Ribociclib Succinate
Class: Antineoplastic Agents
Chemical Name: C23H30N8O
Molecular Formula: 7-Cyclopentyl-N,N-dimethyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
CAS Number: 1211441-98-3
Brands: Kisqali
Medically reviewed on October 16, 2017
Introduction
Antineoplastic agent; a selective inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6).1 2 4 14
Uses for Ribociclib SuccinateBreast Cancer
In combination with an aromatase inhibitor for initial treatment of hormone receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative advanced or metastatic breast cancer in postmenopausal women.1 2
Ribociclib Succinate Dosage and Administration
General
· Commercially available alone (Kisqali) and copackaged with letrozole (Kisqali Femara Co-Pack).1 14
· Obtain CBC and liver function tests at baseline, every 2 weeks for cycles 1 and 2, prior to initiation of cycles 3–6, and then as clinically indicated.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
· Corrected QT (QTc) interval must be <450 msec and electrolyte abnormalities must be corrected prior to initiation of ribociclib therapy.1
· Consult respective manufacturers' labelings for information on dosage and administration (including dosage adjustments), adverse effects, and contraindications of other antineoplastic agents used in combination regimens.1
AdministrationOral Administration
Administer orally once daily without regard to food at approximately the same time each day, preferably in the morning.1
Swallow tablets whole; do not break, chew, crush, or split.1
If a dose is missed or vomited, take the next dose at the regularly scheduled time.1 Do not double the dose or take extra doses.1
Dosage
Available as ribociclib succinate; dosage expressed in terms of ribociclib.1
AdultsBreast CancerInitial Therapy for Advanced Breast Cancer
Oral
600 mg once daily on days 1–21 of each 28-day cycle in combination with letrozole 2.5 mg orally once daily given continuously during 28-day cycle.1 In principal efficacy study, therapy was continued until disease progression or unacceptable toxicity occurred.1 2
Dosage ModificationOral
Adverse effects may require temporary interruption, dosage reduction, or permanent discontinuance.1Adjust dosage based on individual safety and tolerability.1
Up to 2 dosage reductions for toxicity may be made.1 If dosage reduction from 600 mg once daily is necessary, initially reduce dosage to 400 mg once daily.1
If further dosage reduction necessary, reduce dosage to 200 mg once daily.1
Dosages <200 mg once daily not recommended; discontinue drug if 200-mg daily dosage is not tolerated.1
Hematologic Toxicity
Oral
If grade 4 neutropenia (ANC <500/mm3) occurs, temporarily interrupt ribociclib therapy.1 When neutropenia improves to grade 2 or less, resume therapy at reduced dosage.1
If grade 3 febrile neutropenia (ANC 500 to <1000/mm3 with fever ≥38.5ºC or fever >38ºC lasting >1 hour and/or infection) occurs, temporarily interrupt ribociclib therapy.1 When neutropenia improves to grade 2 or less, resume therapy at reduced dosage.1
For first occurrence of grade 3 neutropenia (ANC 500 to <1000/mm3), temporarily interrupt ribociclib therapy; upon recovery to grade 2 or less, resume therapy at same dosage.1 For subsequent occurrences of grade 3 neutropenia, temporarily interrupt ribociclib therapy; upon return to grade 2 or less, resume therapy at reduced dosage.1
If grade 1 or 2 neutropenia (ANC 1000/mm3 to less than the lower limit of normal [LLN]), no dosage modification required.1
Hepatic Toxicity
Oral
If grade 4 serum ALT and/or AST elevations (>20 times the ULN) with total bilirubin concentrations ≤2 times the ULN occur, discontinue ribociclib therapy.1
For first occurrence of grade 3 serum ALT and/or AST elevations (>5 times the ULN, but ≤20 times the ULN) with total bilirubin concentrations ≤2 times the ULN, temporarily interrupt ribociclib therapy; upon recovery to baseline or better grade, resume therapy at reduced dosage.1 If grade 3 hepatotoxicity recurs at reduced dosage, discontinue ribociclib therapy.1
