ACN_7.12_Full Issue_digital | Page 34

Table 1 : Adverse Reactions ≥10 % in Patients Receiving VERZENIO Plus Fulvestrant and ≥2 % Higher Than Placebo Plus Fulvestrant in MONARCH 2

a Includes abdominal pain , abdominal pain upper , abdominal pain lower , abdominal discomfort , abdominal tenderness . b Includes upper respiratory tract infection , urinary tract infection , lung infection ,

pharyngitis , conjunctivitis , sinusitis , vaginal infection , sepsis . c Includes neutropenia , neutrophil count decreased .

d Includes anemia , hematocrit decreased , hemoglobin decreased , red blood cell count decreased . e Includes leukopenia , white blood cell count decreased .

f Includes platelet count decreased , thrombocytopenia . g Includes asthenia , fatigue .

Additional adverse reactions in MONARCH 2 include venous thromboembolic events ( deep vein thrombosis , pulmonary embolism , cerebral venous sinus thrombosis , subclavian vein thrombosis , axillary vein thrombosis , and DVT inferior vena cava ), which were reported in 5 % of patients treated with VERZENIO plus fulvestrant as compared to 0.9 % of patients treated with fulvestrant plus placebo .

Table 2 : Laboratory Abnormalities ≥10 % in Patients Receiving VERZENIO Plus Fulvestrant and ≥2 % Higher Than Placebo Plus Fulvestrant in MONARCH 2

Creatinine Increased

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters , without affecting glomerular function . In clinical studies , increases in serum creatinine ( mean increase , 0.2 mg / dL ) occurred within the first 28-day cycle of VERZENIO dosing , remained elevated but stable through the treatment period , and were reversible upon treatment discontinuation . Alternative markers such as BUN , cystatin C , or calculated glomerular filtration rate ( GFR ), which are not based on creatinine , may be considered to determine whether renal function is impaired .

DRUG INTERACTIONS Effect of Other Drugs on VERZENIO

CYP3A Inhibitors Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity .

Ketoconazole Avoid concomitant use of ketoconazole . Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold .

Other Strong CYP3A Inhibitors 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 with concomitant use of strong CYP3A inhibitors other than ketoconazole . 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 with concomitant use of strong CYP3A inhibitors . If a patient taking VERZENIO discontinues a strong CYP3A inhibitor , increase the VERZENIO dose ( after 3-5 half-lives of the inhibitor ) to the dose that was used before starting the inhibitor . Patients should avoid grapefruit products .

Moderate CYP3A Inhibitors With concomitant use of moderate CYP3A inhibitors , monitor for adverse reactions and consider reducing the VERZENIO dose in 50 mg decrements , if necessary .

Strong and Moderate CYP3A Inducers Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity . Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents .

USE IN SPECIFIC POPULATIONS Pregnancy

Risk Summary Based on findings in animals and its mechanism of action , VERZENIO can cause fetal harm when administered to a pregnant woman . 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 at least 3 weeks after the last dose .

Females and Males of Reproductive Potential

Pregnancy Testing Based on animal studies , VERZENIO can cause fetal harm when administered to a pregnant woman . Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with VERZENIO .

Contraception Females VERZENIO can cause fetal harm when administered to a pregnant woman . Advise females of reproductive potential to use effective contraception during VERZENIO treatment and for at least 3 weeks after the last dose .

Infertility Males Based on findings in animals , VERZENIO may impair fertility in males of reproductive potential .