Dosing & Uses
Dosage Forms & Strengths
capsule
- 100mg
tablet, film-coated
- 100mg
Mantle Cell Lymphoma
Indicated for mantle cell lymphoma (MCL) in patients who have received ≥1 prior therapy
100 mg PO q12hr
Continue until disease progression or unacceptable toxicity
Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Indicated for treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
Monotherapy
- 100 mg PO q12hr
- Continue until disease progression or unacceptable toxicity
Combination with obinutuzumab
- Indicated for patients with previously untreated CLL or SLL
- Start acalabrutinib at Cycle 1 (each cycle is 28 days)
- Start obinutuzumab at Cycle 2 for a total of 6 cycles
- Refer to obinutuzumab for infusion rates
-
Cycle 1
- Days 1-28: Acalabrutinib 100 mg PO q12hr
-
Cycle 2
- Days 1-28: Acalabrutinib 100 mg PO q12hr
- Day 1: Obinutuzumab 100 mg IV infusion
- Day 2: Obinutuzumab 900 mg IV infusion
- Days 8 and 15: Obinutuzumab 1000 mg IV infusion
-
Cycles 3-7
- Day 1-28: Acalabrutinib 100 mg PO q12hr
- Day 1: Obinutuzumab 1000 mg IV infusion
-
Cycle 8 and subsequent cycles
- Day 1-28: Acalabrutinib 100 mg PO q12hr
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
Refer to the obinutuzumab prescribing information for management of obinutuzumab toxicities
Renal impairment
- Mild-to-moderate (eGFR ≥30 mL/min/1.73m²): No clinically relevant pharmacokinetics (PK) difference observed
- Severe (eGFR <30 mL/min/1.73m²) or patients on dialysis: Acalabrutinib PK has not been evaluated
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
- Severe (Child-Pugh C): Avoid use
Management of Grade ≥3 adverse reactions
- Grade ≥3 nonhematologic toxicities,
- Grade 3 thrombocytopenia with bleeding,
- Grade 4 thrombocytopenia, OR
- Grade 4 neutropenia lasting >7 days
-
First to second occurrence
- Interrupt drug
- Once toxicity resolves to Grade ≤1, resume dose at 100 mg PO BID
-
Third occurrence
- Interrupt drug
- Once toxicity resolves to Grade ≤1, reduce dose to 100 mg PO qDay
-
Fourth occurrence
- Discontinue drug
Coadministration with CYP3A4 inhibitors or inducers
- Strong CYP3A4 inhibitors: Avoid concomitant use; if CYP3A4 inhibitors will be used short-term (eg, anti-infectives for ≤7 days), interrupt treatment
- Moderate CYP3A4 inhibitor: 100 mg PO qDay
- Strong CYP3A4 inducers: Avoid concomitant use; if these inducers cannot be avoided, increase dose to 200 mg PO BID
Coadministration with gastric acid reducing agents
- Applies to capsule dosage form only
- Proton pump inhibitors: Avoid concomitant use
- H2-receptor antagonists: Take dose 2 hr before taking a H2-receptor antagonist
- Antacids: Separate dosing by at least 2 hr
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (60)
- abametapir
abametapir will increase the level or effect of acalabrutinib 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.
- alpelisib
acalabrutinib will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.
- apalutamide
apalutamide will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- carbamazepine
carbamazepine will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- chloramphenicol
chloramphenicol will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- clarithromycin
clarithromycin will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- cobicistat
cobicistat will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- conivaptan
conivaptan will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- dabrafenib
dabrafenib will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- darunavir
darunavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- deferiprone
deferiprone, acalabrutinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- dexamethasone
dexamethasone will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- dexlansoprazole
dexlansoprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- enzalutamide
enzalutamide will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- esomeprazole
esomeprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.
- fexinidazole
fexinidazole will increase the level or effect of acalabrutinib 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.
