Prilosec (omeprazole) and Nexium (esomeprazole) should not be taken together. They both are classified as proton pump inhibitors, PPIs for short, and have the same mechanism of action. Taking both together will generally not result in additive benefits.
How Proton Pump Inhibitors Work
Proton pump inhibitors, like Prilosec and Nexium, work by blocking "proton pumps", also known as H+/K+ ATPase, which are primarily responsible for the acidification of the stomach. Blocking proton pumps will reduce acidity in the stomach and is beneficial for relieving heartburn, preventing ulcers and treating other related conditions.
PPI medications irreversibly block the proton pumps and the use of more than one at a time has not been shown to provide any additional benefit than using one agent alone.
PPI medications are more effective when taken about 60 minutes before a meal as opposed to with a meal. This allows time for the medication to be absorbed and ready to work when food intake occurs, which activates proton pumps.
Taking PPIs and Other Acid Blockers
While taking two PPIs has not shown more benefit versus one alone, there is evidence that using a PPI with an H2 blocker, such as Zantac, is more effective than a PPI alone in certain situations. In addition, products like Zegerid contain a PPI and sodium bicarbonate for more immediate relief.
Be sure to speak with your doctor regarding the best course of therapy for your situation.