Dosing & Uses
Dosage Forms & Strengths
tablet
- 160mg
- 200mg
Breast Cancer
Indicated in combination with fulvestrant for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with ≥1 PIK3CA/AKT1/PTEN-alterations, following progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy
Capivasertib weekly dose schedule
- 400 mg PO BID (~12 hr apart) x 4 consecutive days followed by 3 days off
- Repeat weekly schedule until disease progression or unacceptable toxicity
Fulvestrant regimen during clinical trial
- 28-day cycles
- Cycle 1: 500 mg IM cycle 1 days 1 and 15
- Subsequent cycles: 500 mg IM on day 1
- Premenopausal and perimenopausal women: Administer a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards
- Men: Consider administering a LHRH agonist according to current clinical practice standards
Dosage Modifications
Dose reductions for adverse reactions
- First dose reduction: 320 mg BID x 4 days followed by 3 days off
- Second dose reduction: 200 mg BID x 4 days followed by 3 days off
Hyperglycemia
- Recommendations based on fasting glucose (FG)
-
FG >ULN-160 mg/dL (8.9 mmol/L) or HbA1C >7%
- Consider initiation or intensification of oral antidiabetic treatment
-
FG 161-250 mg/dL (9-13.9 mmol/L)
- Withhold until FG decrease ≤160 mg/dL (or ≤8.9 mmol/L)
- If recovery occurs in ≤28 days, resume at same dose
- If recovery occurs in >28 days, resume at 1 lower dose
-
FG 251-500 mg/dL (14-27.8 mmol/L)
- Withhold until FG decrease ≤160 mg/dL (or ≤8.9 mmol/L)
- If recovery occurs in ≤28 days, resume at 1 lower dose
- If recovery occurs in >28 days, permanently discontinue
-
FG >500 mg/dL (>27.8 mmol/L) or life-threatening sequelae of hyperglycemia at any FG level
- Life-threatening sequelae of hyperglycemia or if FG persists at ≥500 mg/dL after 24 hr: Permanently discontinue
- If FG ≤500 mg/dL (or ≤27.8 mmol/L) within 24 hr, follow above guidance for relevant grade
Diarrhea
-
Grade 2
- Withhold until recovery to Grade ≤1
- If recovery occurs in ≤28 days: Resume at same dose or 1 lower dose as clinically indicated
- If recovery occurs in >28 days: Resume at 1 lower dose
- For recurrence: Reduce by 1 lower dose
-
Grade 3
- Withhold until recovery to Grade ≤1
- If recovery occurs in ≤28 days: Resume at same dose or 1 lower dose as clinically indicated
- If recovery occurs in >28 days: Permanently discontinue
-
Grade 4
- Permanently discontinue
Cutaneous reactions
-
Grade 2
- Withhold until recovery to Grade ≤1 then resume at same dose
- Persistent or recurrent: Reduce by 1 lower dose
-
Grade 3
- Withhold until recovery to Grade ≤1
- If recovery occurs in ≤28 days: Resume at same dose
- If recovery occurs in >28 days: Resume at 1 lower dose
- For recurrence: Permanently discontinue
-
Grade 4
- Permanently discontinue
Other adverse reactions
-
Grade 2
- Withhold until recovery to Grade ≤1
- Resume at same dose
-
Grade 3
- Withhold until recovery to Grade ≤1
- If recovery occurs in ≤28 days: Resume at same dose
- If recovery occurs in >28 days: Resume at 1 lower dose
-
Grade 4
- Permanently discontinue
Strong and moderate CYP3A inhibitors
- Strong inhibitor: Avoid coadministration; if unavoidable, reduce dose to 320 mg BID x 4 days followed by 3 days off
- Moderate inhibitor: Reduce dose to 320 mg PO BID x 4 days followed by 3 days off
- After discontinuing strong or moderate CYP3A inhibitor, resume capivasertib dosage (after 3-5 half-lives of CYP3A inhibitor) that was taken before initiating strong or moderate CYP3A inhibitor
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment required
- Severe (CrCl 15-29 mL/min): Not studied
Hepatic impairment
- Mild (bilirubin
ULN or bilirubin >1-1.5x ULN and any AST): No dosage adjustment required - Moderate (bilirubin >1.5-3x ULN and any AST): Monitor for adverse reactions due to potential increased capivasertib exposure
- Severe (bilirubin >3x ULN and any AST): Not studied
Dosing Considerations
Verify pregnancy status of females of reproductive potential before initiating
Patient section
- Select patients based on presence of ≥1 genetic alterations in tumor tissue of PIK3CA/AKT1/PTEN
- Information on FDA-approved tests is available at Companion Diagnostic Tools
Monitoring
- Evaluate fasting blood glucose and hemoglobin A1C (HbA1C) before initiating and at regular intervals during treatment
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (69)
- amobarbital
amobarbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- apalutamide
apalutamide will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- armodafinil
armodafinil will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- atazanavir
atazanavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- belzutifan
belzutifan will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- bexarotene
bexarotene will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- bosentan
bosentan will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- butabarbital
butabarbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- butalbital
butalbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- carbamazepine
carbamazepine will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- cenobamate
cenobamate will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- chloramphenicol
chloramphenicol will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- clarithromycin
clarithromycin will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- cobicistat
cobicistat will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- conivaptan
conivaptan will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- dabrafenib
dabrafenib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- darunavir
darunavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- duvelisib
duvelisib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- efavirenz
efavirenz will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- elagolix
elagolix will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- encorafenib
encorafenib, capivasertib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Encorafenib may inhibit or induce CYP3A. .
