Dosing & Uses
Dosage Forms & Strengths
tablet
- 50mg
- 100mg
- 150mg
- 200mg
Early Breast Cancer
Indicated in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, nodepositive, early breast cancer at high risk of recurrence
150 mg PO BID PLUS tamoxifen or an aromatase inhibitor (see Prescribing Information)
Continue for 2 years, or until disease recurrence or unacceptable toxicity
Advanced or Metastatic Breast Cancer
Monotherapy
- Indicated as monotherapy for adults with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in metastatic setting
- 200 mg PO BID
- Continue until disease progression or unacceptable toxicity
Combination therapy with aromatase inhibitor
- Indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for HR-positive, HER2-negative advanced or metastatic breast cancer
- 150 mg PO BID PLUS an aromatase inhibitor (see Prescribing Information)
- Continue until disease progression or unacceptable toxicity
Combination therapy with fulvestrant
- Indicated, in combination with fulvestrant, for adults with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy
- 150 mg PO BID PLUS
- Fulvestrant 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dosage modifications for adverse effects
-
Combined with fulvestrant, tamoxifen, or aromatase inhibitor
- Starting dose: 150 mg BID
- First dose reduction: 100 mg BID
- Second dose reduction: 50 mg BID
- Discontinue if unable to tolerate 50 mg BID
-
Monotherapy
- Starting dose: 200 mg BID
- First dose reduction: 150 mg BID
- Second dose reduction: 100 mg BID
- Third dose reduction: 50 mg BID
- Discontinue if unable to tolerate 50 mg BID
Hematologic toxicities
- Monitor complete blood cell counts (CBC) before initiating therapy, q2Weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated
- Grade 1 or 2: No dose modification required
- Grade 3: Suspend dose until toxicity resolves to Grade ≤2; dose reduction is not required
- Grade 4 or Grade 3 recurrent: Suspend dose until toxicity resolves to Grade ≤2; resume at next lower dose
- If blood cell growth factors are required, suspend dose for at least 48 hr after last dose of blood cell growth factor and until toxicity resolves to Grade ≤2; resume at next lower dose unless already used for the toxicity
Diarrhea
- At first sign of loose stools, start treatment with antidiarrheal agents and increase hydration
-
No dose modification required
- Grade 1
- Grade 2: If toxicity does not resolve within 24 hr to ≤Grade 1, suspend dose until resolution
-
Suspend dose until toxicity resolves to baseline or Grade 1 (resume at next lower dose)
- Persistent or recurrent Grade 2 diarrhea despite maximal supportive measures
- Grade 3 or 4 diarrhea or requires hospitalization
Hepatotoxicity
- Monitor ALT, AST, and serum bilirubin before initiating therapy, q2Weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated
-
No dose modification required
- Grade 1 (ALT/AST >ULN to 3x ULN)
- Grade 2 (ALT/AST >3 to 5x ULN; without an increase in total bilirubin >2x ULN)
-
Suspend dose until toxicity resolves to baseline or Grade 1 (resume at next lower dose)
- Persistent or recurrent Grade 2 or Grade 3 (ALT/AST >5 to 20x ULN) without increase in total bilirubin >2x ULN
-
Discontinue
- Elevation in AST and/or ALT >3x ULN with total bilirubin >2x ULN (without cholestasis)
- Grade 4 (ALT/AST >20x ULN)
Other toxicities
-
No dose modification required
- Grade 1 or 2 toxicities
-
Suspend dose until toxicity resolves to baseline or Grade 1 (resume at next lower dose)
- Persistent or recurrent Grade 2 toxicity unresolved with maximal supportive measures within 7 days to baseline or Grade 1
- Grade 3 or 4
Interstitial lung disease/pneumonitis (ILD)
- Grade 1 or 2: No dose interruption or adjustment required
- Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures within 7 days to Grade ≤1: Suspend dose until recovery to Grade ≤1; resume at the next lower dose level
- Grade 3 or 4: Discontinue treatment
Strong CYP3A inhibitors
- Avoid concomitant use of ketoconazole
-
Other strong CYP3A inhibitors
- With concomitant use of other strong CYP3A inhibitors, in patients with recommended starting doses of 150 mg or 200 mg BID, reduce dose to 100 mg BID
- In patients who have had a dose reduction to 100 mg BID, further reduce the dose to 50 mg BID
-
Discontinuing strong CYP3A inhibitor
- If a strong CYP3A inhibitor is discontinued, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the strong inhibitor
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dose adjustment required
- Severe (Child-Pugh C): Reduce dosing frequency to once daily
Renal impairment
- Mild or moderate (CrCl 30-89 mL/min): No dose adjustment required
- Severe, ESRD, or dialysis: Not studied
Dosing Considerations
Premenopausal or perimenopausal women and men
- Combination therapy with aromatase inhibitor or fulvestrant: Treat with a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (42)
- amobarbital
amobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of abemaciclib 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.
