During the first three weeks of the four-week cycle, you’ll take Ibrance or Kisqali every day. You take Verzenio every day as well.
The following is the dosing schedule for each drug.
Ibrance: 125 milligrams (mg) (one pill) once a day for three weeks, then one week off
Kisqali: 600 mg (three pills) three times a day for three weeks, then one week off
Verzenio: 150 mg or 200 mg (one pill) twice every day
Like any other cancer drug, CDK 4/6 inhibitors have possible side effects, but there are things you can do to manage them. “We have the ability to decrease the dose if their initial dose is high, and give them supportive medication,” says Neelam Desai, MD, a breast medical oncologist at Atrium Health Levine Cancer Institute in Matthews, North Carolina.
Neutropenia
Neutropenia is the name for a low white blood cell count, and it’s one of the most common side effects seen with CDK4/6 inhibitors — especially Ibrance and Kisqali. In a long-term safety analysis of three studies looking at Ibrance, more than 80 percent of participants who were taking Ibrance developed neutropenia. Studies of Kisqali found that neutropenia affected around 75 percent of people who took it.
Neutropenia may occur because these medications reduce many cells in your body that need CDK 4/6 proteins to divide, not just cancer cells. “These drugs can lower blood counts, including white blood cells, which are your infection-fighting blood cells,” says Dr. Desai. CDK4/6 inhibitors also reduce the number of red blood cells that carry oxygen to your tissues (causing anemia), and platelets that help your blood clot, she says.
People with neutropenia are at higher risk for infections. The most common infections linked to CDK4/6 inhibitors are respiratory tract infections, urinary tract infections, colds, and gastroenteritis (“stomach flu”), says Dr. Callahan.
You don’t have to live in a bubble, but do avoid close contact with anyone who is sick, says Callahan. Wash your hands often with warm water and soap. Watch for symptoms of infections and report them to your doctor.
“We generally tell our patients to call us if they have any signs of fever, congestion, cough, trouble breathing, burning during urination, increased frequency of urination, cloudy or foul-smelling urine, or diarrhea that’s significant,” Desai says.
Neutropenia will usually improve on its own within a few weeks. You’ll get regular blood tests to check for this side effect. If you have severe neutropenia, your doctor can lower the CDK4/6 inhibitor dose, stop it temporarily, or delay the next cycle until your white blood cell count goes back up.
Fatigue
Tiredness is a possible side effect with all three drugs. Neutropenia and anemia are two of the main causes of fatigue. For severe fatigue you may need to talk to your oncologist about lowering the medication dose.
Mild fatigue is usually easy to manage on your own at home. “People who do some sort of exercise, even if it’s a small amount but they do it consistently on most days, have a better chance of fighting the fatigue,” Desai says. “Good nutrition helps, although it’s not specifically going to increase blood counts.”
A diet rich in these foods is helpful for fighting fatigue:
Colorful fruits and vegetables like oranges, berries, spinach, and broccoli
Whole grains like oats and brown rice
Omega-3 fats from oily fish like salmon, walnuts, and flaxseeds
Lean protein from chicken, beef, beans, or tofu
Diarrhea
Any of the CDK4/6 inhibitors can cause diarrhea, but especially Verzenio, says Desai. Up to 90 percent of people who take Verzenio get diarrhea, most within the first week of treatment.
The first treatment to try is an anti-diarrhea drug like Imodium. Drink more water and other fluids to prevent dehydration. A change in diet is also helpful. “The introduction of yogurt, probiotics, or banana flakes, and the avoidance of spicy, greasy, and heavy foods works really well,” says Callahan.
Depending on how severe the diarrhea is, your doctor might lower the CDK4/6 inhibitor dose or ask you to stop taking the drug until this side effect resolves.
Liver Damage
Liver damage is a possible but rare side effect of Verzenio. Kisqali is more likely to harm the liver, as well as the bile ducts.
You’ll have tests to check your liver function before you start taking Verzenio or Kisqali. Then you’ll get tested every two weeks for the first two months on the medicine, and once a month after that. If you have abnormal results, your doctor might lower the dose, delay the next treatment cycle, pause the drug, or stop it altogether.
Lung Disease
Interstitial lung disease and pneumonitis can happen with any of the CDK4/6 inhibitors. These lung conditions are rare, affecting fewer than 1 percent of people who take these medicines, but they can be serious.
Tell your doctor right away if you have symptoms like shortness of breath or a cough. Imaging tests diagnose interstitial lung disease and pneumonitis. If you have lung disease, your doctor will have you pause the medicine right away. For severe pneumonitis or interstitial lung disease, you’ll need to permanently stop taking the CDK4/6 inhibitor.
Prolonged QT Interval
The QT interval is how long it takes an electrical signal to travel through your heart’s lower chambers and make it beat, then relax. Rarely, Kisqali prolongs the QT interval, which increases the risk for a life-threatening irregular heart rhythm.
“I don’t consider this dangerous for the overwhelming majority of patients, but it does require monitoring of EKGs [electrocardiograms],” says Callahan. Your doctor will do a baseline EKG when you start taking Kisqali, repeat it in two weeks, and then as needed, says Desai. “Once you have determined that this [medicine] is not causing any issue with the electrical activity, then you don’t need to check additional EKGs,” says Callahan.
If you do develop a prolonged QT interval, stopping Kisqali should reverse this side effect.
Blood Clots
Between 2 percent and 5 percent of people who took Verzenio in studies developed blood clots such as deep vein thrombosis (DVT) and pulmonary embolism. Because a blood clot could be very serious, report symptoms like these to your doctor:
Swelling, pain, redness, or warmth in an arm or leg
Belly or side pain
Shortness of breath
Chest pain that gets worse when you exercise or take a breath
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