abemaciclib (Rx)

Brand and Other Names:Verzenio
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 50mg
  • 100mg
  • 150mg
  • 200mg

Breast Cancer

Indicated for HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy as either monotherapy or in combination with fulvestrant

Combination therapy

  • Abemaciclib: 150 mg PO BID
  • Fulvestrant: 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter
  • Continue until disease progression or unacceptable toxicity

Monotherapy

  • 200 mg PO BID
  • Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage changes for adverse effects

  • Combined with fulvestrant
    • Starting dose: 150 mg BID
    • First dose reduction: 100 mg BID
    • Second dose reduction: 50 mg BID
    • Discontinue if unable to tolerate 50 mg BID
  • Monotherapy
    • Starting dose: 200 mg BID
    • First dose reduction: 150 mg BID
    • Second dose reduction: 100 mg BID
    • Third dose reduction: 50 mg BID
    • Discontinue if unable to tolerate 50 mg BID

Hematologic toxicities

  • Monitor complete blood cell counts before initiating therapy, q2Weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated
  • Grade 1 or 2: No dose modification required
  • Grade 3: Suspend dose until toxicity resolves to ≤Grade 2; dose reduction is not required
  • Grade 3 recurrent or Grade 4: Suspend dose until toxicity resolves to ≤Grade 2; resume at next lower dose
  • If blood cell growth factors are required, suspend dose for at least 48 hr after 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

Diarrhea

  • At first sign of loose stools, start treatment with antidiarrheal agents and increase hydration
  • No dose modification required
    • Grade 1
    • Grade 2: If toxicity does not resolve within 24 hr to ≤Grade 1, suspend dose until resolution
  • Suspend dose until toxicity resolves to baseline or Grade 1 (resume at next lower dose)
    • Persistent or recurrent Grade 2 diarrhea despite maximal supportive measures
    • Grade 3 or 4 diarrhea or requires hospitalization

Hepatotoxicity

  • Monitor ALT, AST, and serum bilirubin before initiating therapy, q2Weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated
  • No dose modification required
    • Grade 1 (ALT/AST >ULN to 3 x ULN)
    • Grade 2 (ALT/AST >3 to 5 x ULN; total bilirubin ≤2 ULN)
  • Suspend dose until toxicity resolves to baseline or Grade 1 (resume at next lower dose)
    • Persistent or recurrent Grade 2 or Grade 3 (ALT/AST >5 to 20 x ULN) without increase in total bilirubin >2 x ULN
  • Discontinue
    • Elevation in AST and/or ALT >3 x ULN with total bilirubin >2 x ULN (without cholestasis)
    • Grade 4 (ALT/AST >20 x ULN)

Other toxicities

  • No dose modification required
    • Grade 1 or 2 toxicities
  • Suspend dose until toxicity resolves to baseline or Grade 1 (resume at next lower dose)
    • Persistent or recurrent Grade 2 toxicity unresolved with maximal supportive measures within 7 days to baseline or Grade 1
    • Grade 3 or 4

Strong CYP3A inhibitors

  • Avoid concomitant use of the strong CYP3A inhibitor ketoconazole
  • Other strong CYP3A inhibitors
    • With concomitant use of other strong CYP3A inhibitors, in patients with recommended starting doses of 150 mg or 200 mg BID, reduce dose to 100 mg BID
    • In patients who have had a dose reduction to 100 mg BID, further reduce the dose to 50 mg BID
  • Discontinuing strong CYP3A inhibitor
    • If a strong CYP3A inhibitor is discontinued, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the strong inhibitor

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dose adjustment required
  • Severe (Child-Pugh C): Reduce dose frequency to once daily

Renal impairment

  • Mild or moderate (CrCl 30-89 mL/min): No dose adjustment required
  • Severe, ESRD, or dialysis: Not studied

Safety and efficacy not established

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Interactions

Interaction Checker

and abemaciclib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            Adverse effects listed are for all grades of toxicity unless otherwise noted

            >10% (Monotherapy)

            Creatinine increased (98%)

            Diarrhea (90%)

            Decreased WBCs (91%)

            Decreased neutrophil count (88%)

            Anemia (68%)

            Fatigue (65%)

            Nausea (64%)

            Decreased appetite (45%)

            Decreased lymphocyte count (42%)

            Decreased platelet count (41%)

            Abdominal pain (39%)

            Neutropenia (37%)

            Vomiting (35%)

            Infection (31%)

            ALT increased (31%)

            AST increased (30%)

            Decreased WBC, grade 3 (28%)

            Anemia (25%)

            Decreased neutrophil count, grade 3 (22%)

            Thrombocytopenia (20%)

            Diarrhea, grade 3 (20%)

            Headache (20%)

            Cough (19%)

            Neutropenia, grade 3 (19%)

            Constipation (17%)

            Leukopenia (17%)

            Arthralgia (15%)

            Dry mouth (14%)

            Stomatitis (14%)

            Weight decreased (14%)

            Decreased lymphocyte count, grade 3 (13%)

            Dysgeusia (12%)

            Alopecia (12%)

