Drug Interactions between cobicistat / elvitegravir / emtricitabine / tenofovir and quizartinib

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of quizartinib. According to the prescribing information, quizartinib is primarily metabolized via oxidation by CYP450 3A4/5 in vitro, and its major circulating active metabolite AC886 is formed and metabolized by CYP450 3A4/5. Following coadministration of a single 53 mg dose of quizartinib with ketoconazole, a potent CYP450 3A4 inhibitor, quizartinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 17% and 94%, respectively, while the Cmax and AUC of AC886 decreased by 60% and 94%, respectively. Increased exposure to quizartinib may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: When concomitant use with a potent CYP450 3A4 inhibitor is required, the prescribing information recommends reducing the dosage of quizartinib. Patients prescribed 53 mg once daily should have the dosage reduced to 26.5 mg once daily, and patients prescribed 35.4 mg or 26.5 mg once daily should have the dosage reduced to 17.7 mg once daily. For patients whose current dosage is 17.7 mg once daily, treatment with quizartinib should be interrupted while the potent CYP450 3A4 inhibitor is in use and until discontinuation of the inhibitor for 5 half-lives. More frequent monitoring with electrocardiograms (ECGs) is also recommended to guide continued treatment. All patients treated with quizartinib should have ECGs performed as well as potassium and magnesium serum levels measured prior to initiation of treatment, at regular intervals during treatment, and when clinically indicated such as following dose escalation or during episodes of diarrhea or vomiting. Do not initiate quizartinib or escalate the dose if QTcF interval is greater than 450 ms. In addition, hypokalemia and hypomagnesemia should be corrected before and during treatment. If QTcF increases to greater than 480 ms during treatment, reduce the dose, interrupt therapy, or permanently discontinue quizartinib as clinically appropriate in accordance with the prescribing information. 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.

Using cobicistat together with tenofovir can increase the effects of tenofovir, which can cause new or worse kidney problems. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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.

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Cobicistat is a medication used to boost the effects of some medications that treat HIV infection. However, using cobicistat together with other HIV medications, such as emtricitabine, may alter the blood levels and effects of both medications. Using emtricitabine with cobicistat may reduce or increase blood levels of cobicistat. Reduced blood levels of cobicistat may make cobicistat less effective and may cause overall HIV treatment to be less effective. Cobicistat may increase blood levels of emtricitabine which may increase the risk of side effects. Talk to your doctor or pharmacist if you have any questions on how to use these medications properly. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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.

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