The FDA has approved vonoprazan (Voquezna – Phathom), a potassium-competitive acid blocker, for healing and maintenance of healing of all grades of erosive esophagitis and relief of associated heartburn in adults. Vonoprazan is also available copackaged with amoxicillin (Voquezna Dual Pak) and with amoxicillin and clarithromycin (Voquezna Triple Pak) for treatment of Helicobacter pylori infection in adults.

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

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. Use of opioids for pain will be reviewed in a future issue.

View the Comparison Table: Some Nonopioid Analgesics for Pain

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.

About 50% of the world’s population is infected with Helicobacter pylori. These gastric bacteria can cause chronic inflammation and have been associated with development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Eradication of H. pylori can promote gastric healing, prevent recurrence of duodenal and gastric ulcers, and reduce the incidence of gastric cancer. Guidelines for treatment of H. pylori infection were updated recently.

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.

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.

Pain can be acute or chronic. The two major types of chronic pain are nociceptive pain and neuropathic pain. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

The FDA has approved Duexis (Horizon), a fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and the H2-receptor antagonist (H2RA) famotidine, for symptomatic relief of osteoarthritis and rheumatoid arthritis and to decrease the risk of developing gastric and duodenal ulcers in patients at risk for NSAID-associated ulcers. Vimovo, a combination of the NSAID naproxen and the proton pump inhibitor (PPI) esomeprazole, is also approved by the FDA for prevention of NSAID-associated gastric ulcers.

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.

The FDA has approved the marketing of Vimovo (AstraZeneca), a fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID) naproxen and the proton pump inhibitor (PPI) esomeprazole, for symptomatic relief of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis and to decrease the risk of developing gastric ulcers in patients at risk for NSAID-associated ulcers.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are common causes of peptic ulcer disease. Patients infected with Helicobacter pylori who take aspirin or another NSAID have an especially high risk. Drugs that have been tried for prevention of ulcers in patients taking NSAIDs including H₂-receptor antagonists, proton pump inhibitors (PPIs), aluminum- or magnesium-containing antacids, the prostaglandin misoprostol (Cytotec, and others), and antibiotics to eradicate H. pylori.

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The FDA has approved the proton-pump inhibitor (PPI) dexlansoprazole (Kapidex - Takeda), a delayed release formulation of the R-enantiomer of lansoprazole (Prevacid - Takeda), for treating and maintaining healing of erosive esophagitis and for treatment of heartburn associated with non-erosive gastroesophageal reflux disease (GERD).

The majority of patients with insomnia do not have a predisposing psychiatric disease. Rather, untreated insomnia may be a risk factor for development of psychiatric problems such as depression or anxiety.

Clopidogrel (Plavix), which prevents arterial thrombosis by inhibiting platelet activation, is commonly prescribed (usually with aspirin) for months after acute coronary syndromes and stent implantation. It may also, however, increase the risk of bleeding. Therefore, a proton pump inhibitor (PPI) such as omeprazole (Prilosec, and others) is often given concurrently to decrease the risk of gastrointestinal (GI) bleeding. Some reports have suggested that omeprazole may interfere with the antiplatelet effect of clopidogrel.

Peptic ulcers caused by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly gastric ulcers. Most duodenal and other gastric ulcers are caused by the gram-negative bacillus Helicobacter pylori. Gastroesophageal reflux disease (GERD) is caused by gastric acid reflux into the esophagus. Drugs that suppress gastric acid production are the primary treatment for GERD and peptic ulcers.

A recent advertisement for the proton pump inhibitor (PPI) lansoprazole (Prevacid - TAP) suggests that children who cough at night, complain of abdominal pain, refuse to eat, or have a bad taste in their mouths may all have gastroesophageal reflux disease (GERD). A Bunny's Tummy Trouble, a children's book about GERD published by TAP, is now available as a patient handout in pediatricians' waiting rooms. The use of acid-suppressive drugs in infants and children has increased markedly in recent years and many of these drugs are now available in child-friendly formulations. A table in the article lists some of the drugs used to treat GERD in children.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori. The majority of NSAID-related ulcers are gastric. H. pylori infection causes both duodenal and gastric ulcers. Eradication of H. pylori promotes healing and markedly decreases recurrence of both duodenal and gastric ulcers (A Shiotamni and DY Graham, Med Clin North Am 2002; 86:1447; FKL Chan and WK Leung, Lancet 2002; 360:933). The first step in the management of peptic ulcers is the diagnosis and treatment of H. pylori.

Recently pharmaceutical manufacturers have marketed a stereoisomer of a successful drug nearing patent expiration as a new drug. Examples, such as esomeprazole (Nexium) , levalbuterol (Xopenex), escitalopram (Lexapro) and dexmethylphenidate

Esomeprazole magnesium (Nexium - AstraZeneca), the S-isomer of omeprazole (Prilosec), is the fifth benzimidazole proton pump inhibitor to become available in the United States. Omeprazole, which was the first, is going off patent this year.