- fosamprenavir
fosamprenavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- fosphenytoin
fosphenytoin will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- grapefruit
grapefruit will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- idelalisib
idelalisib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- imatinib
imatinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- indinavir
indinavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- isoniazid
isoniazid will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- itraconazole
itraconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- ivosidenib
ivosidenib will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- lansoprazole
lansoprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.
- levoketoconazole
levoketoconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- lonafarnib
lonafarnib will increase the level or effect of acalabrutinib 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 acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- mitotane
mitotane will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- nefazodone
nefazodone will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- nelfinavir
nelfinavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- nevirapine
nevirapine will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- nicardipine
nicardipine will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- omeprazole
omeprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- ozanimod
acalabrutinib increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .
- palifermin
palifermin increases toxicity of acalabrutinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- pantoprazole
pantoprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.
- phenobarbital
phenobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- phenytoin
phenytoin will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- posaconazole
posaconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- primidone
primidone will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- rabeprazole
rabeprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.
- rifabutin
rifabutin will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- rifampin
rifampin will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- rifapentine
rifapentine will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- rimegepant
acalabrutinib will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.
- ritonavir
ritonavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, acalabrutinib. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- saquinavir
saquinavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- St John's Wort
St John's Wort will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.
- talazoparib
acalabrutinib will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.
- tipranavir
tipranavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- voriconazole
voriconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.
- voxelotor
voxelotor will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (174)
- abciximab
acalabrutinib increases effects of abciximab by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- albendazole
acalabrutinib, albendazole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- alemtuzumab
acalabrutinib, alemtuzumab. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- allopurinol
acalabrutinib, allopurinol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- aluminum hydroxide
aluminum hydroxide decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Separate dosing by at least 2 hr between administration of antacids and acalabrutinib.
- amiodarone
amiodarone will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- amobarbital
amobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- apixaban
acalabrutinib increases effects of apixaban by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- aprepitant
aprepitant will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- argatroban
acalabrutinib increases effects of argatroban by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- arsenic trioxide
acalabrutinib, arsenic trioxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- aspirin
acalabrutinib increases effects of aspirin by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Separate dosing by at least 2 hr between administration of antacids and acalabrutinib.
- atazanavir
atazanavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- atorvastatin
acalabrutinib increases levels of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- belzutifan
belzutifan will decrease the level or effect of acalabrutinib 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.
- berotralstat
acalabrutinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.
- bicalutamide
bicalutamide will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- bivalirudin
acalabrutinib increases effects of bivalirudin by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- bosentan
bosentan will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- busulfan
acalabrutinib, busulfan. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- butabarbital
butabarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- calcium carbonate
calcium carbonate decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Separate dosing by at least 2 hr between administration of antacids and acalabrutinib.
- cangrelor
acalabrutinib increases effects of cangrelor by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- carboplatin
acalabrutinib, carboplatin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- carmustine
acalabrutinib, carmustine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- cenobamate
cenobamate will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- ceritinib
ceritinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- chlorambucil
acalabrutinib, chlorambucil. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- chlorothiazide
acalabrutinib increases levels of chlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- cidofovir
acalabrutinib, cidofovir. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- cimetidine
cimetidine decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Administer acalabrutinib 2 hr before an H2-receptor antagonist.
