Kisqali

Kisqali is used to treat certain types of early, advanced, or metastatic HR-positive HER2-negative breast cancer in combination with an endocrine-based agent. It is an oral tablet taken once daily for 21 consecutive days out of a 28-day cycle.

Kisqali (ribociclib) is a CDK4/6 inhibitor that works by blocking enzymes driving cell division. Combined with hormonal therapy such as letrozole or fulvestrant, it slows growth and shrinks estrogen receptor-positive breast tumors.

Kisqali gained FDA approval on March 13, 2017.

Kisqali (ribociclib) is a kinase inhibitor approved for adults:

• In combination with an aromatase inhibitor (such as letrozole) for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence
• For HR-positive, HER2-negative advanced or metastatic breast cancer in combination with: an aromatase inhibitor (such as letrozole) as the first endocrine-based therapy, or fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.

Kisqali is available in combination with letrozole as Kisqali Femara Co-Pack.

Take Kisqali exactly as your healthcare provider tells you.

• Do not change your dose or stop taking Kisqali without talking to your healthcare provider.
• Kisqali is usually taken 1 time a day for 21 days, followed by 7 days off treatment. This is called a cycle of treatment. Kisqali is usually taken in combination with an aromatase inhibitor or fulvestrant.
• Kisqali may be taken with or without food.
• Swallow Kisqali tablets whole. Do not chew, crush, or split Kisqali tablets before swallowing them.
• Take Kisqali each day at about the same time, preferably in the morning.
• Do not take any Kisqali tablets that are broken, cracked, or that look damaged.

Before taking Kisqali, tell your healthcare provider about all of your medical conditions, including if you have:

• Any heart problems, including heart failure, irregular heartbeats, and QT prolongation
• Ever had a heart attack
• A slow heartbeat (bradycardia)
• High blood pressure that is not controlled
• Decreased thyroid gland function (hypothyroidism)
• Problems with the amount of potassium, calcium, phosphorus, or magnesium in your blood
• A fever, chills, or any other signs or symptoms of infection
• Liver problems
• Kidney problems
• Plans to become pregnant, or are pregnant
• Plans to breastfeed or are breastfeeding.

Pregnancy

Kisqali can harm your unborn baby.

• If you can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Kisqali.
• Females who can become pregnant and who take Kisqali should use effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali.
• Talk to your healthcare provider about birth control methods that may be right for you during this time.

If you become pregnant or think you are pregnant, tell your healthcare provider right away.

Breastfeeding

It is not known if Kisqali passes into your breast milk. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali.

Common side effects

The most common side effects of Kisqali in adults with early breast cancer are:

• Decreased white blood cell counts
• Decreased red blood cell counts
• Increased liver function tests
• Infections
• Increased kidney function tests
• Decreased platelet counts
• Nausea
• Headache
• Tiredness.

The most common side effects of Kisqali in adults with advanced or metastatic breast cancer are:

• Decreased white blood cell counts
• Decreased red blood cell counts
• Increased liver function tests
• Infections
• Nausea
• Increased kidney function tests
• Tiredness
• Decreased platelet counts
• Diarrhea
• Vomiting
• Headache
• Constipation
• Hair loss
• Cough
• Rash
• Back pain
• Low blood sugar level.

Serious side effects and warnings

Kisqali may cause the following serious side effects.

Lung problems

Kisqali may cause severe or life-threatening inflammation of the lungs during treatment that may lead to death. Tell your healthcare provider right away if you have any new or worsening symptoms, including:

• trouble breathing or shortness of breath
• cough with or without mucus
• chest pain.

Severe skin reactions

Kisqali may cause a skin rash. Tell your healthcare provider or get medical help right away if you get a severe rash; your rash worsens; red skin; flu-like symptoms; skin pain or burning; blistering of the lips, eyes, or mouth; blisters on the skin; or skin peeling, with or without fever.

Heart rhythm problems (QT prolongation)

Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death.

• Your healthcare provider should check your heart and do blood tests before and during treatment with Kisqali.
• Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you feel dizzy or faint.

