Treatment Guidelines from The Medical Letter® Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Peptic Ulcer Disease and GERD p 25 The Medical Letter ® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 12 (Issue 140) April 2014 Tables (supercedes vol [Issue 109] September 2011) Some Drugs for Peptic Ulcer Disease and GERD Some Multi-Drug Regimens for H Pylori Infection www.medicalletter.org Page 27 Page 28 Drugs for Peptic Ulcer Disease and GERD Related article(s) since publication RECOMMENDATIONS: Peptic ulcer disease (PUD) is generally caused by nonsteroidal antiinflammatory drugs (NSAIDs) or Helicobacter pylori infection Most patients with active PUD should be treated with antisecretory drugs Proton pump inhibitors (PPIs) are more effective than H2-receptor antagonists (H2RAs) in healing ulcers All PPIs appear to be similar in efficacy When patients with PUD are infected with H pylori, eradication of the infection with a combination of antibacterial drugs markedly decreases the incidence of recurrence Gastroesophageal reflux disease (GERD) can be caused by transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, delayed gastric emptying, or hormonal changes due to pregnancy Antacid or H2RA therapy may be adequate for patients with mild, intermittent symptoms Treatment with a PPI is preferred for more severe disease Guidelines for management of GERD have recently been published.1 DRUGS H2-RECEPTOR ANTAGONISTS (H2RAs) — Currently available H2RAs are listed in Table These drugs inhibit the action of histamine at the H2receptor 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.2 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 Adverse Effects – Severe adverse effects are uncommon with H2RAs, but headache, lethargy, depression, and cognitive impairment can occur with high doses These agents have rarely been associated with hepatitis and hematologic toxicity Cimetidine is weakly anti-androgenic and may rarely cause reversible impotence and gynecomastia with chronic use Drug Interactions – All H2RAs may decrease serum concentrations of drugs that require gastric acidity for absorption, such as itraconazole (Sporanox, and others) Cimetidine is a moderate inhibitor of CYP1A2, 2C19, and 2D6 Clinically significant drug interactions have occurred when cimetidine was taken with drugs that are both substrates of these isoenzymes and have a narrow therapeutic window, such as theophylline (Theo-Dur, and others), warfarin (Coumadin, and others), phenytoin (Dilantin, and others), and lidocaine (Xylocaine, and others).3 Ranitidine, famotidine, and nizatidine are less likely to interfere with the hepatic metabolism of other drugs PROTON PUMP INHIBITORS (PPIs) — Currently available PPIs are listed in Table These drugs bind to the activated proton pump on the apical membrane of the gastric parietal cell, inhibiting secretion of hydrogen ions into the gastric lumen PPIs inhibit a higher percentage of 24-hour acid secretion and heal peptic ulcers more rapidly than H2RAs They are also more effective than H2RAs in relieving symptoms of GERD and in healing erosive esophagitis PPIs have short serum half-lives, but their duration of action is longer than that of H2RAs, allowing for once-daily dosing in most patients Unlike H2RAs, tolerance does not occur with PPIs Rebound acid hypersecretion and dyspeptic symptoms have been reported after stopping a PPI.4 Adverse Effects – PPIs are generally well tolerated Headache, nausea, abdominal pain, constipation, flatulence, and diarrhea can occur Gynecomastia and hepatic failure have occurred rarely Subacute myopathy, arthralgia, severe rash, and acute interstitial nephritis have been reported Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines 25 Drugs for Peptic Ulcer Disease and GERD Observational studies have suggested a number of safety concerns associated with long-term use of PPIs, but only a few of these concerns are supported by plausible mechanisms or consistent data.5 The FDA has issued safety warnings regarding associations between PPIs and Clostridium difficile-associated diarrhea (CDAD), fracture risk, and hypomagnesemia Whether acid suppression could increase the risk of bacterial gastroenteritis and CDAD is controversial Long-term use of PPIs has been associated with a small increase in the risk of fractures in some observational studies, but a causal relationship has not been established and no association with osteoporosis has been demonstrated.6 Hypomagnesemia has occurred rarely with prolonged PPI use and is often accompanied by