VERZENIO

Small Molecule Antineoplastic Cyclin-Dependent Kinase (CDK) Inhibitors

Emetic Risk
Moderate/High
Administer routine antiemetic prophylaxis prior to treatment.

Oral Administration Oral Solid Formulations

Abemaciclib may be taken with or without food.
Instruct patients to take abemaciclib at approximately the same times every day.
Patients should swallow tablets whole; do not chew, crush, or split tablets. Instruct patients not to take abemaciclib tablets that have been broken, cracked, or are not otherwise intact.
If the patient vomits or misses a dose, do not administer an additional dose. The patient should take the next dose at its scheduled time.

Severe

diarrhea / Early / 8.0-20.0
fatigue / Early / 1.8-13.0
elevated hepatic enzymes / Delayed / 1.5-6.6
infection / Delayed / 4.5-5.7
thromboembolism / Delayed / 2.0-5.0
nausea / Early / 0.5-4.5
anorexia / Delayed / 0.6-3.0
anemia / Delayed / 0-2.6
abdominal pain / Early / 1.2-2.5
dehydration / Delayed / 0-2.3
vomiting / Early / 0.5-1.2
rash / Early / 0-1.0
pneumonitis / Delayed / 0.5-1.0
interstitial lung disease / Delayed / 0.5-1.0
pruritus / Rapid / 0.4-0.9
renal failure (unspecified) / Delayed / 0-0.9
constipation / Delayed / 0-0.8
dizziness / Early / 0-0.7
headache / Early / 0-0.7
fever / Early / 0-0.7
weight loss / Delayed / 0-0.6
dyspnea / Early / 0-0.6
pulmonary fibrosis / Delayed / 0.6-0.6
stomatitis / Delayed / 0-0.5
stroke / Early / 0-0.2
hepatotoxicity / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known

Moderate

peripheral edema / Delayed / 0-12.0
Onychomadesis / Delayed / Incidence not known
sarcoidosis / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known

Mild

alopecia / Delayed / 11.0-27.0
cough / Delayed / 13.0-19.0
dysgeusia / Early / 5.0-18.0
arthralgia / Delayed / 0-15.0
xerostomia / Early / 0-14.0
influenza / Delayed / 0-10.0
dyspepsia / Early / 0-8.0
lacrimation / Early / 0-6.0
pharyngitis / Delayed / 5.0
onycholysis / Delayed / Incidence not known
nail discoloration / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
sinusitis / Delayed / Incidence not known

VERZENIO

Rx

Inhibitor of cyclin-dependent kinases 4 and 6
Used in combination with an aromatase inhibitor (AI) or tamoxifen for HR-positive, HER2-negative, high-risk early breast cancer, and alone or in combination with fulvestrant or an AI for certain types of HR-positive, HER2-negative advanced or metastatic breast cancer
Diarrhea is the most common adverse reaction and requires prompt treatment; neutropenia, hepatotoxicity, and thromboembolism may also occur

For the treatment of breast cancer. For the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting, as monotherapy. Oral dosage Adults

200 mg PO twice daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label clinical trial, previously treated women with measurable HR-positive, HER2-negative metastatic breast cancer with progression after endocrine therapy treated with abemaciclib (n = 132) had an investigator-assessed objective response rate (ORR) of 19.7% with a median duration of 8.6 months; the ORR by independent review was 17.4% for a median duration of 7.2 months.

For the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy, in combination with fulvestrant. Oral dosage Adults

150 mg PO twice daily, in combination with fulvestrant (500 mg IM as two 250-mg (5 mL) injections, 1 injection in each buttock (gluteal area), on days 1, 15, 29 and once monthly thereafter) until disease progression or unacceptable toxicity. Pre- and perimenopausal women should also be treated with a gonadotropin-releasing hormone agonist according to current clinical practice standards. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with fulvestrant plus abemaciclib significantly improved the primary endpoint of median progression-free survival (PFS) compared with fulvestrant plus placebo in a multicenter, randomized clinical trial of women with HR-positive, HER2-negative metastatic breast cancer with disease progression following adjuvant or metastatic endocrine therapy (MONARCH-2) (16.4 months vs. 9.3 months); both arms were also treated with goserelin for at least 4 weeks prior to starting and continuing for the duration of the study. The objective response rate for patients with measurable disease was 48.1% in the abemaciclib arm compared with 21.3% in the placebo arm. An interim analysis after a median follow-up of 47.7 months found that median overall survival was also significantly improved in the abemaciclib arm (46.7 months vs. 37.3 months).