acalabrutinib increases levels of cimetidine by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP. - cisplatin
acalabrutinib, cisplatin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- cladribine
acalabrutinib, cladribine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- clopidogrel
acalabrutinib increases effects of clopidogrel by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- clozapine
acalabrutinib, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- colchicine
acalabrutinib, colchicine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- crizotinib
crizotinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- cyclophosphamide
acalabrutinib, cyclophosphamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- cyclosporine
cyclosporine will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- cytarabine
acalabrutinib, cytarabine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- dabigatran
acalabrutinib increases effects of dabigatran by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- dacarbazine
acalabrutinib, dacarbazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- dactinomycin
acalabrutinib, dactinomycin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- dalteparin
acalabrutinib increases effects of dalteparin by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- dasatinib
acalabrutinib, dasatinib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- daunorubicin
acalabrutinib increases levels of daunorubicin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, daunorubicin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - decitabine
acalabrutinib, decitabine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- dexrazoxane
acalabrutinib, dexrazoxane. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- diltiazem
diltiazem will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- dipyridamole
acalabrutinib increases effects of dipyridamole by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
acalabrutinib increases levels of dipyridamole by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP. - docetaxel
acalabrutinib, docetaxel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- doxorubicin
acalabrutinib increases levels of doxorubicin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, doxorubicin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - doxycycline
doxycycline will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- dronedarone
dronedarone will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- duvelisib
duvelisib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
acalabrutinib will increase the level or effect of duvelisib by Other (see comment). Use Caution/Monitor. Coadministration of duvelisib (a BCRP substrate) with a BCRP transport inhibitor may increase levels or effects of duvelisib. - efavirenz
efavirenz will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- elagolix
elagolix will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- encorafenib
encorafenib, acalabrutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- enoxaparin
acalabrutinib increases effects of enoxaparin by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- epirubicin
acalabrutinib, epirubicin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- eptifibatide
acalabrutinib increases effects of eptifibatide by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- erythromycin base
erythromycin base will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- estramustine
acalabrutinib, estramustine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- etoposide
acalabrutinib, etoposide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- etravirine
etravirine will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- famotidine
famotidine decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Administer acalabrutinib 2 hr before an H2-receptor antagonist.
- fedratinib
fedratinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fluconazole
fluconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- fludarabine
acalabrutinib, fludarabine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- fluorouracil
acalabrutinib, fluorouracil. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- fluvastatin
acalabrutinib increases levels of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- fluvoxamine
fluvoxamine will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease dose to 100 mg once daily if coadministered with CYP3A4 inhibitor
- fosaprepitant
fosaprepitant will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- ganciclovir
acalabrutinib, ganciclovir. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- gemcitabine
acalabrutinib, gemcitabine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- gemtuzumab
acalabrutinib, gemtuzumab. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- glyburide
acalabrutinib increases levels of glyburide by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- haloperidol
haloperidol will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
acalabrutinib, haloperidol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - heparin
acalabrutinib increases effects of heparin by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- hydroxyurea
acalabrutinib, hydroxyurea. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- idarubicin
acalabrutinib, idarubicin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- ifosfamide
acalabrutinib, ifosfamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- iloperidone
iloperidone will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- imatinib
acalabrutinib increases levels of imatinib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- interferon alfa 2b
acalabrutinib, interferon alfa 2b. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- interferon beta 1a
acalabrutinib, interferon beta 1a. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- interferon beta 1b
acalabrutinib, interferon beta 1b. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- interferon gamma 1b
acalabrutinib, interferon gamma 1b. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- irinotecan
acalabrutinib increases levels of irinotecan by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, irinotecan. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - istradefylline
istradefylline will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- ixabepilone
acalabrutinib, ixabepilone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- lapatinib
lapatinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
acalabrutinib increases levels of lapatinib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP. - ledipasvir/sofosbuvir
acalabrutinib increases levels of ledipasvir/sofosbuvir by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- leflunomide
acalabrutinib increases levels of leflunomide by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- lenacapavir
lenacapavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates. Reduce acalabrutinib dose from 100 mg PO Q12hr to 100 mg PO qDay when coadministered with lenacapavir.
- lenalidomide
acalabrutinib, lenalidomide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- lenvatinib
acalabrutinib increases levels of lenvatinib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- levetiracetam
acalabrutinib, levetiracetam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- linezolid
acalabrutinib, linezolid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- lomustine
acalabrutinib, lomustine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- lorlatinib
lorlatinib will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- magnesium oxide
magnesium oxide decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Separate dosing by at least 2 hr between administration of antacids and acalabrutinib.
