Kryxana Drug Interactions

Drugs That May Increase Ribociclib Plasma Concentrations: CYP3A4 Inhibitors: Coadministration of a strong CYP3A4 inhibitor (ritonavir) increased ribociclib exposure in healthy subjects by 3.2-fold [see Pharmacology: Pharmacokinetics under Actions]. Avoid concomitant use of strong CYP3A inhibitors (e.g., boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole) and consider alternative concomitant medications with less potential for CYP3A inhibition.
If coadministration of KRYXANA with a strong CYP3A inhibitor cannot be avoided, reduce the dose of KRYXANA to 400 mg once daily [see Dose Modifications under Dosage & Administration].
Instruct patients to avoid grapefruit or grapefruit juice, which are known to inhibit cytochrome CYP3A enzymes and may increase the exposure to ribociclib.
Drugs That May Decrease Ribociclib Plasma Concentrations: CYP3A4 Inducers: Coadministration of a strong CYP3A4 inducer (rifampin) decreased the plasma exposure of ribociclib in healthy subjects by 89% [see Pharmacology: Pharmacokinetics under Actions]. Avoid concomitant use of strong CYP3A inducers and consider an alternate concomitant medication with no or minimal potential to induce CYP3A (e.g., phenytoin, rifampin, carbamazepine and St John's Wort (Hypericum perforatum)).
Effect of KRYXANA on Other Drugs: CYP3A Substrates with Narrow Therapeutic Index: Coadministration of midazolam (a sensitive CYP3A4 substrate) with multiple doses of KRYXANA (400 mg) increased the midazolam exposure by 3.8-fold in healthy subjects, compared with administration of midazolam alone [see Pharmacology: Pharmacokinetics under Actions]. KRYXANA given at the clinically relevant dose of 600 mg is predicted to increase the midazolam AUC by 5.2-fold. Therefore, caution is recommended when KRYXANA is administered with CYP3A substrates with a narrow therapeutic index. The dose of a sensitive CYP3A substrate with a narrow therapeutic index, including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus and tacrolimus, may need to be reduced as ribociclib can increase their exposure.
Drugs That Prolong the QT Interval: Avoid coadministration of KRYXANA with medicinal products with a known potential to prolong QT such as antiarrhythmic medicines (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol), and other drugs that are known to prolong the QT interval (including, but not limited to, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide, and ondansetron) [see QT Interval Prolongation under Precautions and Pharmacology: Pharmacodynamics under Actions].