For initial endocrine-based treatment of HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor. Oral dosage Adults

150 mg PO twice daily, plus an aromatase inhibitor at the recommended dose, until disease progression or unacceptable toxicity. Pre/perimenopausal women and men treated with abemaciclib plus an AI should be treated with a gonadotropin-releasing hormone (GnRH) agonist according to current clinical practice standards. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. At a preplanned interim analysis of a phase 3 clinical trial, first-line treatment with abemaciclib plus an aromatase inhibitor significantly improved progression-free survival (PFS) compared with placebo plus an aromatase inhibitor in patients with HR-positive, HER2-negative breast cancer. In a subgroup analysis, the PFS benefit was significant in patients with visceral metastases but not in patients with only bone metastases. It was also significant in patients who had received either adjuvant aromatase inhibitor therapy or no prior endocrine therapy, but not in patients who had received other prior endocrine therapy, and in patients with measurable disease versus no measurable disease. Patients with de novo metastatic disease or recurrence within 36 months of last endocrine treatment may also derive more benefit.

For the adjuvant treatment of hormone receptor (HR)-positive, HER2-negative, node-positive, early breast cancer in high-risk patients, in combination with endocrine therapy (tamoxifen or aromatase inhibitors). Oral dosage Adults

150 mg PO twice daily with fulvestrant, tamoxifen, or an aromatase inhibitor (AI) for 2 years or until disease recurrence or unacceptable toxicity. In the clinical trial, endocrine therapy alone was continued beyond 2 years (for a total of 5 to 10 years) as clinically indicated. Pre/perimenopausal women and men treated with abemaciclib plus an AI should be treated with a gonadotropin-releasing hormone (GnRH) agonist according to current clinical practice standards. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A phase 3 randomized clinical trial (the monarchE study) found that adjuvant treatment with abemaciclib in combination with endocrine therapy (after completion of radiation and chemotherapy, if appropriate) significantly improved invasive disease-free survival (IDFS) at 2 years in patients with HR-positive, HER2-negative, node-positive, high-risk early breast cancer (85.5% vs. 78.6%); in the clinical trial, "high risk" was defined as patients with 4 or more positive axillary lymph nodes, or 1 to 3 positive axillary lymph nodes with tumor size greater than 5 cm, grade 3 histology, or Ki-67 greater than 20%.

Hepatic Impairment

Baseline Hepatic Impairment:
Mild to moderate hepatic impairment (Child-Pugh A or B): No dosage adjustments are necessary.
Severe hepatic impairment (Child-Pugh C): Reduce the frequency of abemaciclib dosing to once daily.
Treatment-Related Hepatotoxicity:
Grade 1 (AST/ALT 1.1 to 3 times the upper limit of normal (ULN)), without an increase in total bilirubin above 2 times ULN: No dosage adjustments are necessary.
Grade 2 (AST/ALT 3.1 to 5 times ULN), WITHOUT an increase in total bilirubin above 2 times ULN, first occurrence: No dosage adjustments are necessary. If grade 2 hepatotoxicity persists, hold abemaciclib. Upon resolution to baseline or grade 1, resume abemaciclib at the next lower dose level.
Persistent or recurrent Grade 2 (AST/ALT 3.1 to 5 times ULN), or Grade 3 (AST/ALT 5.1 to 20 times ULN), WITHOUT an increase in total bilirubin above 2 times ULN: Hold abemaciclib. Upon resolution to baseline or grade 1, resume abemaciclib at the next lower dose level.
Grade 2 or 3 (AST/ALT 3.1 to 20 times ULN) WITH total bilirubin greater than 2 times ULN, in the absence of cholestasis: Discontinue abemaciclib.
Grade 4 (AST/ALT greater than 20 times ULN): Discontinue abemaciclib.