- mebendazole
acalabrutinib, mebendazole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- mercaptopurine
acalabrutinib, mercaptopurine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- methotrexate
acalabrutinib increases levels of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - metronidazole
metronidazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- mifepristone
mifepristone will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If mifepristone use necessary, limit dose of acalabrutinib to 100 mg once daily and monitor closely for drug-related toxicity and need for further adjustment or interruption of acalbrutinib therapy
- mitomycin
acalabrutinib, mitomycin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- mitoxantrone
acalabrutinib increases levels of mitoxantrone by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, mitoxantrone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - nafcillin
nafcillin will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nelarabine
acalabrutinib, nelarabine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- nilotinib
acalabrutinib, nilotinib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- nitrofurantoin
acalabrutinib increases levels of nitrofurantoin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- nizatidine
nizatidine decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Acalabrutinib solubility decreases with increasing gastric pH. Administer acalabrutinib 2 hr before an H2-receptor antagonist.
- ofatumumab SC
ofatumumab SC, acalabrutinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.
- osimertinib
acalabrutinib increases levels of osimertinib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- oxaliplatin
acalabrutinib, oxaliplatin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- paclitaxel
acalabrutinib, paclitaxel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- pantoprazole
acalabrutinib increases levels of pantoprazole by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- pazopanib
acalabrutinib increases levels of pazopanib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, pazopanib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - peginterferon alfa 2a
acalabrutinib, peginterferon alfa 2a. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- peginterferon alfa 2b
acalabrutinib, peginterferon alfa 2b. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- pentobarbital
pentobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pentostatin
acalabrutinib, pentostatin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- pitavastatin
acalabrutinib increases levels of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- prasugrel
acalabrutinib increases effects of prasugrel by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- primaquine
acalabrutinib, primaquine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- procarbazine
acalabrutinib, procarbazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- pyrimethamine
acalabrutinib, pyrimethamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- ribociclib
ribociclib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- riociguat
acalabrutinib increases levels of riociguat by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- rivaroxaban
acalabrutinib increases effects of rivaroxaban by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- rosuvastatin
acalabrutinib increases levels of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- rucaparib
rucaparib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- schisandra
schisandra will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- secobarbital
secobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- selexipag
acalabrutinib increases effects of selexipag by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- sertraline
sertraline will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- siponimod
siponimod and acalabrutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sodium zirconium cyclosilicate
sodium zirconium cyclosilicate will decrease the level or effect of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.
- sofosbuvir
acalabrutinib increases levels of sofosbuvir by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- sofosbuvir/velpatasvir
sofosbuvir/velpatasvir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- stiripentol
stiripentol, acalabrutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- streptozocin
acalabrutinib, streptozocin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- sulfasalazine
acalabrutinib increases levels of sulfasalazine by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - sunitinib
acalabrutinib, sunitinib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- tazemetostat
tazemetostat will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temozolomide
acalabrutinib, temozolomide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- teniposide
acalabrutinib, teniposide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- tenofovir AF
acalabrutinib increases levels of tenofovir AF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- tenofovir DF
acalabrutinib increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- tetracycline
tetracycline will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- thioguanine
acalabrutinib, thioguanine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- ticagrelor
acalabrutinib increases effects of ticagrelor by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- ticlopidine
acalabrutinib increases effects of ticlopidine by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- tirofiban
acalabrutinib increases effects of tirofiban by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- topotecan
acalabrutinib increases levels of topotecan by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, topotecan. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - trastuzumab
trastuzumab, acalabrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- trastuzumab deruxtecan
trastuzumab deruxtecan, acalabrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- velpatasvir
acalabrutinib increases levels of velpatasvir by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- vemurafenib
acalabrutinib increases levels of vemurafenib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- verapamil
verapamil will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.
- vinorelbine
acalabrutinib, vinorelbine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
- vorapaxar
acalabrutinib increases effects of vorapaxar by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
- warfarin
acalabrutinib increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.
