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Ribociclib and Vfend

Determining the interaction of Ribociclib and Vfend and the possibility of their joint administration.

Check result:
Ribociclib <> Vfend
Relevance: 20.09.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using ribociclib together with voriconazole can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a relatively rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). In addition, voriconazole may increase the blood levels of ribociclib. This can increase the risk of an irregular heart rhythm as well as other side effects such as nausea; vomiting; diarrhea; loss of appetite; mouth sores; abdominal pain, hair loss; weakness; headache; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of anemia, bleeding problems, and infections. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Talk to your doctor if you have any questions or concerns. You should seek immediate medical attention if you develop sudden or excessive drowsiness, dizziness, lightheadedness, fainting, confusion, shortness of breath, heart palpitations, bleeding problems, fever, or signs of infection during treatment with these medications, whether together or alone. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

GENERALLY AVOID: Ribociclib can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

GENERALLY AVOID: Coadministration with potent CYP450 3A4 inhibitors may increase the plasma concentrations and the risk of adverse effects of ribociclib, which is primarily metabolized by the isoenzyme. In healthy subjects, administration of a single 400 mg dose of ribociclib with ritonavir (100 mg twice daily for 14 days), a potent CYP450 3A4 inhibitor, resulted in a 1.7-fold and 3.2-fold increase in ribociclib peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to ribociclib administered alone. In addition, administration of erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase ribociclib Cmax and AUC by 1.3-fold and 1.9-fold, respectively. The risk of adverse effects such as infections, neutropenia, leucopenia, anemia, thrombocytopenia, nausea, vomiting, diarrhea, stomatitis, anorexia, alopecia, fatigue, headache, and abnormal liver function may be increased.

MANAGEMENT: Coadministration of ribociclib with other drugs that can prolong the QT interval and are CYP450 3A4 inhibitors should generally be avoided. Since the magnitude of QT prolongation may increase with increasing plasma concentrations of ribociclib, caution and close clinical monitoring are recommended if concomitant use with these drugs is unavoidable. Alternative agents with no or minimal CYP450 3A4 inhibitory potential are recommended whenever possible. If no alternatives exist, the dose of ribociclib should be reduced to 400 mg once daily. Following discontinuation of the potent CYP450 3A4 inhibitor, the ribociclib dosage should be returned (after at least 5 half-lives of the inhibitor) to that used prior to initiation of the inhibitor. In addition, ECGs should be assessed prior to initiation of treatment, during treatment when clinically necessary, and more frequently if QTcF prolongation occurs at any time during treatment. Ribociclib should be permanently discontinued if the QTcF interval prolongation is either greater than 500 msec or there is a greater than 60 msec change from baseline and associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia.

References
  • "Product Information. Kisqali (ribociclib)." Novartis Pharmaceuticals, East Hanover, NJ.
Ribociclib

Generic Name: ribociclib

Brand name: Kisqali

Synonyms: n.a.

Vfend

Generic Name: voriconazole

Brand name: Vfend, Vfend

Synonyms: Vfend Injection

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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