Proton Pump Inhibitors (PPIs)

Proton pump inhibitors (PPIs) reduce the production of acid by blocking the enzyme in the wall of the stomach that produces acid. Acid is necessary for the formation of most ulcers in the esophagus, stomach, and duodenum, and the reduction of acid with PPIs prevents ulcers and allows any ulcers that exist in the esophagus, stomach, and duodenum to heal.

• Esophageal duodenal and stomach ulcers
• NSAID-associated ulcer
• Ulcers
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome

They also are used in combination with antibiotics for eradicating Helicobacter pylori, a bacterium that together with acid causes ulcers of the stomach and duodenum.

Proton pump inhibitors are very similar in action and there is no evidence that one is more effective than another. They differ in how they are broken-down by the liver and their drug interactions. The effects of some PPIs may last longer; therefore, they may be taken less frequently.

The most common side effects of proton pump inhibitors are:

• Headache
• Diarrhea
• Constipation
• Abdominal pain
• Flatulence
• Fever
• Vomiting
• Nausea
• Rash

Nevertheless, proton pump inhibitors generally are well tolerated.

PPIs may increase the risk of Clostridium difficile infection of the colon. High doses and long-term use (1 year or longer) may increase the risk of osteoporosis-related fractures of the hip, wrist, or spine. Prolonged use also reduces absorption of vitamin B12 (cyanocobalamin).

Long-term use of PPIs has also been associated with low levels of magnesium (hypomagnesemia). Analysis of patients taking PPIs for long periods of time showed an increased risk of heart attacks.

Therefore, it is important to use the lowest doses and shortest duration of treatment necessary for the condition being treated.

Other serious side effects associate with PPIs include:

• Serious allergic reactions
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Reduced kidney function
• Pancreatitis
• Reduced liver function
• Erythema multiforme

Proton pump inhibitors interact with few drugs.

• The absorption into the body of some drugs is affected by the presence of acid in the stomach, and because PPIs reduce acid in the stomach, they may affect the absorption of these drugs. Specifically, PPIs reduce the absorption and concentration in the blood of ketoconazole (Nizoral) and increase the absorption and concentration of digoxin (Lanoxin). This may lead to reduced effectiveness of ketoconazole and an increase in digoxin toxicity.
• Proton pump inhibitors can reduce the break-down of some drugs by the liver and lead to an increase in their concentration in the blood. Omeprazole (Prilosec) is more likely than the other PPIs to reduce the break-down of drugs by the liver. For example, omeprazole (Prilosec) may increase the concentration in the blood of diazepam (Valium), warfarin (Coumadin) and phenytoin (Dilantin).
• Omeprazole (Prilosec, Prilosec OTC) reduces the effect of clopidogrel (Plavix) by blocking the conversion of clopidogrel to its active form. This combination should be avoided.

Available proton pump inhibitors include:

• omeprazole (Prilosec, Prilosec OTC)
• aspirin and omeprazole (Yosprala)
• lansoprazole (Prevacid, Prevacid IV, Prevacid 24-Hour)
• dexlansoprazole (Dexilent, Dexilent Solutab)
• rabeprazole (Aciphex, Aciphex Sprinkle)
• pantoprazole (Protonix)
• esomeprazole (Nexium, Nexium IV, Nexium 24 HR)
• esomeprazole magnesium/naproxen (Vimovo)
• omeprazole/sodium bicarbonate (Zegerid, Zegerid OTC)

Note: The brand name Kapidex was changed to Dexilent to avoid confusion with other drugs.