PPIs vs. NSAIDs

• PPIs (proton pump inhibitors) are gastric acid reducers used to treat gastroesophageal reflux disease (GERD) and ulcers.
• NSAIDs (nonsteroidal anti-inflammatories) are non-narcotic pain relievers used to treat pain and reduce inflammation. They are also used as fever reducers.
• Examples of PPIs include omeprazole (Prilosec, Prilosec OTC, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), esomeprazole (Nexium), and dexlansoprazole (Dexilant).
• Examples of NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), diclofenac (Cataflam, Voltaren), indomethacin (Indocin), oxaprozin (Daypro), and piroxicam (Feldene).
• Side effects of both PPIs and NSAIDs are somewhat similar and include:
  • Diarrhea
  • Constipation
  • Abdominal upset or pain
  • Vomiting
  • Nausea
  • Skin rash
  • Headache
• Other common side effects of PPIs that are different from NSAIDs include:
  • Gas
  • Fever
• Other common side effects of NSAIDs that are different from PPIs include:
  • Loss of appetite
  • Stomach ulcers
  • Ringing in the ears
  • Dizziness
  • Drowsiness
• PPIs may be used to treat ulcers caused by taking NSAIDs.

• PPIs (proton pump inhibitors) work by blocking acid production in the stomach. They are used to prevent and treat acid-related conditions such as, ulcers (including NSAID-associated ulcers), gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome.
• NSAIDs (nonsteroidal anti-inflammatory drugs) are used to treat pain and reduce inflammation from a variety of causes, such as headaches, injuries, arthritis, menstrual cramps, and muscle aches. NSAIDs are also used as fever reducers. NSAIDs work by blocking two forms of an enzyme called cyclooxygenase (COX).
  • COX-1 protects the stomach lining from digestive acids, and helps maintain kidney function. COX-2 is produced when joints are injured or inflamed. Blocking both forms of this enzyme reduces inflammation, pain, and fever, but can also cause gastrointestinal side effects.

Side effects of PPIs

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

Side effects of NSAIDs

NSAIDs are associated with several side effects. The frequency of side effects varies among NSAIDs.

Common side effects are:

• nausea,
• vomiting,
• diarrhea,
• constipation,
• decreased appetite,
• rash,
• dizziness,
• headache, and
• drowsiness.

Other important side effects are:

• kidney failure (primarily with chronic use),
• liver failure,
• ulcers, and
• prolonged bleeding after injury or surgery.

NSAIDs can cause fluid retention which can lead to edema, which is most commonly manifested by swelling of the ankles.

WARNING:

• Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is taken. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.
• Use of aspirin in children and teenagers with chickenpox or influenza has been associated with the development of Reye's syndrome, a serious and sometimes fatal liver disease. Therefore, aspirin and non-aspirin salicylates (for example, salsalate [Amigesic]) should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.
• NSAIDs increase the risk of potentially fatal, stomach and intestinal adverse reactions (for example, bleeding, ulcers, and perforation of the stomach or intestines). These events can occur at any time during treatment and without warning symptoms. Elderly patients are at greater risk for these adverse events. NSAIDs (except low dose aspirin) may increase the risk of potentially fatal heart attacks, stroke, and related conditions. This risk may increase with duration of use and in patients who have underlying risk factors for heart and blood vessel disease. Therefore, NSAIDs should not be used for the treatment of pain resulting from coronary artery bypass graft (CABG) surgery.

PPI drug interactions

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.

NSAID drug interactions

• NSAIDs reduce blood flow to the kidneys and therefore reduce the action of diuretics ("water pills") and decrease the elimination of lithium (Eskalith, Lithobid) and methotrexate (Rheumatrex, Trexall). As a result, the blood levels of these drugs may increase as may their side effects.
• NSAIDs also decrease the ability of the blood to clot and therefore increase bleeding. When used with other drugs that also increase bleeding (for example, warfarin [Coumadin]), there is an increased likelihood of serious bleeding or complications of bleeding. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid prolonged use of NSAIDs.
• NSAIDs also may increase blood pressure in patients with hypertension (high blood pressure) and therefore antagonize the action of drugs that are used to treat hypertension.
• NSAIDs increase the negative effect of cyclosporine on kidney function.
• Persons who have more than three alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking NSAIDs.

PPI medication list

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.

NSAID medication list

The following list is an example of NSAIDs available:

• aspirin
• celecoxib (Celebrex)
• diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
• diflunisal (Dolobid - discontinued brand)
• etodolac (Lodine - discontinued brand)
• ibuprofen (Motrin, Advil)
• indomethacin (Indocin)
• ketoprofen (Active-Ketoprofen [Orudis - discontinued brand])
• ketorolac (Toradol - discontinued brand)
• nabumetone (Relafen - discontinued brand)
• naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
• oxaprozin (Daypro)
• piroxicam (Feldene)
• salsalate (Disalsate [Amigesic - discontinued brand])
• sulindac (Clinoril - discontinued brand)
• tolmetin (Tolectin - discontinued brand)