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Letrozole / Ribociclib Dosage

Applies to the following strengths: 2.5 mg-200 mg

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

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.

Comments: This product is comprised of ribociclib tablets co-packaged with letrozole tablets to provide a 28-day treatment regimen.

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

Renal Dose Adjustments

Data not available.

Liver Dose Adjustments

-MILD HEPATIC IMPAIRMENT (Child-Pugh A): No adjustment recommended for both ribociclib and letrozole.
-MODERATE HEPATIC IMPAIRMENT (Child-Pugh B): Reduce the initial dose of ribociclib to 400 mg once a day; no adjustment recommended for letrozole.
-SEVERE HEPATIC IMPAIRMENT (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.

IF HEPATOBILIARY TOXICITY DEVELOPS DURING THERAPY:
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 both ribociclib and letrozole.
-GRADE 2 (Greater than 3 to 5 x ULN):
*Baseline at Grade 2: No dose interruption for both ribociclib and letrozole.
*Baseline 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.
-GRADE 2 RECURRENCE OR 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 treatment.

COMBINED ELEVATIONS IN AST AND/OR ALT GREATER THAN 3 x ULN (WITH total bilirubin greater than 2 x ULN irrespective of baseline grade, in the absence of cholestasis): Discontinue treatment.

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 LEVELS 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 treatment 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 1/2 (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.

RIBOCICLIB DOSING FOR QT PROLONGATION:
-QTcF GREATER THAN 480 MSEC: Interrupt dose until QTcF resolves to less than 481 msec, then resume at the same dose; resume at next lower dose with recurrence.
-QTcF GREATER THAN 500 MSEC (on at least 2 separate ECGs within the same visit): Interrupt dose until QTcF resolves to less than 481 msec, then resume at next lower dose.
-QTcF 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): Permanently discontinue treatment.

RIBOCICLIB DOSING FOR OTHER TOXICITIES:
-GRADE 1/2: 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.
-GRADE 4: Discontinue treatment.

Precautions

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 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.

Storage Requirements:
-Store in the original package at 20 to 25 degrees Celsius (68 to 77 Fahrenheit).

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 treatment.
-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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