Renal Impairment

Baseline Renal Impairment:
Mild to moderate renal impairment (CrCL greater than or equal to 30 mL/min): No dosage adjustment necessary.
Severe renal impairment, end-stage renal disease, or dialysis: Specific guidelines are not available. The pharmacokinetics of abemaciclib in these patients is unknown.

Adagrasib: (Major) If coadministration with adagrasib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If adagrasib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of adagrasib. Abemaciclib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Amiodarone: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with amiodarone is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Amobarbital: (Major) Avoid coadministration of amobarbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and amobarbital is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) If coadministration with clarithromycin is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If clarithromycin is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of clarithromycin. Abemaciclib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with clarithromycin increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Apalutamide: (Major) Avoid coadministration of apalutamide with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Aprepitant, Fosaprepitant: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with a multi-day regimen of aprepitant is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of butalbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Atazanavir: (Major) If coadministration with atazanavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If atazanavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of atazanavir. Abemaciclib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Atazanavir; Cobicistat: (Major) If coadministration with atazanavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If atazanavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of atazanavir. Abemaciclib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients. (Major) If coadministration with cobicistat is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If cobicistat is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of cobicistat. Abemaciclib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Berotralstat: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with berotralstat is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Bexarotene: (Major) Avoid coadministration of bexarotene with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Bosentan: (Major) Avoid coadministration of bosentan with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Butabarbital: (Major) Avoid coadministration of butabarbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and butabarbital is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Butalbital; Acetaminophen: (Major) Avoid coadministration of butalbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of butalbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of butalbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of butalbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Carbamazepine: (Major) Avoid coadministration of carbamazepine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Cenobamate: (Major) Avoid coadministration of cenobamate with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Ceritinib: (Major) If coadministration with ceritinib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ceritinib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ceritinib. Abemaciclib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Chloramphenicol: (Major) If coadministration with chloramphenicol is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If chloramphenicol is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of chloramphenicol. Abemaciclib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with ciprofloxacin is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Clarithromycin: (Major) If coadministration with clarithromycin is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If clarithromycin is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of clarithromycin. Abemaciclib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with clarithromycin increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Cobicistat: (Major) If coadministration with cobicistat is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If cobicistat is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of cobicistat. Abemaciclib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Colony Stimulating Factors: (Major) Do not administer abemaciclib for at least 48 hours after the last dose of colony stimulating factors, if required. Hematologic toxicities should also be resolved to grade 2 or less prior to resuming treatment with abemaciclib.
Conivaptan: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with conivaptan is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Crizotinib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with crizotinib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Cyclosporine: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with cyclosporine is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Dabrafenib: (Major) Avoid coadministration of dabrafenib with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Danazol: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with danazol is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Darunavir: (Major) If coadministration with darunavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If darunavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of darunavir. Abemaciclib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Darunavir; Cobicistat: (Major) If coadministration with cobicistat is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If cobicistat is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of cobicistat. Abemaciclib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients. (Major) If coadministration with darunavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If darunavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of darunavir. Abemaciclib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) If coadministration with cobicistat is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If cobicistat is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of cobicistat. Abemaciclib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients. (Major) If coadministration with darunavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If darunavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of darunavir. Abemaciclib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Delavirdine: (Major) If coadministration with delavirdine is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If delavirdine is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of delavirdine. Abemaciclib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Diltiazem: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with diltiazem is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. Coadministration with diltiazem is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 2.4-fold.
Dronedarone: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with dronedarone is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and dronedarone is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Duvelisib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with duvelisib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Efavirenz: (Major) Avoid coadministration of efavirenz with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of efavirenz with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of efavirenz with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Eflapegrastim: (Major) Do not administer abemaciclib for at least 48 hours after the last dose of colony stimulating factors, if required. Hematologic toxicities should also be resolved to grade 2 or less prior to resuming treatment with abemaciclib.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) If coadministration with cobicistat is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If cobicistat is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of cobicistat. Abemaciclib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) If coadministration with cobicistat is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If cobicistat is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of cobicistat. Abemaciclib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Enzalutamide: (Major) Avoid coadministration of enzalutamide with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Erythromycin: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with erythromycin is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Eslicarbazepine: (Major) Avoid coadministration of eslicarbazepine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Etravirine: (Major) Avoid coadministration of etravirine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Fedratinib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fedratinib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Filgrastim, G-CSF: (Major) Do not administer abemaciclib for at least 48 hours after the last dose of colony stimulating factors, if required. Hematologic toxicities should also be resolved to grade 2 or less prior to resuming treatment with abemaciclib.
