Kisqali

What Is Kisqali and What Is It Used For?

Kisqali (ribociclib) is a targeted cancer medicine that inhibits cyclin-dependent kinases 4 and 6 (CDK4/6). It is used to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer, both in early-stage disease after surgery and in advanced or metastatic disease.

Kisqali contains the active substance ribociclib, which belongs to a class of medicines called CDK4/6 inhibitors. These medicines target specific proteins – cyclin-dependent kinases 4 and 6 – that play a critical role in regulating the cell cycle. In cancer cells, these kinases are often overactive, driving uncontrolled cell division and tumour growth. By selectively blocking CDK4 and CDK6, ribociclib halts the transmission of growth signals inside cancer cells, preventing them from progressing through the cell cycle and dividing.

In early breast cancer, Kisqali is used after surgery (adjuvant therapy) in patients whose cancer has certain characteristics that increase the risk of recurrence. The aim is to reduce the chance that the cancer comes back. In this setting, Kisqali is taken in combination with an aromatase inhibitor (such as letrozole or anastrozole) as hormonal therapy. Women who have not yet reached menopause also receive a luteinising hormone-releasing hormone (LHRH) agonist (such as goserelin) to suppress ovarian function.

In advanced or metastatic breast cancer, the cancer has either grown beyond the breast into nearby lymph nodes (locally advanced) or spread to other parts of the body (metastatic). Kisqali is used in combination with an aromatase inhibitor or fulvestrant as hormonal cancer therapy. Again, pre-menopausal women receive an LHRH agonist alongside the treatment. The goal in advanced disease is to delay disease progression, extend the period before the cancer worsens, and improve overall survival.

The landmark MONALEESA clinical trial programme – comprising MONALEESA-2, MONALEESA-3, and MONALEESA-7 – demonstrated that adding ribociclib to endocrine therapy significantly improved both progression-free survival and overall survival in patients with HR+/HER2− advanced breast cancer. These trials included pre-menopausal, peri-menopausal, and post-menopausal women, establishing ribociclib as an effective treatment across a broad patient population. More recently, the monarchE and NATALEE trials have supported the use of CDK4/6 inhibitors in the early breast cancer setting.

What Should You Know Before Taking Kisqali?

Before starting Kisqali, your doctor will check your liver function, blood cell counts, electrolyte levels, and heart rhythm (ECG). You must not take Kisqali if you are allergic to ribociclib, peanut, or soya. Tell your doctor about all your medical conditions, especially liver disease, heart problems, or current infections.

Contraindications

You must not take Kisqali if any of the following apply to you:

• Allergy to ribociclib or any of the other ingredients in this medicine (listed in the contents section below)
• Allergy to peanut or soya – Kisqali tablets contain soya lecithin (E322) in the film coating. If you have a known allergy to peanut or soya, you must not take this medicine

If you think you may be allergic, consult your doctor before taking Kisqali.

Warnings and Precautions

Talk to your doctor, pharmacist, or nurse before taking Kisqali if any of the following apply to you:

• Fever, sore throat, or mouth ulcers caused by infections – these may be signs of a low white blood cell count (neutropenia), which is a common side effect of Kisqali
• Liver problems or a history of liver disease – Kisqali is metabolised by the liver and can cause hepatotoxicity. Your doctor will monitor your liver function closely
• Heart disease or abnormal heart rhythm – including a condition known as long QT syndrome or QT prolongation. Kisqali can prolong the QT interval on an ECG, which may lead to serious heart rhythm disturbances
• Low levels of potassium, magnesium, calcium, or phosphate in your blood – electrolyte imbalances can increase the risk of QT prolongation. Your doctor will check and correct these before and during treatment

During treatment with Kisqali, tell your doctor immediately if you experience:

• Severe skin reactions: skin rash, redness, blistering of the lips, eyes, or mouth, peeling skin, high fever, flu-like symptoms, or swollen lymph nodes – these may be signs of a serious skin reaction such as toxic epidermal necrolysis (TEN). Your doctor will advise you to stop Kisqali immediately
• Breathing difficulty, cough, or shortness of breath – these may be signs of interstitial lung disease (ILD) or pneumonitis. Your doctor may reduce your dose, pause, or permanently stop Kisqali treatment

