abemaciclib

High Alert

Adjuvant treatment of hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence (in combination with tamoxifen or an aromatase inhibitor).
Advanced or metastatic HR-positive, HER2-negative breast cancer in patients with disease progression following endocrine therapy (in combination with fulvestrant).
HR-positive, HER2-negative advanced or metastatic breast cancer in patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting (as monotherapy).
HR-positive, HER2-negative advanced or metastatic breast cancer (as initial endocrine-based therapy in combination with an aromatase inhibitor).

Action ⬆ ⬇

Inhibits kinases (cyclin-dependent kinases 4 and 6) that are part of the signaling pathway for cell proliferation.

Therapeutic effects:

Improved survival and decreased spread of breast cancer.

Pharmacokinetics ⬆ ⬇

Absorption: 45% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: 96%.

Metabolism/Excretion: Primarily metabolized in the liver by CYP3A4 to several active metabolites; 81% excreted in feces, 3% in urine.

Half-Life: 18.3 hr.

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	8 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment (CCr <30 mL/min);
Severe hepatic impairment (↓ dose);
History of venous thromboembolism;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, VENOUS THROMBOEMBOLISM

Derm: alopecia, pruritus, rash

GI: ↓appetite, ↑liver enzymes, abdominal pain, constipation, diarrhea, dry mouth, nausea, stomatitis, vomiting, HEPATOTOXICITY

GU: ↑serum creatinine, ↓fertility (males)

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia

Metab: ↓weight

MS: arthralgia

Neuro: dizziness, dysgeusia, fatigue, headache

Resp: cough, INTERSTITIAL LUNG DISEASE/PNEUMONITIS

Misc: fever, infection

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inhibitors, including itraconazole or ketoconazole may ↑ abemaciclib levels and risk of toxicity; avoid concurrent use with ketoconazole; ↓ abemaciclib dose when using other strong CYP3A4 inhibitors (resume original dose after 3–5 half-lives of offending drug have passed following discontinuation).
Strong CYP3A inducers, including rifampin may ↓ abemaciclib levels and its effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): With fulvestrant, tamoxifen, or an aromatase inhibitor: 150 mg twice daily; for early breast cancer, continue for 2 years or until disease progression or unacceptable toxicity; for advanced or metastatic breast cancer, continue until disease progression or unacceptable toxicity. As monotherapy: 200 mg twice daily; continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A inhibitor (other then ketoconazole): 100 mg twice daily (with fulvestrant, tamoxifen, an aromatase inhibitor, or as monotherapy); if dose already at 100 mg twice daily due to adverse reactions, ↓ dose to 50 mg twice daily; for early breast cancer, continue for 2 years or until disease progression or unacceptable toxicity; for advanced or metastatic breast cancer, continue until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment (Child-Pugh C): With fulvestrant, tamoxifen or an aromatase inhibitor: 150 mg once daily; for early breast cancer, continue for 2 years or until disease progression or unacceptable toxicity; for advanced or metastatic breast cancer, continue until disease progression or unacceptable toxicity. As monotherapy: 200 mg once daily; continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A inhibitor (other than ketoconazole): 100 mg once daily (with fulvestrant, tamoxifen, an aromatase inhibitor, or as monotherapy); if dose already at 100 mg once daily due to adverse reactions, ↓ dose to 50 mg once daily; for early breast cancer, continue for 2 years or until disease progression or unacceptable toxicity; for advanced or metastatic breast cancer, continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 50 mg; 100 mg; 150 mg; 200 mg

Assessment ⬆ ⬇

Monitor for diarrhea, may result in dehydration and infection. Grade 1: no dose modification required. Grade 2: If diarrhea resolves in 24 hrs to ≤Grade 1, suspend therapy until resolution. No dose reduction required. Grade 2 that persists or recurs after resuming same dose despite maximum supportive measures: Hold dose until diarrhea resolves to ≤Grade 1. Resume at next lower dose. Grade 3 or 4 diarrhea or diarrhea that requires hospitalization, hold abemaciclib until diarrhea resolves to ≤Grade 1, then resume at next lower dose.
Monitor for signs and symptoms of venous thrombosis and pulmonary embolism and treat as needed.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC before starting, every 2 wk for first 2 mo, monthly for next 2 mo, and as clinically indicated. Grade 1 or 2 neutropenia: No dose reduction required. Grade 3: Hold dose until resolves to ≤Grade 2. Grade 3 recurrent or Grade 4: Hold therapy until resolved to ≤ Grade 2. Resume at next lower dose.
- Monitor ALT, AST, and serum bilirubin prior to starting therapy, every 2 wk for first 2 mo, monthly for next 2 mo, and as clinically indicated. If Grade 1 (>ULN to 3 times ULN), Grade 2 (>3.0 to 5.0 times ULN, without ↑ in total bilirubin >2 times ULN): no dose reduction required. If persistent or recurrent Grade 2, or Grade 3 (>5.0–20.0 × ULN), without ↑ in total bilirubin above 2 × ULN: Hold therapy until toxicity resolves to baseline or Grade 1. Resume at next lower dose. If elevation in AST and/or ALT >3 × ULN with total bilirubin >2 × ULN, in the absence of cholestasis or Grade 4 (>20.0 × ULN): discontinue therapy.
- May cause ↑ serum creatinine without glomerular function being affected. Monitor BUN, cystatin C, or calculated glomerular filtration rate to determine impaired renal function.

Implementation ⬆ ⬇

Dose Reduction Recommendations:Starting dose, 150 mg twice daily for therapy in combination with fulvestrant or an aromatase inhibitor OR 200 mg twice daily for monotherapy. 1st dose reduction, 100 twice daily for combination therapy OR 150 mg twice daily for monotherapy. 2nd dose reduction, 50 mg twice daily for combination therapy OR 100 mg twice daily for monotherapy. 3rd dose reduction, discontinue combination therapy OR 50 mg twice daily for monotherapy.
PO: Administer twice daily, at the same times each day, without regard to food. DNC: Swallow tablets whole; do not crush, break, or chew.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take abemaciclib at the same times each day as directed. If patient vomits or misses a dose, omit dose and take next dose as scheduled. Do not ingest tablets that are broken, cracked, or not intact. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient that at first sign of diarrhea, start antidiarrheal therapy (loperamide), increase oral fluids, and notify health care professional.
Advise patient to notify health care professional if signs and symptoms of infection (fever, chills), liver problems (feeling very tired, pain on upper right side of abdomen, loss of appetite, unusual bleeding or bruising), or venous thromboembolism (pain or swelling in arms or legs, shortness of breath, chest pain, rapid breathing, rapid heart rate) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 3 wk after last dose of therapy. Inform male patient may impair fertility.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