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Letrozole / Ribociclib Dosage

Medically reviewed by Drugs.com. Last updated on Apr 8, 2019.

Applies to the following strengths: 2.5 mg-200 mg

Usual Adult Dose for Breast Cancer

Letrozole: 2.5 mg orally once a day throughout the 28-day cycle
Ribociclib: 600 mg orally once a day for 21 consecutive days followed by 7 days off for a 28-day cycle

Use: Initial endocrine-based therapy for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer

Renal Dose Adjustments

LETROZOLE:
-Mild (CrCl 60 to less than 90 mL/min) to moderate (CrCl 30 to less than 60 mL/min) renal impairment: No adjustment recommended.
-Severe (CrCl 15 to less than 30 mL/min) renal impairment: Start with 200 mg orally once a day in healthy subjects; there is no data for severe renal impairment dosing in breast cancer patients
-End-stage renal disease (ESRD [eGFR less than 15 mL/min/1.73 m2]: Data not available

RIBOCICLIB:
-CrCl 10 mL/min or greater: No adjustment recommended.
-CrCl less than 10 mL/min: Data not available

Liver Dose Adjustments

Mild hepatic dysfunction (Child-Pugh A): No adjustment recommended (for both ribociclib and letrozole).
Moderate hepatic dysfunction (Child-Pugh B): Reduce the initial dose of ribociclib to 400 mg once a day; no adjustment recommended for letrozole.
Severe hepatic dysfunction (Child-Pugh C) and/or cirrhosis: Reduce the initial dose of ribociclib to 400 mg once a day; reduce the dose of letrozole by 50% to 2.5 mg every other day.

DOSE MODIFICATION OF RIBOCICLIB FOR HEPATOBILIARY TOXICITY:
AST and/or ALT ELEVATIONS FROM BASELINE (WITHOUT total bilirubin increase above 2 times upper limit of normal [ULN]):
-GRADE 1 (Greater than ULN to 3 x ULN): No adjustment recommended for either ribociclib or letrozole.
-GRADE 2 (Greater than 3 to 5 x ULN):
*Baseline at less than Grade 2: Interrupt ribociclib dose until recovery to baseline or less, then resume at the same dose; no dose adjustment recommended for letrozole.
*Baseline at Grade 2: No dose interruption.
-GRADE 3 (Greater than 5 to 20 x ULN): Interrupt ribociclib dose until recovery to baseline or less, then resume at the next lower dose; no dose adjustment recommended for letrozole.
-GRADE 3 RECURRENCE OR GRADE 4 (Greater than 20 x ULN): Discontinue therapy.
-COMBINED ELEVATIONS IN AST and/or ALT WITH TOTAL BILIRUBIN INCREASE, IN THE ABSENCE OF CHOLESTASIS: If patients develop ALT and/or AST greater than 3 x ULN along with total bilirubin greater than 2 x ULN irrespective of baseline Grade: Discontinue therapy.

Dose Adjustments

CONCOMITANT USE WITH STRONG CYP450 3A INDUCERS AND/OR STRONG CYP450 3A INHIBITORS: Avoid concomitant use if possible; consider alternative concomitant medications.
-IF CONCOMITANT USE OF STRONG CYP450 3A INHIBITOR IS NECESSARY: Reduce the dose of ribociclib to 400 mg once a day; no dose adjustment recommended for letrozole.
-IF STRONG CYP450 3A INHIBITOR DISCONTINUED: Change the ribociclib dose (AFTER at least 5 half-lives of the strong CYP450 3A inhibitor) to the dose used prior to the initiation of the strong CYP450 3A inhibitor; no dose adjustment recommended for letrozole.

RIBOCICLIB DOSE REDUCTION FOR ADVERSE REACTIONS (neutropenia, QT prolongation, other toxicities):
-Initial dose: 600 mg/day
-First dose reduction: 400 mg/day
-Second dose reduction: 200 mg/day
-Discontinue ribociclib if further dose reduction below 200 mg/day is required.
-Comments: No dose adjustment recommended for letrozole when it is administered with ribociclib (for the adverse reactions of ribociclib).

