Drug Interactions between Adriamycin and Akynzeo

MONITOR: Theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk of an individual agent or a combination of these 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).

MANAGEMENT: Caution and clinical monitoring are recommended if multiple agents associated with QT interval prolongation are prescribed together. 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.

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MONITOR: Coadministration with netupitant or its prodrug, fosnetupitant, may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by netupitant and its desmethyl metabolite. When a single 7.5 mg oral dose of midazolam, a CYP450 3A4 probe substrate, was administered with netupitant 300 mg, mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 36% and 126%, respectively. When a 500 mg dose of erythromycin, another CYP450 3A4 substrate, was coadministered with netupitant 300 mg, the mean Cmax and AUC of erythromycin were increased by 92% and 56%, respectively, although the systemic exposure of erythromycin was highly variable.

MANAGEMENT: Caution is advised when netupitant or fosnetupitant is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever netupitant or fosnetupitant is added to or withdrawn from therapy. The inhibitory effect on CYP450 3A4 can last for 6 days after administration of a single dose of netupitant or fosnetupitant.

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