Abemaciclib

• Verzenio

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia occurred in nearly half of patients treated with abemaciclib in combination with fulvestrant and in over one-third of patients treated with abemaciclib as a single-agent. Grade 3 or higher neutropenia has been observed in nearly one-third of patients (either as monotherapy or in combination with fulvestrant). The median time to first episode of neutropenia (>grade 3) was 29 days and the median duration of grade 3 or higher neutropenia was 15 days. Anemia, leukopenia, and thrombocytopenia have also been observed. Monitor complete blood counts prior to treatment initiation, every 2 weeks for the first 2 months, then monthly for the next 2 months, and as clinically indicated. Grade 3 or 4 neutropenia may require treatment interruption, dose reduction, or treatment delay. Febrile neutropenia has occurred rarely, and deaths due to neutropenic sepsis have been observed (case reports).

• Gastrointestinal toxicity: Diarrhea occurred in most patients treated with abemaciclib (either as monotherapy or when used in combination with fulvestrant). Grade 3 diarrhea has occurred. Diarrhea had been associated with dehydration and infection. The incidence of diarrhea was higher during the initial month of abemaciclib; the median time to onset of the first diarrhea event was 6 days and the median duration of grade 2 and 3 diarrhea was 9 days and 6 days, respectively. Patients should initiate antidiarrheal medications (eg, loperamide) and increase oral fluid intake at the first sign of loose stools. Diarrhea may require treatment interruption, and/or dose reduction. Nausea and vomiting (usually mild) may occur; stomatitis has also been reported.

• Hepatotoxicity: Grade 3 or higher increases in ALT and AST have been reported with abemaciclib. The median time to onset of grade 3 or higher ALT elevation was 57 days and the median time to resolution (to below grade 3) was 14 days; the median time to onset of grade 3 or higher AST elevation was 185 days and the median time to resolution was 13 days. Monitor liver function tests prior to treatment initiation, every 2 weeks for the first 2 months, then monthly for the next 2 months, and as clinically indicated. Hepatotoxicity may require treatment interruption, dose reduction, treatment delay, and/or discontinuation.

• Thromboembolism: VTE events have been reported in patients treated with abemaciclib in combination with fulvestrant. VTEs reported included deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis, some VTEs were fatal. Monitor for signs and symptoms of venous thrombosis and pulmonary embolism; manage as medically appropriate.

Disease-related concerns:

• Hepatic impairment: Reduced initial doses are recommended for preexisting severe impairment (Child-Pugh class C).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Based on the mechanism of action and data from animal reproduction studies, use during pregnancy may cause fetal harm. Pregnancy testing is recommended prior to treatment in females of reproductive potential. Women of reproductive potential should use effective contraception during therapy and for at least 3 weeks after the last abemaciclib dose. Abemaciclib may impair fertility in males of reproductive potential (based on findings in animal studies).

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• CYP3A Inhibitors: Avoid concomitant use of ketoconazole. Reduce the abemaciclib dose with concomitant use of other strong CYP3A inhibitors.1

• CYP3A Inducers: Avoid concomitant use of strong CYP3A inducers.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• CYP3A Inhibitors: Avoid concomitant use of ketoconazole. Reduce the abemaciclib dose with concomitant use of other strong CYP3A inhibitors.1

• CYP3A Inducers: Avoid concomitant use of strong CYP3A inducers.1

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• It is common to have diarrhea when taking abemaciclib. Sometimes, diarrhea has been very bad and may cause dehydration or an infection. Most of the time, diarrhea happened during the first month of treatment. If you get diarrhea, follow what your doctor told you to do. If you are not sure what to do if you get diarrhea, talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
• Talk with your doctor before getting any vaccines. Use with this medicine may either raise the chance of an infection or make the vaccine not work as well.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Blood clots have happened with abemaciclib. Sometimes, these blood clots have been deadly. Talk with the doctor.
• Avoid grapefruit and grapefruit juice.
• This medicine may affect being able to father a child. Talk with the doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting this medicine. Talk with your doctor.
• Use birth control that you can trust to prevent pregnancy while taking abemaciclib and for at least 3 weeks after your last dose.
• If you get pregnant while taking this medicine or within 3 weeks after your last dose, call your doctor right away.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Very loose stools (diarrhea).
• Loose stools (diarrhea) that will not go away.
• Feeling very tired or weak.
• Any unexplained bruising or bleeding.
• Fast breathing.
• A fast heartbeat.
• Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take abemaciclib or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to abemaciclib. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: November 1, 2017

