Reviewed on 6/23/2023

What Is Ribociclib-Letrozole and How Does It Work?

Ribociclib-Letrozole is a combination medication indicated as initial endocrine-based therapy for the treatment of pre/perimenopausal, postmenopausal women, or men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)­-negative advanced or metastatic breast cancer.

  • Ribociclib-Letrozole is available under the following different brand names: Kisqali/Femara Copack

What Are Side Effects Associated with Using Ribociclib-Letrozole?

Common side effects of Ribociclib-Letrozole include:

Serious side effects of Ribociclib-Letrozole include:

  • hives
  • difficulty breathing
  • swelling of the face, lips, tongue, or throat
  • shortness of breath
  • nausea
  • vomiting
  • stomach pain
  • yellowing of the eyes or skin (jaundice)
  • dark urine
  • fast, or irregular heartbeat
  • severe dizziness
  • fainting
  • chest pain
  • sore throat
  • fever
  • swollen lymph nodes
  • chills
  • cough

Rare side effects of Ribociclib-Letrozole include:

  • none

Seek medical care or call 911 at once if you have the following serious side effects:

  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Are Dosages of Ribociclib-Letrozole?

Adult dosage

Tablets, copackaged cartons

  • Packaged for a 28-day medication cycle depending on the ribociclib daily dose
  • 3 blister packs, containing 21 tablets (200 mg/tablet; 600 mg daily dose) of ribociclib plus one 28-tablet count bottle of letrozole 2.5 mg/tablet
  • 3 blister packs, containing 14 tablets (200 mg/tablet; 400 mg daily dose) of ribociclib plus one 28-tablet count bottle of letrozole 2.5 mg/tablet
  • 1 blister pack, containing 21 tablets (200 mg/tablet; 200 mg daily dose) of ribociclib plus one 28-tablet count bottle of letrozole 2.5 mg/tablet

Breast Cancer

Adult dosage

  • Ribociclib (initial dose): 600 mg orally every day for 21 consecutive days followed by 7 days off treatment resulting in a 28-day cycle
  • Letrozole: 2.5 mg orally every day taken through the 28-day cycle
  • Treat men or pre/perimenopausal women with a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin, leuprolide) according to clinical practice standards

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Other Drugs Interact with Ribociclib-Letrozole?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Ribociclib-Letrozole has severe interactions with the following drugs:
    • aprepitant
    • budesonide
    • conivaptan
    • elvitegravir
    • fluconazole
    • fosaprepitant
    • lefamulin
    • lonafarnib
    • methadone
    • naloxegol
    • posaconazole
    • ranolazine
    • saquinavir
  • Ribociclib-Letrozole has serious interactions with at least 216 other drugs
  • Ribociclib-Letrozole has moderate interactions with at least 254 other drugs
  • Ribociclib-Letrozole has minor interactions with at least 69 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Ribociclib-Letrozole?


  • Hypersensitivity to active substance (letrozole), or to excipients of the formulation

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Ribociclib-Letrozole?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Ribociclib-Letrozole?”


  • May cause fetal harm; advise women of reproductive potential to use effective contraception
  • Severe cutaneous reactions
    • Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) can occur
    • If signs or symptoms occur, interrupt treatment until the etiology of the reaction determined
    • Early consultation with a dermatologist is recommended to ensure greater diagnostic accuracy and appropriate management
    • If SJS, TEN, or DiHS/DRESS is confirmed, permanently discontinue; do not reintroduce in patients who have experienced SCARs or other life-threatening cutaneous reactions during treatment
  • Interstitial lung disease/pneumonitis
    • Severe, life-threatening, or fatal ILD and/or pneumonitis can occur; additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea
    • In patients who have new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis, interrupt therapy immediately and evaluate the patient; permanently discontinue therapy in patients with recurrent symptomatic or severe ILD/pneumonitis
  • QT prolongation
    • Prolongs the QT interval in a concentration-dependent manner, with an estimated mean increase in QTc interval exceeding 20 ms following administration at 600 mg once daily dose
    • Avoid use in patients who already have or who are at significant risk of developing QTc prolongation, including those with electrolyte abnormalities, long QT syndrome, or uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmia
    • Avoid use in patients taking drugs known to prolong QTc interval and/or strong CYP3A inhibitors as this may lead to prolongation of the QTcF interval
    • Based on observed QT prolongation during treatment, the drug may require dose interruption, reduction or discontinuation
    • Increased in QT prolongation with concomitant use of tamoxifen; not indicated for concomitant use
  • Hepatobiliary toxicity
    • Increased transaminases were observed in clinical trials; Grade 3 or 4 increases in ALT and AST reported
    • In patients who had a Grade of 3 and more ALT/AST elevation, the median time-to-onset was 57 days; whereas, Grade of 2 and below was 24 days
  • Neutropenia
    • Neutropenia is the most frequently reported adverse effect
    • Among patients with neutropenia, the median time to Grade 2 and more is 17 days
    • Median time to resolution of Grade 3 and more (to normalization or Grade less than 3) is 12 days
    • Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated; based on the severity of the neutropenia, therapy may require dose interruption, reduction, or discontinuation
  • Drug interaction overview
    • Ribociclib is a CYP3A4 substrate and CYP3A4 inhibitor
      • Drugs that may increase ribociclib plasma concentrations
      • Avoid concomitant use of strong CYP3A inhibitors (eg, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole) and consider alternative concomitant medications with less potential for CYP3A inhibition
      • If coadministration with a strong CYP3A inhibitor cannot be avoided, reduce the ribociclib dose to 400 mg/day 
      • Instruct patients to avoid pomegranates or pomegranate juice, grapefruit, all of which are known to inhibit cytochrome CYP3A enzymes and may increase the exposure to ribociclib
      • Drugs that may decrease ribociclib plasma concentrations
      • Avoid concomitant use of strong CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, St John’s Wort) and consider an alternate concomitant medication with no or minimal potential to induce CYP3A
    • Effect of ribociclib on other drugs
      • Caution if ribociclib is coadministered with CYP3A4 substrates that have a narrow therapeutic index (NTI), as ribociclib can increase their systemic exposure
      • The dose of sensitive CYP3A substrates with an NTI may need to be reduced
      • CYP3A substrates with a NTI include (but are not limited to) alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus
    • Drugs that prolong QT interval
      • Avoid coadministration of ribociclib with drugs with a known potential to prolong QT
      • Examples include antiarrhythmic medicines (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol), and other drugs that are known to prolong the QT interval (eg, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, pimozide, ondansetron IV)

Pregnancy and Lactation

  • There are no available human data informing the drug-associated risk
  • Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman
  • In animal reproduction studies, administration during organogenesis resulted in increased incidences of postimplantation loss and reduced fetal weights in rats and increased incidences of fetal abnormalities in rabbits at exposures 0.6 or 1.5 times the exposure in humans
  • Infertility: Based on animal studies, may impair fertility in males Contraception
  • Women of reproductive potential should have a pregnancy test prior to starting treatment
  • Women: Advise women of reproductive potential to use effective contraception (methods that result in less than 1 % pregnancy rates) during treatment and for at least 3 weeks after the last dose
  • Lactation
    • Unknown if distributed in human breast milk
    • Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking ribociclib and for at least 3 weeks after the last dose
    • In lactating rats administered a single dose of 50 mg/kg, exposure to ribociclib was 3.56-fold higher in milk compared to maternal plasma

Health Solutions From Our Sponsors