Drug Interactions between amoxicillin / clarithromycin / vonoprazan and levomethadyl acetate

CONTRAINDICATED: Levomethadyl acetate may 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. High dosages of levomethadyl acetate alone have been associated with QT interval prolongation and torsade de pointes. 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). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking levomethadyl acetate with certain other drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Coadministration of levomethadyl acetate with other drugs that can prolong the QT interval is considered contraindicated.

CONTRAINDICATED: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and duration of action of levomethadyl acetate, which is a substrate of the isoenzyme. High plasma levels of levomethadyl acetate may increase the risk of QT interval prolongation, which is thought to be associated with serious cardiac events such as ventricular arrhythmias (e.g., torsade de pointes, ventricular tachycardia), cardiac arrest, and sudden death. Cases of QT prolongation and torsade de pointes have been reported with levomethadyl acetate alone during postmarketing use.

MANAGEMENT: Concomitant use of levomethadyl acetate with CYP450 3A4 inhibitors is considered contraindicated.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.