Summary

Omeprazole can significantly increase diazepam blood levels by inhibiting the CYP2C19 enzyme responsible for diazepam metabolism. This interaction may lead to enhanced sedation, prolonged benzodiazepine effects, and increased risk of adverse reactions, particularly in elderly patients or those taking higher doses.

Introduction

Omeprazole 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 H+/K+-ATPase enzyme in gastric parietal cells, reducing stomach acid production. Diazepam is a long-acting benzodiazepine used for anxiety disorders, muscle spasms, seizures, and sedation. It enhances the effect of gamma-aminobutyric acid (GABA) at GABA-A receptors in the central nervous system, producing anxiolytic, sedative, and muscle relaxant effects.

Mechanism of Interaction

The interaction between omeprazole and diazepam occurs through cytochrome P450 enzyme inhibition. Omeprazole is a potent inhibitor of CYP2C19, the primary enzyme responsible for metabolizing diazepam to its active metabolite desmethyldiazepam. When omeprazole inhibits CYP2C19, diazepam clearance is significantly reduced, leading to increased plasma concentrations and prolonged half-life. This pharmacokinetic interaction can result in diazepam levels that are 2-3 times higher than normal, with effects lasting considerably longer than expected.

Risks and Symptoms

The primary clinical risks of this interaction include excessive sedation, cognitive impairment, increased fall risk, and respiratory depression, particularly in elderly patients. Patients may experience prolonged drowsiness, confusion, memory problems, and impaired motor coordination. The risk is heightened in individuals who are poor CYP2C19 metabolizers (approximately 2-5% of Caucasians and 15-20% of Asians), as they already have reduced diazepam clearance. Concurrent use may also increase the risk of benzodiazepine dependence and withdrawal symptoms due to higher effective doses. In severe cases, particularly when combined with other CNS depressants, this interaction could lead to significant respiratory depression requiring medical intervention.

Management and Precautions

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.

Diazepam interactions with food and lifestyle

Diazepam has significant interactions with alcohol that patients must be aware of. Concurrent use of diazepam with alcohol can cause dangerous additive central nervous system depression, leading to severe sedation, respiratory depression, coma, and potentially death. This interaction is consistently warned against in all major clinical guidelines and drug databases. Patients taking diazepam should completely avoid alcohol consumption. Additionally, grapefruit juice may increase diazepam blood levels by inhibiting CYP3A4 metabolism, though this interaction is less clinically significant than the alcohol interaction. Patients should also be cautioned about activities requiring mental alertness, such as driving or operating machinery, as diazepam can cause significant drowsiness and impair cognitive function.