For first occurrence of grade 2 serum ALT and/or AST elevations (>3 times the ULN, but ≤5 times the ULN) with total bilirubin concentrations ≤2 times the ULN in patients with preexisting ALT and/or AST concentrations ≤3 times the ULN, temporarily interrupt ribociclib therapy; upon recovery to baseline or better grade, resume therapy at same dosage.1 For subsequent occurrences, temporarily interrupt ribociclib therapy; upon recovery to baseline or better grade, resume therapy at reduced dosage.1
If grade 2 serum ALT and/or AST elevations with total bilirubin concentrations ≤2 times the ULN persist in patients with preexisting ALT and/or AST concentrations >3 times the ULN, but ≤5 times the ULN, continue ribociclib therapy without interruption.1
If grade 1 serum ALT and/or AST elevations (i.e., exceeding the ULN, but ≤3 times the ULN) with total bilirubin concentrations ≤2 times the ULN occur, no dosage modification required.1
If serum ALT and/or AST elevations >3 times the ULN with concomitant total bilirubin concentrations >2 times the ULN (irrespective of baseline hepatic function) occur in the absence of cholestasis, discontinue ribociclib therapy.1
Cardiovascular Toxicity
Oral
If QTc interval >480 msec occurs, temporarily interrupt ribociclib therapy; resume therapy at same dosage when QTc interval improves to <481 msec.1 If QTc-interval prolongation (i.e., ≥481 msec) recurs, temporarily interrupt ribociclib therapy; resume therapy at reduced dosage when QTc interval improves to <481 msec.1
If QTc interval >500 msec occurs on ≥2 separate ECGs during a single visit, temporarily interrupt ribociclib therapy; resume therapy at reduced dosage when QTc interval improves to <481 msec.1
When QTc-interval prolongation (>500 msec or increase of >60 msec from baseline) occurs concurrently with torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs and/or symptoms of serious arrhythmia, permanently discontinue ribociclib therapy.1
Other Toxicity
Oral
If grade 4 adverse reactions occur, discontinue ribociclib therapy.1
If grade 3 adverse reactions occur, temporarily interrupt ribociclib therapy; resume therapy at same dosage when toxicity improves to grade 1 or less.1 For subsequent occurrences of grade 3 adverse reactions, temporarily interrupt ribociclib therapy; resume therapy at reduced dosage when toxicity improves to grade 1 or less.1
If grade 1 or 2 adverse reactions occur, no dosage modification required; initiate appropriate medical therapy and additional monitoring as clinically indicated.1
Concomitant Use with Drugs and Foods Affecting Hepatic Microsomal EnzymesOral
If used concomitantly with a potent CYP3A inhibitor, reduce ribociclib dosage to 400 mg once daily.1(See Drugs and Foods Affecting Hepatic Microsomal Enzymes under Interactions.)
Prescribing LimitsAdultsBreast CancerOral
Dosages <200 mg once daily not recommended.1
Special PopulationsHepatic Impairment
Moderate or severe preexisting hepatic impairment (Child-Pugh class B or C): 400 mg once daily.1 (See Hepatic Impairment under Cautions.)
Mild preexisting hepatic impairment (Child-Pugh class A): No dosage adjustment required.1
Preexisting grade 3 or greater ALT and/or AST elevations: No specific dosage recommendations at this time.1
Renal Impairment
No specific dosage recommendations at this time.1 (See Renal Impairment under Cautions.)
Geriatric Patients
No specific dosage recommendations at this time.1 (See Geriatric Use under Cautions.)
Cautions for Ribociclib SuccinateContraindications
· Manufacturer states none known.1
Warnings/PrecautionsProlongation of QT Interval
QTc-interval prolongation, including one fatal case, reported.1 2 Prolongation appears to occur in a plasma concentration-dependent manner.1 Usually occurs within first 4 weeks of therapy and recovers upon dosage interruption.1 Torsades de pointes not observed in principal efficacy study.1
Avoid use in patients with congenital long QT syndrome, uncontrolled or clinically important cardiac disease (e.g., MI, CHF, unstable angina, bradyarrhythmias), electrolyte abnormalities, or other risk factors for developing prolongation of QT interval.1
Avoid concomitant use with potent CYP3A inhibitors or with drugs known to prolong the QT interval.1(See Specific Drugs and Foods under Interactions.)
