Ribociclib

Ribociclib is a prescription medicine used to treat the symptoms of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

• Ribociclib is available under the following different brand names: Kisqali

Adult dosage

Tablet

• 200mg

Breast Cancer

Adult dosage

• 600 mg orally once daily for 21 consecutive days followed by 7 days off treatment resulting in a 28-day cycle

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Ribociclib include:

• tiredness,
• diarrhea,
• headache,
• back pain,
• nausea,
• vomiting,
• loss of appetite,
• vomiting,
• temporary hair loss, 
• pain or sores in the mouth or throat,
• cough,
• rash, and
• low white blood cells, infections.

Serious side effects of Ribociclib include:

• fast, or irregular heartbeat,
• fainting,
• chest pain,
• chills, 
• muscle aches, severe 
• allergic reaction: hives, difficult breathing, swelling in the face or throat,
• severe skin reaction: fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling, swollen glands, and weakness
• signs of inflammation in the lungs: new or worsening cough, painful or difficult breathing, wheezing, feeling short of breath even while resting, and
• liver problems--loss of appetite, upper stomach pain, tiredness, easy bruising or bleeding, dark urine, jaundice (yellowing of the skin or eyes).

Rare side effects of Ribociclib include:

• none 

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.

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 has severe interactions with the following drugs:
  • aprepitant
  • budesonide
  • conivaptan
  • elvitegravir
  • fluconazole
  • lefamulin
  • lonafarnib
  • methadone
  • naloxegol
  • posaconazole
  • ranolazine
  • saquinavir
• Ribociclib has serious interactions with at least 198 other drugs.
• Ribociclib has moderate interactions with at least 245 other drugs.
• Ribociclib has minor interactions with at least 67 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 health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• 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-recommended ensuring 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 at the mean steady-state peak plasma concentration 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,
    • Patients with uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias
    • In patients taking drugs known to prolong QTc interval and/or strong CYP3A inhibitors, this may lead to prolongation of the QTcF interval
• Hepatobiliary toxicity
  • Increased transaminases were observed in clinical trials
  • In patients who had a Grade more than or equal to 3 ALT/AST elevation, the median time-to-onset was 57 days; whereas, Grade less than or equal to 2 was 24 days
  • Perform LFTs before initiating therapy; monitor LFTs every 2 weeks for the first 2 cycles, at beginning of each subsequent 4 cycles, and as clinically indicated; Based on the severity of transaminase elevations, therapy may require dose interruption, reduction, or discontinuation
• Neutropenia
  • Neutropenia is the most frequently reported adverse effect
  • Among patients with neutropenia, the median time to Grade is more than or equal to 2 in 16 days
  • The median time to resolution of Grade more than or equal to 3 (to normalization or Grade less than 3) is 15 days
  • Perform complete blood count (CBC) before initiating therapy; monitor CBC every 2 weeks for the first 2 cycles, at beginning of each subsequent 4 cycles, and as clinically indicated; based on the severity of neutropenia, the drug 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)
    • 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 (also see Dosage Modifications)
    • 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)
  • Drugs that are known to prolong the QT interval (eg, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, pimozide, ondansetron IV)
  • Not indicated for concomitant use with tamoxifen; in a clinical trial, an increase of more than 60 ms from baseline in the QTcF interval was observed in 16% of patients in the ribociclib and tamoxifen combination

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
  • Females of reproductive potential should have a pregnancy test before starting treatment
  • Females: Advise females 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