Ribociclib

Indications

Ribociclib is used for: Hormone receptor positive, HER2-negative locally advanced carcinoma of breast, Hormone receptor positive, HER2-negative metastatic carcinoma of breast

Adult Dose

Oral Hormone receptor positive, HER2-negative locally advanced carcinoma of breast, Hormone receptor positive, HER2-negative metastatic carcinoma of breast Adult: In combination with an aromatase inhibitor, or in combination with fulvestrant in postmenopausal women: 600 mg once daily preferably in the morning for 21 days followed by 7-days off to complete 28 days cycle. Pre/perimenopausal women should be treated with luteinising hormone-releasing hormone (LHRH) agonist. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability. Management of adverse reactions adjustment:1st reduction: 400 mg once daily; 2nd dose: 200 mg once daily; discontinue if dose reduction below 200 mg once daily is required. Hepatic impairment Mild (Child-Pugh A): No dose adjustment required Moderate-to-severe (Child-Pugh B or C): Reduce starting dose to 400 mg/day

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (CrCl ?30 mL/min): No dose adjustment necessary Severe (CrCl 15-30 mL/min): Decrease starting dose to 200 mg/day Only studied healthy subjects and noncancer subjects with severe renal impairment

Administration

May be taken with or without food.

Contra Indications

Pregnancy and lactation.

Precautions

Severe renal and hepatic impairment.

Pregnancy-Lactation

Pregnancy There are no available human data informing the drug-associated risk Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman In animal reproduction studies, administration during organogenesis resulted in increased incidences of postimplantation loss and reduced fetal weights in rats and increased incidences of fetal abnormalities in rabbits at exposures 0.6 or 1.5 times the exposure in humans Infertility: Based on animal studies, may impair fertility in males Contraception Females of reproductive potential should have a pregnancy test prior to starting treatment Females: Advise females of reproductive potential to use effective contraception (methods that result in <1% pregnancy rates) during treatment and for at least 3 weeks after the last dose Lactation Unknown if distributed in human breast milk Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking ribociclib and for at least 3 weeks after the last dose In lactating rats administered a single dose of 50 mg/kg, exposure to ribociclib was 3.56-fold higher in milk compared to maternal plasma

Interactions

Increased risk of QT prolongation with antiarrhythmic drugs (e.g. amiodarone, disopyramide) and other drugs which are known to prolong QT interval (e.g. chloroquine, bepridil, pimozide, moxifloxacin, tamoxifen). May increase the plasma concentration and risk of toxicity with strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, nefazodone) and increase plasma concentration of CYP3A4 substrates (e.g. ergotamine, quinidine, cisapride). May decrease efficacy with CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine).

Adverse Effects

Side effects of Ribociclib : >10% Neutropenia (75%) Nausea (52%) Neutropenia, grade 3 (50%) Fatigue (37%) Diarrhea (35%) Leukopenia (33%) Alopecia (33%) Vomiting (29%) Constipation (25%) Headache (22%) Leukopenia, grade 3 (20%) Back pain (20%) Decreased appetite (19%) Anemia (18%) Abnormal LFTs (18%) Rash (17%) Pruritus (14%) Pyrexia (13%) Peripheral edema (12%) Stomatitis (12%) Insomnia (12%) Dyspnea (12%) Lymphopenia (11%) Urinary tract infection (11%) Abdominal pain (11%) 1-10% Neutropenia, grade 2 (10%)

Mechanism of Action

Ribociclib selectively inhibits cyclin-dependent kinases (CDK) 4 and 6 which are involved in cell proliferation. The interaction between cyclin D and CDK 4 and 6 is blocked, preventing the phosphorylation of tumour suppressor protein retinoblastoma and the progression of cell cycle from G1 into S phase thereby inhibiting cancer cell growth.