Summary

Quetiapine and omeprazole have a potential pharmacokinetic interaction where omeprazole may inhibit quetiapine metabolism, potentially leading to increased quetiapine plasma levels. This interaction is generally considered minor to moderate in clinical significance but requires monitoring for enhanced quetiapine effects.

Introduction

Quetiapine (brand name Seroquel) is an atypical antipsychotic medication primarily used to treat schizophrenia, bipolar disorder, and major depressive disorder as adjunctive therapy. It belongs to the dibenzothiazepine class and works by blocking dopamine and serotonin receptors. Omeprazole (brand name Prilosec) is a proton pump inhibitor (PPI) commonly prescribed for gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related disorders. It works by irreversibly blocking the hydrogen-potassium ATPase enzyme in gastric parietal cells, reducing stomach acid production.

Mechanism of Interaction

The interaction between quetiapine and omeprazole occurs through cytochrome P450 enzyme inhibition. Omeprazole is a moderate inhibitor of CYP2C19 and a weak inhibitor of CYP2D6, both of which are involved in quetiapine metabolism. Quetiapine is primarily metabolized by CYP3A4, but CYP2D6 also plays a role in its biotransformation. When omeprazole inhibits CYP2D6, it can reduce the clearance of quetiapine, potentially leading to increased plasma concentrations and prolonged half-life of the antipsychotic medication.

Risks and Symptoms

The primary clinical risk of this interaction is the potential for enhanced quetiapine effects due to increased plasma levels. This may manifest as increased sedation, dizziness, orthostatic hypotension, and extrapyramidal symptoms. Patients may experience greater anticholinergic effects such as dry mouth, constipation, and urinary retention. There is also a theoretical increased risk of QT interval prolongation, though this is rare. Elderly patients and those with hepatic impairment may be at higher risk for clinically significant effects. The interaction is generally considered minor to moderate in severity for most patients.

Management and Precautions

Monitor patients closely when initiating omeprazole in those already taking quetiapine, or vice versa. Watch for signs of increased quetiapine effects including excessive sedation, dizziness, confusion, or movement disorders. Consider starting with lower doses of quetiapine if omeprazole therapy is necessary, and titrate carefully based on clinical response. Regular assessment of vital signs, particularly blood pressure and heart rate, is recommended. If significant adverse effects occur, consider alternative acid suppression therapy such as H2 receptor antagonists (famotidine, ranitidine) which have less potential for drug interactions. Patients should be counseled about potential increased drowsiness and advised to avoid driving or operating machinery until effects are known.

Quetiapine interactions with food and lifestyle

Quetiapine should not be taken with alcohol as it can increase the risk of drowsiness, dizziness, and impaired coordination. Grapefruit juice may increase quetiapine levels in the blood and should be avoided. Patients should be cautious when driving or operating machinery due to potential sedation effects. Smoking may decrease quetiapine effectiveness, and patients should discuss smoking cessation with their healthcare provider.

Omeprazole interactions with food and lifestyle

Omeprazole should be taken on an empty stomach, preferably 30-60 minutes before meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be limited or avoided while taking omeprazole, as alcohol can increase stomach acid production and counteract the medication's acid-reducing effects. Additionally, alcohol may worsen gastroesophageal reflux disease (GERD) symptoms that omeprazole is treating. Smoking should be avoided or discontinued, as tobacco use increases stomach acid production and can reduce the effectiveness of omeprazole therapy. Patients should also be aware that omeprazole may interact with certain dietary supplements, particularly those containing magnesium, as long-term use of omeprazole can lead to magnesium deficiency.