Monitoring During Treatment

You will have regular blood tests before and during treatment with Kisqali to check your liver function, blood cell counts (white blood cells, red blood cells, and platelets), and electrolytes (blood salts such as potassium, calcium, magnesium, and phosphate). Your heart rhythm will also be monitored using an ECG (electrocardiogram) before and during treatment. If necessary, kidney function tests may also be performed. Based on these results, your doctor may reduce the Kisqali dose or temporarily pause treatment to allow your blood values, liver function, or heart rhythm to recover. Your doctor may also decide to stop Kisqali permanently if needed.

Use in Children and Adolescents

Kisqali is not intended for use in children and adolescents under 18 years of age. There is no relevant use of ribociclib in the paediatric population for the approved indications.

Pregnancy and Breastfeeding

Kisqali must not be used during pregnancy as it may harm the developing baby. If you are a woman of childbearing potential, your doctor will require a negative pregnancy test before starting treatment. You must use effective contraception (for example, double barrier methods such as condom and diaphragm) while taking Kisqali and for at least 21 days after the last dose. Ask your doctor about suitable contraceptive options.

You must not breastfeed while taking Kisqali and for at least 21 days after the last dose. It is not known whether ribociclib passes into human breast milk, but a risk to the breastfed infant cannot be excluded.

Driving and Operating Machinery

Kisqali may cause tiredness, dizziness, or a spinning sensation (vertigo). If you experience any of these effects, you should exercise caution when driving vehicles or operating machinery during treatment.

Soya Lecithin Content

Kisqali film-coated tablets contain soya lecithin (E322). If you are allergic to peanut or soya, do not use this medicine. This is an important safety consideration that must be discussed with your healthcare provider before starting treatment.

How Does Kisqali Interact with Other Drugs?

Kisqali can interact with many medications, including antifungals, HIV antivirals, antibiotics, anti-epileptics, and heart rhythm drugs. It is metabolised by CYP3A4 and can also affect the blood levels of other medicines. You must avoid grapefruit and grapefruit juice during treatment. Always tell your doctor about all medications and supplements you are taking.

Ribociclib is primarily metabolised by the liver enzyme CYP3A4. Drugs that inhibit CYP3A4 can significantly increase ribociclib blood levels, potentially increasing the risk of side effects. Drugs that induce CYP3A4 can reduce ribociclib blood levels, potentially reducing its effectiveness. Additionally, Kisqali itself can alter the blood levels of certain other medicines. The following tables summarise the most clinically important interactions.

Major Interactions – Drugs That Increase Kisqali Levels

Major Interactions – Drugs That Decrease Kisqali Levels

QT-Prolonging Drug Interactions

Because Kisqali can prolong the QT interval, it should be used with extreme caution or avoided with other medicines known to prolong the QT interval. Combining Kisqali with QT-prolonging drugs significantly increases the risk of serious heart rhythm disturbances.

Drugs Whose Blood Levels Are Affected by Kisqali

Kisqali may increase or decrease the blood levels of certain other medicines. Tell your doctor if you are taking any of the following:

• Alfuzosin (for benign prostatic hyperplasia)
• Tamoxifen (for breast cancer)
• Simvastatin / Lovastatin / Pitavastatin / Pravastatin / Rosuvastatin (cholesterol-lowering statins)
• Metformin (for diabetes)
• Digoxin (for heart conditions)
• Sildenafil (for pulmonary arterial hypertension or erectile dysfunction)
• Ergotamine / Dihydroergotamine (for migraine)
• Midazolam / Triazolam (sedatives)
• Alfentanil / Fentanyl (opioid pain relievers)
• Cisapride (for gastrointestinal disorders)
• Cyclosporine / Tacrolimus / Sirolimus (immunosuppressants for organ transplant)
• Everolimus (for various cancers and organ transplant rejection)

Food and Drink Interactions

You must avoid grapefruit and grapefruit juice during treatment with Kisqali. Grapefruit inhibits the CYP3A4 enzyme responsible for metabolising ribociclib, which can lead to increased drug levels in your blood and a higher risk of side effects. Kisqali tablets can be taken with or without food.

