Verzenio
(abemaciclib)Dosage & Administration
VERZENIO tablets are taken orally with or without food.
By using PrescriberAI, you agree to the AI Terms of Use.
Verzenio Prescribing Information
Early Breast Cancer
VERZENIO® (abemaciclib) is indicated:
- in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence [see Clinical Studies ].
Advanced or Metastatic Breast Cancer
VERZENIO (abemaciclib) is indicated:
- in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
- in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
- as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
Recommended Dose and Schedule
- When used in combination with fulvestrant, tamoxifen, or an aromatase inhibitor, the recommended dose of VERZENIO is 150 mg taken orally twice daily. Refer to the Full Prescribing Information for the recommended dose of the fulvestrant, tamoxifen, or aromatase inhibitor being used.
- Pre/perimenopausal women and men treated with the combination of VERZENIO plus an aromatase inhibitor should be treated with a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards.
- Pre/perimenopausal women treated with the combination of VERZENIO plus fulvestrant should be treated with a GnRH according to current clinical practice standards
- When used as monotherapy, the recommended dose of VERZENIO is 200 mg taken orally twice daily.
- For early breast cancer, continue VERZENIO until completion of 2 years of treatment or until disease recurrence, or unacceptable toxicity.
- For advanced or metastatic breast cancer, continue treatment until disease progression or unacceptable toxicity.
VERZENIO may be taken with or without food [see Clinical Pharmacology ].
Instruct patients to take their doses of VERZENIO at approximately the same times every day.
If the patient vomits or misses a dose of VERZENIO, instruct the patient to take the next dose at its scheduled time. Instruct patients to swallow VERZENIO tablets whole and not to chew, crush, or split tablets before swallowing. Instruct patients not to ingest VERZENIO tablets if broken, cracked, or otherwise not intact.
Dose Modification
Dose Modifications for Adverse Reactions
The recommended VERZENIO dose modifications for adverse reactions are provided in Tables 1- 7. Discontinue VERZENIO for patients unable to tolerate 50 mg twice daily.
| Dose Level | VERZENIO Dose Combination with Fulvestrant, Tamoxifen, or an Aromatase Inhibitor | VERZENIO Dose for Monotherapy |
| Recommended starting dose | 150 mg twice daily | 200 mg twice daily |
| First dose reduction | 100 mg twice daily | 150 mg twice daily |
| Second dose reduction | 50 mg twice daily | 100 mg twice daily |
| Third dose reduction | not applicable | 50 mg twice daily |
Abbreviation: CTCAE = Common Terminology Criteria for Adverse Events. | |
a If blood cell growth factors are required, suspend VERZENIO dose for at least 48 hours after the last dose of blood cell growth factor and until toxicity resolves to ≤Grade 2. Resume at next lower dose unless already performed for the toxicity that led to the use of the growth factor. Growth factor use as per current treatment guidelines. | |
| Monitor complete blood counts prior to the start of VERZENIO therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. | |
| CTCAE Grade | VERZENIO Dose Modifications |
| Grade 1 or 2 | No dose modification is required. |
| Grade 3 | Suspend dose until toxicity resolves to ≤Grade 2. Dose reduction is not required. |
| Grade 3 recurrent, or Grade 4 | Suspend dose until toxicity resolves to ≤Grade 2. Resume at next lower dose. |
| At the first sign of loose stools, start treatment with antidiarrheal agents and increase intake of oral fluids. | |
| CTCAE Grade | VERZENIO Dose Modifications |
| Grade 1 | No dose modification is required. |
| Grade 2 | If toxicity does not resolve within 24 hours to ≤Grade 1, suspend dose until resolution. No dose reduction is required. |
| Grade 2 that persists or recurs after resuming the same dose despite maximal supportive measures | Suspend dose until toxicity resolves to ≤Grade 1. Resume at next lower dose. |
| Grade 3 or 4 or requires hospitalization | Suspend dose until toxicity resolves to ≤Grade 1. Resume at next lower dose. |
Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit of normal. | |
| Monitor ALT, AST, and serum bilirubin prior to the start of VERZENIO therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. | |
| CTCAE Grade for ALT and AST | VERZENIO Dose Modifications |
| Grade 1 (>ULN-3.0 x ULN) Grade 2 (>3.0-5.0 x ULN), WITHOUT increase in total bilirubin above 2 x ULN | No dose modification is required. |
| Persistent or Recurrent Grade 2, or Grade 3 (>5.0-20.0 x ULN), WITHOUT increase in total bilirubin above 2 x ULN | Suspend dose until toxicity resolves to baseline or Grade 1. Resume at next lower dose. |
| Elevation in AST and/or ALT >3 x ULN WITH total bilirubin >2 x ULN, in the absence of cholestasis | Discontinue VERZENIO. |
| Grade 4 (>20.0 x ULN) | Discontinue VERZENIO. |
| CTCAE Grade | VERZENIO Dose Modifications |
| Grade 1 or 2 | No dose modification is required. |
| Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1 | Suspend dose until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose. |
| Grade 3 or 4 | Discontinue VERZENIO. |
| CTCAE Grade | VERZENIO Dose Modifications |
| Early Breast Cancer | |
| Any Grade | Suspend dose and treat as clinically indicated. Resume VERZENIO when the patient is clinically stable. |
| Advanced or Metastatic Breast Cancer | |
| Grade 1 or 2 | No dose modification is required. |
| Grade 3 or 4 | Suspend dose and treat as clinically indicated. Resume VERZENIO when the patient is clinically stable. |
a Excluding diarrhea, hematologic toxicity, hepatotoxicity, ILD/pneumonitis, and VTEs. | |
| CTCAE Grade | VERZENIO Dose Modifications |
| Grade 1 or 2 | No dose modification is required. |
| Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1 | Suspend dose until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose. |
| Grade 3 or 4 | Suspend dose until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose. |
Refer to the Full Prescribing Information for coadministered fulvestrant, tamoxifen, or an aromatase inhibitor for dose modifications and other relevant safety information.