            Dizziness (11%)

            Pyrexia (11%)

            >10% (Combination Therapy)

            Creatinine increased (98%)

            Decreased WBCs (90%)

            Decreased neutrophil count (87%)

            Diarrhea (86%)

            Anemia (84%)

            Decreased lymphocyte count (63%)

            Decreased platelet count (53%)

            Neutropenia (46%)

            Fatigue (46%)

            Nausea (45%)

            Infections (43%)

            ALT increased (41%)

            AST increased (37%)

            Abdominal pain (35%)

            Decreased neutrophil count, grade 3 (29%)

            Anemia (29%)

            Leukopenia (28%)

            Decreased appetite (27%)

            Vomiting (26%)

            Neutropenia, grade 3 (24%)

            Decreased WBC, grade 3 (23%)

            Headache (20%)

            Dysgeusia (18%)

            Thrombocytopenia (16%)

            Alopecia (16%)

            Stomatitis (15%)

            Pruritus (13%)

            ALT increased (13%)

            AST increased (12%)

            Diarrhea, grade 3 (13%)

            Cough (13%)

            Dizziness (12%)

            Decreased lymphocyte count, grade 3 (12%)

            Peripheral edema (12%)

            Rash (11%)

            Pyrexia (11%)

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            Warnings

            Contraindications

            None

            Cautions

            Also see Dosage Modifications for guidance on dose interruption and/or reduction, and monitoring for the cautions listed below

            Venous thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, inferior vena cava thrombosis) were reported in patients receiving abemaciclib and fulvestrant; monitor for signs and symptoms of venous thrombosis and pulmonary embolism and appropriately treat

            May cause fetal harm; advise women of reproductive potential to use effective contraception (see Pregnancy)

            Hepatotoxicity

            • Increased transaminases were observed in clinical trials
            • In patients who had grade ≥3 ALT elevation, median time-to-onset was 57 days; whereas, grade <3 was 14 days
            • In patients who had grade ≥3 AST elevation, median time-to-onset was 185 days; whereas, grade <3 was 13 days
            • Monitor liver function tests (LFTs) at baseline, q2Weeks for first 2 months, monthly for the next 2 months, and as clinically indicated

            Neutropenia

            • Neutropenia and febrile neutropenia observed in clinical trials
            • In patients with grade >3 neutropenia, median time time-to-onset was 29 days and median duration was 15 days
            • Monitor complete blood cell counts at baseline, q2Weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated

            Diarrhea

            • Diarrhea reported in clinical trials; episodes of diarrhea have been associated with dehydration and infection
            • Initiate antidiarrheal therapy (eg, loperamide) and increase oral fluids if loose stools appear

            Drug interaction overview

            • Abemaciclib is metabolized to several metabolites primarily by CYP3A4
            • Strong CYP3A4 inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity
            • Ketoconazole: Avoid coadministration
            • Other strong CYP3A inhibitors: Decrease recommended starting dose (see Dosage Modifications)
            • Strong CYP3A inducers: Avoid coadministration
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            Pregnancy

            Pregnancy

            There are no available human data informing the drug-associated risk

            Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman

            In animal data, administration of abemaciclib during organogenesis was teratogenic and caused decreased fetal weight at maternal exposures that were similar to human clinical exposure based on AUC at the maximum recommended human dose

            Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment

            Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after the last dose

            Based on findings in animals, abemaciclib may impair fertility in males of reproductive potential

            Lactation

            Unknown if distributed in human breast milk

            Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking abemaciclib and for at least 3 weeks after the last dose

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Inhibits cyclin-dependent kinases (CDKs) 4 and 6

            These kinases are activated upon binding to D cyclins and play a crucial role in signaling pathways, which lead to cell cycle progression and cellular proliferation

            In ER-positive breast cancer cells, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation

            Absorption

            Bioavailability: 45% (200 mg single dose)

            Peak plasma time: 8 hr (200 mg single dose)

            Increase of AUC of abemaciclib and metabolites (9%) and peak plasma concentration (26%) with high-fat, high-calorie meal

            Distribution

            Protein bound: 96.3% (abemaciclib); M2 (93.4%); M18 (96.8%); M20 (97.8%)

            Vd: 690.3 L

            Metabolism

            Abemaciclib is hepatically metabolized by CYP3A4 to several metabolites (N-desethylabemaciclib [M2], hydroxyabemaciclib [M20], hydroxy-N-desethylabemaciclib [M18], and an oxidative metabolite [M1])

            M2, M18, and M20 are equipotent to abemaciclib and their AUCs accounted for 25%, 13%, and 26% of the total circulating analytes in plasma

            Elimination

            Excretion, single 150-mg dose: Feces (81%); urine (~3%)

            Majority of the dose eliminated in feces was metabolites

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            Administration

            Oral Administration

            May take with or without food

            Instruct patient to take dose at approximately the same time each day

            Missed dose: Take the next dose at its scheduled time

            Swallow table whole; do not chew, crush, or split tablets before swallowing

            Do not ingest if tablet is broken, cracked, or otherwise not intact

            Storage

            Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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