What are the risks of QT interval prolongation when using omeprazole (Proton Pump Inhibitor) and Lexapro (Escitalopram), an SSRI (Selective Serotonin Reuptake Inhibitor), together?

From the Guidelines

The combined use of omeprazole and escitalopram (Lexapro) carries a moderate risk of QT interval prolongation that warrants monitoring but doesn't typically require avoiding the combination. Both medications can independently cause QT prolongation, with escitalopram carrying a more significant risk, especially at doses above 20mg daily 1. When used together, these effects may be additive, potentially increasing the risk of dangerous heart rhythm disturbances like Torsades de Pointes. Patients with additional risk factors such as electrolyte abnormalities (particularly low potassium or magnesium), heart disease, advanced age, or those taking other QT-prolonging medications face higher risks.

Key Considerations

• Patients should be assessed for cardiac risk before initiation of treatment, and the QT interval should be evaluated before initiation of treatment and during titration of dose 1.
• Healthcare providers should obtain baseline ECGs before starting treatment and monitor periodically, particularly after dose adjustments.
• Patients should report symptoms like palpitations, dizziness, or fainting immediately.
• Maintaining normal electrolyte levels and avoiding other QT-prolonging substances (including certain antibiotics, antipsychotics, and grapefruit juice) can help minimize risks.

Risk Minimization

• Concomitant treatment with more than one drug with the propensity of prolonging the QT interval should be avoided if possible 1.
• If cardiac risks are identified, the cardiac risk factors should be optimized and/or a drug with a more favourable risk profile should be preferred if possible in the clinical situation 1.
• In case of structural heart disease, QT prolongation or cardiac symptoms referral to a cardiologist should be considered 1. The benefit of treating both conditions often outweighs these risks for most patients without pre-existing cardiac issues.

From the FDA Drug Label

The overall incidence rates of adverse events in 10 mg Escitalopram-treated patients (66%) was similar to that of the placebo-treated patients (61%), while the incidence rate in 20 mg/day Escitalopram-treated patients was greater (86%) ECG Changes Electrocardiograms from Escitalopram (N=625) and placebo (N=527) groups were compared with respect to outliers defined as subjects with QTc changes over 60 msec from baseline or absolute values over 500 msec post-dose, and subjects with heart rate increases to over 100 bpm or decreases to less than 50 bpm with a 25% change from baseline (tachycardic or bradycardic outliers, respectively). None of the patients in the Escitalopram group had a QTcF interval >500 msec or a prolongation >60 msec compared to 0.2% of patients in the placebo group. Citalopram Clinical Impact: Increased exposure of citalopram leading to an increased risk of QT prolongation [see Clinical Pharmacology (12. 3)]. The following have been reported with Escitalopram tablet overdosage: • Seizures, which may be delayed, and altered mental status including coma. • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, and torsade de pointes

QT Interval Prolongation Risk:

• Escitalopram: The risk of QT interval prolongation is present, particularly in cases of overdosage or when used in combination with other drugs that may prolong the QT interval.
• Omeprazole: May increase the risk of QT interval prolongation when used with certain drugs, such as citalopram.
• Combination Therapy: The concurrent use of omeprazole and escitalopram may increase the risk of QT interval prolongation due to the potential for increased exposure of escitalopram. The FDA drug label recommends caution when using these medications together, and monitoring for signs of QT interval prolongation is advised 2, 3, 2.

From the Research

QT Interval Prolongation Risks with Omeprazole and Lexapro

• The use of omeprazole, a proton pump inhibitor (PPI), and Lexapro (escitalopram), a selective serotonin reuptake inhibitor (SSRI), together may increase the risk of QT interval prolongation 4, 5, 6, 7, 8.
• A study found that PPIs, including omeprazole, were associated with a higher risk of QT interval prolongation compared to histamine 2 receptor antagonists (H2RAs) and non-acid suppression therapy (non-AST) 4.
• Another study found that omeprazole and lansoprazole tended to prolong the QT interval and QTcV, and rabeprazole mildly but significantly prolonged them in a dose-related manner 5.
• Escitalopram overdose has been reported to lead to QTc interval prolongation, and prescribers should exercise caution when administering escitalopram to patients with suicidal ideations and depression 6.
• A nationwide population-based cohort study found that concomitant use of citalopram and omeprazole was associated with an increased risk of sudden cardiac arrest (SCA) compared to use of citalopram or omeprazole alone 7.
• A comparison of the risk of QT prolongation among SSRIs found that escitalopram may have a dose-related risk of QT prolongation, while fluoxetine, fluvoxamine, and sertraline appear to have a low risk of QT prolongation 8.

Key Findings

• Omeprazole and escitalopram may increase the risk of QT interval prolongation when used together 4, 5, 6, 7, 8.
• The risk of QT interval prolongation may be higher with concomitant use of PPIs and SSRIs compared to use of either medication alone 4, 7.
• Prescribers should exercise caution when administering escitalopram to patients with suicidal ideations and depression, and consider alternative SSRIs with a lower risk of QT prolongation 6, 8.