Dose Modification for Use with Strong and Moderate CYP3A Inhibitors
Avoid concomitant use of the strong CYP3A inhibitor ketoconazole.
With concomitant use of strong CYP3A inhibitors other than ketoconazole, in patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the VERZENIO dose to 100 mg twice daily. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the VERZENIO dose to 50 mg twice daily. If a patient taking VERZENIO discontinues a CYP3A inhibitor, increase the VERZENIO dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the strong inhibitor [see Drug Interactions and Clinical Pharmacology ].
With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the VERZENIO dose in 50 mg decrements as demonstrated in Table 1, if necessary.
Dose Modification for Patients with Severe Hepatic Impairment
For patients with severe hepatic impairment (Child Pugh-C), reduce the VERZENIO dosing frequency to once daily [see Use in Specific Populations and Clinical Pharmacology ].
Refer to the Full Prescribing Information for the coadministered fulvestrant, tamoxifen, or aromatase inhibitor for dose modification requirements for severe hepatic impairment.
50 mg tablets: oval beige tablet with “Lilly” debossed on one side and “50” on the other side.
100 mg tablets: oval white to practically white tablet with “Lilly” debossed on one side and “100” on the other side.
150 mg tablets: oval yellow tablet with “Lilly” debossed on one side and “150” on the other side.
200 mg tablets: oval beige tablet with “Lilly” debossed on one side and “200” on the other side.
Pregnancy
Risk Summary
Based on findings in animals and its mechanism of action, VERZENIO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ]. There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus. In animal reproduction studies, 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 (see Data). Advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.
Data
Animal Data
In an embryo-fetal development study, pregnant rats received oral doses of abemaciclib up to 15 mg/kg/day during the period of organogenesis. Doses ≥4 mg/kg/day caused decreased fetal body weights and increased incidence of cardiovascular and skeletal malformations and variations. These findings included absent innominate artery and aortic arch, malpositioned subclavian artery, unossified sternebra, bipartite ossification of thoracic centrum, and rudimentary or nodulated ribs. At 4 mg/kg/day in rats, the maternal systemic exposures were approximately equal to the human exposure (AUC) at the recommended dose.
Lactation
Risk Summary
There are no data on the presence of abemaciclib in human milk, or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed infants from VERZENIO, advise lactating women not to breastfeed during VERZENIO treatment and for 3 weeks after the last dose.
Females and Males of Reproductive Potential
Based on animal studies, VERZENIO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ].
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating treatment with VERZENIO.
Contraception
Females
Advise females of reproductive potential to use effective contraception during VERZENIO treatment and for 3 weeks after the last dose.
Infertility
Males
Based on findings in animals, VERZENIO may impair fertility in males of reproductive potential [see Nonclinical Toxicology ].
Pediatric Use
The safety and effectiveness of VERZENIO have not been established in pediatric patients.
The safety and effectiveness of VERZENIO in combination with chemotherapy was assessed but not established in an open label, dose-finding trial (NCT04238819) in 43 pediatric patients aged 1 to < 17 years with relapsed/refractory solid tumors. No new safety signals were observed in pediatric patients in this study. Abemaciclib exposure in pediatric patients was within the range of the values previously observed in adults given a similar dose per body surface area.
Geriatric Use
Of the 2791 VERZENIO-treated patients in monarchE, 15% were 65 years of age or older and 2.7% were 75 years of age or older.
