Drug Detail:Abemaciclib (Abemaciclib [ a-bem-a-sye-klib ])
Drug Class: CDK 4/6 inhibitors
Usual Adult Dose for 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
Comments:
- 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.
Comments: Monitor ALT, AST, and serum bilirubin prior to therapy initiation, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated.
Dose Adjustments
- Discontinue therapy in patients unable to tolerate 50 mg 2 times a day.
- Refer to the manufacturer product information aromatase inhibitor or fulvestrant for dose modifications.
DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
STARTING DOSE:
- Combination therapy: 150 mg 2 times a day
- Monotherapy: 200 mg orally 2 times a day
- Combination therapy: 100 mg orally 2 times a day
- Monotherapy: 150 mg orally 2 times a day
- Combination therapy: 50 mg orally 2 times a day
- Monotherapy: 100 mg orally 2 times a day
- 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 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 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.
Precautions
CONTRAINDICATIONS:
- None
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
Other Comments
Administration Advice:
- Instruct patients not to ingest drug tablets if they are broken, cracked, or otherwise not intact.
- Instruct patients to take their doses at approximately the same times every day with or without food.
- Advise patients to swallow the drug tablets whole and not to chew, crush, or split them before swallowing.
- In the event of a vomited or missed dose, direct patients to skip that dose and to take the next dose at the usual time.
Storage Requirements:
- Store at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit); excursions permitted to 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit).
General:
- There is no known antidote for this drug; use general supportive measures to treat overdose.
Monitoring:
- Cardiovascular: Signs/symptoms of venous thrombosis and pulmonary embolism (during treatment)
- Hematologic: CBC (prior to initiation of this drug, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated)
- Hepatic: ALT, AST, and serum bilirubin (prior to initiation of this drug, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated)
- Respiratory: Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis.
Patient Advice:
- Avoid eating and drinking grapefruit products while taking this drug.
- This drug may cause side effects such as dizziness; avoid potentially dangerous activities such as driving and operating machinery until you know how this drug affects you.
- Advise patients to immediately report new or worsening respiratory symptoms.
Frequently asked questions
- Is Verzenio better than Ibrance?
- How long do you take Verzenio for?
- Can you take Verzenio after Ibrance fails?
- How long does it take Verzenio to work?
- Is Verzenio (abemaciclib) a chemo drug?
- How effective is Verzenio?
