AUDIENCE: Patient, Health Professional, Oncology
ISSUE: FDA is warning that palbociclib (Ibrance®), ribociclib (Kisqali®), and abemaciclib (Verzenio®) used to treat some patients with advanced breast cancers may cause rare but severe inflammation of the lungs. FDA has approved new warnings about this risk to the prescribing information and Patient Package Insert for the entire class of these cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor medicines. The overall benefit of CDK 4/6 inhibitors is still greater than the risks when used as prescribed.
BACKGROUND: CDK 4/6 inhibitors are a class of prescription medicines that are used in combination with hormone therapies to treat adults with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer that has spread to other parts of the body. CDK 4/6 inhibitors block certain molecules involved in promoting the growth of cancer cells. FDA approved palbociclib in 2015, and both ribociclib and abemaciclib in 2017. CDK 4/6 inhibitors have been shown to improve the amount of time after the start of treatment the cancer does not grow substantially and the patient is alive, called progression-free survival (See List of FDA-Approved CDK 4/6 Inhibitors below).
RECOMMENDATION:Patients should notify your health care professional right away if you have any new or worsening symptoms involving your lungs, as they may indicate a rare but life-threatening condition that can lead to death. Symptoms to watch for include:
- Difficulty or discomfort with breathing
- Shortness of breath while at rest or with low activity
Do not stop taking your medicine without first talking to your health care professional. All medicines have side effects even when used correctly as prescribed, but in general the benefits of taking these medicines outweigh these risks. It is important to know that people respond differently to all medicines depending on their health, the diseases they have, genetic factors, other medicines they are taking, and many other factors. Specific risk factors to determine how likely it is that a particular person will experience severe lung inflammation when taking palbociclib, ribociclib, or abemaciclib have not been identified.
Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease (ILD) and/or pneumonitis. Signs and symptoms may include:
- interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded.
Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe ILD and/or pneumonitis.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
Abemaciclib is used along with fulvestrant (Faslodex) to treat a certain type of hormone receptor-positive, advanced breast cancer (breast cancer that depends on hormones such as estrogen to grow) or breast cancer that has spread to other parts of the body after treatment with an antiestrogen medication such as tamoxifen (Nolvadex). Abemaciclib is also used along with anastrozole (Arimidex), exemestane (Aromasin), or letrozole (Femara) as a first treatment of hormone receptor-positive, advanced breast cancer or breast cancer that has spread to other parts of the body. Abemaciclib is also used alone to treat a certain type of hormone receptor-positive, advanced breast cancer or breast cancer that has spread to other parts of the body in people who have already been treated with an antiestrogen medication and chemotherapy. Abemaciclib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.
How should this medicine be used?
Abemaciclib comes as a tablet to take by mouth. It is usually taken twice daily with or without food. Take abemaciclib at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take abemaciclib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the tablets whole; do not split, chew, or crush them. Do not take tablets that are broken, cracked, or damaged in any way.
If you vomit after taking abemaciclib, do not take another dose. Continue your regular dosing schedule.
Your doctor may decrease your dose or temporarily or permanently stop your treatment if you experience certain side effects. This depends on how well the medication works for you and the side effects you experience. Be sure to tell your doctor how you are feeling during your treatment with abemaciclib.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking abemaciclib,
- tell your doctor and pharmacist if you are allergic to abemaciclib, any other medications, or any of the ingredients in abemaciclib tablets. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: clarithromycin (Biaxin, in Prevpac), diltiazem (Cardizem, Tiazac, others), itraconazole (Sporanox), ketoconazole (Nizoral), rifampin (Rifadin, Rimactane, in Rifater), and verapamil (Calan, Verelan, others). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with abemaciclib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have a fever, chills, or any other signs of an infection or if you have or have ever had liver or kidney disease.
- tell your doctor if you are pregnant or plan to become pregnant. You will need to take a pregnancy test before you start treatment and should use birth control to prevent pregnancy during your treatment and for at least 3 weeks after your final dose. If you become pregnant while taking abemaciclib, call your doctor immediately. Abemaciclib may harm the fetus.
- tell your doctor if you are breastfeeding or plan to breastfeed. You should not breastfeed while taking abemaciclib and for at least 3 weeks after your final dose.
- you should know that this medication may decrease fertility in men. Talk to your doctor about the risks of taking abemaciclib.
- you should know that abemaciclib often causes diarrhea, which can be severe. Your doctor will probably tell you to drink plenty of liquids and to take anti-diarrhea medication to prevent dehydration (loss of too much water from your body) when you first experience diarrhea or loose stools. Call your doctor immediately if you experience any of the following symptoms of dehydration: extreme thirst, dry mouth or skin, decreased urination, or fast heartbeat.
What special dietary instructions should I follow?
Do not eat grapefruit or drink grapefruit juice while taking this medication.
What should I do if I forget a dose?
Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Abemaciclib may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- sores on the lips, mouth, or throat
- decreased appetite
- weight loss
- hair loss
- changes in taste
- joint pain
Some side effects can be serious. If you experience any of these symptoms or any in the SPECIAL PRECAUTIONS section, call your doctor immediately:
- pain in the upper right part of the stomach
- yellowing of the skin or eyes
- loss of appetite
- bleeding or bruising easily
- pain in arms or legs
- swelling of the hands, feet, legs or ankles
- shortness of breath
- chest pain
- rapid breathing
- fast, irregular, or pounding heartbeat
- fever, chills, cough or other signs of infection
- pale skin
Abemaciclib may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests before and during your treatment to check your body's response to abemaciclib.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.