A reader commented that our recent article on Drugs for GERD and Peptic Ulcer Disease did not include enough information on dexlansoprazole (Dexilant, and generics), a proton pump inhibitor (PPI) claimed to provide "all-day and all-night relief from heartburn". Dexlansoprazole recently became available generically, but it is much more expensive than other generic PPIs.

Gastroesophageal reflux disease (GERD) is the most common GI condition encountered in the outpatient setting; it affects about 20% of people in the US.

View the Comparison Table: H2-Receptor Antagonists and PPIs

Gastroesophageal reflux disease (GERD) is the most frequent GI condition encountered in the outpatient setting; it affects about 20% of the US population. Heartburn and regurgitation are the classic symptoms of GERD.

View the Comparison Table: Drugs for GERD and Peptic Ulcer Disease

Proton pump inhibitors (PPIs), which are used for treatment of gastroesophageal reflux disease (GERD) and for prevention of upper gastrointestinal adverse effects caused by NSAIDs and aspirin, are one of the most commonly prescribed classes of drugs in the US. All PPIs are similarly effective and generally well tolerated, but their long-term use has been associated with a number of safety concerns. Recommendations addressing these concerns have recently been published.

The antiplatelet drug clopidogrel (Plavix, and others) reduces major cardiovascular events, but can cause bleeding. Proton pump inhibitors (PPIs) are often used with clopidogrel to prevent gastrointestinal bleeding, however, some evidence suggests that PPIs may interfere with the activation of clopidogrel and diminish its antiplatelet effect. FDA-approved labeling recommends avoiding concurrent use of the PPIs omeprazole and esomeprazole with clopidogrel.

Therapeutics (AZCERT) has recently added the proton pump inhibitors (PPIs) omeprazole (Prilosec, and others), esomeprazole (Nexium, and others), lansoprazole (Prevacid, and others), and pantoprazole (Protonix, and generics) to its lists of Drugs with Conditional Risk of Torsades de Pointes (TdP) and Drugs to Avoid in Patients with Congenital Long QT Syndrome.1

PPIs do not directly cause prolongation of the QT interval, but they can cause hypomagnesemia, which is often accompanied by hypocalcemia and hypokalemia and can result in cardiac repolarization disturbances such as QT interval prolongation.2 Reports have described cases of QT interval prolongation and TdP associated with severe PPI-induced hypomagnesemia.3,4 TdP has also been reported in patients taking a PPI concomitantly with drugs that directly prolong the QT interval.5,6 The newer PPIs dexlansoprazole (Dexilant) and rabeprazole (Aciphex, and generics) have not been linked to QT interval prolongation or TdP to date, but they have been associated with hypomagnesemia.

Serum magnesium levels should be monitored periodically in patients taking a PPI for an extended period of time (>2 weeks). If possible, extended PPI therapy should be avoided in patients who require treatment with drugs that carry a known risk of TdP7 and in those with long QT syndrome. If extended PPI therapy must be used with a drug that prolongs the QT interval, close monitoring of magnesium levels and the QT interval is recommended.

1. AZCERT. New drugs added to CredibleMeds drugs lists. November 2, 2016. Available at: www.crediblemeds.org. Accessed November 22, 2016.
2. In brief: PPIs and hypomagnesemia. Med Lett Drugs Ther 2011; 53:25.
3. EJ Hoorn et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 2010; 56:112.
4. BA Hansen and Ø Bruserud. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole. Oxf Med Case Reports 2016; 2016:147.
5. H Asajima et al. Lansoprazole precipitated QT prolongation and torsade de pointes associated with disopyramide. Eur J Clin Pharmacol 2012; 68:331.
6. JN Bibawy et al. Pantoprazole (proton pump inhibitor) contributing to torsades de pointes storm. Circ Arrhythm Electrophysiol 2013; 6:e17.
7. RL Woosley and KA Romero. QT drugs list. Available at: www.crediblemeds. org. Accessed November 22, 2016.

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An article published in the New York Times on May 1, 2015 listed the 10 drugs on which Medicare Part D spent the most in 2013. The most costly ($2.53 billion) was the proton pump inhibitor (PPI) Nexium (esomeprazole magnesium), which has recently become available generically.

Antiplatelet drugs are the drugs of choice for prevention and treatment of arterial thrombosis. Anticoagulants are the drugs of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation.

The FDA has approved the proton pump inhibitor (PPI) esomeprazole strontium for use in adults for the same indications as esomeprazole magnesium (Nexium): treatment of gastroesophageal reflux disease (GERD), prevention of NSAID-induced gastric ulcers, eradication of Helicobacter pylori, and treatment of pathological hypersecretory conditions. It was first marketed in December 2013 as a branded drug (Esomeprazole Strontium) and a month later as a generic drug.

Strontium is incorporated into bone. It is not recommended for use in children or during pregnancy because of the absence of safety data in those populations. Use of esomeprazole strontium is not recommended for patients with severe renal impairment.

Esomeprazole strontium is the seventh PPI to become available as a single agent in the US. No new clinical trials were required for its approval, which was based on earlier clinical trials with esomeprazole magnesium. All of the PPIs appear to be equally effective.1

1. Drugs for peptic ulcer disease and GERD. Treat Guidel Med Lett 2014; 12:25.

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H2-RECEPTOR ANTAGONISTS (H2RAs) — Currently available H2RAs are listed in Table 1. These drugs inhibit the action of histamine at the H2-receptor of the gastric parietal cell, decreasing basal acid secretion and, to a lesser degree, food-stimulated acid secretion. All H2RAs are about equally effective for treatment of PUD and GERD. H2RAs are faster acting than PPIs in relieving symptoms of dyspepsia or GERD, but they are not as effective as PPIs in relieving symptoms or in healing erosive esophagitis. Repeated administration of H2RAs leads to pharmacologic tolerance and has been associated with the development of new dyspeptic symptoms. Rebound acid hypersecretion can occur after stopping H2RAs.

Peptic ulcer disease (PUD) is usually caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or by infection with Helicobacter pylori. Gastroesophageal reflux disease (GERD) can be caused by transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, hiatal hernia, delayed gastric emptying or hormonal changes due to pregnancy. Acid suppressive therapy is the cornerstone of management for both PUD and GERD.