- zidovudine
acalabrutinib, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10% (Monotherapy)
All grades
- Hemoglobin decreased (46%)
- Platelets decreased (44%)
- Headache (39%)
- Neutrophils decreased (36%)
- Diarrhea (31%)
- Fatigue (28%)
- Myalgia (21%)
- Bruising (21%)
- Nausea (19%)
- Rash (18%)
- Abdominal pain (15%)
- Constipation (15%)
Grade ≥3
- Vomiting (13%)
- Neutrophil decreased (15%)
- Platelets decreased (12%)
- Hemoglobin decreased (10%)
>10% (Combination with Obinutuzumab)
All grades
- Infection (69%)
- Neutropenia (53%)
- Anemia (52%)
- Thrombocytopenia (51%)
- Headache (40%)
- Upper respiratory tract infection (39%)
- AST increased (38%)
- Musculoskeletal pain (37%)
- Fatigue (34%)
- Bruising (31%)
- ALT increased (30%)
- Diarrhea (29%)
- Uric acid increase (29%)
- Rash (26%)
- Lower respiratory tract infection (24%)
- Arthralgia (22%)
- Dizziness (20%)
- Nausea (20%)
- Hemorrhage (20%)
- Urinary tract infection (15%)
- Bilirubin increase (13%)
- Lymphocytosis (12%)
Grade≥3
- Neutropenia (37%)
- Uric acid increased (29%)
- Infection (22%)
- Anemia (12%)
- Thrombocytopenia (12%)
- Lymphocytosis (11%)
1-10% (Monotherapy)
All grades
- Hemorrhage (8%)
- Epistaxis (6%)
Grade ≥3
- ALT increased (7%)
- AST increased (5%)
- Diarrhea (3.2%)
- Headache (1.6%)
- Abdominal pain (1.6%)
- Vomiting (1.6%)
1-10% (Combination with Obinutuzumab)
Grade ≥3
- Lower respiratory tract infection (8%)
- Diarrhea (4.5%)
- Upper respiratory tract infection (2.8%)
- Fatigue (2.2%)
- Rash (2.2%)
- Musculoskeletal pain (2.2%)
- Hemorrhage (1.7%)
- Arthralgia (1.1%)
- Headache (1.1%)
<1% (Monotherapy)
Grade≥3
- Nausea (0.8%)
- Fatigue (0.8%)
- Myalgia (0.8%)
- Rash (0.8%)
- Hemorrhage (0.8%)
- Bilirubin increase (0.6%)
Postmarketing Reports
Serious and opportunistic infections
Warnings
Contraindications
None
Cautions
Serious hemorrhagic events, including fatal events, reported; the mechanism for the bleeding events is not well understood; acalabrutinib may further increase hemorrhage risk in patients receiving antiplatelet or anticoagulant therapies, and patients should be monitored for signs of bleeding; consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending on the type of surgery and the risk of bleeding
Serious infections (bacterial, viral, or fungal), including fatal events and opportunistic infections, reported; monitor for infection and consider prophylaxis in patients who are at increased risk for opportunistic infections
Cytopenias reported, including neutropenia, anemia, lymphopenia, and thrombocytopenia; monitor complete blood cell counts monthly during treatment; interrupt treatment, reduce dose, or discontinue treatment as warranted
Second primary malignancies, including nonskin carcinomas, have occurred in patients with hematologic malignancies treated with acalabrutinib; the most frequent was skin cancer; advise patients regarding need for protection from sun exposure
Atrial fibrillation and flutter occurred (rare) during clinical trials; monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate
Drug interaction overview
-
Coadministration with CYP3A inhibitors or inducers
- Acalabrutinib is predominantly metabolized by CYP3A enzymes
- CYP3A inhibitors are expected to increase acalabrutinib systemic exposure
- CYP3A inducers are expected to decrease acalabrutinib systemic exposure
- See Dosage Modifications
-
Coadministration with gastric acid-reducing agents
- Applies to capsule dosage form only
- Coadministration with PPIs, H2-antagonists, or antacids may decrease acalabrutinib plasma concentrations
- See Dosage Modifications
Pregnancy & Lactation
Pregnancy
Based on findings in animals, may cause fetal harm when administered to pregnant women