Monitor ECGs at baseline, around day 14 of cycle 1, prior to initiation of cycle 2, and then as clinically indicated.1 More frequent ECG monitoring recommended in patients who develop QTc-interval prolongation during therapy.1
Monitor serum electrolytes (i.e., potassium, calcium, phosphorus, magnesium) at baseline, prior to initiation of cycles 1–6, and then as clinically indicated.1
QTc intervals must be <450 msec and electrolyte abnormalities must be corrected prior to initiation of therapy.1
If QTc-interval prolongation occurs, temporary interruption, dosage reduction, or discontinuance of ribociclib may be necessary.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
Hepatic Toxicity
Drug-induced hepatotoxicity reported.1 Median time to onset of grade 3 or greater elevations in ALT/AST concentrations: 57 days; resolution to grade 2 or less occurred in approximately 24 days.1
Monitor liver function tests at baseline, every 2 weeks for cycles 1 and 2, prior to initiation of cycles 3–6, and then as clinically indicated.1 More frequent testing necessary in patients who develop AST/ALT elevations.1
If hepatotoxicity occurs, temporary interruption, dosage reduction, or discontinuance of ribociclib may be necessary.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
Neutropenia
Grade 3 or 4 neutropenia occurs frequently.1 Median time to onset of grade 2 or greater neutropenia: 16 days.1 Median duration of grade 3 or greater neutropenia: 15 days.1 Febrile neutropenia also reported.1
Monitor CBC at baseline, every 2 weeks for cycles 1 and 2, prior to initiation of cycles 3–6, and then as clinically indicated.1
If neutropenia occurs, temporary interruption, dosage reduction, or discontinuance of ribociclib may be necessary.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm based on mechanism of action; embryofetal toxicity and teratogenicity demonstrated in animals.1
Confirm pregnancy status prior to initiating ribociclib therapy.1 Avoid pregnancy during therapy.1 Use effective contraceptive methods in women of childbearing potential while receiving ribociclib and for ≥3 weeks after drug is discontinued.1 Apprise patients of potential fetal hazard.1
Impairment of Fertility
Animal studies suggest ribociclib may impair male fertility.1
Specific PopulationsPregnancy
May cause fetal harm.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Confirm pregnancy status prior to initiating ribociclib therapy.1
Lactation
Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing during therapy and for ≥3 weeks after drug discontinuance.1
Pediatric Use
Safety and efficacy not established in pediatric patients.1
Dose-limiting toxicities were fatigue and thrombocytopenia in pediatric patients with relapsed or refractory neuroblastoma, malignant rhabdoid tumors, or other tumors with documented cyclin D-CDK4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway (cyclin D-CDK4/6-INK4-Rb pathway) abnormalities.16 Hematologic dose-limiting toxicities not observed in patients receiving ribociclib 350 mg/m² once daily.16
Dosage of 350 mg/m² orally once daily for 21 days followed by a 7-day rest period recommended for phase 2 studies in pediatric patients.16
Geriatric Use
No overall differences in safety and efficacy relative to younger patients.1
Hepatic Impairment
Mild preexisting hepatic impairment (Child-Pugh class A): Systemic exposure not substantially altered.1 3
Moderate to severe preexisting hepatic impairment (Child-Pugh class B or C): Increased mean systemic exposure less than twofold.1 3 Dosage adjustment required.1 (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Mild to moderate renal impairment (estimated GFR 30 to <90 mL/minute per 1.73 m2): Systemic exposure not substantially altered.1
Severe renal impairment (estimated GFR <30 mL/minute per 1.73 m2): Not studied.1
Common Adverse Effects
Combination therapy with letrozole: Neutropenia,1 2 nausea,1 2 infection (most commonly urinary tract and upper respiratory tract infections),1 2 fatigue,1 2 diarrhea,1 2 alopecia,1 2 leukopenia,1 2 vomiting,1 2constipation,1 2 headache,1 2 hot flush,2 back pain,1 2 decreased appetite,1 2 anemia,1 2 elevated AST/ALT concentrations,1 2 rash,1 2 pruritus,1 pyrexia,1 dyspnea,1 insomnia,1 peripheral edema,1 stomatitis,1abdominal pain,1 lymphopenia,1 decreased platelet count,1 elevated Scr concentrations,1 decreased serum phosphorus or potassium concentrations.1
Interactions for Ribociclib Succinate
Metabolized principally by CYP3A4.1 In vitro, reversible inhibitor of CYP1A2, 2E1, and 3A4/5 at clinically relevant concentrations; inhibition of CYP3A4/5 is time dependent.1
In vitro, does not inhibit CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2D6; cause time-dependent inhibition of CYP1A2, 2C9, and 2D6; or induce CYP1A2, 2B6, 2C9, and 3A4 at clinically relevant concentrations.1
In vitro, may inhibit breast cancer resistance protein (BCRP), organic cation transporter (OCT) 2, multidrug and toxic compound extrusion (MATE) 1, and bile salt export pump (BSEP); low potential for inhibition of P-glycoprotein (P-gp), MATE2K, OCT1, organic anion transport protein (OATP) 1B1, and OATP1B3 at clinically relevant concentrations.1
Drugs and Foods Affecting Hepatic Microsomal Enzymes
