Medications remain the cornerstone of the effort to prevent or ameliorate heartburn when lifestyle modifications are ineffective. In a survey, only 55% of males and 66% of females with heartburn requested assistance from a physician. Over 75% of survey respondents first chose nonprescription medications for heartburn. Thus, pharmacists may be asked to guide therapy for hundreds of thousands of patients every day. Among heartburn self-care choices are antacids, which neutralize the acid. More effective interventions inhibit gastric acid secretion. The goal of therapy is to raise stomach pH to 4 or above for as long as possible. If this goal can be achieved during reflux episodes, heartburn and its accompanying sequelae may be prevented.
Proton Pump Inhibitors (PPIs)
The final step in the production and secretion of gastric acid involves the enzyme H+/K+ adenosine phosphatase, commonly known as the proton pump, in the parietal cell. PPIs irreversibly inhibit this pump, halting both basal and meal-stimulated gastric acid secretion. In order for cells to resume normal gastric acid production, the proton pump must be regenerated, a process that takes three to five days. Thus, PPIs provide a more sustained duration of action than H2 blockers or antacids. For this reason, proton pump inhibitors are generally considered the most effective agents available to suppress gastric acid. Their effect reaches a peak after three or more days of dosing.
Because of their relatively greater efficacy, PPIs are referred to as superior to “any other class of drugs for the relief of gastroesophageal reflux disease (GERD) symptoms, for healing esophagitis, and for maintaining patients in remission.” Gastroenterologists advise beginning therapy with a proton pump inhibitor for patients with frequent GERD symptoms.
Omeprazole was marketed as a self-care product for the treatment of frequent heartburn in mid-September 2003 under the trade name Prilosec OTC. Each delayed-release tablet contains 20.6 mg of omeprazole magnesium, equivalent to 20 mg of omeprazole. Nonprescription omeprazole is the first innovative therapeutic entity for heartburn since the prescription-to-OTC switch of nizatidine in June 1996. Patients contemplating use of nonprescription omeprazole should be advised that it is indicated for frequent heartburn (heartburn that occurs two or more days each week). It is not intended for those who experience unpredictable or episodic heartburn. Approximately 50% of patients obtain heartburn relief on the first dose; efficacy increases over the next four days.
Dosing for nonprescription omeprazole is one 20-mg tablet daily for 14 consecutive days, for those age 18 and older. The pharmacist should advise patients about optimal dosage timing with omeprazole. The goal is to optimize absorption by parietal cells. Food ingestion stimulates parietal cell activity; enhanced parietal cell activity promotes PPI uptake. This fact can be used to maximize PPI absorption by advising patients to take a PPI in the morning, 30 to 60 minutes before eating. The label of nonprescription omeprazole states that the patient should take one tablet with a glass of water before eating in the morning.
Patients must not use nonprescription omeprazole if they have difficulty or pain when swallowing food, vomitus containing blood, or bloody or black stools. Patients are further cautioned to ask the advice of a physician prior to use of the product if they are pregnant or breast-feeding or if they have any of the following:
- Heartburn that has persisted longer than three months.
- Heartburn with lightheadedness, sweating, or dizziness.
- Chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck, or shoulders; or lightheadedness.
- Frequent chest pain.
- Frequent wheezing, particularly with heartburn.
- Unexplained weight loss.
- Nausea or vomiting.
- Stomach pain.
Patients must stop using the product and seek the advice of a health care professional if heartburn continues or worsens, if they need to take the product longer than 14 days (unless instructed to do so by a physician), or if they need more than one course of treatment every four months. In all cases, patients should understand that they may take only one 14-day course of treatment every four months. Patients are also directed on the label to ask a physician or pharmacist if they are currently taking warfarin, prescription antifungal or antiyeast medicines, diazepam, or digoxin. Those who consult with a pharmacist prior to purchase should be specifically asked about these medications to prevent drug interactions.
As prescription products, proton pump inhibitors have a long history of being well-tolerated. It is expected that they will retain their overall safety as nonprescription products, especially in light of the 14-day regimen.
Compared to antacids and H2 blockers, PPIs appear to be the most effective agents for frequent heartburn. Research has confirmed the superiority of omeprazole 10 mg and 20 mg once daily over ranitidine 150 mg twice daily. In one study, 533 patients were given ranitidine 150 mg twice daily for up to eight weeks; omeprazole 20 mg once daily was significantly superior in relieving moderate to severe heartburn.
With a long history of safe use as a prescription product and proven efficacy, omeprazole is the medication of choice for frequent heartburn. Control of frequent heartburn may require medication along with lifestyle modifications. Further, at present, there is no other nonprescription product specifically indicated for prevention of frequent heartburn symptoms occurring two or more days per week.
The Pregnant Patient With Heartburn
The frequency with which heartburn occurs in pregnancy virtually ensures that pharmacists will be asked to recommend a product for a pregnant woman. The most prudent course of action is to refer the patient to her obstetrician. Generally, calcium-containing antacids and ranitidine are the safest choices, considering potential harm to the fetus, but this choice is best left to the physician.
H2-Receptor Antagonists (H2 Blockers)
H2 blockers act on parietal cells to block histamine-2 receptors, which has the effect of reducing accumulation of cyclic adenosine monophosphate inside the cells. Their effect is less pronounced than that of PPIs, perhaps because they cannot exert a sustained 24-hour action.