Of the 900 patients who received VERZENIO in MONARCH 1, MONARCH 2, and MONARCH 3, 38% were 65 years of age or older and 10% were 75 years of age or older. The most common adverse reactions (≥5%) Grade 3 or 4 in patients ≥65 years of age across MONARCH 1, 2, and 3 were: neutropenia, diarrhea, fatigue, nausea, dehydration, leukopenia, anemia, infections, and ALT increased.
No overall differences in safety or effectiveness of VERZENIO were observed between these patients and younger patients.
Renal Impairment
No dosage adjustment is required for patients with mild or moderate renal impairment (CLcr ≥30-89 mL/min, estimated by Cockcroft-Gault [C-G]). The pharmacokinetics of abemaciclib in patients with severe renal impairment (CLcr <30 mL/min, C-G), end stage renal disease, or in patients on dialysis is unknown [see Clinical Pharmacology ].
Hepatic Impairment
No dosage adjustments are necessary in patients with mild or moderate hepatic impairment (Child-Pugh A or B).
Reduce the dosing frequency when administering VERZENIO to patients with severe hepatic impairment (Child-Pugh C) [see Dosage and Administration and Clinical Pharmacology ].
None.
Diarrhea
Severe diarrhea associated with dehydration and infection occurred in patients treated with VERZENIO.
Across four clinical trials in 3691 patients, diarrhea occurred in 81% to 90% of patients who received VERZENIO. Grade 3 diarrhea occurred in 8% to 20% of patients receiving VERZENIO [see Adverse Reactions ].
Most patients experienced diarrhea during the first month of VERZENIO treatment. The median time to onset of the first diarrhea event ranged from 6 to 8 days; and the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to 11 days and 5 to 8 days, respectively. Across trials, 19% to 26% of patients with diarrhea required a VERZENIO dose interruption and 13% to 23% required a dose reduction.
Instruct patients to start antidiarrheal therapy such as loperamide at the first sign of loose stools, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow up [see Patient Counseling Information ]. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue VERZENIO until toxicity resolves to ≤Grade 1, and then resume VERZENIO at the next lower dose [see Dosage and Administration ].
Neutropenia
Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, occurred in patients treated with VERZENIO.
Across four clinical trials in 3691 patients, neutropenia occurred in a 37% to 46% of patients receiving VERZENIO. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 19% to 32% of patients receiving VERZENIO. Across trials, the median time to the first episode of Grade ≥3 neutropenia ranged from 29 days to 33 days, and the median duration of Grade ≥3 neutropenia ranged from 11 days to 16 days [see Adverse Reactions ].
Febrile neutropenia has been reported in <1% of patients exposed to VERZENIO across trials. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider [see Patient Counseling Information ].
Monitor complete blood counts prior to the start of VERZENIO therapy, every 2 weeks for the first 2 months, monthly for the 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 [see Dosage and Administration ].
Interstitial Lung Disease (ILD) or Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur in patients treated with VERZENIO and other CDK4/6 inhibitors. In VERZENIO-treated patients in early breast cancer (monarchE, N=2791), 3% of patients experienced ILD or pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality (0.1%). In VERZENIO-treated patients in advanced or metastatic breast cancer (N=900) (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of VERZENIO-treated patients had ILD or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD or pneumonitis have been observed in the postmarketing setting, with fatalities reported [see Adverse Reactions ].
Monitor patients for pulmonary symptoms indicative of ILD or pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations.
Dose interruption or dose reduction is recommended for patients who develop persistent or recurrent Grade 2 ILD or pneumonitis. Permanently discontinue VERZENIO in all patients with Grade 3 or 4 ILD or pneumonitis [see Dosage and Administration ].
Hepatotoxicity
Grade ≥3 ALT (2% to 6%) and AST (2% to 3%) were reported in patients receiving VERZENIO.
Across three clinical trials in 3559 patients (monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade ≥3 ALT increases ranged from 57 to 87 days and the median time to resolution to Grade <3 was 13 to 14 days. The median time to onset of Grade ≥3 AST increases ranged from 71 to 185 days and the median time to resolution to Grade <3 ranged from 11 to 15 days.
Monitor liver function tests (LFTs) prior to the start of VERZENIO therapy, every 2 weeks for the first 2 months, monthly for the 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 any Grade 3 or Grade 4 hepatic transaminase elevation [see Dosage and Administration ].
5.5 Venous Thromboembolism
Across three clinical trials in 3559 patients (monarchE, MONARCH 2, MONARCH 3), venous thromboembolic events were reported in 2% to 5% of patients treated with VERZENIO. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. In clinical trials, deaths due to venous thromboembolism have been reported in patients treated with VERZENIO.
VERZENIO has not been studied in patients with early breast cancer who had a 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 [see Dosage and Administration ].
Embryo-Fetal Toxicity
Based on findings from animal studies and the mechanism of action, VERZENIO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VERZENIO and for 3 weeks after the last dose [see Use in Specific Populations and Clinical Pharmacology ].