Abemaciclib is a drug used to treat advanced or metastatic breast cancer in postmenopausal women. It is prescribed in combination with an aromatase inhibitor to postmenopausal patients who are hormone receptor positive and human epidermal growth factor receptor 2 negative. It is also given in combination with fulvestrant in advanced or metastatic breast cancer in women with disease progression following endocrine therapy and prior chemotherapy in the metastatic disease.

Abemaciclib Dose in adults

Initial endocrine-based therapy in postmenopausal women:

150 mg twice daily along with aromatase inhibitors (Monarch 3 trial). It should be continued till disease progression or the drug is no more tolerated.

Dose of abemaciclib following endocrine therapy and before the initiation of chemotherapy:

200 mg twice daily as monotherapy (Monarch 1). It should be continued until disease progression or until the drug cannot be tolerated.

Progressive disease on prior endocrine therapy:

150 mg twice daily in combination with fulvestrant ( a steroidal estrogen receptor antagonist) ( and a gonadotropin-releasing hormone agonist in premenopausal women) until disease progression or the drug cannot be tolerated.

Abemaciclib Dose in Childrens

Not applicable

Pregnancy risk category X

• It is unknown if Abemaciclib can be used in pregnancy. 
• Animal studies have shown that Abemaciclib can cause harm to fetuses. 
• Major birth defects were found in 2 to 4% of pregnancies that were clinically diagnosed.
• The rate of miscarriages was between 15 and 20%.
• Effective contraception should be used by women of reproductive age during and for at least three weeks following the last dose abemaciclib.
• It can also cause infertility among males, according to animal studies.

Use of abemaciclib in lactating women

• The manufacturer warns breastfeeding mothers not to use abemaciclib during treatment or for at least 3 weeks after their last dose due to the possible adverse effects on neonates.

Abemaciclib Dose in Liver Disease:

CrCl of more than 30 mL/minute: Dose adjustment is not necessary.

CrCl of less than 30 mL/minute: The manufacturer has not provided any information on dose adjustment. End-stage renal disease: No information is available (The drug has not been studied in patients with end-stage renal disease).

Abemaciclib Dose in Renal Disease:

• Mild to moderate Liver disease (Child class A or B):
  • No dose adjustment is necessary
• Moderately-severe Liver disease (Child class C):
  • Reduce the dose to once daily If the patient develops hepatotoxicity while on treatment:
    • Discontinue abemaciclib treatment in Grade 4 hepatotoxicity and Grade 2 or 3 with Bilirubin more than 2 times the ULN.
    • No dose adjustment is necessary in Grade 1 or 2 hepatotoxicity without an increase in the serum bilirubin of more than 2 times the ULN.
    • In patients with persistent Grade 2 or 3 hepatotoxicity without an increase in the Bilirubin of more than 2 times the ULN should withhold abemaciclib until the normalization of AST and ALT to baseline or to Grade 1.
    • Grade 1 hepatotoxicity: AST and ALT more than the upper limits of normal to less than 3 times the ULN.
    • Grade 2: AST and ALT more than 3 to 5 times the ULN
    • Grade 3: AST and ALT more than 5 to 20 times the ULN
    • Grade 4: AST and ALT more than 20 times the ULN

Common side effects of abemaciclib:

• CNS:
  • Fatigue, lethargy, headache, and dizziness.
• Skin:
  • Alopecia and hair loss
• Endocrine:
  • Weight loss
• Gastrointestinal:
  • Diarrhea, nausea, anorexia, abdominal pain, vomiting, constipation, stomatitis, distaste, and dry mouth.
• Hematologic:
  • Anemia, lymphopenia, neutropenia, thrombocytopenia, and leukopenia
• Hepatic:
  • Increase ALT and AST
• Neuromuscular:
  • Arthralgia
• Renal:
  • Increased creatinine levels
• Miscellaneous:
  • Infections, cough, fever, venous thromboembolism, and dehydration.

Contraindication to Abemaciclib include:

No contraindications have been listed in the manufacturer's labeling.

Warnings & Precautions

• Suppression of bone marrow:
  • Anemia, thrombocytopenia and leukopenia are all common, but neutropenia is more common. 
  • A grade 3 neutropenia may lead to neutropenic sepsis, which can cause death.
  • Blood CP (CBC) should first be notified at least twice a month, then monthly for the second two months.
  • Then, as indicated, continue to advise as needed. In severe cases, treatment should be stopped and restarted when the count is stable.
• Gastrointestinal toxicities:
  • Most patients experience diarrhea, which can lead to dehydration. 
  • A gastrointestinal infection can also cause diarrhea. 
  • Mild to moderate diarrhea can occur within 6-8 days, while severe diarrhea is usually experienced after 10-12 days.
  • At the first sign of loose stool, patients should increase fluid intake. 
  • In severe cases, patients may need to reduce or withhold their dose. Oral rehydration therapy is also available.
• Hepatotoxicity:
  • Patients may develop hepatotoxicity of grade 3 or higher after 2 to 3 months.
  • This may disappear in two to four weeks. Patients may have to stop or withhold the drug until the liver enzymes are normalized.
  • As with Blood CP, liver function tests should be performed at weekly intervals during the first two months, then monthly thereafter.
• Venous thromboembolism
  • Abemaciclib has been used to treat deep vein thrombosis and other conditions such as pulmonary embolism, pulmonary embolisms, subclavian, axillary, and pelvic vein thrombosis.  

Read Verzinio (Abemaciclib) package insert here

Monitoring Parameters:

Blood CBC, AST, ALT, and bilirubin should be monitored twice monthly for the past two months, then monthly for the next two months, and then as indicated. All patients should be monitored for loose stools and signs & symptoms of dehydration and venous thromboembolism. Female patients in the reproductive age group should have a pregnancy test done prior to initiating therapy with abemaciclib (verzinio).

How to Administer Abemaciclib?

• Take the tablets whole with or without food.
• A high fat diet and grapefruit increases the drug levels.
• It should not be taken with concomitant administration of grapefruit.

Mechanism of action of Abemaciclib:

• It blocks cyclin dependent protein kinase 4/6, which stops cell proliferation at the G phase of the cell cycle. 
• Abemaciclib can be used alone or combined with endocrine treatment to reduce tumor size.

Protein binding is 93 - 96% Metabolism is via hepatic Bioavailability is around 45%. Half-life elimination is around 18 hours Time to peak plasma concentration is 8 hours Excretion is via feces

International Brands of Abemaciclib:

Verzinio

Prices in the US: Tablets (Verzenio Oral):

50 mg: $241.74 per tablet 100 mg: $241.74 per tablet 150 mg: $241.74 per tablet 200 mg: $241.74 per tablet

Abemaciclib Brands in Pakistan:

Verzinio is not available in Pakistan

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