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Updates in Nonprescription Therapy for Heartburn and GERD

W. Steven Pray, PhD, DPh
Bernhardt Professor, Nonprescription Products and Devices

College of Pharmacy

Southwestern Oklahoma State University

Weatherford, Oklahoma



10/21/2009

US Pharm. 2009;34(10):52-55. 

Pharmacists have fielded questions from patients about stomach discomfort for many years, advising patients about the use of antacids and related products, such as H2 antagonists and proton pump inhibitors (PPIs). Two relatively recent events should cause pharmacists to reconsider heartburn, gastroesophageal reflux disease (GERD), and their treatment. Further, manufacturers have introduced several new products for heartburn and GERD. 

Recent Position Statement

The American Gastroenterological Association (AGA) issued a 2008 medical position statement on management of GERD.1 To create the statement, the AGA assembled numerous reputable authorities to answer 12 questions critical to GERD, with use of the most current evidence and/or expert opinions. Their recommendations will be discussed in more detail later. 

Advances in Nonprescription Therapy for Heartburn/GERD

A second important event in self-care of GERD is the recent introduction of a new pharmaceutical entity to the nonprescription arena. Prevacid 24HR, which was approved by the FDA on May 14, 2009, is the second PPI (after Prilosec OTC) approved for OTC use.2 Pharmacists should become thoroughly familiar with its labeling to make appropriate patient recommendations. The OTC product is expected to launch in November 2009. [NOTE: Available as of November 12, 2009.]

Definitions of Heartburn/GERD

The hallmark symptom of reflux and GERD is heartburn, a burning sensation in the retrosternal area (i.e., the area of the heart), that often radiates toward the neck, throat, and back.3 However, not all cases of heartburn approach a degree of severity as to be defined as GERD. The AGA statement clarified this issue by differentiating episodic heartburn from GERD.1 Episodic heartburn is a minor problem that does not cause troublesome symptoms and/or complications. By contrast, the AGA accepted the opinion of world experts that the patient has GERD when reflux results in symptoms and/or complications that adversely affect the patient’s well-being. 

Another useful definition is that of frequent heartburn. The FDA, in determining which patients may self-medicate with Prilosec OTC or Prevacid 24HR, determined that frequent heartburn is an episode occurring on two or more days per week.2,3 Thus, patients with heartburn occurring once weekly or less are not candidates for OTC PPIs. 

Prevalence of Heartburn/GERD

The exact incidence of heartburn and/or GERD is difficult to determine, but experts estimate that 40% of adults experience it monthly, 7% to 30% weekly, 8% to 26% two or three times weekly, and 7% to 10% on a daily basis.4-9 The annual prevalence is 60%, and the annual cost for GERD in the United States is $10 billion.4,6 Further, the risk of experiencing symptomatic reflux is increasing yearly.7,10 Ten years after being diagnosed with GERD, 66% of patients still report symptoms.5 

Epidemiology of Heartburn/GERD

While heartburn and/or GERD is often viewed as a condition occurring exclusively in older patients, many children and adolescents are also affected, and GERD in childhood may signal those who will also suffer from the condition as adults.5 There is little reliable research to indicate strong differences in the incidence of GERD according to gender or racial identity. Interestingly, the prevalence in Asian countries is less than 5%.11 

Some patients are genetically predisposed to experience GERD.10 They may inherit a tendency to hiatal hernia, an inherently lower pressure in the lower esophageal sphincter (LES), or lower esophageal motility.11 Studies in monozygotic (identical) versus dizygotic (fraternal) twins reveal that 31% to 43% of the risk of GERD is due to genetic factors.11 If an individual appears to be at genetic risk, implementation of lifestyle changes may prevent or minimize symptoms. 

Etiology of Heartburn/GERD

An important aspect of human physiology in preventing reflux episodes is the LES.3 The LES is a small muscular sphincter located at the juncture of the esophagus and stomach. It has a normal closed resting tone of 10 to 35 mm Hg.7 When an individual swallows food or drink, the LES opens to allow the material to enter the upper stomach. After the ingested materials have cleared the esophagus, the LES normally closes tightly until the patient swallows again. After the meal, the LES should remain closed, keeping the food and drink in the stomach. However, should the LES pressure drop below 10 mm Hg, food and drink can reflux backward into the esophagus. The LES may at times relax completely even though the patient has not swallowed, a phenomenon known as transient LES relaxations (TLESRs).7 

Acid is only one component of refluxate that damages esophageal tissue, and other components are also destructive, such as bile.4,6 In addition, symptoms occur from mechanical stimulation such as distension and contraction. 