Fluconazole: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fluconazole is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Fluoxetine: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fluoxetine is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate. Fluoxetine is a weak CYP3A4 inhibitor, but its metabolite, norfluoxetine, is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Fluvoxamine: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fluvoxamine is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Fosamprenavir: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fosamprenavir is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Fosphenytoin: (Major) Avoid coadministration of fosphenytoin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Grapefruit juice: (Major) Advise patients to avoid grapefruit products during abemaciclib treatment due to the potential for increased abemaciclib exposure. Abemaciclib is a CYP3A4 substrate and grapefruit is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Idelalisib: (Major) If coadministration with idelalisib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If idelalisib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of idelalisib. Abemaciclib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Imatinib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with imatinib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Indinavir: (Major) If coadministration with indinavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If indinavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of indinavir. Abemaciclib is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Isavuconazonium: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with isavuconazonium is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of rifampin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of rifampin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Itraconazole: (Major) If coadministration with itraconazole is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If itraconazole is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of itraconazole. Abemaciclib is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Ketoconazole: (Major) Avoid coadministration of abemaciclib with ketoconazole. Abemaciclib is a CYP3A4 substrate and ketoconazole is a strong CYP3A inhibitor. Ketoconazole is predicted to increase the AUC of abemaciclib up to 16-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) If coadministration with clarithromycin is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If clarithromycin is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of clarithromycin. Abemaciclib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with clarithromycin increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Lefamulin: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with oral lefamulin is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Lenacapavir: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with lenacapavir is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Letermovir: (Moderate) In patients receiving abemaciclib and letermovir WITHOUT concomitant cyclosporine, monitor for an increase in abemaciclib-related adverse reactions; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. In patients who are also receiving treatment with cyclosporine, a dose reduction of abemaciclib is required because the magnitude of this interaction may be amplified. Reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. If letermovir and cyclosporine are discontinued, resume the original dose of abemaciclib after 3 to 5 half-lives. Abemaciclib is a CYP3A4 substrate and letermovir is a moderate CYP3A4 inhibitor; however, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold. Coadministration with a strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Levoketoconazole: (Major) Avoid coadministration of abemaciclib with ketoconazole. Abemaciclib is a CYP3A4 substrate and ketoconazole is a strong CYP3A inhibitor. Ketoconazole is predicted to increase the AUC of abemaciclib up to 16-fold.
Lonafarnib: (Major) If coadministration with lonafarnib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If lonafarnib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of lonafarnib. Abemaciclib is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Lopinavir; Ritonavir: (Major) If coadministration with ritonavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ritonavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ritonavir. Abemaciclib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Mavacamten: (Major) Avoid coadministration of mavacamten with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with other moderate CYP3A inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Methohexital: (Major) Avoid coadministration of methohexital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and methohexital is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Mifepristone: (Major) If coadministration with mifepristone is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the 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 the dose of abemaciclib to the original dose after 3 to 5 half-lives of mifepristone. Abemaciclib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Mitotane: (Major) Avoid coadministration of mitotane with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Modafinil: (Major) Avoid coadministration of modafinil with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29%.
Nafcillin: (Major) Avoid coadministration of nafcillin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Nefazodone: (Major) If coadministration with nefazodone is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If nefazodone is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of nefazodone. Abemaciclib is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Nelfinavir: (Major) If coadministration with nelfinavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If nelfinavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of nelfinavir. Abemaciclib is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with netupitant is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Nilotinib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with nilotinib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Nirmatrelvir; Ritonavir: (Major) If coadministration with ritonavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ritonavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ritonavir. Abemaciclib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Olanzapine; Fluoxetine: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with fluoxetine is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate. Fluoxetine is a weak CYP3A4 inhibitor, but its metabolite, norfluoxetine, is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of rifabutin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Pegfilgrastim: (Major) Do not administer abemaciclib for at least 48 hours after the last dose of colony stimulating factors, if required. Hematologic toxicities should also be resolved to grade 2 or less prior to resuming treatment with abemaciclib.
Pentobarbital: (Major) Avoid coadministration of pentobarbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and pentobarbital is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Pexidartinib: (Major) Avoid coadministration of pexidartinib with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Phenobarbital: (Major) Avoid coadministration of phenobarbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of phenobarbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Phenytoin: (Major) Avoid coadministration of phenytoin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Posaconazole: (Major) If coadministration with posaconazole is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If posaconazole is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of posaconazole. Abemaciclib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Primidone: (Major) Avoid coadministration of primidone with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and primidone, which is metabolized to phenobarbital, is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Ribociclib: (Major) If coadministration with ribociclib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ribociclib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ribociclib. Abemaciclib is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M1