Contraindications

None

Cautions

Also see Dosage Modifications for guidance on dose interruption and/or reduction, and monitoring for the cautions listed below

Venous thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, inferior vena cava thrombosis) were reported in patients receiving abemaciclib and fulvestrant; monitor for signs and symptoms of venous thrombosis and pulmonary embolism and appropriately treat

May cause fetal harm; advise women of reproductive potential to use effective contraception (see Pregnancy)

Hepatotoxicity

• Increased transaminases were observed in clinical trials
• In patients who had grade ≥3 ALT elevation, median time-to-onset was 57 days; whereas, grade <3 was 14 days
• In patients who had grade ≥3 AST elevation, median time-to-onset was 185 days; whereas, grade <3 was 13 days
• Monitor liver function tests (LFTs) at baseline, q2Weeks for first 2 months, monthly for the next 2 months, and as clinically indicated

Neutropenia

• Neutropenia and febrile neutropenia observed in clinical trials
• In patients with grade >3 neutropenia, median time time-to-onset was 29 days and median duration was 15 days
• Monitor complete blood cell counts at baseline, q2Weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated

Diarrhea

• Diarrhea reported in clinical trials; episodes of diarrhea have been associated with dehydration and infection
• Initiate antidiarrheal therapy (eg, loperamide) and increase oral fluids if loose stools appear

Drug interaction overview

• Abemaciclib is metabolized to several metabolites primarily by CYP3A4
• Strong CYP3A4 inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity
• Ketoconazole: Avoid coadministration
• Other strong CYP3A inhibitors: Decrease recommended starting dose (see Dosage Modifications)
• Strong CYP3A inducers: Avoid coadministration

Grapefruit and grapefruit juice may interact with abemaciclib and lead to unwanted side effects. Avoid the use of grapefruit products while taking abemaciclib.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe or ongoing diarrhea;

• pain or burning when you urinate;

• liver problems--right-sided upper stomach pain, loss of appetite, easy bruising or bleeding, feeling very tired; or

• low blood cell counts--fever, chills, flu-like symptoms, cough with mucus, mouth sores, skin sores, pale skin, cold hands and feet, feeling light-headed or short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

• nausea, vomiting, stomach pain;

• loss of appetite;

• feeling tired;

• headache; or

• low blood cell counts.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Medicines used to treat cancer are very strong and can have many side effects. Before receiving abemaciclib, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take abemaciclib exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

abemaciclib comes with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Swallow the capsule whole. Do not open, crush, break, or chew it.

You may take abemaciclib with or without food.

Do not eat grapefruit or drink grapefruit juice while you are using abemaciclib.

Dosing

The dose of abemaciclib will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of abemaciclib. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For advanced or metastatic breast cancer with fulvestrant:
    • Adults—At first, 150 milligrams (mg) two times a day. Your doctor may adjust your dose as needed or tolerated.
    • Children—Use and dose must be determined by your doctor.
  • For advanced or metastatic breast cancer used alone:
    • Adults—At first, 200 milligrams (mg) two times a day. Your doctor may adjust your dose as needed or tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of abemaciclib, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose or vomit after you take abemaciclib, do not take another dose on the same day. Wait until your next dose and take it when you normally would.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• chest pain
• chills
• confusion
• cough
• decreased urination
• diarrhea
• difficulty breathing
• dizziness
• dry mouth
• fainting
• fever
• hoarseness
• increased heart rate
• irregular heartbeat
• lightheadedness
• lower back or side pain
• pain in the chest, groin, or legs, especially the calves
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• rapid breathing
• rapid weight gain
• severe, sudden headache
• slurred speech
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sunken eyes
• swollen glands
• thirst
• tingling of the hands or feet
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vision changes
• wrinkled skin

• Blurred vision
• clay-colored stools
• dark urine
• decreased appetite
• fast heartbeat
• general feeling of discomfort or illness
• itching
• loss of appetite
• nausea
• numbness or tingling in the face, arms, or legs
• rapid, shallow breathing
• severe headache
• skin rash
• stomach pain or tenderness
• swelling of the feet or lower legs
• thickening of bronchial secretions
• trouble speaking or walking
• vomiting
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Change in taste
• dry mouth
• loss of taste
• loss or thinning of hair
• swelling or inflammation of the mouth

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Loose stools (diarrhea).
• Feeling tired or weak.
• Upset stomach or throwing up.
• Not hungry.
• Belly pain.
• Headache.
• Hard stools (constipation).
• Dry mouth.
• Mouth irritation or mouth sores.
• Joint pain.
• Change in taste.
• Dizziness.
• Hair loss.
• Weight loss.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.