Risk Factors for Heartburn/GERD

Several medical conditions are known to increase the risk of heartburn and/or GERD, including pregnancy, obesity, delayed gastric emptying, and hiatal hernia. 

The U.S. is currently in the throes of an epidemic of obesity, defined as a body mass index (BMI) of 30 or above.10 Various research studies confirm a strong link between obesity and GERD. Figures for BMI can easily be placed into strata, from lightest patients to heaviest. Researchers have observed a clear linear relationship between added weight and the occurrence of reflux symptoms.7 One reason for the increased risk is chronically low LES pressure, and research confirms an inverse relationship between weight and LES pressure.7 Another finding is that obese patients undergo a significantly greater number of TLESRs.7 Obese patients also have a greater incidence of hiatal hernia and motor abnormalities of the esophagus and stomach. 

A long-recognized risk factor for reflux is delayed gastric emptying.6 It seems axiomatic that in most cases, when ingested food exits the stomach, it is no longer available to reflux. The exception is when a patient experiences duodenogastric reflux, wherein materials reflux from the duodenum into the stomach, then upward to the esophagus.6 

Helicobacter pylori infection appears to confer a certain degree of protection against the development of GERD, perhaps due to continual gastritis, which induces the stomach lining to reduce acid secretion, causing an elevation of intragastric pH.11 

Nocturnal Heartburn

During the day, gravity works for the patient by helping keep gastric contents in the stomach. However, when the patient lies down at night, gastric contents are prone to leak upward into the esophagus if the LES tone is entirely relaxed or low. Nocturnal reflux disrupts sleep and may force patients to sleep in a sitting position.11 

Manifestations of Heartburn/GERD

Heartburn of reflux or GERD is a burning sensation beginning in the stomach and/or lower chest region, rising toward the mid chest, and radiating to the neck, throat, and/or back.11 It may occur after large meals, after exercising, upon bending over, after lying down, or while asleep.3 The pain mimics anginal pain, often so closely that patients with prior anginal attacks often think that one is occurring. 

Patients also experience additional GERD-associated problems, such as dysphagia, odynophagia, globus hystericus, and cough.11 They may notice water brash phenomenon, the sudden appearance of salty salivary fluid in the mouth that often occurs along with an episode of reflux or prior to emesis.3 GERD also causes a host of manifestations that are not directly due to esophageal damage. These extraesophageal manifestations include asthma, dental erosion, laryngitis, and recurrent pneumonitis.11 

Complications of Heartburn/GERD

Some complications of GERD do not increase the risk of mortality or malignancy, such as erosive esophagitis, esophageal strictures, and esophageal ulcerations.5 Other nonmalignant GERD complications can be deadly. These include perforation, aspiration, and hemorrhage.5 

GERD is the most critical risk factor in development of Barrett’s esophagus, a condition in which reflux causes the normal squamous epithelium at the distal esophagus to resemble columnar mucosa, replete with goblet cells.11 This tissue abnormality is a physiologic marker for the development of adenocarcinoma of the esophagus.4 The incidence of patients in the U.S. with esophageal adenocarcinoma increased sixfold in the period from 1975 to 2001.10 

Lifestyle Interventions to Prevent Heartburn/GERD

The AGA position statement explored the feasibility of recommending a full set of lifestyle changes for all patients, but then recommended a targeted approach where patients are individually counseled to avoid any lifestyle choice that brings the condition about, increases its frequency, or worsens its severity.1 

The AGA statement placed lifestyle modifications into three classes.1 The first is to avoid any food or drink that causes reflux to occur, such as coffee, alcohol, chocolate, and fatty foods. The second is avoidance of low pH foods and drinks that induce heartburn, such as citrus juices or fruits, carbonated beverages, and spicy foods (e.g., onions, peppers, pizza, tomato-based sauces or drinks). The third is to lessen the risk of acid exposure, through such means as losing weight, raising the head of the bed, ceasing use of alcohol and tobacco, eating small meals, eating the last meal 3 to 4 hours prior to bedtime, and remaining upright for 2 to 3 hours after a meal. Not all patients respond to dietary interventions, and it is difficult to determine in advance who will be helped.1 

Nonprescription Products for Heartburn/GERD

Physicians recognize a number of ancillary symptoms occurring with heartburn that signal the presence of serious underlying disease: black/bloody stools, choking, chronic cough, dysphagia, early satiety during a meal, hematemesis, hoarseness, iron deficiency anemia, odynophagia, and weight loss.8 Patients with these complaints should always be referred to a physician. 