hypokalemia and hypocalcemia; it can cause serious adverse effects including muscle spasms, convulsions, and cardiac arrhythmias.7,8 Decreased absorption and subsequent deficiency of vitamin B12 can occur with chronic use of PPIs and/or H2RAs, particularly with high doses and prolonged use and in elderly patients.9 Drug Interactions – All PPIs may decrease serum concentrations of drugs that require gastric acidity for absorption, such as itraconazole (Sporanox, and others) The PPIs omeprazole and esomeprazole are moderate inhibitors of CYP2C19 and can increase serum concentrations of drugs metabolized by this pathway, such as diazepam (Valium, and others) and phenytoin (Dilantin, and others) Clopidogrel (Plavix, and generics) is converted to its active form by CYP2C19; inhibition of CYP2C19 may interfere with its activation, and some studies have shown lower serum levels of the active metabolite when taken concurrently with omeprazole or esomeprazole Concurrent administration of clopidogrel and omeprazole or esomeprazole has not resulted in clinically significant adverse cardiovascular outcomes.10 Nevertheless, it would be prudent to treat patients taking clopidogrel who have a clinical indication for a PPI with an alternative PPI, such as pantoprazole, dexlansoprazole, or lansoprazole.11,12 SUCRALFATE — An aluminum hydroxide complex of sucrose thought to act locally to protect the ulcer from exposure to peptic acid, sucralfate (Carafate, and generics) has been used for acute treatment of PUD and maintenance treatment to prevent recurrence Multiple daily doses are required, and it may not be effective in relieving ulcer pain Adverse Effects – Sucralfate is generally well tolerated, but may cause constipation and aluminum toxicity, particularly in patients with renal impairment Drug Interactions – Sucralfate decreases the absorption of many other drugs including ketoconazole, fluoroquinolones, tetracyclines, and levothyroxine; administration should be separated by at least hours 26 MISOPROSTOL — Misoprostol (Cytotec, and generics), a prostaglandin E1 analog, can prevent gastric and duodenal ulcers in patients on chronic NSAID therapy It may be as effective as a PPI in preventing NSAID-related ulcers, but requires multiple daily doses and is not as well tolerated It has no established role in healing ulcers Adverse Effects – Abdominal pain and dose-related diarrhea are the most common adverse effects of misoprostol Severe nausea, constipation, dyspepsia, and flatulence can also occur Misoprostol is an abortifacient and should not be used in women who could become pregnant ANTACIDS — Aluminum- and magnesiumcontaining antacids can provide rapid, but transient relief of PUD and GERD symptoms Aluminum-based antacids can be constipating, and magnesium-based antacids can cause diarrhea Antacids may decrease the absorption of some other drugs PEPTIC ULCER DISEASE The first step in the management of PUD is to identify potential underlying causes such as NSAID use or H pylori infection Eradication of H pylori can promote healing and prevent recurrences of both duodenal and gastric ulcers If the underlying cause is identified and addressed (e.g., eradicating H pylori or stopping the NSAID), long-term antisecretory therapy may not be needed For patients with idiopathic peptic ulcers, however, long-term use of a PPI is recommended.13 TESTING FOR H PYLORI — The sensitivity of ureabased tests (breath and biopsy) and the stool antigen test for H pylori is reduced by use of PPIs, bismuthcontaining products, or antibiotics Patients should not take these drugs for at least weeks before testing Urea Breath Tests – A urea breath test (BreathTek; PYtest) can be used for office-based diagnosis The patient ingests a urea solution or capsule labeled with a carbon isotope and then breathes into a container In the presence of H pylori, urease hydrolyzes the urea to release ammonia and labeled CO2, which can be detected by a mass spectrophotometer These tests typically have >90% sensitivity and specificity.14 The BreathTek, used with a desktop infrared spectrophotometer, can provide results within 20 minutes Stool Antigen Tests – A stool antigen enzyme immunoassay (Premier Platinum HpSA Plus) has a sensitivity of about 95% and specificity of about 95% Serology – Serologic antibody tests for H pylori are useful in ruling out the diagnosis, but they lack Treatment Guidelines from The Medical Letter • Vol 12 (Issue 140) • April 2014 Drugs for Peptic Ulcer Disease and GERD Table Some Drugs for Peptic Ulcer Disease and GERD Drug