What Is the Correct Dosage of Kisqali?

Kisqali is taken once daily for 21 consecutive days followed by 7 days off in each 28-day treatment cycle. The starting dose is 400 mg (2 tablets) daily for early breast cancer or 600 mg (3 tablets) daily for advanced or metastatic breast cancer. Take at the same time each day, preferably in the morning.

Always take Kisqali exactly as your doctor, pharmacist, or nurse has told you. Do not change your dose or treatment schedule without consulting your doctor. Kisqali tablets should be swallowed whole – do not chew, crush, or split them before swallowing. Do not take a tablet that is broken, cracked, or otherwise damaged.

Dosing Schedule

Each treatment cycle lasts 28 days. Take Kisqali once daily on days 1 through 21 of each cycle. Do not take Kisqali on days 22 through 28 of the cycle. After the 7-day break, start the next cycle.

When to Take Kisqali

Take Kisqali once daily at the same time each day, preferably in the morning. Taking it at a consistent time makes it easier to remember your dose and to notice any side effects promptly so you can contact your doctor. You can take Kisqali with or without food.

Dose Adjustments

In certain situations – for example, if you experience side effects, or if you have liver or kidney problems – your doctor may prescribe a lower dose of Kisqali. Your doctor may also temporarily pause treatment to allow your blood counts, liver function, electrolytes, or heart rhythm to recover before resuming at a reduced dose. It is crucial that you follow your doctor’s instructions regarding dose adjustments.

Missed Dose

If you vomit after taking your dose or forget to take a dose, skip the missed dose for that day. Take the next dose at your usual time the following day. Do not take a double dose to make up for a missed one.

Overdose

Stopping Kisqali

Do not stop taking Kisqali unless your doctor tells you to. If you feel your dose is too high or too low, speak with your doctor. Stopping treatment without medical guidance may allow the cancer to progress. In early breast cancer, treatment up to 3 years is recommended. In advanced or metastatic breast cancer, Kisqali is a long-term treatment and your doctor will regularly assess whether the treatment continues to provide benefit.

What Are the Side Effects of Kisqali?

The most common side effects of Kisqali include infections, low white blood cell count (neutropenia), abnormal liver function tests, nausea, fatigue, hair loss, diarrhoea, and headache. Some side effects can be serious and require immediate medical attention. Your doctor will monitor you regularly with blood tests and ECG.

Like all medicines, Kisqali can cause side effects, although not everybody gets them. The side effects listed here include those observed in both the early breast cancer and advanced/metastatic breast cancer settings. Read this section carefully and tell your doctor immediately if you experience any of the serious side effects described below.

Early Breast Cancer Side Effects

Advanced or Metastatic Breast Cancer Side Effects

The frequency of toxic epidermal necrolysis (TEN) – a severe skin reaction – is not known (cannot be estimated from available data). If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor, pharmacist, or nurse. Reporting suspected side effects helps ongoing monitoring of the medicine’s benefit-risk balance.

How Should You Store Kisqali?

Store Kisqali tablets at no more than 25°C for up to 2 months. Keep in the original packaging. Store out of the reach and sight of children. Do not use after the expiry date on the carton and blister.

Pharmacies store Kisqali under refrigeration (2°C to 8°C) for up to 10 months. Once dispensed to you, store at room temperature (no more than 25°C) for up to 2 months. Keep the tablets in their original blister packaging to protect them from moisture and light.

Check the expiry date on the carton and blister pack before taking any tablets. The expiry date refers to the last day of the stated month. Do not take this medicine if the packaging is damaged or shows signs of tampering.