8, and M20) by 2.5-fold in cancer patients.
Ribociclib; Letrozole: (Major) If coadministration with ribociclib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ribociclib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ribociclib. Abemaciclib is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Rifabutin: (Major) Avoid coadministration of rifabutin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Rifampin: (Major) Avoid coadministration of rifampin with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Rifapentine: (Major) Avoid coadministration of rifapentine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Ritlecitinib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with ritlecitinib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Ritonavir: (Major) If coadministration with ritonavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ritonavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ritonavir. Abemaciclib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Saquinavir: (Major) If coadministration with saquinavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If saquinavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of saquinavir. Abemaciclib is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid coadministration of secobarbital with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and secobarbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Sotorasib: (Major) Avoid coadministration of sotorasib with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of St Johns Wort with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and St Johns Wort is a strong CYP3A4 inducer. The amount of individual constituents in various St Johns Wort products may alter the inducing effects, making drug interactions unpredictable. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Tbo-Filgrastim: (Major) Do not administer abemaciclib for at least 48 hours after the last dose of colony stimulating factors, if required. Hematologic toxicities should also be resolved to grade 2 or less prior to resuming treatment with abemaciclib.
Tipranavir: (Major) If coadministration with tipranavir is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If tipranavir is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of tipranavir. Abemaciclib is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Trandolapril; Verapamil: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with verapamil is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration with verapamil is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6-fold.
Tucatinib: (Major) If coadministration with tucatinib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If tucatinib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of tucatinib. Abemaciclib is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Verapamil: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with verapamil is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration with verapamil is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) If coadministration with clarithromycin is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If clarithromycin is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of clarithromycin. Abemaciclib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration with clarithromycin increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Voriconazole: (Major) If coadministration with voriconazole is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If voriconazole is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of voriconazole. Abemaciclib is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Voxelotor: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with voxelotor is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.

VERZENIO Oral Tab: 50mg, 100mg, 150mg, 200mg

Adults

Monotherapy: 200 mg PO twice daily.
Combination with fulvestrant or an aromatase inhibitor: 150 mg PO twice daily.

Geriatric

Monotherapy: 200 mg PO twice daily.
Combination with fulvestrant or an aromatase inhibitor: 150 mg PO twice daily.

Abemaciclib is a cyclin-dependent kinase (CDK) 4 and 6 inhibitor; CDK4 and CDK6 are activated upon binding to D cyclins. Cyclin D1 and CDK 4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cellular proliferation in estrogen receptor (ER)-positive breast cancer cell lines. In vitro, continuous exposure to abemaciclib inhibited Rb phosphorylation and blocked progression from G1 into S phase of the cell cycle, resulting in senescence and apoptosis. In breast cancer xenograft models, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size.

