Ribociclib and letrozole (Oral)

Ribociclib and letrozole combination is used to treat hormone receptor (HR)-positive, HER-2 negative advanced or metastatic (cancer that has spread) breast cancer in pre/perimenopausal women, postmenopausal women, or men.

Ribociclib belongs to a group of medicines called antineoplastics. It works by interfering with the growth of cancer cells, which are eventually destroyed. Since this medicine can also affect the growth of normal cells, it may cause other unwanted effects. Some of these effects can be serious and should be reported to your doctor.

Some hormones that naturally occur in the body can promote the growth of certain breast cancers. Letrozole helps by reducing the levels of these hormones in the body.

This medicine is available only with your doctor's prescription.

It is very important for your doctor to check your progress at regular visits to ensure this medicine is working correctly. Blood tests may be necessary to look for unwanted effects.

It is unlikely for a postmenopausal woman to become pregnant. However, using this medicine while pregnant can harm your unborn baby. If you can have children, your doctor may give you a pregnancy test before starting this medicine to confirm you are not pregnant. Use an effective form of birth control to prevent pregnancy during treatment and for at least 3 weeks after your last dose. If you think you might be pregnant while using this medicine, inform your doctor immediately.

If you plan to have children, discuss this with your doctor before using this medicine. Some men and women using this medicine have become infertile (unable to have children).

Interstitial lung disease or pneumonitis can happen while using this medicine. This can be life-threatening and requires immediate medical attention. Contact your doctor right away if you experience chest pain, cough, difficulty breathing, fever, or chills.

Serious skin reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms (DRESS) can occur with this medicine. Contact your doctor immediately if you have black, tarry stools, blistering, peeling, or loosening of the skin, chest pain, chills, cough, fever, painful or difficult urination, red skin lesions, sore throat, sores, ulcers, or white spots on the lips or in the mouth, swollen glands, unusual bleeding or bruising, or unusual tiredness or weakness while using this medicine.

Get in touch with your doctor right away if you notice any changes to your heart rhythm. You may feel dizzy or faint, or you might experience a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem, including QT prolongation.

Contact your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellowing of your eyes or skin. These could be signs of a serious liver problem.

Ribociclib and letrozole combination can temporarily reduce the number of certain types of blood cells in your blood. Because of this, you may bleed or get infections more easily. To help with these issues, avoid close contact with people who are sick or have infections. Wash your hands frequently. Stay away from rough sports or situations where you could get bruised, cut, or injured. Brush and floss your teeth gently. Be careful when using sharp objects, like razors and fingernail clippers.

Do not take other medicines unless you have discussed them with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.

In deciding to use a medication, the chances of taking the drug must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Inform your physician if you have ever had any unusual or allergic reaction to this medication or any other medicines. Also inform your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of ribociclib and letrozole combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ribociclib and letrozole combination in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant chance when using this medication during breastfeeding. Weigh the potential benefits against the potential chances prior to taking this medicine while breastfeeding.

Interactions with Medicines

Although certain medications should not be used together at all, in other cases two different drugs may be used together even if an interaction might occur. In these cases, your physician may want to change the dose, or other precautions may be necessary. When you are using this medicine, it is especially essential that your healthcare professional know if you are taking any of the medications listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following drugs is not advised. Your doctor may decide not to treat you with this medication or change some of the other drugs you take.

• Bepridil
• Cisapride
• Colchicine
• Dronedarone
• Fluconazole
• Gepirone
• Ketoconazole
• Levoketoconazole
• Mavacamten
• Mesoridazine
• Pimozide
• Piperaquine
• Posaconazole
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how frequently you use one or both of the medications.

• Abametapir
• Adagrasib
• Alfentanil
• Alfuzosin
• Amiodarone
• Amisulpride
• Amitriptyline
• Anagrelide
• Apomorphine
• Aprepitant
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Bedaquiline
• Boceprevir
• Bosutinib
• Buprenorphine
• Buserelin
• Carbamazepine
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cilostazol
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clothiapine
• Clozapine
• Cobicistat
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Daridorexant
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Dexmedetomidine
• Dihydroergotamine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Ebastine
• Efavirenz
• Elexacaftor
• Encorafenib
• Entrectinib
• Enzalutamide
• Ergotamine
• Eribulin
• Erythromycin
• Escitalopram
• Etrasimod
• Everolimus
• Famotidine
• Fedratinib
• Felbamate
• Fentanyl
• Fexinidazole
• Fingolimod
• Flecainide
• Flibanserin
• Fluoxetine
• Fluticasone
• Formoterol
• Fosaprepitant
• Foscarnet
• Fosphenytoin
• Fostemsavir
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Idelalisib
• Iloperidone
• Imipramine
• Indinavir
• Inotuzumab Ozogamicin
• Itraconazole
• Ivabradine
• Ivacaftor
• Ivosidenib
• Lapatinib
• Lefamulin
• Lenvatinib
• Leuprolide
• Levofloxacin
• Levomilnacipran
• Lofexidine
• Lopinavir
• Lumacaftor
• Lumefantrine
• Lurbinectedin
• Macimorelin
• Mefloquine
• Methadone
• Methotrimeprazine
• Metronidazole
• Midazolam
• Mifepristone
• Mirtazapine
• Mitotane
• Mizolastine
• Mobocertinib
• Moricizine
• Moxifloxacin
• Nafarelin
• Nefazodone
• Nelfinavir
• Nifedipine
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Omaveloxolone
• Ondansetron
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Oxycodone
• Ozanimod
• Pacritinib
• Paliperidone
• Palovarotene
• Panobinostat
• Papaverine
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Perphenazine
• Phenobarbital
• Phenytoin
• Pimavanserin
• Pipamperone
• Pitolisant
• Ponesimod
• Pralsetinib
• Primidone
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Quizartinib
• Ranolazine
• Relugolix
• Rifampin
• Risperidone
• Ritonavir
• Selpercatinib
• Sertindole
• Sertraline
• Sevoflurane
• Simvastatin
• Siponimod
• Sirolimus
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• St John's Wort
• Sultopride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Tegafur
• Telaprevir
• Telavancin
• Telithromycin
• Temsirolimus
• Tetrabenazine
• Tezacaftor
• Tocilizumab
• Tolterodine
• Toremifene
• Trazodone
• Triclabendazole
• Trimipramine
• Triptorelin
• Valbenazine
• Vamorolone
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinflunine
• Voclosporin
• Voriconazole
• Vorinostat
• Zolpidem
• Zotepine
• Zuclopenthixol
• Zuranolone