Nonprescription options the pharmacist can recommend for heartburn and GERD include antacids, H2 antagonists, and PPIs.3 The minimum ages and dosages for self-care are presented in TABLE 1.

Antacids and Combinations: The AGA statement recommended that patients who wish treatment only as symptoms arise should choose a rapidly acting medication, and pointed out that antacids would be the most logical choice when this criterion alone is applied.1 Antacids are also the logical choice when the patient merely wishes to consider expense, as they are generally the least expensive of the potential options. However, they should not be used for more than 2 weeks without consulting a physician, as sustained abdominal discomfort might indicate a more serious underlying condition that requires physician diagnosis. 

Antacids were the sole nonprescription treatments for heartburn and/or GERD until the advent of the H2 antagonists. They were once available in many formulas and combinations, and in several dosage forms. At this time, calcium carbonate, magnesium, and bismuth subsalicylate are the more commonly used antacids, with single-entity aluminum products having decreased in popularity due to their potential adverse reactions (e.g., hypophosphatemia, constipation, aluminum accumulation).3 While their onset of action is rapid, their duration of action is shorter than that of other categories of medications. Antacids are quite useful in short-term treatment of occasional postprandial heartburn.3 

Calcium carbonate is an excellent antacid that is rapid acting and possesses good neutralizing capacity, although it carries the risk of constipation, milk-alkali syndrome, and kidney stones if overused.3 Patients may purchase the well-known products, such as Tums (500 mg/tablet), Tums E-X (750 mg/tablet), Tums Ultra (1,000 mg/tablet), and Children’s Mylanta (400 mg/tablet). Several relatively new products have expanded patients’ choices of single-entity calcium carbonate products. One is a smooth dissolving tablet, Tums Smoothies (750 mg/tablet). Another is a higher-dosage tablet marketed for children, Tums Kids (750 mg/tablet). A new dosage form is Tums QuikPak, containing 1,000 mg of calcium carbonate in a packet that is poured onto the tongue after opening and allowed to dissolve.3 

Bismuth subsalicylate has been available for many years as Pepto-Bismol, and a new branded product known as Maalox Total Relief Liquid (525 mg/15 mL) now contains the same ingredient. Pharmacists must exercise caution when patients attempt to purchase this product, as the Maalox trade name has traditionally been associated with magnesium-aluminum combinations. Patients must be warned that this version of the Maalox trade name contains salicylates, with all of the label precautions, warnings, and drug interactions that salicylates must carry (e.g., gastrointestinal [GI] upset, Reye’s syndrome, tinnitus).3 

The standard antacid combinations remain available. Some contain calcium carbonate and magnesium hydroxide (e.g., Mylanta Supreme Liquid, Mylanta Ultimate Strength Tablets). Others incorporate aluminum hydroxide with magnesium hydroxide and simethicone (e.g., Mylanta Regular Strength Liquid, Maalox Advanced Liquid). With such combinations, the patient may experience diarrhea from magnesium or constipation from aluminum. A recently introduced combination also targets children. Maalox Plus Junior is a combination of 400 mg of calcium carbonate and 24 mg of simethicone per tablet.3 

H2 Antagonists and Combinations: The four H2 antagonists currently available (Axid AR, Pepcid AC, Tagamet HB, Zantac; see TABLE 1) share several important attributes. Their onset is slower than that of antacids, but their duration is longer. All prevent heartburn and/or GERD if taken before food or drink that usually causes the problem.3 None can be used longer than 2 weeks without a physician diagnosis. All warn patients to cease use and consult a physician if the stomach pain continues or worsens. All are contraindicated in patients who are pregnant or breastfeeding. [NOTE: These products should not be recommended by the pharmacist in patients who are breastfeeding due to lack of safety information. Rather, the decision should be left to the women's physician.] Tagamet HB 200 advertising states that it is the only acid reducer that can be taken before, during, or after a meal. However, it is also the only one in its category to carry drug interaction labels warning against concomitant use with theophylline, warfarin, and phenytoin. Famotidine 20 mg tablets (e.g., Pepcid AC Maximum Strength) are the only nonprescription H2 antagonists to carry a warning against use if the patient has kidney disease.3 These products are relatively free of adverse effects. 