- bosentan
bosentan will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- butabarbital
butabarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- butalbital
butalbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- carbamazepine
carbamazepine will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- ceritinib
ceritinib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with chloramphenicol necessary, reduce dose of abemaciclib to 100 mg PO BID in patients on either of recommended starting doses whether 200 mg or 150 mg BID; In patients who have had already had a dose reduction to 100 mg BID due to adverse reactions, further reduce dose of abemaciclib to 50 mg PO BID; discontinue abemaciclib if patient unable to tolerate 50 mg BID; if chloramphenicol discontinued, increase dose of abemaciclib to original dose after 3-5 half-lives of chloramphenicol
- dabrafenib
dabrafenib will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- deferiprone
deferiprone, abemaciclib. 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 abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- efavirenz
efavirenz will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- enzalutamide
enzalutamide will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- etravirine
etravirine will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- fexinidazole
fexinidazole will increase the level or effect of abemaciclib 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.
- fosphenytoin
fosphenytoin will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- grapefruit
grapefruit will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Patient should avoid grapefruit products.
- ivosidenib
ivosidenib will decrease the level or effect of abemaciclib 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 abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Ketoconazole increases abemaciclib AUC by up to 16-fold.
- levoketoconazole
levoketoconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Ketoconazole increases abemaciclib AUC by up to 16-fold.
- lonafarnib
lonafarnib will increase the level or effect of abemaciclib 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.
- lorlatinib
lorlatinib will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- methohexital
methohexital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mitotane
mitotane will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- nafcillin
nafcillin will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- nevirapine
nevirapine will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- palifermin
palifermin increases toxicity of abemaciclib 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.
- pentobarbital
pentobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- phenobarbital
phenobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- phenytoin
phenytoin will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- primidone
primidone will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- rifabutin
rifabutin will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- rifampin
rifampin will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- rifapentine
rifapentine will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, abemaciclib. 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.
- secobarbital
secobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- sotorasib
sotorasib will decrease the level or effect of abemaciclib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- St John's Wort
St John's Wort will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.
- voxelotor
voxelotor will increase the level or effect of abemaciclib 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 (45)
- atazanavir
atazanavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- belzutifan
belzutifan will decrease the level or effect of abemaciclib 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
berotralstat will increase the level or effect of abemaciclib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- cenobamate
cenobamate will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- clarithromycin
clarithromycin will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- cobicistat
cobicistat will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a patient taking abemaciclib discontinues a strong CYP3A inhibitor, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.
- conivaptan
conivaptan will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- darunavir
darunavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- dengue vaccine
abemaciclib decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- duvelisib
duvelisib will increase the level or effect of abemaciclib 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.
- elagolix
elagolix will decrease the level or effect of abemaciclib 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.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- encorafenib
encorafenib, abemaciclib. 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.
- fedratinib
fedratinib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fosamprenavir
fosamprenavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- idelalisib
idelalisib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- imatinib
imatinib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- indinavir
indinavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- isoniazid
isoniazid will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- istradefylline
istradefylline will increase the level or effect of abemaciclib 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.
- itraconazole
itraconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. In patients with starting doses of 150 or 200 mg BID, reduce abemaciclib dose to 100 mg BID when coadminister with strong CYP3A inhibitors. In patients who reduced dose to 100 mg BID due to adverse reactions, further reduce abemaciclib dose to 50 mg BID when coadministered with strong CYP3A inhibitors. If the strong CYP3A inhibitoris discontinued, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.
- lenacapavir
lenacapavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lopinavir
lopinavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- mifepristone
mifepristone will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who have had dose reduction to 100 mg twice daily due to adverse reactions, may further reduce dose of abemaciclib to 50 mg PO twice daily; discontinue abemaciclib for patients unable to tolerate 50 mg twice daily; if mifepristone is discontinued, increase dose of abemaciclib to original dose after 3 to 5 half-lives of mifepristone
- nefazodone
nefazodone will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- nelfinavir
nelfinavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- nicardipine
nicardipine will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- nirmatrelvir
nirmatrelvir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce abemaciclib dose if coadministered with strong or moderate CYP3A4 inhibitors.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce abemaciclib dose if coadministered with strong or moderate CYP3A4 inhibitors.
- ofatumumab SC
ofatumumab SC, abemaciclib. 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.
- posaconazole
posaconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- ribociclib
ribociclib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- rucaparib
rucaparib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
saquinavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- sarecycline
sarecycline will increase the level or effect of abemaciclib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- siponimod
siponimod and abemaciclib 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.