There are no available data in pregnant women to inform the drug-associated risk
Pregnancy testing recommended for females of reproductive potential before initiating therapy
Animal data
- In animal reproduction studies, administration of acalabrutinib to pregnant rabbits during organogenesis resulted in reduced fetal growth; rabbit maternal exposures (AUC) were ~4 times that of humans given a dose of 100 mg BID
- Advise pregnant women of the potential risk to a fetus
Contraception
- Embryofetal harm and dystocia may occur when administered to pregnant women
- Females of reproductive potential: Use effective contraception during treatment and for at least 1 week following the last dose; if used during pregnancy, or if patient becomes pregnant while taking drug, inform patient of the potential hazard to a fetus
Lactation
No data are available regarding the presence of acalabrutinib or its active metabolite in human milk, its effects on the breastfed child, or on milk production
Acalabrutinib and its active metabolite were present in the milk of lactating rats
Owing to the potential for adverse reactions in a breastfed child, advise lactating women not to breastfeed while taking acalabrutinib and for at least 2 weeks after 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
Bruton tyrosine kinase (BTK) inhibitor; acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity
BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways; in B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion
Absorption
Absolute bioavailability: 25%; tablets and capsules are bioequivalent
Peak plasma concentration 563 ng/mL (acalabrutinib); 451 ng/mL (ACP-5862)
AUC: 1843 ng·hr/mL (acalabrutinib); 3947 ng·hr/mL (ACP-5862)
Peak plasma time
- 0.9 hr (capsule); 1.6 hr (ACP-5862 capsule)
- 0.5 hr (tablet); 0.75 hr (ACP-5862 tablet)
Effect of food
- In healthy subjects, administration of a single 75-mg dose with a high-fat, high-calorie meal (~918 calories, 59 grams carbohydrate, 59 grams fat, and 39 grams protein) resulted in peak plasma concentration decreased by 73% and peak plasma time was delayed by 1-2 hr
Distribution
Protein bound: 97.5% (acalabrutinib); 98.6% (ACP-5862)
Vd (steady-state): ~101 L (acalabrutinib); 67 L (ACP-5862)
Metabolism
Predominantly metabolized by CYP3A enzymes, and to a minor extent, by glutathione conjugation and amide hydrolysis, based on in vitro studies
Active metabolite: ACP-5862 with mean exposure (AUC) ~2- to 3-fold higher than the exposure of acalabrutinib; ACP-5862 is ~50% less potent than acalabrutinib with regard to BTK inhibition
Elimination
Half-life: 1 hr (acalabrutinib); 3.5 hr (ACP-5862)
Oral clearance 71 L/hr (acalabrutinib); 13 L/hr (ACP-5862)
Excretion: 84% feces; 12% urine
Administration
Oral Administration
Take with or without food
Swallow capsule/tablet whole with water
Capsules: Do not open, break, or chew
Tablets: Do not chew, crush, dissolve, or cut
Administer acalabrutinib before obinutuzumab when given on the same day
Film-coated tablet may be coadministered with acid-reducing drugs
Capsule dosage form with gastric acid reducing agents
- Proton pump inhibitors: Avoid concomitant use
- H2-receptor antagonists: Take dose 2 hr before taking a H2-receptor antagonist
- Antacids: Separate dosing by at least 2 hr
Missed dose
- If a dose is missed by >3 hr, skip dose; take next dose at its regularly scheduled time
- Do not take extra capsules to make up for a missed dose
Storage
Capsules or tablets: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
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Formulary
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