Kisqali Femara Co-Pack contains 2 different types of medicines the violet tablet contains the medicine Kisqali (ribociclib), the yellow tablet contains the medicine Femara (letrozole).

It is not known if Kisqali Femara Co-Pack is safe and effective in children.

Description

KISQALI FEMARA CO-PACK consists of ribociclib 200 mg film coated tablets copackaged with letrozole 2.5 mg tablets.

Ribociclib

KISQALI (ribociclib) is a kinase inhibitor.

Ribociclib succinate is a light yellow to yellowish brown crystalline powder. The chemical name of ribociclib succinate is: Butanedioic acid—7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl) pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (1/1).

The molecular formula for ribociclib succinate is C23H30N8O.C4H6O4 and the molecular weight is 552.64 g/mol [Free base: 434.55 g/mol].

The chemical structure of ribociclib is shown below:

KISQALI film-coated tablets are supplied for oral use and contain 200 mg of ribociclib free base (equivalent to 254.40 mg ribociclib succinate). The tablets also contain colloidal silicon dioxide, crospovidone, hydroxypropylcellulose, magnesium stearate, and microcrystalline cellulose. The film-coating contains iron oxide black, iron oxide red, lecithin (soya), polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide, and xanthan gum as inactive ingredients.

Letrozole

FEMARA (letrozole) is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis).

Letrozole is a white to yellowish crystalline powder, practically odorless, freely soluble in dichloromethane, slightly soluble in ethanol, and practically insoluble in water. It has a molecular weight of 285.31 g/mol, empirical formula C17H11N5, and a melting range of 184°C to 185°C.

The chemical name of letrozole is 4,4′-(1H-1,2,4-Triazol-1ylmethylene) dibenzonitrile, and its structural formula is

FEMARA is available as 2.5 mg tablets for oral administration.

Inactive Ingredients: colloidal silicon dioxide, ferric oxide, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc, and titanium dioxide.

 Mechanism of Action

Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways, which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb).

In vitro, ribociclib decreased pRb phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation.

Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues. In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme.

In vivo studies, using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g., letrozole) resulted in increased tumor growth inhibition compared to each drug alone.

What is the most important information I should know about Kisqali Femara Co-Pack?

Kisqali Femara Co-Pack may cause serious side effects, including:

• 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. Tell your healthcare provider or get medical help right away if you get severe rash or rash that keeps getting worse, reddened skin, flu-like symptoms, skin pain/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 Femara Co-Pack 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 Femara Co-Pack. 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 Femara Co-Pack can cause serious liver problems. Your healthcare provider will do blood tests to check your liver before you start and while you take Kisqali Femara Co-Pack. 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 when taking Kisqali Femara Co-Pack 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 Femara Co-Pack. 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.

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.

See “What are the possible side effects of Kisqali Femara Co-Pack?” for more information about side effects.

Who should not take Kisqali Femara Co-Pack?

Do not take Kisqali Femara Co-Pack if you are allergic to letrozole or any of the ingredients of Femara.

See the end of this Patient Information for a list of the ingredients in Kisqali Femara Co-Pack.

What should I tell my healthcare provider before taking Kisqali Femara Co-Pack?

Before you take Kisqali Femara Co-Pack, tell your healthcare provider about all your medical conditions, including if you:

• have any heart problems, including heart failure, irregular heartbeats, and QT prolongation
• have ever had a heart attack
• have a slow heartbeat (bradycardia)
• have problems with the amount of potassium, calcium, phosphorus, or magnesium in your blood
• have fever, chills, or any other signs or symptoms of infection
• have liver problems
• are pregnant, or plan to become pregnant. Kisqali Femara Co-Pack can harm your unborn baby.
  • If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Kisqali Femara Co-Pack.
  • Females who are able to become pregnant and who take Kisqali Femara Co-Pack should use effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali Femara Co-Pack.
  • 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.
• are breastfeeding or plan to breastfeed. It is not known if Kisqali Femara Co-Pack passes into your breast milk. Do not breastfeed during treatment with Kisqali Femara Co-Pack and for at least 3 weeks after the last dose of Kisqali Femara Co-Pack.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Kisqali Femara Co-Pack and other medicines may affect each other causing side effects. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

How should I take Kisqali Femara Co-Pack?

• Take Kisqali Femara Co-Pack exactly as your healthcare provider tells you.
• Do not change your dose or stop taking Kisqali Femara Co-Pack unless your healthcare provider tells you.
• Kisqali Femara Co-Pack comes in a carton that contains enough Kisqali tablets and Femara tablets for 28 days of treatment.
• Take Kisqali Femara Co-Pack each day at about the same time, preferably in the morning.
• You may take Kisqali Femara Co-Pack with food or without food.
• Swallow Kisqali tablets and Femara tablets whole. Do not chew, crush or split tablets before swallowing them.
• Do not take any Kisqali tablets and Femara tablets that are broken, cracked, or that look damaged.
• If you miss a dose or vomit after taking a dose of Kisqali Femara Co-Pack, do not take another dose on that day. Take your next dose at your regular time.
• If you take too much Kisqali Femara Co-Pack, call your healthcare provider right away or go to the nearest hospital emergency room.
• Inform your healthcare provider if you are pre- or peri-menopausal.

What should I avoid while taking Kisqali Femara Co-Pack?

• Avoid eating grapefruit and avoid drinking grapefruit juice during treatment with Kisqali Femara Co-Pack since these may increase the amount of Kisqali in your blood.

What are the possible side effects of Kisqali Femara Co-Pack?

Kisqali Femara Co-Pack may cause serious side effects.

• See “What is the most important information I should know about Kisqali Femara Co-Pack?”

The most common side effects of Kisqali Femara Co-Pack include:

• neutropenia
• leukopenia
• headache
• anemia
• nausea
• diarrhea
• constipation
• infections
• hair loss (alopecia)
• back pain
• fatigue
• vomiting
• rash

Kisqali Femara Co-Pack may cause fertility problems in females and males, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of Kisqali Femara Co-Pack.

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

General information about the safe and effective use of Kisqali Femara Co-Pack

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Kisqali Femara Co-Pack for a condition for which it was not prescribed. Do not give Kisqali Femara Co-Pack to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for more information about Kisqali Femara Co-Pack that is written for health professionals.

How should I store Kisqali Femara Co-Pack?

• Store Kisqali Femara Co-Pack at 68°F to 77°F (20°C to 25°C).
• Keep Kisqali Femara Co-Pack in its original container.

Keep Kisqali Femara Co-Pack and all medicines out of the reach of children.

What are the ingredients in Kisqali Femara Co-Pack?

Kisqali (ribociclib) tablets:

Active ingredient: ribociclib
Inactive ingredients: colloidal silicon dioxide, crospovidone, hydroxypropylcellulose, magnesium stearate and microcrystalline cellulose. The film-coating contains iron oxide black, iron oxide red, lecithin (soya), polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide, and xanthan gum

Femara (letrozole) tablets:

Active ingredient: letrozole
Inactive ingredients: colloidal silicon dioxide, ferric oxide, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc, and titanium dioxide

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