Liver problems

Kisqali can cause serious liver problems. Your healthcare provider should do blood tests to check your liver before and during treatment with Kisqali. Tell your healthcare provider right away if you get any of the following signs and symptoms of liver problems:

• yellowing of your skin or the whites of your eyes (jaundice)
• dark or brown (tea-colored) urine
• feeling very tired
• loss of appetite
• pain on the upper right side of your stomach area (abdomen)
• bleeding or bruising more easily than normal.

Low white blood cell counts (neutropenia)

Low white blood cell counts are very common during treatment with Kisqali and may result in infections that may be severe. Your healthcare provider should check your white blood cell counts before and during treatment with Kisqali. Tell your healthcare provider right away if you have signs and symptoms of low white blood cell counts or infections, such as fever and chills.

Fertility in males

Kisqali may cause fertility problems in males, which may affect your ability to father a child. Talk to your healthcare provider if this is a problem for you.

Notes

Your healthcare provider may tell you to decrease your dose, temporarily stop, or completely stop taking Kisqali if you develop certain serious side effects during treatment with Kisqali.

Tell your healthcare provider if you have any side effect that bothers you or that do not go away. These are not all of the possible side effects of Kisqali. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Kisqali (ribociclib) works by blocking two enzymes called cyclin-dependent kinases 4 and 6 (CDK4/6). These enzymes play a key role in cell growth and division by adding phosphate groups to a protein called retinoblastoma (pRb). Laboratory research shows that Kisqali reduces pRb phosphorylation in breast cancer cells, which stops them from dividing and slows their growth. Studies in animals have confirmed that Kisqali can shrink tumors.

In studies using estrogen receptor-positive breast cancer samples from patients, combining ribociclib with hormonal therapy (such as letrozole or fulvestrant) worked better than either treatment alone, resulting in greater tumor shrinkage.

Kisqali belongs to the drug class called kinase inhibitors. It may also be called a CDK 4/6 inhibitor.

Adult Dose of Kisqali for Early Breast Cancer

• Starting dose: 400 mg orally (two 200 mg tablets) 1 time a day for 21 consecutive days, followed by 7 days off treatment.

Adult Dose of Kisqali for Advanced or Metastatic Breast Cancer

• Starting dose: 600 mg orally (three 200 mg tablets) 1 time a day for 21 consecutive days, followed by 7 days off treatment.

If you miss a dose of Kisqali or vomit after taking a dose of Kisqali, do not take another dose on that day. Take your next dose at your regular time.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take:

• CYP3A inhibitors: Avoid concomitant use of Kisqali with strong CYP3A inhibitors, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and grapefruit. If strong inhibitors cannot be avoided, reduce the dose of Kisqali.
• CYP3A4 inducers, such as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids. Avoid concomitant use.
• CYP3A substrates, such as midazolam, felodipine, buspirone, lovastatin, eletriptan, sildenafil, simvastatin, triazolam, dexamethasone, antipyrine, quinine: The dose of CYP3A substrates may need to be reduced when given concurrently with Kisqali.
• QT-prolonging drugs, such as haloperidol, ziprasidone, quetiapine, thioridazine, olanzapine, risperidone, droperidol, amiodarone, sotalol, dofetilide, procainamide, quinidine, flecainide, macrolides, fluoroquinolones. Avoid concomitant use.
• Tamoxifen: Kisqali is not for use with tamoxifen because it can increase your risk of heart rhythm problems (QT prolongation).

Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. See the Kisqali Prescribing Information for a full list of interactions.

Store at room temperature between 68°F and 77°F (20°C and 25°C) for up to 2 months.

• Store in the original blister package to protect from moisture.

Keep out of the reach of children.

Active ingredient: ribociclib

Inactive ingredients: colloidal silicon dioxide, crospovidone, hydroxypropyl cellulose, magnesium stearate, and microcrystalline cellulose.

Film-coating: iron oxide black, iron oxide red, lecithin (soya), polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide, and xanthan gum.

Available as Kisqali 200 mg tablets.

Kisqali is manufactured by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936.