Some Available Formulations Usual Adult Dosage1 Cost2 200-400 mg bid3 $9.00 20-40 mg bid3 16.20 3.60 H2-Receptor Antagonists Cimetidine* – generic Tagamet (GSK) Famotidine*4 – generic Pepcid (Marathon) Nizatidine* – generic Axid (Braintree) Ranitidine* – generic Zantac (GSK) 200, 300, 400, 800 mg tabs; 300 mg/2 mL soln for inj; 300 mg/5 mL oral soln 200, 300, 400, 800 mg tabs 20, 40 mg tabs; 10 mg/mL soln for inj; 40 mg/5 mL susp 20, 40 mg tabs; 40 mg/5 mL susp5 150, 300 mg caps; 15 mg/mL oral soln 15 mg/mL oral soln 75 mg tabs; 150, 300 mg tabs, caps; 25 mg/mL soln for inj; 15 mg/mL oral syrup 150, 300 mg tabs; 25 mg/mL soln for inj 6; 15 mg/mL oral syrup 150 mg bid3 150 mg bid3 185.40 64.20 438.00 4.80 262.50 Proton Pump Inhibitors7 Dexlansoprazole – Dexilant (Takeda) Esomeprazole magnesium8 – Nexium (AstraZeneca) Esomeprazole sodium – Nexium IV Esomeprazole strontium – generic9 Esomeprazole Strontium (Amneal)9 Lansoprazole*11 – generic Prevacid (Takeda) Omeprazole*12 – generic Prilosec (AstraZeneca) Omeprazole/sodium bicarbonate* – Zegerid (Salix) Pantoprazole – generic Protonix (Pfizer) Rabeprazole – generic Aciphex (Eisai) Aciphex Sprinkle 30, 60 mg delayed-release caps 20, 40 mg delayed-release caps; 2.5, 5, 10, 20, 40 mg powder for delayed-release susp 20, 40 mg vial for inj 49.3 mg delayed-release caps10 30-60 mg once/d 20-40 mg once/d 15, 30 mg ODT; 15, 30 mg delayedrelease caps 10, 20, 40 mg delayed-release caps 10, 20, 40 mg delayed-release caps; 2.5, 10 mg powder for delayed-release susp 20, 40 mg/packet for susp13; 20 mg/1.1 g, 40 mg/1.1 g caps14 20, 40 mg delayed-release tabs; 40 mg vial for inj 20, 40 mg delayed-release tabs; 40 mg delayed-release granules for susp; 40 mg vial for inj 20 mg delayed-release tabs 15-30 mg once/d 49.3 mg once/d 20-40 mg once/d 167.30 236.70 1164.60 60.00 200.80 55.60 251.10 14.40 204.30 20-40 mg once/d 40 mg once/d 348.60 9.30 210.60 20 mg once/d 60.90 349.90 349.90 200 mcg bid or tid or qid g qid 63.00 172.80 49.20 243.60 5, 10 mg delayed-release sprinkle caps15 Other Drugs Misoprostol16,17 – generic Cytotec (Searle) Sucralfate18 – generic Carafate (Aptalis) 100, 200 mcg tabs g tabs; g/10 mL oral susp ODT = orally disintegrating tabs * Also available over the counter The lower end of the range is generally used for initial treatment of GERD Higher or more frequent doses may be needed for patients with erosive esophagitis, peptic ulcer disease, hypersecretory conditions such as Zollinger-Ellison syndrome, or for treatment of H pylori infection Approximate wholesale acquisition cost (WAC) for 30 days’ treatment with the lowest usual oral dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledgeTM) March 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Taking the total daily dose at once in the evening may also be effective Also available in combination with ibuprofen (Duexis) Pepcid oral suspension is manufactured by Salix Zantac injection solution is manufactured by Covis PPIs are generally taken 30-60 minutes before the first meal of the day Taking one before the evening meal or taking the drug twice daily may be more effective for nocturnal acid control PPIs should generally be swallowed whole and should not be crushed or chewed Also available in combination with naproxen (Vimovo, and generics) Branded and generic formulations are marketed by Amneal under the same name 10 Equivalent to 40 mg of esomeprazole 11 Also available in combination with amoxicillin/clarithromycin (Prevpac, and generics) and in combination with naproxen (Prevacid Naprapac) 12 Also available in combination with amoxicillin/clarithromycin 13 Each packet also contains 1680 mg of sodium bicarbonate 14 Each capsule contains 1.1 g of sodium bicarbonate; therefore, two 20-mg caps are not equivalent to one 40-mg cap 15 Contents of capsule should be sprinkled on food or liquid and taken within 15 minutes 16 FDA-approved only for prevention of NSAID-induced gastric ulcers 17 Also available in combination with diclofenac (Arthrotec, and generics) 18 FDA-approved only for short-term treatment and maintenance therapy for duodenal ulcers Treatment Guidelines from The Medical Letter • Vol 12 (Issue 140) • April 2014 27 Drugs for Peptic Ulcer Disease and GERD Table Some Multi-Drug Regimens for Helicobacter Pylori Infection Drug Daily Adult Dosage Duration1 g bid 500 mg bid 500 mg bid 14 days tablets (525 mg) qid or 30 mL tid or qid 500 mg tid 500 mg qid 14 days g bid 500 mg bid 500 mg bid 14 days g bid days 500 mg bid 500 mg bid days 500 mg once/d g bid 14 days Triple Therapy Amoxicillin (Amoxil, and others) + Clarithromycin (Biaxin, and others) or + Metronidazole3 (Flagyl, and others) + a PPI4 Bismuth-based Quadruple Therapy Bismuth subsalicylate (Pepto-Bismol, and others) + Metronidazole3 (Flagyl, and others) + Tetracycline (Sumycin, and others) + a PPI4 or H2RA Clarithromycin-based Quadruple Therapy Amoxicillin + Clarithromycin + Metronidazole3 + a PPI4 Sequential Therapy Amoxicillin (Amoxil, and others) + a PPI4 followed by: Clarithromycin (Biaxin, and others) + Metronidazole3 + a PPI4 Levofloxacin-based Triple or Quadruple Therapy Levofloxacin + Amoxicillin + a PPI4 +/- Bismuth Combination Products Prevpac (Takeda) Pylera (Aptalis) bid 14 daily blister cards, each containing lansoprazole 30-mg caps, amoxicillin 500-mg caps, and clarithromycin 500-mg tabs 120 capsules, each containing bismuth subcitrate potassium 140 mg, metronidazole 125 mg and tetracycline HCl 125 mg (3 caps qid) plus a PPI3 Antisecretory drugs may be needed for a longer duration to heal the ulcer Only when H pylori infection is proven to be susceptible Or tinidazole (Tindamax, and generics) Standard oral PPI dosages are: esomeprazole 40 mg once daily, lansoprazole 30 mg bid, omeprazole 20 mg bid, pantoprazole 40 mg bid, rabeprazole 20 mg bid Some experts now recommend doubling the dose (e.g., omeprazole 40 mg bid) specificity and are not reliable (because of persisting antibodies) for documenting eradication TREATMENT OF H PYLORI — Regimens for treatment of H pylori infectionare listed in Table In large clinical trials, combinations of antimicrobial drugs active against H pylori have been successful in eradicating the organism in up to 90% of patients In practice, however, eradication rates are considerably lower due to antimicrobial resistance and poor patient adherence to these multi-drug regimens Eradication rates with commonly prescribed triple therapy regimens have fallen below 80% While still considered first line and most commonly prescribed,15 the effectiveness of clarithromycin-based triple therapy has diminished because of increasing rates of resistance to clarithromycin.16 Resistance to metronidazole is also increasing, but resistance to both drugs at the same time remains relatively rare Quadruple therapy is more effective for eradication of H pylori and is now recommended for initial treatment.16-18 Sequential therapy may also be beneficial, but is generally inferior or, at best, equal to clarithromycin-based quadruple therapy.19,20 28 Patients should be tested at least four weeks after completion of therapy for successful eradication of H pylori Those still infected after treatment with different regimens should receive salvage therapy with a different regimen, such as levofloxacin-based therapy If salvage therapy is required, resistance testing should be considered to tailor the antibiotic regimen Adverse Effects – Bismuth subsalicylate temporarily turns the tongue and stool black and can cause tinnitus Amoxicillin may cause diarrhea Metronidazole, tinidazole, and tetracycline frequently cause mild gastrointestinal disturbances, and metronidazole causes a metallic taste Clarithromycin causes fewer gastrointestinal symptoms, but commonly causes disturbances in taste that some patients find intolerable Clarithromycin, metronidazole, and tetracycline interact adversely with many other drugs Both metronidazole and tinidazole can cause a disulfiram-like reaction to alcohol GASTROESOPHAGEAL REFLUX DISEASE GERD affects 10-20% of the population It is a benign condition, although complications such as strictures and Treatment Guidelines from The Medical Letter • Vol 12 (Issue 140) • April 2014 Drugs for Peptic Ulcer Disease and GERD Barrett’s esophagus can occur Lifestyle modifications are a critical component of GERD management in all individuals, and the frequency and duration of antisecretory therapy is dependent on the severity of symptoms and whether there is evidence of erosive esophagitis on endoscopy Endoscopy is recommended for patients with heartburn and severe symptoms, for those who not respond to a 4-8 week trial of a twice-daily PPI, and generally in men >50 years old with chronic symptoms who are at risk of Barrett’s esophagus.21 LIFESTYLE MODIFICATION — Common lifestyle changes include avoiding recumbancy for 2-3 hours after a meal and elevating the head of the bed Weight loss should be considered a cornerstone of GERD management in patients with a BMI >25 or recent weight gain irrespective of BMI In one study, reduction of BMI by 3.5 kg/m2 resulted in a 40% reduction in GERD