- phenobarbital
phenobarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- phenytoin
phenytoin will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- pimozide
olutasidenib will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- pirtobrutinib
olutasidenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
- primidone
primidone will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- quinidine
olutasidenib will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- quinine
olutasidenib will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- quizartinib
olutasidenib will decrease the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifabutin
rifabutin will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- rifampin
rifampin will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- rifapentine
rifapentine will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- secobarbital
secobarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- sirolimus
olutasidenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- sotorasib
sotorasib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- St John's Wort
St John's Wort will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- tacrolimus
olutasidenib will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- telotristat ethyl
telotristat ethyl will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- triazolam
olutasidenib will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- warfarin
olutasidenib will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
- zanubrutinib
olutasidenib will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.
Monitor Closely (2)
- lenacapavir
lenacapavir will increase the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir 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.
- norgestrel
olutasidenib will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods
Minor (0)
Adverse Effects
>10%
All grades
- AST increased (47%)
- ALT increased (46%)
- Potassium decreased (46%)
- Sodium decreased (42%)
- Alkaline phosphatase increased (42%)
- Creatinine increased (38%)
- Fatigue/malaise (36%)
- Arthralgia (28%)
- Lymphocytes increased (26%)
- Bilirubin increased (26%)
- Uric acid increased (25%)
- Leukocytosis (25%)
- Lipase increased (24%)
- Pyrexia (24%)
- Dyspnea (24%)
- Rash (24%)
- Mucositis (23%)
- Diarrhea (20%)
- Transaminitis (20%)
- Edema (18%)
- Abdominal pain (18%)
- Vomiting (17%)
- Cough (17%)
- Differentiation syndrome (16%)
- Decreased appetite (16%)
- Headache (13%)
Grades 3 or 4
- ALT increased (13%)
- Transaminitis (12%)
1-10%
All grades
- Hypertension (10%)
Grades 3 or 4
- AST increased (10%)
- Potassium decreased (9%)
- Leukocytosis (9%)
- Differentiation syndrome (8%)
- Lipase increased (8%)
- Sodium decreased (7%)
- Alkaline phosphatase increased (7%)
- Dyspnea (5%)
- Hypertension (5%)
- Mucositis (3%)
- Fatigue/malaise (3%)
- Edema (3%)
- Arthralgia (3%)
- Lymphocytes increased (3%)
- Uric acid increased (3%)
- Creatinine increased (2%)
- Bilirubin increased (2%)
- Decreased appetite (2%)
- Diarrhea (1%)
- Abdominal pain (1%)
- Vomiting (1%)
- Pyrexia (1%)
- Cough (1%)
- Rash (1%)
Warnings
Black Box Warnings
Differentiation syndrome
- Associated with rapid proliferation and differentiation of myeloid cells; may be life-threatening or fatal
- Some patients may recover after treatment or after dosage interruption
- May occur as early as 1 day and up to 18 months after treatment initiation; has been observed with or without concomitant leukocytosis
- Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain
- If differentiation syndrome suspected, withhold olutasidenib and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution
- May recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment after treating for concomitant leukocytosis
Contraindications
None
Cautions
Differentiation syndrome
- Can cause differentiation syndrome
- If suspected, withhold dose and initiate corticosteroids (eg, dexamethasone 10 mg IV q12hr for at least 3 days)
- See dosage modifications further information
Hepatotoxicity
- Can cause hepatotoxicity, presenting as increased ALT, increased AST, increased blood alkaline phosphatase, and/or elevated bilirubin
- Monitor frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice
- If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue based on recurrence/severity
Drug interaction overview
- CYP3A substrate and inducer
-
Strong or moderate CYP3A inducers
- Avoid coadministration
- Coadministration with strong or moderate CYP3A inducers decreases olutasidenib Cmax and AUC, which may reduce efficacy
-
Sensitive CYP3A substrates
- Avoid coadministration, unless otherwise instructed in the substrates’ prescribing information
- If concomitant use is unavoidable, monitor for loss of therapeutic effect of these drugs
Pregnancy & Lactation
Pregnancy
Based on animal embryofetal toxicity studies, may cause fetal harm when administered to pregnant females
Animal studies
- Resulted in embryofetal death and altered fetal growth when administered to pregnant rats and rabbits during organogenesis at exposures up to 10 times and 0.7 times, respectively, the human exposure at the recommended daily dose
Lactation
Data are not available on presence in human milk, effects on breastfed children, or effects on milk production
Advise females not to breastfeed during treatment and for 2 weeks after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits mutated isocitrate dehydrogenase-1 (IDH1), an enzyme that turns isocitrate into 2-ketoglutarate, an oncometabolite
Inhibition of IDH1 induces cellular differentiation and prevents cellular proliferation in IDH1 expressing cells
Absorption
Peak plasma time: ~4 hr
Steady-state reached: 14 days
Peak plasma concentration (steady-state): 3473 ng/mL
AUC (0-12 hr at steady-state): 43,050 ng⋅h/mL
Effect of food
- High-fat meal: Peak plasma concentration increased by 191% (20.6%) and AUC increased by 83% (18.3%) following administration of a single 150 mg dose
Distribution
Protein bound: 93%
Vd: 319 L
Metabolism
N-dealkylation, demethylation, oxidative deamination followed by oxidation, monooxidation with subsequent glucuronidation
Primarily (90%) metabolized by CYP3A4, with minor contributions from CYP2C8, CYP2C9, CYP1A2, and CYP2C19
Elimination
Half-life: ~67 hr
Oral clearance: 4 L/hr
Excretion: Feces 75% (35% unchanged); urine 17% (1% unchanged)
Administration
Oral Administration
Take on empty stomach at least 1 hr before or 2 hr after a meal
Administer at about the same time each day
Do not administer 2 doses within 8 hr
Swallow capsule whole; do not break, open, or chew
Vomited dose
- Do not administer a replacement dose
- Wait until next scheduled dose is due
Missed dose
- If dose is missed or not taken at the usual time, administer dose as soon as possible and at least 8 hr before next scheduled dose
- Return to normal schedule the following day
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