Do not dispose of unused medicines via wastewater or household waste. Return any unused or expired medication to your pharmacy for safe disposal to protect the environment.

What Does Kisqali Contain?

Each Kisqali film-coated tablet contains 200 mg of ribociclib (as ribociclib succinate). The tablet coating contains soya lecithin – patients with peanut or soya allergy must not use this medicine.

Active Ingredient

The active substance is ribociclib. Each film-coated tablet contains ribociclib succinate equivalent to 200 mg ribociclib.

Inactive Ingredients (Excipients)

Tablet core: microcrystalline cellulose, crospovidone type A, low-substituted hydroxypropyl cellulose, magnesium stearate, colloidal anhydrous silica.

Film coating: black iron oxide (E172), red iron oxide (E172), soya lecithin (E322), polyvinyl alcohol (partially hydrolysed), talc, titanium dioxide (E171), xanthan gum.

Tablet Appearance and Packaging

Kisqali 200 mg tablets are light greyish-purple, round, unscored, film-coated tablets debossed with “RIC” on one side and “NVR” on the other side.

Pack sizes: 21, 42, or 63 film-coated tablets, and multi-packs of 63 (3 packs of 21), 126 (3 packs of 42), or 189 (3 packs of 63) film-coated tablets.

• 63-tablet packs are for the 600 mg daily dose (3 tablets once daily)
• 42-tablet packs are for the 400 mg daily dose (2 tablets once daily)
• 21-tablet packs are for the 200 mg daily dose (1 tablet once daily, reduced dose)

Not all pack sizes may be marketed in every country. The outer carton includes a “calendar tool” to help you track your daily Kisqali dose by marking a circle for each tablet taken during the 28-day cycle.

How Does Kisqali Work in the Body?

Kisqali works by selectively inhibiting CDK4 and CDK6, proteins that drive cancer cell division. By blocking these kinases, ribociclib arrests the cell cycle at the G1 phase, preventing cancer cells from growing and spreading. In early breast cancer, this helps prevent recurrence; in advanced disease, it slows tumour progression.

Cancer cells grow and divide in a controlled sequence of events known as the cell cycle. Two key proteins – cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) – act as molecular switches that propel cells from the G1 (resting/growth) phase into the S (DNA synthesis) phase, where the cell prepares to divide. In hormone receptor-positive breast cancer, the oestrogen signalling pathway activates cyclin D, which binds to CDK4/6, triggering the phosphorylation of the retinoblastoma protein (Rb). Phosphorylated Rb releases E2F transcription factors, allowing the cell to progress through the cell cycle.

Ribociclib selectively and reversibly binds to CDK4 and CDK6, preventing them from phosphorylating Rb. With Rb remaining in its unphosphorylated (active tumour-suppressor) state, E2F transcription factors are not released and the cell cycle is arrested at the G1 phase. This cytostatic effect halts cancer cell proliferation without necessarily killing the cells outright. By combining ribociclib with hormonal therapy (which blocks the oestrogen signalling pathway), a dual blockade is achieved that more effectively suppresses tumour growth than either agent alone.

Pharmacokinetic Profile

After oral administration, ribociclib is rapidly absorbed, reaching peak plasma concentrations within 1 to 4 hours. The drug exhibits linear pharmacokinetics over the therapeutic dose range. Ribociclib is extensively metabolised in the liver, primarily by the CYP3A4 enzyme. The mean plasma elimination half-life is approximately 32 to 43 hours, which supports once-daily dosing. Steady-state concentrations are achieved after approximately 8 days of repeated daily dosing.

Ribociclib is moderately protein-bound in plasma. It is excreted primarily through faeces (approximately 69%) and urine (approximately 23%), both as metabolites and unchanged drug. Hepatic impairment increases ribociclib exposure, which may necessitate dose reduction in patients with moderate to severe liver disease. The pharmacokinetic profile supports the 3-weeks-on, 1-week-off dosing schedule, allowing the body to recover from myelosuppressive effects during the treatment-free week.

Frequently Asked Questions About Kisqali