symptoms.22 ACID-SUPPRESSIVE THERAPY — Medications that suppress gastric acid are the mainstay of GERD therapy The choice of drug depends on the severity and frequency of symptoms and the presence or absence of esophagitis For mild, intermittent symptoms, asneeded therapy with an H2RA or antacid may be sufficient For more severe symptoms or erosive esophagitis on endoscopy, a PPI is recommended Non-Erosive Ref ux Disease (NERD) – Antacids and H2RAs may be adequate for symptom relief in patients with mild NERD While these agents have similar peak potency, antacids have a faster onset of action and H2RAs have a longer duration of action (up to 10 hours) PPIs are used less frequently for symptom relief because their onset of action is delayed Patients with more severe NERD may require more frequent dosing or continuous therapy with an H2RA or a PPI PPIs have been shown to maintain remission of symptoms and are generally preferred For patients with severe nocturnal symptoms, the addition of an H2RA at bedtime to a twice-daily PPI may be effective Erosive Esophagitis – A PPI for weeks is the treatment of choice for acute and chronic management of erosive esophagitis PPIs decrease symptoms and heal esophagitis more effectively than other drugs In one study, symptom relief occurred in 27% of patients treated with placebo, in 60% with an H2RA, and in 83% with a PPI, and healing of esophageal erosions occurred in 24% of patients treated with placebo, in 50% with an H2RA, and in 78% with a PPI.23 ADJUNCTIVE TREATMENT — Baclofen (Lioresal, and others) is a gamma-aminobutyric acid (B) (GABAB) receptor agonist that inhibits transient lower esophageal sphincter relaxation and decreases postprandial acid reflux in patients with GERD It may be effective in reduc- ing symptoms refractory to PPI therapy Baclofen is not approved by the FDA for use in GERD Common side effects include drowsiness, dizziness, confusion, lightheadedness, nausea and, rarely, hypotension GERD IN PREGNANCY — Heartburn occurs in approximately 30-50% of pregnancies, and is largely attributed to a progesterone-mediated decrease in lower esophageal sphincter tone Antacids can be helpful, but those containing sodium bicarbonate should be avoided during pregnancy because of the risks of maternal or fetal alkalosis and fluid overload.24 Antacids or sucralfate should be tried first for symptomatic relief; an H2RA can be added if needed.25 Sucralfate and H2RAs are classified by the FDA as category B (no evidence of risk in animals; no human studies) for use during pregnancy If symptoms persist on an H2RA, a PPI may be considered Although generally considered safe, clinical data on the use of PPIs during pregnancy are limited A meta-analysis of observational studies of first-trimester use (predominantly with omeprazole) found no increase in the risk of congenital malformations, and a cohort study confirmed these findings.26,27 PPIs are classified as pregnancy category B, with the exception of omeprazole, which is category C (risk cannot be ruled out) despite the meta-analysis and cohort study supporting its safety SURGERY — Weight loss surgery has variable effects on GERD: Roux-en-Y gastric bypass is associated with a decrease in GERD and dyspeptic symptoms, but gastric banding and gastric sleeve have not consistently shown the same benefit.28 Surgical treatment of GERD has not been shown to be superior to medical therapy over the long term Laparoscopic fundoplication is the primary surgical procedure for management of GERD; the gastric fundus is wrapped around the gastroesophageal junction either partially or completely, creating a mechanical barrier.29 Ten to 15 years after surgery, more than 50% of patients require long-term acid suppressive therapy.30 Dysphagia is common in the early post-operative period and may require early endoscopic dilation, but typically resolves after 2-3 months In some patients, dysphagia persists and may require endoscopic dilation or surgical revision Postprandial bloating (gas-bloat syndrome), increased flatus, and diarrhea are common postoperatively ENDOSCOPIC THERAPY — Various modalities of endoscopic reflux therapy have been tried, including application of radiofrequency energy to the gastro-esophageal junction, suture plication of the proximal stomach, and either injection of a biopolymer or implantation of a bioprosthesis at the level of the lower esophageal sphincter Convincing data supporting use of these techniques are lacking.31 Treatment Guidelines from The Medical Letter • Vol 12 (Issue 140) • April 