Abemaciclib is administered orally. It is highly bound to human plasma proteins, serum albumin, and alpha-1-acid glycoprotein independent of concentration from 152 ng/mL to 5,066 ng/mL. In a clinical study, the mean bound fraction was 96.3% (standard deviation (SD), 1.1%) for abemaciclib, 93.4% (SD, 1.3%) for M2, 96.8% (SD, 0.8%) for M18, and 97.8% (SD, 0.6%) for M20. The geometric mean systemic volume of distribution (Vd) is approximately 690.3 L (CV, 49%). In patients with advanced cancer, including breast cancer, concentrations of abemaciclib and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations. The geometric mean hepatic clearance of abemaciclib was 26 L/hour (CV, 51%) and the mean plasma elimination half-life was 18.3 hours (CV, 72%). Approximately 81% of a single radiolabeled 150-mg dose was recovered in feces and approximately 3% in urine; the majority of the dose eliminated in feces as metabolites.[62393]
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A
Abemaciclib is metabolized primarily by CYP3A4 to N-desethylabemaciclib (M2). Additional metabolites include hydroxyabemaciclib (M20), hydroxy-N-desethylabemaciclib (M18), and an oxidative metabolite (M1). The metabolites M2, M18, and M20 are equipotent to abemaciclib, and their AUCs accounted for 25%, 13%, and 26% of the total circulating analytes in plasma, respectively. A dose reduction of abemaciclib is necessary for coadministration with most strong CYP3A4 inhibitors and may be necessary with moderate CYP3A4 inhibitors, depending on treatment-related toxicities. Coadministration with moderate and strong CYP3A inducers should be avoided as the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites is significantly reduced.
 
Abemaciclib and its major active metabolites inhibit the renal transporters OCT2, MATE1, and MATE2-K at concentrations achievable at the approved recommended dosage. Increased serum creatine observed in clinical studies is likely due to inhibition of tubular secretion of creatinine by OCT2, MATE1, and MATE2-K. Abemaciclib is also a substrate and inhibitor of P-glycoprotein (P-gp) and BCRP; the clinical consequences of these findings are unknown.[62393]

Oral Route

Increases in plasma exposure (AUC) and Cmax were approximately dose proportional over a range of 50 mg to 200 mg of abemaciclib administered twice daily. Steady-state was achieved within 5 days following repeated twice daily dosing, and the estimated geometric mean accumulation ratio was 2.3 (CV, 50%) and 3.2 (CV, 59%) based on Cmax and AUC, respectively. The absolute bioavailability (F) of abemaciclib after a single 200-mg dose is 45% (CV, 19%). The median Tmax is 8 hours (range, 4.1 to 24 hours). A high-fat, high calorie meal (approximately 800 to 1,000 calories with 150 calories from protein, 250 calories from carbohydrate, and 500 to 600 calories from fat) administered to healthy subjects increased the AUC of abemaciclib plus its active metabolites by 9% and increased Cmax by 26%.

Pregnancy

Pregnancy should be avoided by females of reproductive potential during abemaciclib treatment and for 3 weeks after the last dose. Abemaciclib may cause fetal harm based on its mechanism of action and animal studies; however, there are no well-controlled studies in pregnant women. Women who are pregnant or who become pregnant while receiving abemaciclib should be apprised of the potential hazard to the fetus. In animal studies, abemaciclib was teratogenic and caused decreased fetal weight at maternal exposures similar to human clinical exposures based on AUC at the maximum recommended human dose. In an embryo-fetal development study in pregnant rats, abemaciclib exposures approximately equal to the human exposure (AUC) at the recommended dose caused decreased fetal body weights and an increased incidence of cardiovascular and skeletal malformations and variations, including absent innominate artery and aortic arch, malpositioned subclavian artery, unossified sternebra, bipartite ossification of thoracic centrum, and rudimentary or nodulated ribs, when administered to pregnant rats during organogenesis.

It is not known whether abemaciclib is excreted into human milk. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in a nursing infant, advise women to discontinue breast-feeding during treatment with abemaciclib and for 3 weeks after the last dose.