Abemaciclib – Uses, Dosage, Side Effects, Interactions

Abemaciclib is approved to treat:

• Breast cancer that is hormone receptor-positive (HR+) and HER2 negative (HER2-). It is used:
  • In adults whose cancer is advanced or has metastasized (spread to other parts of the body). It is used:
    • With fulvestrant in adults whose cancer got worse after treatment with hormone therapy.
    • Alone in adults whose cancer got worse after treatment with hormone therapy and chemotherapy given for metastatic cancer.
    • With an aromatase inhibitor given as first-line hormone therapy in men and postmenopausal women.
  • Tamoxifen citrate or an aromatase inhibitor as adjuvant therapy in adults with early-stage breast cancer that has spread to the lymph nodes and has a high risk of coming back.

Abemaciclib is also being studied in the treatment of other types of cancer.

Contraindications

The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:

• low levels of a type of white blood cell called neutrophils
• severe liver disease
• excessive diarrhea
• abnormal liver function tests
• pregnancy
• a patient who is producing milk and breastfeeding
• lung tissue problem
• Child-Pugh class C liver impairment

Dosage

Applies to the following strengths: 50 mg; 100 mg; 150 mg; 200 mg

Breast Cancer

IN COMBINATION WITH FULVESTRANT OR AN AROMATASE INHIBITOR:
150 mg orally 2 times a day

MONOTHERAPY:
200 mg orally 2 times a day

Duration of Therapy: Until disease progression or unacceptable toxicity

• If using this drug in combination with fulvestrant on pre/perimenopausal women, treat these patients with a gonadotropin-releasing hormone agonist according to current clinical practice standards.
• When used in combination with this drug, the recommended dose of fulvestrant is 500 mg on Days 1, 15, and 29, then once monthly thereafter; refer to the manufacturer product information for fulvestrant.

Uses:

• In combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• In combination with fulvestrant for women 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 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

Renal Dose Adjustments

• Mild to Moderate Renal Impairment (CrCl 30 to 89 mL/min): No adjustment recommended.
• Severe Renal Impairment (CrCl less than 30 mL/min): Data not available
• End Stage Renal Disease: Data not available

Liver Dose Adjustments

• Mild or Moderate Hepatic Impairment (Child-Pugh A or B): No adjustment recommended.
• Severe Hepatic Impairment (Child-Pugh C): Reduce the dosing frequency to once a day.

Management of Hepatotoxicity

• Grade 1 (greater than upper limit of normal [ULN] to 3 x ULN) OR Grade 2 (greater than 3 to 5 x ULN); WITHOUT increase in total bilirubin above 2 x ULN: No adjustment recommended.
• Persistent or recurrent Grade 2 OR Grade 3 (greater than 5 to 20 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 greater than 3 x ULN WITH total bilirubin greater than 2 x ULN in the absence of cholestasis OR Grade 4 (greater than 20 x ULN): Discontinue therapy.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS

STARTING DOSE:

• Combination therapy: 150 mg 2 times a day
• Monotherapy: 200 mg orally 2 times a day

FIRST DOSE REDUCTION:

• Combination therapy: 100 mg orally 2 times a day
• Monotherapy: 150 mg orally 2 times a day

SECOND DOSE REDUCTION:

• Combination therapy: 50 mg orally 2 times a day
• Monotherapy: 100 mg orally 2 times a day

THIRD DOSE REDUCTION:

• Combination Therapy: N/A
• Monotherapy: 50 mg orally 2 times a day

HEMATOLOGIC TOXICITIES (monitor complete blood counts prior to the start of therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as indicated):

• Grade 1 or 2: No dose modification required.
• Grade 3: Suspend dose until toxicity resolves to Grade 2 or less; dose reduction not required.
• Recurrent Grade 3 OR Grade 4: Suspend dose until toxicity resolves to Grade 2 or less; resume at next lower dose.
• If blood cell growth factors (BCGF) are required: Suspend dose for at least 48 hours after the last dose of BCGF and until toxicity resolves to Grade 2 or less; resume at the next lower dose unless already performed for the toxicity that led to the use of the growth factor; use growth factor per current treatment guidelines.

DIARRHEA (at the first sign of loose stools, start treatment with antidiarrheal agents and increase intake of oral fluids):

• Grade 1: No adjustment recommended.
• Grade 2: If toxicity does not resolve within 24 hours to Grade 1 or less, suspend dose until resolution; dose reduction not required.
• Persistent or Recurrent Grade 2 (persists or recurs after resuming the same dose despite supportive measures): Suspend dose until toxicity resolves to Grade 1 or less; resume at the next lower dose.
• Grade 3 or 4 or hospitalization required: Suspend dose until toxicity resolves to Grade 1 or less; resume at next lower dose.

INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS:

• Grade 1 or 2: No adjustment recommended.
• 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 or less; resume at next lower dose.
• Grade 3 or 4: Discontinue therapy.

OTHER TOXICITIES (excluding diarrhea, hematologic toxicity, hepatotoxicity and ILD/pneumonitis):

• Grade 1 or 2: No adjustment recommended.
• Persistent or Recurrent Grade 2 that does not resolve within 7 days to baseline or Grade 1 despite supportive measures: Suspend dose until toxicity resolves to baseline or Grade 1 or less; resume at next lower dose.
• Grade 3 or 4: Suspend dose until toxicity resolves to baseline or Grade 1 or less; resume at next lower dose.

CONCOMITANT USE of OTHER STRONG CYP450 3A INHIBITORS (excluding ketoconazole):

• In patients with starting doses of 150 to 200 mg twice a day: 100 mg orally twice a day
• In patients who already had a dose reduction to 100 mg orally twice a day due to adverse reactions: 50 mg orally twice a day
• Once patient discontinues concomitant use of strong CYP450 3A inhibitor: After 3 to 5 half-lives of the inhibitor, increase the dose of this drug to the dose that was used BEFORE the strong inhibitor was started.

Side Effects

The most common

• Pruritus-9%
• Dyspepsia-8%
• Nail disorder-6% (includes nail bed disorder, nail bed inflammation, nail discoloration, nail disorder, nail dystrophy, nail pigmentation, nail ridging, nail toxicity, onychalgia, onychoclasis, onycholysis, onychomadesis)
• Lacrimation increased-6%
• Dysgeusia-5%
• nausea
• infections
• low red blood cell counts (anemia)
• decreased appetite
• headache
• hair thinning or hair loss (alopecia)
• abdominal pain
• tiredness
• low white blood cell counts (leukopenia)
• vomiting
• low platelet count (thrombocytopenia)

Common

In combination with an aromatase inhibitor (i.e., anastrozole or letrozole) for initial treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer:

• Diarrhea,
• neutropenia,
• fatigue,
• infection (most commonly upper respiratory tract infection, lung infection, and pharyngitis),
• nausea,
• abdominal pain,
• anemia,
• vomiting,
• alopecia,
• decreased appetite,
• leukopenia,
• constipation,
• rash,
• cough,
• pruritus,
• dyspnea,
• dizziness,
• decreased weight,
• influenza-like illness,
• thrombocytopenia,
• elevated S_cr concentrations (see Renal Impairment under Cautions),
• decreased lymphocyte count,
• elevated AST and/or ALT concentrations decreased platelet count.

Less Common

• Interstitial lung disease (ILD)/pneumonitis-3% (includes pneumonitis, radiation pneumonitis, interstitial lung disease, pulmonary fibrosis, organizing pneumonia, radiation fibrosis – lung, lung opacity, sarcoidosis)
• Venous thromboembolic events (VTEs)-3% (includes catheter site thrombosis, cerebral venous thrombosis, deep vein thrombosis, device-related thrombosis, embolism, hepatic vein thrombosis, jugular vein occlusion, jugular vein thrombosis, ovarian vein thrombosis, portal vein thrombosis, pulmonary embolism, subclavian vein thrombosis, venous thrombosis limb)
• infection (includes urinary tract and upper respiratory tract infection, lung infection, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis), abdominal pain, anemia, leukopenia, decreased appetite, vomiting, headache, dysgeusia, alopecia, thrombocytopenia, stomatitis, cough, pruritus, constipation, dizziness, peripheral edema, pyrexia, rash, decreased weight, myasthenia,

Drug Interactions

Pregnancy and breastfeeding

Pregnancy

Females should not take abemaciclib if you are pregnant or planning a pregnancy, as it can harm your unborn baby.

• Your healthcare provider will do a pregnancy test before you start treatment with abemaciclib.
• You should use effective birth control (contraception) during treatment with abemaciclib and for 3 weeks after the last dose of abemaciclib.
• Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with abemaciclib.

Males

• Abemaciclib may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if this is a concern for you.

Breastfeeding

Abemaciclib and breastfeeding:

• It is not known if abemaciclib passes into your breast milk. Do not breastfeed during treatment with abemaciclib and for at least 3 weeks after the last dose of abemaciclib.

References

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