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Kaletra and Zykadia

Determining the interaction of Kaletra and Zykadia and the possibility of their joint administration.

Check result:
Kaletra <> Zykadia
Relevance: 06.08.2022 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:

Ritonavir may significantly increase the blood levels of ceritinib. This can increase the risk and/or severity of side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia (high blood sugar), and irregular heart rhythm. 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. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications. 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: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ceritinib, which is a substrate of the isoenzyme. In 19 healthy subjects, administration of a single 450 mg dose of ceritinib with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 14 days) increased ceritinib peak plasma concentration (Cmax) by 22% and systemic exposure (AUC) by 2.9-fold. The steady-state AUC of ceritinib at reduced doses after coadministration with ketoconazole 200 mg twice daily for 14 days was predicted by simulations to be similar to the steady-state AUC of ceritinib administered alone. Because ceritinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.

MANAGEMENT: Concomitant use of ceritinib with potent CYP450 3A4 inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends a reduction of the ceritinib dosage by approximately one-third, rounded to the nearest 150 mg dosage strength. Patients should have periodic ECGs and be monitored for arrhythmias when QT interval is prolonged. A QTc interval exceeding 500 msec on at least two separate ECGs will require suspension of ceritinib therapy and immediate action to correct any concomitant risk factors before resuming treatment with a 150 mg dosage reduction. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Following discontinuation of the potent CYP450 3A4 inhibitor, ceritinib therapy should be resumed at the dosage that was taken prior to initiating the CYP450 3A4 inhibitor.

References
  • "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals, East Hanover, NJ.
Kaletra

Generic Name: lopinavir / ritonavir

Brand name: Kaletra

Synonyms: n.a.

Zykadia

Generic Name: ceritinib

Brand name: Zykadia

Synonyms: n.a.

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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