Potent CYP3A inhibitors: Possible pharmacokinetic interaction (increased plasma concentrations and AUC of ribociclib).1 Avoid concomitant use; consider choosing alternative agent with less CYP3A inhibition potential.1 If concomitant use cannot be avoided, reduce ribociclib dosage to 400 mg once daily.1 If potent CYP3A inhibitor is discontinued, resume ribociclib (after ≥5 terminal half-lives of the CYP3A inhibitor) at dosage used prior to initiation of potent CYP3A inhibitor.1 (See Specific Drugs and Foods under Interactions.)
Potent CYP3A inducers: Possible pharmacokinetic interaction (decreased plasma concentrations and AUC of ribociclib).1 Avoid concomitant use; consider choosing alternative agent with no or minimal CYP3A induction potential.1 (See Specific Drugs and Foods under Interactions.)
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP3A: Possible pharmacokinetic interaction (increased plasma concentrations of CYP3A substrate).1 If concomitant use of ribociclib and CYP3A substrates with a narrow therapeutic index cannot be avoided, consider dosage reduction of CYP3A substrate.1 (See Specific Drugs and Foods under Interactions.)
Drugs Affecting Gastric Acidity
Pharmacokinetic interaction unlikely with drugs that increase gastric pH.1 3
Drugs that Prolong QT Interval
Potential pharmacologic interaction (additive effect on QT-interval prolongation).1 (See Prolongation of QT Interval under Cautions.)
Specific Drugs and Foods
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Drug
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Interaction
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Comments
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Anastrozole
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No effect on pharmacokinetics of anastrozole or ribociclib1
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Antiarrhythmic agents (e.g., amiodarone, disopyramide, procainamide, quinidine, sotalol)
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Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Antiemetic agents that prolong QT interval (e.g., type 3 serotonin [5-HT3] receptor antagonists such as IV ondansetron)
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Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Antifungals, azoles (e.g., itraconazole, ketoconazole, posaconazole, voriconazole)
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Possible increased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
Select alternative agent with less CYP3A inhibition potential; if concomitant use unavoidable, reduce ribociclib dosage to 400 mg once daily1
If potent CYP3A inhibitor discontinued, resume ribociclib (after ≥5 terminal half-lives of the CYP3A inhibitor) at dosage used prior to initiation of potent CYP3A inhibitor1
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Antipsychotic agents that prolong QT interval (e.g., haloperidol, pimozide)
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Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Antiretrovirals, HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, lopinavir/ritonavir, saquinavir)
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Possible increased peak concentrations and exposure of ribociclib1
Ritonavir increased AUC and peak concentrations of ribociclib by 3.2- and 1.7-fold, respectively; AUC and peak concentrations of major metabolite, LEQ803, decreased by 98 and 96%, respectively1
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Avoid concomitant use1
Select alternative agent with less CYP3A inhibition potential; if concomitant use unavoidable, reduce ribociclib dosage to 400 mg once daily1
If potent CYP3A inhibitor discontinued, resume ribociclib (after ≥5 terminal half-lives of the CYP3A inhibitor) at dosage used prior to initiation of potent CYP3A inhibitor1
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Caffeine
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Peak concentrations of caffeine decreased by 10% and AUC increased by 20%1 3
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Carbamazepine
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Possible decreased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
Select alternative agent with no or minimal CYP3A induction potential1
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Chloroquine
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Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Conivaptan
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Possible increased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
Select alternative agent with less CYP3A inhibition potential; if concomitant use unavoidable, reduce ribociclib dosage to 400 mg once daily1
If conivaptan discontinued, resume ribociclib (after ≥5 terminal half-lives of conivaptan) at dosage used prior to initiation of conivaptan1
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Ergot derivatives (e.g., dihydroergotamine, ergotamine)
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Possible increased concentrations of ergot derivative1
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Caution advised with CYP3A substrates with narrow therapeutic index; if concomitant use unavoidable, consider dosage reduction of ergot derivative1