- stiripentol
stiripentol, abemaciclib. 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.
- tazemetostat
tazemetostat will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- tipranavir
tipranavir will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
- trastuzumab
trastuzumab, abemaciclib. 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, abemaciclib. 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. .
- tucatinib
tucatinib will increase the level or effect of abemaciclib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- voriconazole
voriconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
Adverse effects listed are for all grades of toxicity unless otherwise noted
>10% (Monotherapy)
Creatinine increased (98%)
Diarrhea (90%)
Decreased WBCs (91%)
Decreased neutrophil count (88%)
Anemia (68%)
Fatigue (65%)
Nausea (64%)
Decreased appetite (45%)
Decreased lymphocyte count (42%)
Decreased platelet count (41%)
Abdominal pain (39%)
Neutropenia (37%)
Vomiting (35%)
Infection (31%)
ALT increased (31%)
AST increased (30%)
Decreased WBC, grade 3 (28%)
Anemia (25%)
Decreased neutrophil count, grade 3 (22%)
Thrombocytopenia (20%)
Diarrhea, grade 3 (20%)
Headache (20%)
Cough (19%)
Neutropenia, grade 3 (19%)
Constipation (17%)
Leukopenia (17%)
Arthralgia (15%)
Dry mouth (14%)
Stomatitis (14%)
Weight decreased (14%)
Decreased lymphocyte count, grade 3 (13%)
Dysgeusia (12%)
Alopecia (12%)
Dizziness (11%)
Pyrexia (11%)
>10% (Combination Therapy)
Creatinine increased (98%)
Decreased WBCs (90%)
Decreased neutrophil count (80-87%)
Diarrhea (86%)
Anemia (29-82%)
Decreased lymphocyte count (53-63%)
Decreased platelet count (36-53%)
Neutropenia (46%)
Fatigue (46%)
Nausea (45%)
Infections (43%)
ALT increased (13-41%)
AST increased (12-37%)
Abdominal pain (35%)
Decreased neutrophil count, grade 3 (29%)
Leukopenia (28%)
Decreased appetite (27%)
Vomiting (26%)
Neutropenia, grade 3 (24%)
Decreased WBC, grade 3 (23%)
Headache (20%)
Dysgeusia (18%)
Thrombocytopenia (16%)
Alopecia (16%)
Stomatitis (15%)
Pruritus (13%)
Diarrhea, grade 3 (13%)
Cough (13%)
Dizziness (12%)
Decreased lymphocyte count, grade 3 (7-12%)
Peripheral edema (12%)
Rash (11%)
Pyrexia (11%)
1-10% (Monotherapy)
Nausea, grade 3 (5%)
Infections, grade 3 (5%)
Anemia, grade 3 (5%)
Neutropenia, grade 4 (5%)
Leukopenia, grade 3 (5%)
Decreased neutrophils (5%)
Thrombocytopenia, grade 3 (4%)
Increased AST, grade 3 (4%)
Increased ALT, grade 3 (3%)
Decreased platelets (2%)
Abdominal pain, grade 3 (2%)
Dehydration, grade 3 (2%)
Infections, grade 3 (2%)
Vomiting, grade 3 (2%)
1-10% (Combination therapy)
Increased ALT, grade 3 (4-6%)
Increased AST, grade 3 (4%)
Decreased neutrophils, grade 4 (3-4%)
Increased creatinine, grade 3 (2%)
Neutropenia, grade 4 (2%)
Anemia, grade 3 (2-3%)
Decreased platelets, grade 3 (1%)
<1%
Monotherapy
- Increased creatinine, grade 3
- Decreased lymphocytes, grade 4
- Leukopenia, grade 4
- Constipation, grade 3
Combination therapy
- Increased WBC, grade 4
- Decreased lymphocytes, grade 4
- Decreased platelets, grade 4
- Increase ALT, grade 4
- Increased creatinine, grade 3
- Decreased weight, grade 3
- Pyrexia, grade 3 or 4
- Anemia, grade 4
- Leukopenia, grade 3
- Infections, grade 3
- Stomatitis, grade 3
- Vomiting, grade 3
Postmarketing Reports
Interstitial lung disease (ILD)/pneumonitis
Warnings
Contraindications
None
Cautions
May cause fetal harm; advise women of reproductive potential to use effective contraception (see Pregnancy)
Interstitial lung disease
- Severe, life-threatening, or fatal ILD and/or pneumonitis can occur; additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea
- Dose interruption or dose reduction recommended for patients who develop persistent or recurrent Grade 2 ILD/pneumonitis; permanently discontinue therapy in all patients with Grade 3 or 4 ILD or pneumonitis
Venous thromboembolism
- In clinical trials, venous thromboembolic events (VTE) reported in patients treated with abemaciclib plus an aromatase inhibitor (5%) and in patients treated with abemaciclib plus fulvestrant (5%)
- VTE (eg, deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, pelvic venous thrombosis, subclavian and axillary vein thrombosis, inferior vena cava thrombosis) reported in patients receiving abemaciclib and fulvestrant
- Therapy has not been studied in patients with early breast cancer with history of venous thromboembolism
- Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate
- Dose interruption is recommended for early breast cancer patients with any grade venous thromboembolic event and for advanced or metastatic breast cancer patients with a Grade 3 or 4 venous thromboembolic event
Hepatotoxicity
- Increased transaminases were observed in clinical trials
