Kisqali 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 KISQALI with a strong CYP3A inhibitor cannot be avoided, reduce the dose of KISQALI to 400 mg once daily (see Dose Modifications under Dosage & Administration).
Instruct patients to avoid grapefruit juice or grapefruit, which are known to inhibit cytochrome CYP3A enzymes and may increase the exposure to ribociclib (see Patient Counselling Information).
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 KISQALI on Other Drugs: CYP3A substrates with narrow therapeutic index: Coadministration of midazolam (a sensitive CYP3A4 substrate) with multiple doses of KISQALI (400 mg) increased the midazolam exposure by 3.8-fold in healthy subjects, compared with administration of midazolam alone (see Pharmacology: Pharmacokinetics under Actions). KISQALI 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 KISQALI 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 KISQALI 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: Pharmacokinetics under Actions).