Proton Pump Inhibitors: Prilosec OTC (omeprazole magnesium delayed-release tablet 20.6 mg) and Prevacid 24HR (lansoprazole delayed-release capsules 15 mg) are the only PPIs to have attained nonprescription status at this time.2,3,12 At the time of this writing, Prevacid 24HR has not yet been released; however, its labeling shows it to be virtually identical to that of Prilosec OTC in many important regards.3,12 Both products share label warnings and precautions that help ensure safe use. Both are contraindicated under the age of 18 and in patients who are pregnant or breastfeeding. They are only to be recommended when the patient has frequent heartburn, defined as heartburn occurring on 2 or more days per week. Neither will provide immediate relief of heartburn, as the patient may need to administer the product for 1 to 4 days before full relief is apparent. However, the duration of these PPIs is longer than that of other product categories. It is worth noting that many patients do experience relief on the first day of administration. 

Patients are directed to take 1 capsule/tablet with a glass of water before eating in the morning, for 14 consecutive days (TABLE 1).3,12 This 14-day course of therapy must not be repeated more often than every 4 months. Patients should not use either product if they have trouble or pain swallowing food, bloody vomitus, or bloody or black stools. In these cases, a physician should be consulted. Patients should speak to a physician before using either product if they have had heartburn for more than 3 months; heartburn with lightheadedness, sweating, or dizziness; chest or shoulder pain with shortness of breath, sweating, lightheadedness, or pain spreading to the arms, neck, or shoulders; frequent chest pain; frequent wheezing, especially along with heartburn; unexplained weight loss; nausea or vomiting; or stomach pain. 

Patients contemplating purchase of either product are directed to speak to their physician or pharmacist if they are taking warfarin, prescription antifungal or antiyeast medications, diazepam, digoxin, tacrolimus, atazanavir, or other acid reducers.3,12 

Patients should stop using OTC PPIs if their heartburn continues or worsens; if they feel that they need to take them for more than the 14-day period recommended on the label; or if they need to take more than one course of treatment every 4 months.3,12 

Conclusion

The pharmacist fields numerous questions in a typical workweek that center around GI problems. Understanding the relative advantages and disadvantages of antacids, H2 antagonists, and PPIs (and when to recommend each) can provide lasting relief for patients. 

REFERENCES

1. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al; American Gastroenterological Association. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology. 2008;135:1383-1391.
2. Novartis receives approval from FDA to market Prevacid 24HR as first and only OTC proton pump inhibitor in original formulation. Novartis. May 14, 2009. www.novartis.com/newsroom/
media-releases/en/2009/ 1314777.shtml. Accessed September 7, 2009.
3. Pray WS. Nonprescription Product Therapeutics. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
4. Ali T, Miner PB Jr. New developments in gastroesophageal reflux disease diagnosis and therapy. Curr Opin Gastroenterol. 2008;24:502-508.
5. Becher A, El-Serag HB. Mortality associated with gastroesophageal reflux disease and its non-malignant complications: a systematic review. Scand J Gastroenterol. 2008;43:645-653.
6. Fass R. Proton-pump inhibitor therapy in patients with gastro-oesophageal reflux disease: putative mechanisms of failure. Drugs. 2007;67:1521-1530.
7. Friedenberg FK, Xanthopoulos M, Foster GD, Richter JE. The association between gastroesophageal reflux and obesity. Am J Gastroenterol. 2008;103:2111-2122.
8. Heidelbaugh JJ, Gill AS, Van Harrison R, Nostrant TT. Atypical presentations of gastro esophageal reflux disease. Am Fam Physician. 2008;78:483-488.
9. Tokayer AZ. Gastroesophageal disease and chronic cough. Lung. 2008;186(suppl 1):S29-S34.
10. El-Serag H. The association between obesity and GERD: a review of the epidemiological evidence. Dig Dis Sci. 2008;53:2307-2312.
11. Richter JE. The many manifestations of gastroesophageal reflux disease: presentation, evaluation, and treatment. Gastroenterol Clin North Am. 2007;36:577-599.
12. Prevacid 24HR. www.prevacid24hr.com. Accessed September 25, 2009. 

To comment on this article, contact rdavidson@jobson.com.

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