Breast cancer, advanced or metastatic:

Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer (in combination with an aromatase inhibitor) in pre-/perimenopausal or postmenopausal females as initial endocrine-based therapy.

Treatment of HR-positive, HER2-negative advanced or metastatic breast cancer (in combination with fulvestrant) in postmenopausal females as initial endocrine-based therapy or following disease progression on endocrine therapy.

Antineoplastic Agent, Cyclin-Dependent Kinase Inhibitor

Absorption

Effects of food: No effect on rate and extent of absorption.
Tmax, oral: 1 to 4 hours

Distribution

Protein binding, plasma proteins: 70%
Vd: 1090 L

Metabolism

Liver: Extensive
Inhibitor of CYP3A4
Substrate of CYP3A4

Excretion

Renal: 23%; unchanged 12%
Fecal: 69%; unchanged 17%
Oral clearance: 25.5 L/hr
Elimination Half Life: 32 hrs

US manufacturer's labeling : no contraindications

Canadian labeling: 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.

Ribociclib may be expected to cause fetal harm if used during pregnancy.(Based on the mechanism of action and data from animal reproduction studies)
Women of reproductive potential should have a pregnancy test prior to treatment and use effective contraception during treatment and for at least 3 weeks after the last ribociclib dose.

Not known if ribociclib is present in breast milk.
The manufacturer does not recommend breastfeeding during therapy or for at least 3 weeks after the last ribociclib dose.(due to the potential for adverse events in the breastfed infant)

>10% (Very Common):

Hematologic: leukopenia, lymphocytopenia, anemia

Gastrointestinal: nausea, diarrhea, vomiting

Hepatic: elevated transaminases, increased GGT

Dermatologic: alopecia, rash

Nervous & Musculoskeletal: fatigue, headache, arthralgia

Metabolic & Renal: decreased albumin and glucose, increased creatinine

Infections: high incidence of infections

1–10% (Common):

Cardiovascular: QT prolongation

Gastrointestinal & Dermatologic: dysgeusia, xeroderma

Ophthalmic: dry eye

Respiratory: interstitial lung disease, pneumonitis

<1% & Undefined (Rare):

Respiratory & Cardiovascular: acute respiratory distress syndrome (ARDS), pulmonary fibrosis, pulmonary embolism

Metabolic: hypomagnesemia

Breast cancer, advanced or metastatic(for Females (hormone receptor[HR]+, [HER2]-)):

Oral: 600 mg QD for 21 days, followed by a 7-day rest period to complete a 28-day treatment cycle (in combination with either an a romatase inhibitor or fulvestrant).Continue until disease progression or unacceptable toxicity

Dosage adjustment for concomitant strong CYP3A inhibitors: Avoid concomitant use with strong CYP3A inhibitors and consider alternatives with less potential for CYP3A inhibition.
If coadministration with a strong CYP3A inhibitor cannot be avoided, reduce ribociclib dose to 400 mg QD. If the strong inhibitor is discontinued, increase ribociclib dose (after at least 5 inhibitor half-lives of the strong CYP3A4 inhibitor have elapsed) to the dose used prior to initiating the strong CYP3A inhibitor.

Missed doses: If a ribociclib dose is missed or vomited, do not administer an additional dose that day. Resume ribociclib dosing with the next usual dose.

nil

Hepatic impairment at baseline:

- Mild impairment (Child-Pugh class A): No dosage adjustment
- Moderate or severe impairment (Child-Pugh class B or C): Reduce initial dose to 400 mg QD

Hepatobiliary toxicity 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 dosage adjustment
- Grade 2 (ALT and/or AST elevated >3~5 times ULN): If baseline was below grade 2, interrupt 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 >5~20 times ULN): Interrupt 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 in ≦30℃ & keep children away