RIBOCICLIB
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RIBOCICLIB (RIBOCICLIB).
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Selectively inhibits CDK4 and CDK6, leading to reduced phosphorylation of retinoblastoma protein, G1-to-S phase cell cycle arrest, and decreased proliferation of estrogen receptor-positive breast cancer cells.
| Metabolism | Primarily metabolized by CYP3A4. Minor contribution from CYP3A5 and SULT2A1. |
| Excretion | Primarily hepatic metabolism (CYP3A4) with fecal excretion as major route (69% of dose as metabolites, 23% unchanged in feces); renal excretion accounts for approximately 12% (primarily as metabolites, <1% unchanged). |
| Half-life | Terminal elimination half-life is 32.0 hours (range 29.2–40.4 hours), supporting once-daily dosing. |
| Protein binding | Approximately 70% bound to human plasma proteins (mainly albumin and α1-acid glycoprotein). |
| Volume of Distribution | Mean apparent volume of distribution (Vz/F) is 1090 L (approximately 15.6 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 45–65% (absolute bioavailability not formally determined; relative bioavailability from oral formulation is high with Tmax of 1–4 hours). |
| Onset of Action | Clinical effect (CDK4/6 inhibition) begins within hours of oral administration; maximal retinoblastoma protein dephosphorylation observed within 4–8 hours. |
| Duration of Action | The pharmacodynamic effect (cell cycle arrest) persists for the dosing interval of 24 hours; continuous daily dosing maintains sustained target inhibition. |
600 mg orally once daily for 21 consecutive days followed by 7 days off treatment, in combination with an aromatase inhibitor or fulvestrant.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for estimated GFR ≥30 mL/min. For GFR <30 mL/min, consider alternative therapy or reduce dose to 400 mg once daily based on risk-benefit assessment; no recommended dose for GFR <15 mL/min or on dialysis. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 400 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dosing. |
| Geriatric use | No specific dose adjustment beyond standard monitoring; elderly patients may be more susceptible to adverse effects such as neutropenia, QTc prolongation, and hepatotoxicity; monitor CBC, LFTs, and ECGs regularly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RIBOCICLIB (RIBOCICLIB).
| Breastfeeding | No data on the presence of ribociclib in human milk, its effects on the breastfed infant, or on milk production. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for at least 3 weeks after the last dose. M/P ratio: Not available. |
| Teratogenic Risk | Ribociclib is contraindicated in pregnancy. Based on its mechanism of action (CDK4/6 inhibition), it is expected to cause fetal harm. In animal studies, ribociclib was embryotoxic and fetotoxic at maternal exposures below the human clinical exposure. First trimester: High risk of structural abnormalities. Second and third trimesters: Risk of fetal growth restriction and impaired organ development. Adequate contraception is required before and during treatment. |
■ FDA Black Box Warning
No FDA black box warning
| Serious Effects |
["None known (no absolute contraindications listed in prescribing information)"]
| Precautions | ["Neutropenia: Monitor complete blood counts prior to treatment and at the start of each cycle","Interstitial lung disease (ILD)/pneumonitis: Monitor for pulmonary symptoms","Hepatotoxicity: Monitor liver function tests","QT interval prolongation: Avoid in patients with significant QT prolongation or risk factors","Venous thromboembolism: Monitor for signs/symptoms","Embryo-fetal toxicity: Can cause fetal harm. Advise use of effective contraception."] |
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| Fetal Monitoring | Monitor complete blood count (CBC) prior to start of therapy and at the beginning of each cycle, and as clinically indicated due to risk of neutropenia. Monitor liver function tests (ALT, AST, bilirubin) before therapy, at the beginning of each cycle, and as clinically indicated. Monitor ECG for QT interval prolongation before treatment, at cycle 1 day 15, and as clinically indicated. In pregnancy, additional fetal monitoring with ultrasound for growth and anatomy is recommended if exposure occurs. |
| Fertility Effects | Based on animal studies, ribociclib may impair male and female fertility. In female rats, ribociclib caused disruption of the estrous cycle, decreased corpora lutea, and reduced fertility at exposures below clinical levels. In male rats, it caused decreased sperm motility and count. The effect on human fertility is unknown, but reversible upon discontinuation in animal studies. |