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Exemestane
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No effect on pharmacokinetics of exemestane or ribociclib1
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Grapefruit or grapefruit juice
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Possible increased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
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Immunosuppressive agents (e.g., cyclosporine, everolimus, sirolimus, tacrolimus)
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Possible increased concentrations of immunosuppressive agents metabolized by CYP3A1
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Caution advised with CYP3A substrates with narrow therapeutic index; if concomitant use unavoidable, consider dosage reduction of CYP3A substrate1
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Letrozole
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No effect on pharmacokinetics of letrozole or ribociclib1
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Macrolides (e.g., clarithromycin, erythromycin)
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Possible increased peak concentrations and exposure of ribociclib1
Clarithromycin: Possible additive effects on QT-interval prolongation1
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Macrolides that prolong QT interval: Avoid concomitant use1
Potent CYP3A inhibitors: Avoid concomitant use; select alternative agent with less CYP3A inhibition potential1
If concomitant use of potent CYP3A inhibitor unavoidable, reduce ribociclib dosage to 400 mg once daily; if potent CYP3A inhibitor is discontinued, resume ribociclib (after ≥5 terminal half-lives of the CYP3A inhibitor) at dosage used prior to initiation of potent CYP3A inhibitor1
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Methadone
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Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Midazolam
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Ribociclib 400 mg daily increased AUC and peak concentrations of midazolam by 3.8- and 2.1-fold, respectively1 3
Pharmacokinetic models suggest ribociclib 600 mg daily may increase AUC and peak concentrations of midazolam by 5.2- and 2.4-fold, respectively1 3
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Moxifloxacin
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Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Nefazodone
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Possible increased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
Select alternative agent with less CYP3A inhibition potential; if concomitant use unavoidable, reduce ribociclib dosage to 400 mg once daily1
If nefazodone discontinued, resume ribociclib (after ≥5 terminal half-lives of nefazodone) at dosage used prior to initiation of nefazodone1
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Opiate agonists (e.g., alfentanil, fentanyl)
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Possible increased concentrations of opiate agonists metabolized by CYP3A1
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Caution advised with CYP3A substrates with narrow therapeutic index; if concomitant use unavoidable, consider dosage reduction of CYP3A substrate1
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Phenytoin
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Possible decreased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
Select alternative agent with no or minimal CYP3A induction potential1
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Pimozide
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Possible increased concentrations of pimozide1
Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Pomegranate or pomegranate juice
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Possible increased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
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Proton-pump inhibitors
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No substantial effect on absorption of ribociclib1 3
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Quinidine
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Possible increased concentrations of quinidine1
Possible additive effects on QT-interval prolongation1
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Avoid concomitant use1
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Rifampin
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Rifampin decreased AUC and peak concentrations of ribociclib by 89 and 81%, respectively; peak concentrations of major metabolite, LEQ803, increased by 1.7-fold and AUC decreased by 27%1
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Avoid concomitant use1
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St. John’s wort (Hypericum perforatum)
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Possible decreased peak concentrations and exposure of ribociclib1
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Avoid concomitant use1
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Ribociclib Succinate PharmacokineticsAbsorptionBioavailability