- In patients who had grade ≥3 ALT elevation, median time-to-onset was 57 days; whereas, grade <3 was 14 days
- In patients who had grade ≥3 AST elevation, median time-to-onset was 185 days; whereas, grade <3 was 13 days
- Monitor liver function tests (LFTs) prior to start of therapy, every 2 weeks for first 2 months, monthly for next 2 months, and as clinically indicated; dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or Grade 3 or 4, hepatic transaminase elevation
Neutropenia
- Neutropenia observed in clinical trials; in patients with grade >3 neutropenia, median time time-to-onset was 29 days and median duration was 15 days
- Febrile neutropenia reported in <1% of patients exposed to abemaciclib in the MONARCH studies; 2 deaths due to neutropenic sepsis were observed in MONARCH 2
- Monitor complete blood counts prior to start of therapy, every 2 weeks for first 2 months, monthly for next 2 months, and as clinically indicated; dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia; inform patients to promptly report any episodes of fever to their healthcare provider
Diarrhea
- Diarrhea incidence reported to be greatest during first month of dosing
- Diarrhea occurred in 81% of patients receiving abemaciclib plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving abemaciclib plus fulvestrant in MONARCH 2, and 90% of patients receiving abemaciclib alone in MONARCH 1
- Episodes of diarrhea have been associated with dehydration and infection; diarrhea incidence was greatest during the first month of dosing
- Instruct patients that at the first sign of loose stools, they should start antidiarrheal therapy such as loperamide, increase oral fluids, and notify healthcare provider for further instructions and appropriate follow up; for Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue treatment until toxicity resolves to ≤Grade 1, and then resume treatment at next lower dose
Drug interaction overview
- Abemaciclib is metabolized to several metabolites primarily by CYP3A4
- Strong CYP3A4 inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity
- Ketoconazole: Avoid coadministration
- Other strong CYP3A inhibitors: Decrease recommended starting dose (see Dosage Modifications)
- Strong CYP3A inducers: Avoid coadministration
Pregnancy
Pregnancy
There are no available human data informing the drug-associated risk
Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman; advise pregnant women of potential risk to a fetus
In animal data, administration of abemaciclib during organogenesis was teratogenic and caused decreased fetal weight at maternal exposures that were similar to human clinical exposure based on AUC at the maximum recommended human dose
Verify pregnancy status in females of reproductive potential prior to initiating treatment
Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after the last dose
Based on findings in animals, abemaciclib may impair fertility in males of reproductive potential
Lactation
Unknown if distributed in human breast milk
Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking abemaciclib and for at least 3 weeks after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits cyclin-dependent kinases (CDKs) 4 and 6
These kinases are activated upon binding to D cyclins and play a crucial role in signaling pathways, which lead to cell cycle progression and cellular proliferation
In ER-positive breast cancer cells, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation
Absorption
Bioavailability: 45% (single 200-mg dose)
Peak plasma time: 8 hr (single 200-mg dose)
Increase of AUC of abemaciclib and metabolites (9%) and peak plasma concentration (26%) with high-fat, high-calorie meal
Distribution
Protein bound: 96.3% (abemaciclib); M2 (93.4%); M18 (96.8%); M20 (97.8%)
Vd: 690.3 L
Metabolism
Abemaciclib is hepatically metabolized by CYP3A4 to several metabolites (N-desethylabemaciclib [M2], hydroxyabemaciclib [M20], hydroxy-N-desethylabemaciclib [M18], and an oxidative metabolite [M1])
M2, M18, and M20 are equipotent to abemaciclib and their AUCs accounted for 25%, 13%, and 26% of the total circulating analytes in plasma
Elimination
Excretion, single 150-mg dose: Feces (81%); urine (~3%)
Majority of the dose eliminated in feces was metabolites
Administration
Oral Administration
May take with or without food
Instruct patient to take dose at approximately the same time each day
Swallow table whole; do not chew, crush, or split tablets before swallowing
Do not ingest if tablet is broken, cracked, or otherwise not intact
Missed dose
- If patient vomits or misses a dose, take the next dose at its scheduled time
Storage
Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
Images
Formulary
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