Using this drug with any of the following medicines may cause an increased risk of certain adverse effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how frequently you use one or both of the medications.

• Amlodipine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain drugs may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medication with any of the following is normally not advised, but may be unavoidable in some cases. If used together, your doctor may change the dose or how frequently you use this medication, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical issues may affect the use of this medication. Make sure you tell your clinician if you have any other medical problems, especially:

• Angina (severe chest pain), unstable or
• Congestive heart failure or
• Electrolyte imbalance (eg, high or low potassium, calcium, phosphorus, magnesium in the blood) or
• Heart attack, recent or
• Heart rhythm issues (eg, long QT syndrome, slow, fast, or irregular heartbeat)—Avoid use. May cause adverse effects to become worse.

• Infection or
• Neutropenia (low white blood cells)—May lower your body's ability to fight infection.

• Kidney disease, serious or
• Liver disease, severe—Use with caution. The effects may be increased since of slower removal of the medication from the body.

• Lung problems (eg, interstitial lung disease, pneumonitis)—Use with caution. May make these conditions worse.

Along with its needed effects, a medicine may cause some unwanted effects. Not all of these side effects may happen, but if they do, they may need medical attention.

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

More common

• Black, tarry stools
• Bladder pain
• Bleeding gums
• Bloating or swelling of the face, arms, hands, lower legs, or feet
• Bloody or cloudy urine
• Chest tightness
• Chills
• Cough
• Decrease in height
• Difficult, burning, or painful urination
• Fever
• Frequent urge to urinate
• Lower back or side pain
• Pain in the back, ribs, arms, or legs
• Pale skin
• Pinpoint red spots on the skin
• Sore throat
• Tingling of the hands or feet
• Trouble breathing
• Ulcers, sores, or white spots in the mouth
• Unusual bleeding or bruising
• Unusual tiredness or weakness
• Unusual weight gain or loss

Less common

• Chest pain
• Confusion
• Dark urine
• Fainting
• General feeling of discomfort or illness
• Irregular heartbeat
• Loss of appetite
• Mood or mental changes
• Muscle cramps in the hands, arms, feet, legs, or face
• Nausea
• Numbness and tingling around the mouth, fingertips, or feet
• Pain or tenderness in the upper stomach
• Pale stools
• Seizures
• Stomach cramps
• Thickening of bronchial secretions
• Tremor
• Vomiting
• Yellow eyes or skin

Incidence not known

• Blistering, peeling, loosening of skin
• Diarrhea
• Joint or muscle pain
• Rash or itching skin
• Red irritated eyes
• Red skin lesions, often with a purple center
• Swollen glands

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. Your health care professional may also 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:

More common

• Back pain
• Constipation
• Dry skin
• Headache
• Lack or loss of strength
• Loss or thinning of the hair
• Mouth or throat pain
• Swelling or inflammation of the mouth
• Trouble sleeping

Less common

• Belching
• Dry eye
• Heartburn
• Increased tearing
• Indigestion
• Patchy loss of skin color

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

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

In the U.S.

• Kisqali Femara Co-Pack

Available Dosage Forms:

• Tablet

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

Take this medicine 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.

This medicine comes with a patient information insert. Read and follow the instructions carefully. Ask your doctor if you have any questions.

It is important that you take both medicines at the same time each day, preferably in the morning.

Your doctor may also give you luteinizing hormone-releasing hormone medicine together with this medicine.

Swallow the tablet whole. Do not crush, break, or chew it. You may take this medicine with or without food.

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

Dosing

The dose of this medicine 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 this medicine. 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 metastatic breast cancer: Adults— Ribociclib: 600 milligrams (mg) (three 200 mg tablets) taken as a single dose, once a day for 21 days in a row, followed by 7 days without medicine. Your doctor may adjust your dose as needed and tolerated. Letrozole: 2.5 milligrams (mg) once a day for 28 days. Children—Use and dose must be determined by your doctor.

Missed Dose

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

If you vomit after you take this medicine, do not take another dose the same day. Wait and take your next dose when you normally would.

Storage

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.

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

Store the medicine in its original package.