Abemaciclib (Verzenio) is a drug used to treat advanced or metastatic breast cancer in postmenopausal women. It is given in combination with an aromatase inhibitor such as Lestrozole and Anastrozole to postmenopausal patients who are HR-positive (hormone receptor-positive) and HER2-Negative (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 Children

Not applicable

Pregnancy risk category X

Data is very limited regarding its use in pregnancy. However, in animal studies, the drug was found to be toxic to the fetus. Treatment with Abemaciclib resulted in major birth defects in about 2 - 4% of the pregnancies. 

Miscarriages occurred in 15 and 20% of the pregnancies. It is therefore recommended to practice an effective contraception method during the treatment and at least 3 weeks after the last dose.

• 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 Kidney 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 in severe renal disease.
• End-stage renal disease:
  • No information is available.

Abemaciclib Dose in Liver 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 hepatotoxicities without an increase in the serum bilirubin of more than 2 times the ULN.
  • In patients with persistent Grade 2 or 3 hepatotoxicities 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.

• Grades of Hepatotoxicity:

  • 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.

Contraindications to Abemaciclib include:

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

Warnings & Precautions

• Bone marrow suppression:

The drug may result in bone marrow suppression manifesting as pancytopenia (Anemia, thrombocytopenia, and leukopenia). Neutropenia is more commonly observed with the treatment.

Severe neutropenia (grade 3 or higher) may lead to neutropenic sepsis, which can rapidly result in death if not managed timely.

Monitoring for marrow status should be done by performing Blood CP (CBC) at least twice a month initially and then monthly for the next two months. The frequency of monitoring blood CP can be delayed if no marrow-related adverse events are observed during the first few months.

In cases who develop marrow suppression, the treatment should be stopped and restarted only after the blood counts are stable

• Gastrointestinal toxicities:

Diarrhea is one of the common side effects of Abemaciclib. If not treated, it can lead to dehydration and renal failure. Diarrhea can also occur as a result of a GI infection which should be treated with appropriate antibiotics.

Mild to moderate diarrhea can occur within 6-8 days, while severe diarrhea is usually experienced after 10-12 days. Diarrhea should be managed by increasing fluid intake and either stopping the treatment temporarily (in severe cases) or reducing the dose.

• Hepatotoxicity:

Hepatic impairment may develop after a few weeks of treatment and improve when the treatment is stopped or the dose is reduced.

Once LFTs start rising, it is better to reduce the dose or withhold the treatment until the LFTs 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 use may be associated with venous thrombosis including deep vein thrombosis of the legs, pulmonary embolism, subclavian, axillary, and pelvic vein thrombosis.  

Read Verzinio (Abemaciclib) package insert here

Monitoring Parameters:

Monitor Blood CBC, AST, ALT, and bilirubin twice monthly for the first 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. Taking it with a high-fat meal and grapefruit may increase its levels in the blood. It is therefore best to avoid taking it with 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

The 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. It is not available readily in the markets.