Ribociclib and letrozole

In the U.S.

• Kisqali Femara Co-Pack

Available Dosage Forms:

• Tablet

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

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to ribociclib and letrozole or any other medicines. Also tell 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 risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

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

Using ribociclib and letrozole with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Fluconazole
• Ketoconazole
• Mesoridazine
• Piperaquine
• Posaconazole
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using ribociclib and letrozole 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 often you use one or both of the medicines.

• Alfentanil
• Alfuzosin
• Amiodarone
• Amitriptyline
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Bedaquiline
• Boceprevir
• Buserelin
• Carbamazepine
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cilostazol
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Cobicistat
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Dihydroergotamine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Ebastine
• Efavirenz
• Enzalutamide
• Ergotamine
• Eribulin
• Erythromycin
• Escitalopram
• Everolimus
• Famotidine
• Felbamate
• Fentanyl
• Fingolimod
• Flecainide
• Flibanserin
• Fluoxetine
• Formoterol
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Idelalisib
• Iloperidone
• Imipramine
• Indinavir
• Itraconazole
• Ivabradine
• Lapatinib
• Leuprolide
• Levofloxacin
• Lopinavir
• Lumacaftor
• Lumefantrine
• Mefloquine
• Methadone
• Methotrimeprazine
• Metronidazole
• Midazolam
• Mifepristone
• Mitotane
• Mizolastine
• Moricizine
• Moxifloxacin
• Nafarelin
• Nefazodone
• Nelfinavir
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Oxycodone
• Paliperidone
• Panobinostat
• Papaverine
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Perphenazine
• Phenytoin
• Pimavanserin
• Pimozide
• Pipamperone
• Pitolisant
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Rifampin
• Risperidone
• Ritonavir
• Sertindole
• Sevoflurane
• 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
• Tizanidine
• Tolterodine
• Toremifene
• Trazodone
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vinflunine
• Voriconazole
• Vorinostat
• Zotepine
• Zuclopenthixol

Using ribociclib and letrozole with any of the following medicines may cause an increased risk of certain side 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 often you use one or both of the medicines.

• Tamoxifen

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 medicines 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 ribociclib and letrozole with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use ribociclib and letrozole, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice
• Pomegranate
• Pomegranate Juice

Other Medical Problems

The presence of other medical problems may affect the use of ribociclib and letrozole. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina (severe chest pain), unstable or
• Congestive heart failure or
• Electrolyte imbalance or
• Heart attack, recent or
• Heart rhythm problems (eg, long QT syndrome, slow or irregular heartbeat)–Avoid use. May cause prolongation of QT interval.

• Infection—May decrease your body's ability to fight infection.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

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

Take ribociclib and letrozole 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.

ribociclib and letrozole 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.

Swallow the tablet whole. Do not crush, break, or chew it. You may take ribociclib and letrozole with or without food.

Do not eat grapefruit or pomegranate, or drink grapefruit or pomegranate juice while you are using ribociclib and letrozole.

Dosing

The dose of ribociclib and letrozole 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 ribociclib and letrozole. 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 consecutive days, 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 ribociclib and letrozole, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you vomit after taking your medicine, call your doctor or pharmacist for instructions.

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.

Store the medicine in its original package.

• Tell all of your health care providers that you take ribociclib and letrozole. This includes your doctors, nurses, pharmacists, and dentists.
• An unsafe heartbeat that is not normal (long QT on ECG) has happened with this medicine. This may raise the chance of sudden death. Talk with the doctor.
• You will need an ECG before starting ribociclib and letrozole and during treatment. Talk with your doctor.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• This medicine may cause weak bones. This may happen more often if used for a long time. This may raise the chance of broken bones. Call your doctor right away if you have bone pain.
• Have a bone density test as you have been told by your doctor. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Take calcium and vitamin D as you were told by your doctor.
• Avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice while you take this medicine.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking ribociclib and letrozole with your other drugs.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or 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 ribociclib and letrozole 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.

Use ribociclib and letrozole as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to take this medicine as you have been told by your doctor. Do not use more than you were told to use.
• Take with or without food.
• Take in the morning.
• Take ribociclib and letrozole at the same time of day.
• Swallow whole. Do not chew, break, or crush.
• Do not take chipped or broken tablets.
• To gain the most benefit, do not miss doses.
• If you throw up after taking a dose, do not repeat the dose. Take your next dose at your normal time.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

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 a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• 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 electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Dizziness or passing out.
• A fast heartbeat.
• A heartbeat that does not feel normal.
• Feeling very tired or weak.
• Shortness of breath.
• Swelling in the arms or legs.
• Any unexplained bruising or bleeding.