Following oral administration, peak plasma concentrations attained in 1–4 hours.1 15 17
AUC and peak plasma concentrations are more than dose proportional over dosage range of 50–1200 mg; mean accumulation ratio is 2.5.1 15 17
Steady-state concentrations achieved in 8 days.1 15 17
Food
Administration with high-fat, high-calorie meal (approximately 800–1000 calories with approximately 50% of calories from fat) does not substantially affect rate or extent of absorption.1 3
Special Populations
Mean systemic exposure of ribociclib increased less than twofold in individuals with moderate or severe hepatic impairment (Child-Pugh class B or C).1 3 Mild hepatic impairment (Child-Pugh class A) does not affect systemic exposure.1 3
Mild or moderate renal impairment (estimated GFR 30 to <90 mL/minute per 1.73 m²) does not substantially affect systemic exposure.1 Pharmacokinetics not studied in severe renal impairment (estimated GFR <30 mL/minute per 1.73 m²).1
Age (23–84 years), gender, race, and body weight do not have clinically important effects on ribociclib exposure.1 3
DistributionExtent
Not known whether distributed into human milk.1
Plasma Protein Binding
Approximately 70%.1
EliminationMetabolism
Principally metabolized by CYP3A4.1
Elimination Route
Eliminated in feces (69%) and urine (23%).1
Half-life
Mean terminal plasma half-life: 29.7–54.7 hours.1
StabilityStorageOralTablets
20–25°C.1 Store in original container.1
Actions
· Selective inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6).1 2 4 14
· CDK4 and CDK6 involved in regulation of progression from the G1 into S phase of the cell cycle through regulation of phosphorylation of the tumor suppressor protein retinoblastoma.5 6 7 8 9 10 1112 13
· Inhibits the G1 into S phase of the cell cycle and reduces cellular proliferation of breast cancer cells.1 4
· Ribociclib and an antiestrogen (e.g., letrozole) increased cell growth arrest in patient-derived estrogen receptor-positive breast tumor xenografts compared with either drug alone.1
· Ribociclib reduced tumor volume, which correlated with inhibition of retinoblastoma protein phosphorylation, in xenograft models of human cancer.1
Advice to Patients
· Importance of advising patients to swallow ribociclib succinate tablets whole and not to break, chew, crush, or split the tablets.1
· If a dose is missed or vomited, importance of administering the next dose at the regularly scheduled time; do not administer an additional dose to make up for a missed dose.1
· Risk of QT-interval prolongation.1 Importance of informing clinicians immediately if an abnormal heartbeat or feelings of dizziness or faintness occur.1
· Risk of hepatotoxicity.1 Importance of advising patients to immediately report possible symptoms of hepatotoxicity (e.g., fatigue, anorexia, right upper quadrant pain, jaundice, dark urine, bleeding diathesis) to their clinician.1
· Risk of neutropenia.1 Importance of informing clinician immediately if signs or symptoms of neutropenia or infection (e.g., fever, chills) occur.1
· Risk of fetal harm.1 Necessity of advising women of childbearing potential to use an effective method of contraception during treatment and for ≥3 weeks after discontinuance of therapy.1Importance of women informing clinicians if they are or plan to become pregnant.1 Apprise patient of potential fetal hazard if used during pregnancy.1
· Importance of advising women to discontinue nursing during therapy and for ≥3 weeks after discontinuance of the drug.1
· Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses (e.g., hepatic impairment, cardiovascular disease [including congenital long QT syndrome]).1
· Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
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Ribociclib Succinate
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Routes
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Dosage Forms
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Strengths
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Brand Names
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Manufacturer
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Oral
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Tablets, film-coated
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200 mg (of ribociclib)
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Kisqali
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Novartis
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Ribociclib Succinate Combinations
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Routes
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Dosage Forms
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Strengths
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Brand Names
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Manufacturer
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Oral
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Kit
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Ribociclib succinate 200 mg (of ribociclib) (21, 42, or 63 film-coated tablets)
Letrozole 2.5 mg (28 film-coated tablets)
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Kisqali FemaraCo-Pack
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Novartis
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