Early Breast Cancer

KISQALI is indicated in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.

Advanced or Metastatic Breast Cancer

KISQALI is indicated for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with: an aromatase inhibitor as initial endocrine-based therapy; or fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.

Ribociclib是一種CDK4/6抑制劑。CDK4/6在細胞週期中扮演促進細胞增生的重要角色，它會使pRb蛋白磷酸化，進而解除pRb對細胞週期的抑制，讓細胞可以繼續進入分裂階段。 Ribociclib會抑制CDK4/6的活性，使pRb維持在較未磷酸化的狀態，因此細胞週期受到抑制，讓癌細胞不容易繼續分裂和增生。

Distribution: Vss/F: 1,090 L

Protein binding: ~70%.

Metabolism: Extensively hepatic.

Bioavailability: Mean absolute bioavailability: 65.8% (single oral dose of 600 mg).

Half-life: ~30 to 55 hours.

Time to peak: 1 to 4 hours.

Excretion : Feces (69%; 17% as parent drug, 14% as metabolite M1, 3% as other metabolites); Urine (23%; 12% as parent drug, 4% as M1, 3% as other metabolites).

Hypersensitivity to ribociclib or any component of the formulation; untreated congenital long QT syndrome, Fridericia-corrected QT interval (QTcF) 450 msec at baseline and patients at significant risk of developing QTc prolongation.

Based on findings from animal studies and the mechanism of action, KISQALI can cause fetal harm when administered to a pregnant woman.
The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies in the U.S. general population.

It is not known if ribociclib is present in human milk. There are no data on the effects of ribociclib on the breastfed infant or on milk production. Ribociclib and its metabolites readily passed into the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants from KISQALI, advise lactating women not to breastfeed while taking KISQALI and for at least 3 weeks after the last dose.

1. Interstitial Lung Disease/Pneumonitis
2. Severe Cutaneous Adverse Reactions
3. QT Interval Prolongation
4. Hepatotoxicity
5. Neutropenia

Early Breast Cancer

The recommended dosage of KISQALI is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with an aromatase inhibitor. Refer to the Full Prescribing Information for the recommended dosage of the aromatase inhibitor.
In patients with early breast cancer, treatment with KISQALI should continue for 3 years or until disease recurrence or unacceptable toxicity occurs.

Advanced or Metastatic Breast Cancer

The recommended dosage of KISQALI is 600 mg (three 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles.
KISQALI should be given in combination with endocrine therapy (fulvestrant or an aromatase inhibitor). Refer to the Full Prescribing Information for the recommended dose of endocrine therapy.

N/A

eGFR 30 to 89 mL/minute/1.73 m2: No dosage adjustment is necessary.
eGFR <30 mL/minute/1.73 m2: Reduce initial dose to 200 mg once daily.

Hepatic impairment prior to treatment initiation:

1. Early breast cancer:
Mild, moderate, or severe impairment (Child-Turcotte-Pugh class A, B, C): No dosage adjustment necessary.

2. Advanced or metastatic breast cancer:
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Turcotte-Pugh class B, C): Reduce initial ribociclib dose to 400 mg once daily.

Acute hepatotoxicity during treatment - Elevations from baseline without total bilirubin increase >2 times the ULN :
Grade 1 (ALT and/or AST elevated >1 to 3 times ULN):
No ribociclib dosage adjustment necessary.

Grade 2 (ALT and/or AST elevated >3 to 5 times ULN):
If baseline was below grade 2, interrupt ribociclib treatment until recovery to baseline or lower and then resume ribociclib at the same dose level. For recurrent grade 2 elevations, interrupt treatment until recovery and then resume ribociclib at the next lower dose level. If baseline was at grade 2, no dose interruption necessary.

Grade 3 (ALT and/or AST elevated >5 to 20 times ULN):
Interrupt ribociclib treatment until recovery to baseline or lower and then resume ribociclib at the next lower dose level. For recurrent grade 3 elevations, discontinue ribociclib.

Grade 4 (ALT and/or AST elevated >20 times ULN): Discontinue ribociclib.

Combined ALT and/or AST elevations >3 times ULN with total bilirubin increase >2 times ULN (in the absence of cholestasis), regardless of baseline grade: Discontinue ribociclib.

Store at room temperature at 20°C to 25°C, excursions permitted between 15°C and 30°C. Store in the original blister package in order to protect from moisture.