Verzenio (abemaciclib) is a prescription medication used to treat specific types of breast cancer, particularly hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer, and certain high-risk early breast cancers. Patients taking Verzenio often experience diarrhea as a common side effect. This side effect typically manifests within the first month of treatment and can range from mild to severe. Managing this side effect effectively is an important part of the treatment journey.
How Verzenio Works
Verzenio functions as a cyclin-dependent kinase (CDK) 4/6 inhibitor, a type of targeted therapy. CDK4 and CDK6 are proteins that regulate the cell cycle, mediating progression from the G1 phase (preparation for DNA synthesis) to the S phase (DNA replication).
In many cancers, CDK4 and CDK6 become overactive, leading to uncontrolled cell division and tumor growth. Verzenio works by blocking the activity of these overactive CDK4/6 proteins. By inhibiting CDK4/6, the drug prevents cancer cells from advancing through the cell cycle, thereby slowing down their growth and spread. This targeted approach halts the proliferation of cancer cells that rely on these kinases.
The Drug’s Impact on Gut Cells
While Verzenio is designed to target cancer cells, it also affects other rapidly dividing cells in the body. The intestinal epithelial cells lining the gastrointestinal (GI) tract are among the fastest-renewing cells in the body, constantly dividing to maintain gut integrity and function.
Verzenio’s inhibition of CDK4/6 in these healthy gut cells disrupts their normal rapid turnover process. This disruption can lead to inflammation of the intestinal lining and impaired absorption of water and nutrients. Studies in preclinical models have shown that abemaciclib can cause morphological changes in the gut, such as the proliferation of crypt cells, loss of goblet cells, and degeneration of enterocytes. These changes can result in increased fluid secretion into the intestines and reduced fluid reabsorption, leading to diarrhea. The exact mechanism may involve secondary pharmacological targets beyond just CDK4/6 inhibition, as other CDK4/6 inhibitors do not cause diarrhea to the same extent.
Strategies for Managing Diarrhea
Most patients experience Verzenio-induced diarrhea within the first month, making management an important aspect of treatment. At the first sign of diarrhea, start antidiarrheal therapy, such as loperamide (Imodium), and increase oral fluid intake. Loperamide can be taken at the onset of symptoms, with typical adult dosing for acute diarrhea being 4 milligrams initially, followed by 2 milligrams after each loose bowel movement, not exceeding 16 milligrams per day. Patients should have over-the-counter antidiarrheal medication readily available before starting Verzenio.
Dietary modifications can also help manage symptoms. Following a BRAT diet (bananas, rice, applesauce, toast) is beneficial, as these foods are easy to digest. Avoiding high-fiber foods, fatty foods, dairy products, caffeine, and spicy foods can help reduce gut irritation. Drink at least 8-10 glasses of clear fluids and electrolyte-rich drinks daily to prevent dehydration. It is crucial to communicate with the healthcare team for personalized advice and potential dose adjustments, as 19% to 26% of patients may require a dose interruption and 13% to 23% may need a dose reduction due to diarrhea.
Recognizing Serious Symptoms
While common, Verzenio-induced diarrhea can become severe and require immediate medical attention. Be aware of warning signs that indicate the diarrhea is worsening or leading to complications. Symptoms such as dizziness, decreased urination, or a dry mouth can signal dehydration, which can be a serious consequence of prolonged or severe diarrhea.
Other serious symptoms that warrant contacting a doctor or seeking emergency care include fever, severe abdominal pain, or the presence of blood in the stool. Diarrhea that does not improve within 24 hours despite using antidiarrheal medication and increasing fluid intake, or diarrhea that worsens, also indicates a need for medical evaluation. Healthcare providers may recommend temporarily stopping Verzenio, adjusting the dose, or prescribing other medications if these serious symptoms arise.