Four H2 blockers are available as nonprescription products. Cimetidine may be purchased as 200-mg tablets (Tagamet HB 200) or suspension, 200 mg/20 mL (Liquid Tagamet HB 200). Famotidine is available as 10-mg tablets (Pepcid AC tablets, chewable tablets, and gelcaps) and in an antacid combination (Pepcid Complete, containing 10 mg of famotidine with 800 mg of calcium carbonate and 165 mg of magnesium hydroxide per chewable tablet). Ranitidine 75-mg tablets (Zantac 75) and nizatidine 75-mg tablets (Axid AR) are also available. All four H2 blockers are labeled for the relief of heartburn associated with acid indigestion and sour stomach. All also are labeled to prevent those problems when brought on by eating or drinking certain foods and beverages.
H2-blocker labels caution patients against unsupervised self-use if they have persistent abdominal pain or have trouble swallowing (only on nizatidine and ranitidine labels). All warn patients not to use the H2 blocker in maximum daily doses for more than 14 days without the advice of a physician. Patients who are breast-feeding or pregnant should not use them without a health professional’s advice. No patient under the age of 12 years should be given the products, unless a physician has suggested it. All except nizatidine warn patients not to combine them with other acid reducers. Cimetidine has the potential to interact with other medications; packages caution patients not to take the drug with theophylline, warfarin, or phenytoin.
For relief of symptoms, the patient is directed to take one H2-blocker dosage unit (tablet, gelcap, chewable tablet, or 20-mL dose of suspension) with a glass of water, repeating the dose no more than once in any 24-hour period. For prevention of symptoms, patients are directed to take one unit of product just prior to eating to within 60 minutes before eating (nizatidine), right before eating to 30 minutes before eating (cimetidine), 30 to 60 minutes before eating (ranitidine), or 15 to 60 minutes before eating (famotidine).
H2 blockers are well-tolerated and cause few adverse reactions. However, their potential to affect heartburn has occasionally been questioned. In one prospective controlled trial, heartburn patients were given 150 mg of ranitidine twice daily. Of 481 patients treated for six weeks, 59% still had heartburn. Some nonresponders were randomly selected to receive 300 mg of ranitidine twice daily; only a minority obtained relief. H2 blockers, in conjunction with the institution of lifestyle modifications, may be chosen for those patients who experience episodic, infrequent heartburn, while patients with frequent heartburn should be informed that omeprazole is specifically indicated for them.
Antacids are insoluble inorganic compounds that neutralize gastric acids to raise the gastric pH. Antacids do not suppress acid production but only neutralize acid that has already been produced. This “after the fact” mechanism limits their usefulness. However, the pH rise also inhibits pepsin activity, and calcium carbonate (eg, Tums) and aluminum hydroxide absorb pepsin. Furthermore, magnesium hydroxide and aluminum hydroxide bind bile acids and may possess cytoprotective actions. Nevertheless, the development of acid-suppressing H2 blockers and proton pump inhibitors and their subsequent availability as nonprescription products has greatly restricted the usefulness of antacids.
Antacids give rapid relief, but this is counterbalanced by their transient action; taken on an empty stomach, they have only a 20- to 60-minute effect. Yet, if ingested with a meal or within one hour after eating, they act for three hours because of the additive buffering effect of the food itself.
Antacids carry labeling for heartburn, indigestion, sour stomach, and upset stomach associated with any of those problems. Most antacids in the United States are used for heartburn, but their efficacy in this condition has never been completely documented. For patients with mild heartburn, antacid efficacy is approximately equal to that of H2 blockers. Their principal advantage is rapidity of onset, but this is outweighed for most patients by the short duration of action. They may be useful for breakthrough symptoms. Researchers investigated the efficacy of antacids in relieving symptoms for heartburn patients without esophagitis. Antacids were unable to control symptoms in 50% of patients. The use of on-demand omeprazole 20 mg was an effective treatment strategy for these patients.
Like other nonprescription products, antacids carry several warnings, precautions, and contraindications. Labels warn potential users to check with a doctor or pharmacist before using an antacid if they are taking a prescription medication. Labels also provide a maximum number of doses that should not be exceeded in a 24-hour period and warn against taking the maximum dose for more than two weeks without checking with a physician. Although the labels of antacids do not carry a specific age cutoff, their safety in those under age 2 is unknown.
Sodium bicarbonate can cause gastric rupture, milk-alkali syndrome, and rebound hyperacidity. It is obsolete as an antacid. Calcium and aluminum constipate, while magnesium is prone to cause osmotic diarrhea. Magnesium/aluminum combination antacid use is extremely common, opening the patient to risks from both ions. Aluminum binds with dietary phosphate in the stomach, forming aluminum phosphate, which is excreted fecally. With sustained use, the patient may develop osteomalacia, especially if taking doses in excess of those labeled.
Episodic, infrequent heartburn may be helped with antacid therapy (in conjunction with lifestyle modifications), although the need for frequent dosing and the number and frequency of adverse reactions limit antacids‘ usefulness. They are unable to speed healing of reflux esophagitis and cannot prevent nocturnal acid reflux, making them poor choices for frequent heartburn.
The role of antirefluxants is controversial. The ingredient used is sodium alginate or alginic acid, as found in Gaviscon liquid and tablets. When ingested, the alginate forms a nonirritating “raft” of bubbles that floats atop gastric contents. When the LES undergoes transient relaxation, the sodium alginate rather than the more damaging materials enters the esophagus. Thus, the product does not actually prevent reflux but is simply a substitute reflux material. Products containing it list the alginate as an inactive ingredient because it has no inherent antacid capacity. The magnesium and aluminum antacids that are combined with it are listed as active ingredients. Its efficacy in preventing or relieving reflux is controversial. It should not be ingested with simethicone, since this ingredient is a defrothicant, which breaks down bubbles and would compromise the efficacy of the alginate