Names and pronunciation
(uh-beh′-muh-sy′-klib) Verzenio
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Drug reference
(uh-beh′-muh-sy′-klib) Verzenio
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Func. class.: Antineoplastic
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Chem. class.: Kinase inhibitors
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ACTION: It is an inhibitor of the cyclin-dependent kinases 4 and 6, a pro- tein kinase inhibitor
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USES: For the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior che- motherapy, as monotherapy, or in combi- nation with fulvestrant
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CONTRAINDICATIONS: Hyper- sensitivity Precautions: Breastfeeding, contracep- tion requirements, hepatic disease, hepa- totoxicity, infertility, neutropenia, preg- nancy, pregnancy testing, reproductive risk, thromboembolic disease
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SIDE EFFECTS GI: Diarrhea, abdominal pain, anorexia, nausea, vomiting, constipation, stomati- tis, weight loss CNS: Dizziness, drowsiness, fatigue, fever MS: Arthralgia INTEG: Rash, alopecia GU: Renal failure (rare) HEMA: Anemia, leukemia, neutropenia, thrombocytopenia MISC: Infection
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INTERACTIONS • Increase: abemaciclib effect—strong or moderate CYP3A4 inhibitors; avoid concomitant use • Decrease: abemaciclib effect—strong or moderate CYP3A4 inducers; avoid concomitant use
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DOSAGE AND ROUTES HR-positive, HER2-negative advanced or metastatic breast cancer disease progression following endocrine ther- apy and prior chemotherapy, as monotherapy • Adult: PO 200 mg bid until disease progression or unacceptable toxicity HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endo- crine therapy, in combination with fulvestrant • Adult: PO 150 mg bid with fulvestrant (500 mg IM as two 250-mg [5 mL] injections, 1 injection in each buttock, on days 1, 15, 29, and monthly thereafter) until disease progression or unacceptable toxicity. Pre- and perimenopausal women should also be treated with a gonadotropin- releasing hormone agonist Therapeutic drug monitoring: dosage adjustments for treatment- related toxicities Interrupt therapy per specific instruc- tions. Restart as appropriate at the fol- lowing reduced doses: • Starting dose: Monotherapy, 200 mg bid; combination with fulvestrant, 150 mg bid • First occurrence: Monotherapy, 150 mg bid; combination with fulvestrant, 100 mg bid • Second occurrence: Monotherapy, 100 mg bid; combination with fulvestrant, 50 mg bid • Third occurrence: Monotherapy, 50 mg bid; combination with fulvestrant, not ap- plicable Diarrhea • Grade 1: Begin antidiarrheals, increase oral fluid intake. No change needed • Grade 2, first occurrence: Begin antidi- A arrheals, increase oral fluid intake. If diar- rhea does not resolve to grade ≤1 within 24 hr, hold until resolution. No change needed unless grade 2 diarrhea persists; upon resolution to grade ≤1, resume at next lower dose level • Grade 2, recurrent despite maximal supportive measures: Begin antidiarrhe- als, increase oral fluid intake. When diar- rhea resolves to grade ≤1, resume at next lower dose level • Grade 3 or 4, or requires hospitaliza- tion: Begin antidiarrheals, increase oral fluid intake. When diarrhea resolves to grade ≤1, resume at next lower dose level Hepatic dose • Adult: PO Child-Pugh A or B: no change; Child-Pugh C: reduce dosing to once per day; grade 1 (AST/ALT 1.1-3× the upper limit of normal [ULN]), without an increase in total biliru- bin above 2× ULN: no change; grade 2, first occurrence (AST/ALT 3.1-5× ULN), without an increase in total bilirubin above 2× ULN: no change; if grade 2 persists, hold; after resolution to baseline or grade 1, resume at the next lower dose level; grade 2, recurrent (AST/ALT 3.1-5× ULN), without an increase in total bilirubin above 2× ULN: hold; after resolution to baseline or grade 1, resume at the next lower dose level; grade 2 or 3 (AST/ALT 3.1-20× ULN) with total bilirubin greater than 2× ULN, in the absence of cholestasis: discontinue; grade 4 (AST/ALT >20× ULN): discontinue Available forms Tablets 50, 100, 150, 200 mg Administer • With food at the same time every day • Swallow tablets whole; do not chew, crush, or split. Do not take if broken, cracked • If a dose is missed, do not replace missed dose; resume with the next scheduled daily dose
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Assess: • Diarrhea: at the first sign of loose stools, start antidiarrheal therapy, in- crease oral fluids • Neutropenia: CBC baseline then q2wk for the first 2 mo, then monthly for the next 2 mo, and as needed • Venous thromboembolism: monitor for signs, symptoms of thrombosis, pul- monary embolism; treat as needed • PE: chest pain worse when breathing deeply or coughing, coughing up blood, diz- ziness, fainting, tachypnea, rapid heartbeat, irregular heartbeat, shortness of breath • Infection: assess for UTI, lung infec- tion, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis • Hepatotoxicity: monitor LFTs baseline, then q2wk × 2 mo, monthly × next 2 mo, and then as needed; interruption in ther- apy or delay in treatment may be needed • Pregnancy/breastfeeding: Avoid in females of reproductive potential during treatment and for at least 3 wk after last dose; can cause fetal harm or death; dis- continue breastfeeding during treatment and for 3 wk after final dose. Presence in breast milk unknown. Obtain pregnancy test prior to treatment