RIBOCICLIB DOSING FOR NEUTROPENIA:
-GRADE 1 or 2 (Absolute neutrophil count [ANC] 1000/mm3 to less than lower limit of normal [LLN]): No adjustment recommended.
-GRADE 3 (ANC 500/mm3 to less than 1000/mm3): Interrupt dose until recovery to Grade 2 or less, then resume at the same dose.
-GRADE 3 RECURRENCE: Interrupt dose until recovery, then resume at the next lower dose.
-GRADE 3 febrile neutropenia (single episode of fever greater than 38.3 degrees Celsius OR above 38 degrees for more than 1 hour and/or concurrent infection) OR GRADE 4 (ANC Less than 500/mm3): Interrupt dose until recovery to Grade 2 or less, then resume at the next lower dose level.

RIBOCICLIB DOSING FOR QT PROLONGATION:
-ECGs with QTcF greater than 480 msec: Interrupt dose; if QTcF resolves to less than 481 msec, resume therapy at the next lower dose level; if QTcF 481 msec or greater recurs, interrupt dose until QTcF resolves to less than 481 msec; then resume at next lower dose level.
-ECGs with QTcF greater than 500 msec: Interrupt dose if QTcF greater than 500 msec; if QTcF prolongation resolves to less than 481 msec, resume therapy at the next lower dose level.
-Permanently discontinue ribociclib if QTcF interval prolongation is either greater than 500 msec or greater than 60 msec change from baseline AND associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia.

RIBOCICLIB DOSE MODIFICATION AND MANAGEMENT FOR INTERSTITIAL LUNG DISEASE/PNEUMONITIS:
-GRADE 1 (asymptomatic): No dose adjustment or interruption required; initiate medical therapy and monitor as indicated.
-GRADE 2 (symptomatic): Interrupt dose until recovery to Grade 1 or less then consider resuming at the next lower dose level; if Grade 2 recurs, discontinue this drug.

RIBOCICLIB DOSE MODIFICATION FOR OTHER TOXICITIES:
-GRADE 1 or 2: No adjustment recommended; initiate appropriate medical therapy and monitor as clinically indicated.
-GRADE 3: Interrupt dose until recovery to Grade 1 or less, then resume at the same dose.
-GRADE 3 RECURRENCE: Interrupt dose until recovery to Grade 1 or less, then resume at the next lower dose level.
-GRADE 4: Discontinue this drug.

Precautions

CONTRAINDICATIONS:
-Hypersensitivity to the active component or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available.

Other Comments

Administration Advice:
-Administer this drug combination with or without food at approximately the same time each day (preferably in the morning).
-Swallow tablets whole; do not chew, crush, or split tablets.
-Do not make up a missed or vomited dose; administer the next scheduled dose at the usual time.
-This product is comprised of ribociclib tablets (200 mg per tablet) co-packaged with letrozole tablets (2.5 mg per tablet) to provide a 28-day therapy regimen.

Storage Requirements:
-Store in the original package at 20C to 25C (68F to 77F).

General:
-In vivo studies using patient-derived estrogen receptor positive breast cancer xenograft models demonstrated the combination of ribociclib and an antiestrogen (e.g., letrozole) resulted in increased tumor growth inhibition compared to each drug alone.
-There are no known cases of overdose with ribociclib and letrozole; initiate general symptomatic and supportive measures in all cases of overdosage as necessary.

Monitoring:
-CARDIOVASCULAR: ECGs with ribociclib (before treatment initiation, at approximately Day 14 of the first cycle, at the beginning of the second cycle, and as clinically indicated; more frequent monitoring if QTcF prolongation occurs at any given time during treatment); serum electrolytes (before treatment initiation, at the beginning of the first 6 cycles, and as clinically indicated)
-HEMATOLOGICAL: CBC (before treatment initiation, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated)
-HEPATIC: LFTs (before treatment initiation, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated; more frequent monitoring if Grade 2 or greater abnormalities noted)

Patient Advice:
-Avoid pomegranate/pomegranate juice and grapefruit/grapefruit juice during therapy.
-This combination drug product contains 2 different types of medications; the violet tablet is ribociclib and the yellow tablet is letrozole.
-Immediately contact your healthcare provider if you develop a fever, particularly in association with any suspected infection.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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