lated adverse reactions including sedation and respiratory depression; adjust the dose of codeine if necessary. Ribociclib is a moderate CYP3A4 inhibitor. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norocodeine; norcodeine does not have analgesic properties. Concomitant use may result in an increase in codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and increased morphine concentrations.
Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ribociclib unless the use of both agents is imperative. Ribociclib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like ribociclib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
Conivaptan: (Major) Avoid coadministration of ribociclib, a moderate CYP3A4 inhibitor and substrate, with conivaptan, a strong CYP34 inhibitor and substrate, as the systemic exposure of both drugs may be increased resulting in an increase in treatment-related adverse reactions including QT prolongation; consider an alternative treatment with less potential for CYP3A inhibition. According to the manufacturer of conivaptan, subsequent treatment with a CYP3A substrate like ribociclib may be initiated no sooner than 1 week after the infusion of conivaptan is completed, although the manufacturer of ribociclib recommends reducing the dose of ribociclib to 400 mg once daily if concurrent use of a strong CYP3A4 inhibitor is unavoidable. If conivaptan is discontinued, resume the previous ribociclib dose after at least 5 half-lives of conivaptan.
Conjugated Estrogens; Medroxyprogesterone: (Moderate) Use caution if coadministration of ribociclib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4.
Crizotinib: (Major) According to the manufacturer of ribociclib, coadministration with crizotinib should be avoided due to the risk of concentration-dependent QT prolongation; an increase in treatment-related adverse reactions may also occur. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; these ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Crizotinib has also been associated with QT prolongation. Additionally, crizotinib is a moderate CYP3A4 inhibitor and ribociclib is a sensitive CYP3A4 substrate. Coadministration with a strong CYP3A4 inhibitor increased the ribociclib AUC and Cmax by 3.2-fold and 1.7-fold, respectively, in healthy volunte |