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Evaluate: • Therapeutic outcome: decrease in size of cancerous tumor
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • Infection: to report the following to health care provider: increased temperature, fe- ver, shaking, chills, cough, sore throat • Diarrhea: to start antidiarrheal therapy at the first sign of loose stools, increase fluids, and notify health care provider • Thromboembolism: to report immedi- ately chest pain, worse when breathing deeply or coughing, coughing up blood, dizzi- ness, fainting, tachypnea, rapid heartbeat, ir- regular heartbeat, shortness of breath, pain, swelling of the extremity with redness and warmth, discoloration including a bluish color • Pregnancy/breastfeeding: not to use in pregnancy, breastfeeding; to use con- traception during treatment and for at least 3 wk after last dose HIGH ALERT
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PHARMACOKINETICS Protein binding 96.3%; half-life 18.3 hr; fecal excretion 97.1%; metabolized in liver by CYP3A4
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• Adult: PO 200 mg bid until disease progression or unacceptable toxicity HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endo- crine therapy, in combination with fulvestrant
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• Adult: PO 150 mg bid with fulvestrant (500 mg IM as two 250-mg [5 mL] injections, 1 injection in each buttock, on days 1, 15, 29, and monthly thereafter) until disease progression or unacceptable toxicity. Pre- and perimenopausal women should also be treated with a gonadotropin- releasing hormone agonist Therapeutic drug monitoring: dosage adjustments for treatment- related toxicities Interrupt therapy per specific instruc- tions. Restart as appropriate at the fol- lowing reduced doses:
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• Starting dose: Monotherapy, 200 mg bid; combination with fulvestrant, 150 mg bid
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• First occurrence: Monotherapy, 150 mg bid; combination with fulvestrant, 100 mg bid
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• Second occurrence: Monotherapy, 100 mg bid; combination with fulvestrant, 50 mg bid
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• Third occurrence: Monotherapy, 50 mg bid; combination with fulvestrant, not ap- plicable Diarrhea
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• Grade 1: Begin antidiarrheals, increase oral fluid intake. No change needed
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• Grade 2, first occurrence: Begin antidi- A arrheals, increase oral fluid intake. If diar- rhea does not resolve to grade ≤1 within 24 hr, hold until resolution. No change needed unless grade 2 diarrhea persists; upon resolution to grade ≤1, resume at next lower dose level
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• Grade 2, recurrent despite maximal supportive measures: Begin antidiarrhe- als, increase oral fluid intake. When diar- rhea resolves to grade ≤1, resume at next lower dose level
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• Grade 3 or 4, or requires hospitaliza- tion: Begin antidiarrheals, increase oral fluid intake. When diarrhea resolves to grade ≤1, resume at next lower dose level Hepatic dose
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• Adult: PO Child-Pugh A or B: no change; Child-Pugh C: reduce dosing to once per day; grade 1 (AST/ALT 1.1-3× the upper limit of normal [ULN]), without an increase in total biliru- bin above 2× ULN: no change; grade 2, first occurrence (AST/ALT 3.1-5× ULN), without an increase in total bilirubin above 2× ULN: no change; if grade 2 persists, hold; after resolution to baseline or grade 1, resume at the next lower dose level; grade 2, recurrent (AST/ALT 3.1-5× ULN), without an increase in total bilirubin above 2× ULN: hold; after resolution to baseline or grade 1, resume at the next lower dose level; grade 2 or 3 (AST/ALT 3.1-20× ULN) with total bilirubin greater than 2× ULN, in the absence of cholestasis: discontinue; grade 4 (AST/ALT >20× ULN): discontinue Available forms Tablets 50, 100, 150, 200 mg Administer
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• With food at the same time every day
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• Swallow tablets whole; do not chew, crush, or split. Do not take if broken, cracked
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• If a dose is missed, do not replace missed dose; resume with the next scheduled daily dose
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