- enzalutamide
enzalutamide will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- etrasimod
etrasimod, capivasertib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.
- etravirine
etravirine will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- fosphenytoin
fosphenytoin will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- grapefruit
grapefruit will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- idelalisib
idelalisib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- indinavir
indinavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- itraconazole
itraconazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- ivosidenib
ivosidenib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- ketoconazole
ketoconazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- levoketoconazole
levoketoconazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- lonafarnib
lonafarnib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- lopinavir
lopinavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- lorlatinib
lorlatinib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- mavacamten
mavacamten will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- mifepristone
mifepristone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- mitapivat
mitapivat will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- mitotane
mitotane will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- mobocertinib
mobocertinib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- modafinil
modafinil will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- nafcillin
nafcillin will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- nefazodone
nefazodone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- nelfinavir
nelfinavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- olutasidenib
olutasidenib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- pentobarbital
pentobarbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- pexidartinib
pexidartinib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- phenobarbital
phenobarbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- phenytoin
phenytoin will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- posaconazole
posaconazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- primidone
primidone will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- repotrectinib
repotrectinib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- rifabutin
rifabutin will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- rifampin
rifampin will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- rifapentine
rifapentine will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- ritonavir
ritonavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- rucaparib
rucaparib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- saquinavir
saquinavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- secobarbital
secobarbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- sotorasib
sotorasib will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- St John's Wort
St John's Wort will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- stiripentol
stiripentol, capivasertib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Stiripentol may inhibit or induce CYP3A. .
- telotristat ethyl
telotristat ethyl will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- tucatinib
tucatinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
- voriconazole
voriconazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of capivasertib with strong CYP3A inhibitors, reduce capivasertib dose and monitor for adverse effects.
Monitor Closely (43)
- adagrasib
adagrasib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- amiodarone
amiodarone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- aprepitant
aprepitant will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- bicalutamide
bicalutamide will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- ceritinib
ceritinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- crizotinib
crizotinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- cyclosporine
cyclosporine will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- doxycycline
doxycycline will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- dronedarone
dronedarone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- entacapone
entacapone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- erythromycin base
erythromycin base will increase the level or effect of capivasertib by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- erythromycin stearate
erythromycin stearate will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fedratinib
fedratinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fexinidazole
fexinidazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fluconazole
fluconazole will increase the level or effect of capivasertib by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fluvoxamine
fluvoxamine will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fosamprenavir
fosamprenavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fosaprepitant
fosaprepitant will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- fostamatinib
fostamatinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- haloperidol
haloperidol will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- ibrexafungerp
ibrexafungerp will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- iloperidone
iloperidone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- imatinib
imatinib will increase the level or effect of capivasertib by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- isavuconazonium sulfate
isavuconazonium sulfate will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- isoniazid
isoniazid will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- ivacaftor
ivacaftor will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- lapatinib
lapatinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- larotrectinib
larotrectinib will increase the level or effect of capivasertib by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- lefamulin
lefamulin will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- lenacapavir
lenacapavir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- letermovir
letermovir will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- metronidazole
metronidazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- ribociclib
ribociclib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- ritlecitinib
ritlecitinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- schisandra
schisandra will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- sertraline
sertraline will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- tetracycline
tetracycline will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- verapamil
verapamil will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- voxelotor
voxelotor will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
Minor (1)
- diltiazem
diltiazem will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
Adverse Effects
>10%
All grades
- Diarrhea (77%)
- Increased random glucose (58%)
- Cutaneous reactions (56%)
- Decreased lymphocytes (49%)
- Decreased hemoglobin (47%)
- Fatigue (38%)
- Increased fasting glucose (37%)
- Decreased leukocytes (35%)
- Nausea (35%)
- Increased triglycerides (30%)
- Decreased neutrophils (25%)
- Stomatitis (25%)
- Increased ALT (23%)
- Vomiting (21%)
- Decreased corrected calcium (19%)
- Increased creatinine (19%)
- Hyperglycemia (19%)
- Decreased potassium (17%)
- Decreased appetite (17%)
- Headache (17%)
- Urinary tract infection (14%)
- Decreased platelets (12%)
- Renal injury (11%)
Grade 3 or 4
- Cutaneous reactions (15%)
- Diarrhea (12%)
- Decreased lymphocytes (11%)
1-10%
Grade 3 or 4
- Increased random glucose (9%)
- Decreased potassium (4.5%)
- Renal injury (2.6%)
- Increased ALT (2.6%)
- Decreased hemoglobin (2%)
- Decreased neutrophils (1.9%)
- Decreased platelets (1.9%)
- Stomatitis (1.9%)
- Vomiting (1.9%)
- Fatigue (1.9%)
- Hyperglycemia (1.9%)
- Nausea (1.3%)
- Increased creatinine (1.3%)
<1%
Grade 3 or 4
- Increased triglycerides (0.7%)
- Urinary tract infection (0.6%)
- Increased fasting glucose (0.6%)
- Decreased leukocytes (0.6%)
- Decreased corrected calcium (0.6%)
Warnings
Contraindications
Severe hypersensitivity to capivasertib or any of its components
Cautions
May cause fetal harm, based on findings from animals and mechanism of action
Hyperglycemia
- Severe hyperglycemia associated with ketoacidosis occurred in clinical trials
- Safety has not been established in patients with type I diabetes or diabetes requiring insulin; patients with insulin-dependent diabetes were excluded from clinical trials
- Evaluate fasting glucose before initiating and during treatment
- If hyperglycemia occurs after treatment, monitor FG as clinically indicated, and at least twice weekly until FG decreases to normal levels
- See dosage modifications if patient experiences hyperglycemia during treatment
Diarrhea
- Severe diarrhea associated with dehydration may occur
- Monitor for signs and symptoms of diarrhea
- Advise patients to increase oral fluids and start antidiarrheal treatment at first sign of diarrhea while taking capivasertib
- See dosage modifications regarding withholding or reducing dose, or permanently discontinue drug based on severity
Cutaneous reactions
- Cutaneous adverse reactions may occur, which can be severe, including erythema multiforme (EM), palmoplantar erythrodysesthesia, and drug reaction with eosinophilia and systemic symptoms (DRESS)
- Monitor for signs and symptoms of cutaneous reactions
- See dosage modifications regarding withholding or reducing dose, or permanently discontinue drug based on severity
Drug interaction overview
- CYP3A substrate
-
Strong CYP3A inhibitors
- Avoid coadministration; if unable to avoid reduce capivasertib dose and monitor for adverse effects
- Strong CYP3A inhibitors increase capivasertib exposure
-
Moderate CYP3A inhibitors
- Modify dose
- Moderate CYP3A inhibitors increase capivasertib exposure; reduce capivasertib dose if coadministered
-
Strong or moderate CYP3A inducers
- Avoid coadministration
- Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy
Pregnancy & Lactation
Pregnancy
Based on findings in animals and mechanism of action, can cause fetal harm when administered to pregnant females
Advise pregnant females and those who are of reproductive potential of potential fetal risk
Verify pregnancy status of females of reproductive potential before initiating
Animal studies
- When administered to pregnant rats during organogenesis, capivasertib caused adverse developmental outcomes, including embryo-fetal mortality and reduced fetal weights at maternal exposures 0.7 times the human exposure (AUC) at the recommended dose of 400 mg twice daily
Contraception
- Females of reproductive potential: Use effective contraception during treatment with and for 1 month after last dose
- Males with female partners of reproductive potential: Use effective contraception during treatment with and for 4 months after last dose
Lactation
Data are unavailable regarding presence of capivasertib or its metabolites in human milk or their effects on milk production or breastfed children
Advise females not to breastfeed during treatment
Animal data
- Detected in plasma of suckling rat pups
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
AKT (protein kinase B [PKB]) is the collective name of a set of 3 serine/threonine-specific protein kinases
Capivasertib is an adenosine triphosphate (ATP)-competitive inhibitor of all 3 AKT isoforms (AKT1/2/3)
Inhibition of AKT prevents phosphorylation of AKT substrates that mediate cellular processes, such as cell division, apoptosis, and glucose and fatty acid metabolism
Absorption
Bioavailability: 29%
Peak plasma time: 1-2 hr
Peak plasma concentration: 1,371 ng/mL
AUC: 8,069 hr⋅ng/mL
Steady-state attained on 3rd and 4th dosing day each week, starting week 2
Distribution
Protein bound: 22%
Vd: 1,847 L
Plasma-to-blood ratio: 0.71
Metabolism
Primarily metabolized by CYP3A4 and UGT2B7
Elimination
Half-life: 8.3 hr
Oral clearance: 50 L/hr
Renal clearance: 21% of total clearance
Excretion: Urine 45%; feces 50%
Administration
Oral Administration
May take with or without food
Swallow tablets whole; do not chew, crush, or split
Do not take tablets that are broken, cracked, or otherwise not intact
Missed or vomited dose
- Dose missed ≤4 hr of scheduled time: Take dose as soon as possible
- Dose missed by >4 hr of scheduled time: Skip dose and take next dose at its usual scheduled time
- Vomited dose: Do NOT to take an additional dose; take next dose at its usual scheduled time
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
Formulary
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To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
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