2014 29 Drugs for Peptic Ulcer Disease and GERD 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 30 PO Katz et al Guidelines for the diagnosis and management of gastroesophageal reflux disease Am J Gastroenterol 2013; 108:308 U Dutta and P Moayyedi Management of reflux-related symptoms Best Pract Res Clin Gastroenterol 2013; 27:387 Inhibitors and inducers of CYP enzymes and P-glycoprotein Med Lett Drugs Ther 2013; 55:e44 A Niklasson et al Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial Am J Gastroenterol 2010; 105:1531 C Reimer Safety of long-term PPI therapy Best Pract Res Clin Gastroenterol 2013; 27:443 PPIs and fracture risk Med Lett Drugs Ther 2013; 55:15 In brief: PPIs and hypomagnesemia Med Lett Drugs Ther 2011; 53:25 CP Luk et al Proton pump inhibitor-associated hypomagnesemia: what FDA data tell us Ann Pharmacother 2013; 47:773 JR Lam et al Proton pump inhibitor and histamine receptor antagonist use and vitamin B12 deficiency JAMA 2013; 310:2435 LB Gerson Proton pump inhibitors and potential interactions with clopidogrel: an update Curr Gastroenterol Rep 2013; 15:329 In brief: Clopidogrel and omeprazole Med Lett Drugs Ther 2010; 52:93 MD Drepper et al Clopidogrel and proton pump inhibitors – where we stand in 2012? World J Gastroenterol 2012; 18:2161 L Laine and DM Jensen Management of patients with ulcer bleeding Am J Gastroenterol 2012; 107:345 RJ Saad and WD Chey Breath tests for gastrointestinal disease: the real deal or just a lot of hot air? Gastroenterology 2007; 133:1763 A O’Connor et al Treatment of Helicobacter pylori infection 2013 Helicobacter 2013; 18 suppl 1:58 DY Graham et al Rational Helicobacter pylori therapy: evidencebased medicine rather than medicine-based evidence Clin Gastroenterol Hepatol 2014; 12:177 KE McColl Clinical practice Helicobacter pylori infection N Engl J Med 2010; 362:1597 E Rimbara et al Optimal therapy for Helicobacter pylori infections Nat Rev Gastroenterol Hepatol 2011; 8:79 DC Wu et al Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection Clin Gastroenterol Hepatol 2010; 8:36 AG McNicholl et al Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice Gut 2014; 63:244 NJ Shaheen et al Upper endoscopy for gastroesophageal reflux disease: best practice advice from the clinical guidelines committee of the American College of Physicians Ann Intern Med 2012; 157:808 BC Jacobson et al Body-mass index and symptoms of gastroesophageal reflux in women N Engl J Med 2006; 354:2340 KR DeVault et al Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease Am J Gastroenterol 2005; 100:190 JE Richter Review article: the management of heartburn in pregnancy Aliment Pharmacol Ther 2005; 22:749 CJ van der Woude et al Management of gastrointestinal and liver diseases during pregnancy Gut 2014 January 15 (epub) SK Gill et al The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis Am J Gastroenterol 2009; 104:1541 B Pasternak and A Hviid Use of proton-pump inhibitors in early pregnancy and the risk of birth defects N Engl J Med 2010; 363:2114 R Tutuian Obesity and GERD: pathophysiology and effect of bariatric surgery Curr Gastroenterol Rep 2011; 13:205 JP Galmiche et al Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial JAMA 2011; 305:1969 A Lødrup et al Use of proton pump inhibitors after antireflux surgery: a nationwide register-based follow-up study Gut 2014 January 28 (epub) JE Pandolfino and K Krishnan Do endoscopic antireflux procedures fit in the current treatment paradigm of gastroesophageal reflux disease? Clin Gastroenterol Hepatol 2013 January 28 (epub) Coming Soon in Treatment Guidelines: Drugs for Hypertension – May 2014 Adult Immunizations – June 2014 Follow us on Twitter @MedicalLetter Treatment Guidelines from The Medical Letter® EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pflomm, Pharm.D ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine Jane P Gagliardi, M.D., M.H.S., F.A.C.P Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre 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in the form of self-study material The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into practice after assimilating, information presented in materials contained in Treatment Guidelines The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and activities The Medical Letter aims to be a leader in supporting the professional development of healthcare professionals through Core Competencies by providing continuing medical education that is unbiased and free of industry influence The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations GOAL: Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable and timely educational content that they will use to make independent and informed therapeutic choices in their practice LEARNING OBJECTIVES: The objective of this activity is to meet the need of healthcare professionals for unbiased, reliable and timely information on treatment of major diseases The Medical Letter expects to provide the healthcare community with educational content that they will use to make independent and informed therapeutic choices in their practice Participants will be able to select and prescribe, or confirm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in Treatment Guidelines with specific attention to clinical evidence of effectiveness, adverse effects and patient management Upon completion of this program, the participant will be able to: Explain the current approach to the management of peptic ulcer disease and gastroesophageal reflux disease Discuss the pharmacologic options available for treatment of peptic ulcer disease and gastroesophageal reflux disease and compare them based on their efficacy, dosage and administration, potential adverse effects, and drug interactions 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Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 12 (Issue 140) • April 2014 DO NOT FAX OR MAIL THIS EXAM To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 140 Questions Gastroesophageal reflux disease (GERD) can be caused by: a delayed gastric emptying b hormonal changes due to pregnancy c reduced lower esophageal sphincter tone d all of the above Peptic ulcer disease (PUD) is often caused by: a Helicobacter pylori infection b hormonal changes due to pregnancy c reduced lower esophageal sphincter tone d hiatal hernia Which of the following H2-receptor antagonists is most effective for treatment of GERD? a famotidine b ranitidine c nizatidine d all are equally effective Possible long-term adverse effects of proton pump inhibitors include: a Clostridium difficile-associated diarrhea b fracture risk c vitamin B12 deficiency d all of the above A 68-year-old man who is currently taking clopidogrel for acute coronary syndrome has recently been diagnosed with PUD and asks you to recommend a proton pump inhibitor Which of the following would be an appropriate choice for this patient? a omeprazole b esomeprazole c pantoprazole d all of the above Which of the following is true regarding antacid therapy? a aluminum-containing antacids can cause constipation b magnesium-containing antacids can cause diarrhea c antacids can provide rapid, but transient relief of GERD symptoms d all of the above How many weeks after completion of therapy should you wait before using urea breath and stool antigen tests for eradiation of H pylori infection? a b c d Increasing rates of resistance to which of the following drugs has reduced the efficacy of triple therapy for H pylori eradication? a azithromycin b metronidazole c clarithromycin d tinidazole Which of the following drugs can temporarily turn the tongue and stool black? a tinidazole b bismuth subsalicylate c clarithromycin d tetracycline 10 A 54-year-old woman who is taking omeprazole for GERD asks if there is anything she can to alleviate her nighttime symptoms Which of the following would you recommend? a avoid lying down 2-3 hours after a meal b elevating the head of her bed c adding a second dose of omeprazole in the evening d all of the above 11 Which of the following is the drug of choice for treatment of erosive esophagitis? a baclofen b sucralfate c a proton pump inhibitor d an antacid 12 Which of the following is the surgical procedure of choice for management of GERD? a laparoscopic fundoplication b gastric banding c Roux-en Y gastric bypass d gastric sleeve ACPE UPN: 0379-0000-14-140-H01-P; Release: March 2014, Expire: March 2015 Treatment Guidelines from The Medical Letter • Vol 12 (Issue 140) • April 2014 ... September 2011) Some Drugs for Peptic Ulcer Disease and GERD Some Multi-Drug Regimens for H Pylori Infection www.medicalletter.org Page 27 Page 28 Drugs for Peptic Ulcer Disease and GERD Related article(s)... Letter • Vol 12 (Issue 140) • April 2014 Drugs for Peptic Ulcer Disease and GERD Table Some Drugs for Peptic Ulcer Disease and GERD Drug Some Available Formulations Usual Adult Dosage1 Cost2 200-400... 140) • April 2014 29 Drugs for Peptic Ulcer Disease and GERD 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 30 PO Katz et al Guidelines for the diagnosis and management of gastroesophageal