Drug Interactions between amoxicillin / clarithromycin / vonoprazan and escitalopram

MONITOR CLOSELY: Escitalopram can cause dose-dependent 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 a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. 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). Also, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, the risk of experiencing central nervous system (CNS) and/or respiratory depressant effects may be increased when escitalopram is combined with another agent that also has these adverse reactions, particularly in patients who are already at an increased risk, such as debilitated or elderly patients.

MANAGEMENT: Caution is recommended if escitalopram is used in combination with other drugs that can prolong the QT interval. Some authorities consider the concomitant use of these agents to be contraindicated. 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. When escitalopram is used in combination with other drugs that cause CNS and/or respiratory depression, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities. The product labeling of the concomitant medication should be consulted for further guidance, such as specific dosage adjustment and/or management recommendations should serious adverse reactions occur

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.

Coadministration with inhibitors of CYP450 3A4 is not expected to significantly affect the pharmacokinetics of citalopram or escitalopram, both of which are partially metabolized by the isoenzyme. Administration of racemic citalopram (40 mg) in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg) decreased the ketoconazole peak plasma concentration (Cmax) by 21% and systemic exposure (AUC) by 10%, but did not significantly affect the pharmacokinetics of citalopram. Likewise, coadministration of a single 20 mg dose of escitalopram with a single 600 mg dose of ritonavir, another potent CYP450 3A4 inhibitor, did not affect the pharmacokinetics of either drug. Because citalopram and escitalopram are both metabolized by multiple isoenzymes (CYP450 2C19, 3A4, and 2D6), inhibition of a single isoenzyme may not appreciably decrease their clearance.