11/23/2023 0 Comments Ribociclib liver toxicity![]() Drug InteractionsĪbemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Dietary ConsiderationsĪvoid grapefruit and grapefruit juice. Swallow tablets whole do not crush, chew, or split tablets (do not ingest broken or cracked tablets). Administer at approximately the same time each day, preferably in the morning. Oral: May be administered with or without food. If grade 3 toxicity recurs, interrupt treatment until recovery to grade 1 or lower and then resume ribociclib at the next lower dose level. Grade 3: Interrupt treatment until recovery to grade 1 or lower and then resume ribociclib at the same dose level. Initiate appropriate medical management and monitoring as clinically indicated. Grade 1 or 2: No dosage adjustment necessary. Other nonhematologic toxicities (excluding neutropenia, hepatobiliary toxicity, QT interval prolongation, and interstitial lung disease/pneumonitis based on Common Toxicity Criteria for Adverse Events Version 4.03): Grade 3 (severe symptomatic) or 4 (life threatening): Discontinue ribociclib. If grade 2 toxicity recurs, discontinue ribociclib. Grade 2 (symptomatic): Interrupt treatment until recovery to grade 1 or lower and then consider resuming ribociclib at the next lower dose level, based on the risks versus benefits of resuming therapy. ![]() Grade 1 (asymptomatic): No dosage interruption or adjustment necessary. Pulmonary toxicity: Interstitial lung disease/pneumonitis: Grade 4 neutropenia (ANC 480 msec: Interrupt treatment when QTcF resolves to 500 msec: Interrupt treatment for QTcF >500 msec if QTcF resolves to 500 msec or >60 msec increase from baseline AND associated with torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia, permanently discontinue ribociclib. ~70% Use in Specific Populations Special Populations: Renal Function ImpairmentĪUC inf increased by 1.96-fold and C max increased by 1.51-fold in subjects with severe renal impairment (eGFR 15 to 38.3☌ or fever above 38☌ for more than 1 hour and/or concurrent infection): Interrupt treatment until recovery (of neutropenia) to grade 2 or lower and then resume ribociclib at the next lower dose level. Terminal: ~30 to 55 hours Protein Binding Excretionįeces (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) Time to Peak Pharmacokinetics/Pharmacodynamics DistributionĮxtensively hepatic, predominantly via CYP3A4 undergoes oxidation to circulating metabolites M13, M4, and M1, although clinical activity is primarily due to the parent drug. ![]() The combination of ribociclib and fulvestrant resulted in tumor growth inhibition in estrogen receptor-positive breast cancer models. The combination of ribociclib and an aromatase inhibitor causes increased inhibition of tumor growth compared with each agent alone. Ribociclib is a small molecule cyclin-dependent kinase (CDK) inhibitor which is selective for CDK 4 and 6 it blocks retinoblastoma protein phosphorylation and prevents progression through the cell cycle, resulting in arrest at the G1 phase (Hortobagyi 2016).
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