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Kisqali

Generic Name: 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

Introduction

Antineoplastic agent; a selective inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6).1 2 4 14

Uses for Kisqali

Breast 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

Kisqali 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

Administration

Oral 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

Adults

Breast Cancer
Initial 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 Modification
Oral

Adverse effects may require temporary interruption, dosage reduction, or permanent discontinuance.1 Adjust 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 Enzymes
Oral

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 Limits

Adults

Breast Cancer
Oral

Dosages <200 mg once daily not recommended.1

Special Populations

Hepatic 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 Kisqali

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Prolongation 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 Populations

Pregnancy

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 2 constipation,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,1 abdominal pain,1 lymphopenia,1 decreased platelet count,1 elevated Scr concentrations,1 decreased serum phosphorus or potassium concentrations.1

Interactions for Kisqali

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

Drug

Interaction

Comments

Anastrozole

No effect on pharmacokinetics of anastrozole or ribociclib1

Antiarrhythmic agents (e.g., amiodarone, disopyramide, procainamide, quinidine, sotalol)

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Antiemetic agents that prolong QT interval (e.g., type 3 serotonin [5-HT3] receptor antagonists such as IV ondansetron)

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Antifungals, azoles (e.g., itraconazole, ketoconazole, posaconazole, voriconazole)

Possible increased peak concentrations and exposure of ribociclib1

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

Antipsychotic agents that prolong QT interval (e.g., haloperidol, pimozide)

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Antiretrovirals, HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, lopinavir/ritonavir, saquinavir)

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

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

Caffeine

Peak concentrations of caffeine decreased by 10% and AUC increased by 20%1 3

Carbamazepine

Possible decreased peak concentrations and exposure of ribociclib1

Avoid concomitant use1

Select alternative agent with no or minimal CYP3A induction potential1

Chloroquine

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Conivaptan

Possible increased peak concentrations and exposure of ribociclib1

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

Ergot derivatives (e.g., dihydroergotamine, ergotamine)

Possible increased concentrations of ergot derivative1

Caution advised with CYP3A substrates with narrow therapeutic index; if concomitant use unavoidable, consider dosage reduction of ergot derivative1

Exemestane

No effect on pharmacokinetics of exemestane or ribociclib1

Grapefruit or grapefruit juice

Possible increased peak concentrations and exposure of ribociclib1

Avoid concomitant use1

Immunosuppressive agents (e.g., cyclosporine, everolimus, sirolimus, tacrolimus)

Possible increased concentrations of immunosuppressive agents metabolized by CYP3A1

Caution advised with CYP3A substrates with narrow therapeutic index; if concomitant use unavoidable, consider dosage reduction of CYP3A substrate1

Letrozole

No effect on pharmacokinetics of letrozole or ribociclib1

Macrolides (e.g., clarithromycin, erythromycin)

Possible increased peak concentrations and exposure of ribociclib1

Clarithromycin: Possible additive effects on QT-interval prolongation1

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

Methadone

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Midazolam

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

Moxifloxacin

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Nefazodone

Possible increased peak concentrations and exposure of ribociclib1

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

Opiate agonists (e.g., alfentanil, fentanyl)

Possible increased concentrations of opiate agonists metabolized by CYP3A1

Caution advised with CYP3A substrates with narrow therapeutic index; if concomitant use unavoidable, consider dosage reduction of CYP3A substrate1

Phenytoin

Possible decreased peak concentrations and exposure of ribociclib1

Avoid concomitant use1

Select alternative agent with no or minimal CYP3A induction potential1

Pimozide

Possible increased concentrations of pimozide1

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Pomegranate or pomegranate juice

Possible increased peak concentrations and exposure of ribociclib1

Avoid concomitant use1

Proton-pump inhibitors

No substantial effect on absorption of ribociclib1 3

Quinidine

Possible increased concentrations of quinidine1

Possible additive effects on QT-interval prolongation1

Avoid concomitant use1

Rifampin

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

Avoid concomitant use1

St. John’s wort (Hypericum perforatum)

Possible decreased peak concentrations and exposure of ribociclib1

Avoid concomitant use1

Kisqali Pharmacokinetics

Absorption

Bioavailability

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

Distribution

Extent

Not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 70%.1

Elimination

Metabolism

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

Stability

Storage

Oral

Tablets

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 11 12 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.1 Importance 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.

Ribociclib Succinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg (of ribociclib)

Kisqali

Novartis

Ribociclib Succinate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Kit

Ribociclib succinate 200 mg (of ribociclib) (21, 42, or 63 film-coated tablets)

Letrozole 2.5 mg (28 film-coated tablets)

Kisqali Femara Co-Pack

Novartis

AHFS DI Essentials. © Copyright 2017, Selected Revisions October 16, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Novartis Pharmaceuticals. Kisqali (ribociclib succinate) tablets prescribing information. East Hanover, NJ; 2017 Mar.

2. Hortobagyi GN, Stemmer SM, Burris HA et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375:1738-1748. [PubMed 27717303]

3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209092Orig1s000: Multi-discipline review. From FDA website. Accessed 2017 Aug 8.

4. Tripathy D, Bardia A, Sellers WR. Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors. Clin Cancer Res. 2017; [PubMed 28351928]

5. Morikawa A, Henry NL. Palbociclib for the Treatment of Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Clin Cancer Res. 2015; 21:3591-6. [PubMed 26100274]

6. Rocca A, Farolfi A, Bravaccini S et al. Palbociclib (PD 0332991) : targeting the cell cycle machinery in breast cancer. Expert Opin Pharmacother. 2014; 15:407-20. [PubMed 24369047]

7. Murphy CG, Dickler MN. The Role of CDK4/6 Inhibition in Breast Cancer. Oncologist. 2015; 20:483-90. [PubMed 25876993]

8. Mangini NS, Wesolowski R, Ramaswamy B et al. Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer. Ann Pharmacother. 2015; 49:1252-60. [PubMed 26324355]

9. Vidula N, Rugo HS. Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data. Clin Breast Cancer. 2016; 16:8-17. [PubMed 26303211]

10. Hosford SR, Miller TW. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, Src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways. Pharmgenomics Pers Med. 2014; 7:203-15. [PubMed 25206307]

11. Finn RS, Dering J, Conklin D et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009; 11:R77. [PubMed 19874578]

12. Sutherland RL, Musgrove EA. CDK inhibitors as potential breast cancer therapeutics: new evidence for enhanced efficacy in ER+ disease. Breast Cancer Res. 2009; 11:112. [PubMed 20067604]

13. DeMichele A, Clark AS, Tan KS et al. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015; 21:995-1001. [PubMed 25501126]

14. Novartis Pharmaceuticals. Kisqali Femara Co-Pack (ribociclib succinate copackaged with letrozole) tablets prescribing information. East Hanover, NJ; 2017 May.

15. Curigliano G, Gómez Pardo P, Meric-Bernstam F et al. Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study. Breast. 2016; 28:191-8. [PubMed 27336726]

16. Geoerger B, Bourdeaut F, DuBois SG et al. A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors. Clin Cancer Res. 2017; 23:2433-2441. [PubMed 28432176]

17. Infante JR, Cassier PA, Gerecitano JF et al. A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas. Clin Cancer Res. 2016; 22:5696-5705. [PubMed 27542767]

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