Cool that heartburn

Mary Warner

Heartburn is a very common gastrointestinal complaint, often described as a burning sensation in the chest. Heartburn most often occurs at night when patients are lying down. It is the main symptom of GERD, but it may also occur in patients with peptic ulcers, delayed gastric emptying, or gallbladder disease. It occurs when the lower esophageal sphincter muscle allows acidic stomach contents to flow back up into the esophagus and sometimes into the throat or back of the mouth. Heartburn can usually be treated effectively with OTC options, including antacids, H2 receptor agonists (H2RAs), and PPIs.

Antacids

Antacids, which contain magnesium, aluminum, or calcium salts, relieve heartburn by neutralizing gastric acid. Most antacids are relatively inexpensive and widely available, making them a good choice for the temporary relief of mild and infrequent heartburn. They act as buffering agents by reacting with acid to form water (and the corresponding salt).

Antacids are available as chewable tablets and liquids, with the liquid forms acting more quickly. When taken on an empty stomach, most antacids provide about 20 to 60 minutes of action; when taken within an hour after a meal, they can provide relief for up to 3 hours. Common brands of antacids include Tums (calcium carbonate), Mylanta (aluminum hydroxide and magnesium hydroxide), and Rolaids (calcium carbonate and magnesium hydroxide).

Antacids are usually well tolerated, and any adverse effects are generally associated with the specific cation in the active ingredient. Magnesium-containing antacids can cause diarrhea, which can be mitigated by including aluminum hydroxide with the magnesium salt. In addition, because magnesium excretion may be impaired in patients with renal disease, magnesium-containing antacids should not be used by these patients.

H2RAs

H2RAs relieve and prevent heartburn by inhibiting histamine, which reduces the amount of acid produced by the stomach. They typically start to work within 1 to 3 hours. Common OTC H2RAs include Tagamet HB (cimetidine) and Pepcid (famotidine). Two previously available OTC treatments for heartburn are no longer available: Azid AR (nizatidine) was discontinued by the manufacturer, and ranitidine (Zantac) was removed from pharmacy shelves in April 2020 because of contamination by N-nitrosodimethylamine (NDMA), a probable human carcinogen.

Heartburn relief with H2RAs is not as rapid as with antacids, but the duration of relief is longer, usually 4 to 10 hours. They can be taken either at the onset of symptoms or 30 to 60 minutes before heartburn is expected. Because tolerance to the effects of H2RAs may develop with daily use, patients should take these medications on an as-needed basis rather than regularly. A reduced dose is recommended for patients with impaired renal function.

 H2RAs are associated with a low incidence of adverse effects, the most common of which are headache, diarrhea, constipation, dizziness, and drowsiness. Cimetidine is associated with a weak antiandrogenic effect and should not be taken by men at high doses.

PPIs

OTC PPIs are used to treat frequent heartburn (2 or more days per week). Because they may take up to 4 days for full effect, they are not intended for immediate relief of heartburn. PPIs reduce the amount of acid produced by inhibiting hydrogen potassium ATPase (the proton pump) and irreversibly blocking the final step in gastric acid secretion in the stomach. Bioavailability of PPIs is reduced if taken after a meal compared to fasting, so these medications should be taken 30 to 60 minutes prior to eating, preferably first thing in the morning.

OTC PPIs include Prevacid (lansoprazole), Nexium (esomeprazole), Prilosec OTC (omeprazole), and Zegerid OTC (omeprazole and sodium bicarbonate). Differences in efficacy among these PPIs have not been established. Tablets and capsules should never be chewed or crushed, as this would compromise the enteric coating that is necessary for effectiveness of the drug. Adverse effects with short-term use of PPIs are uncommon.

What to tell your patients

Because antacids, H2RAs, and PPIs can interact with a variety of other medications, patients should regularly check in with their pharmacist to ensure these interactions are avoided. If antacids are used more than twice a week or regularly for more than 2 weeks, patients should be advised to consider switching to a longer acting product, such as an H2RA or a PPI.

Patients who need an OTC PPI to control heartburn for more than 2 weeks or whose heartburn recurs within 4 months, should be advised to consult their physician for further evaluation.

For further information on heartburn and its treatment, see Chapter 13 of the Handbook of Nonprescription Drugs, available in print at pharmacist.com and online in Pharmacy Library.  ■

Interactions with OTC heartburn medications

Medication	Drug(s)/drug class	Potential interaction	Management/preventive measures
Antacids	Itraconazole, ketoconazole, iron, atazanavir	Increased gastric pH may decrease disintegration, dissolution, or ionization of drug leading to decreased absorption.	Separate doses by at least 2 hours.
	Amphetamines	Absorption of amphetamines is increased and excretion decreased.	Avoid concurrent use or monitor response to therapy.
	Rosuvastatin	Absorption of rosuvastatin is decreased.	Separate doses by at least 2 hours. Infrequent use of antacids is unlikely to cause clinically significant interaction.
	Enteric-coated medications	Increased gastric pH may cause premature breakdown of enteric coating.	Separate doses by at least 2 hours.
Calcium carbonate, magnesium hydroxide, aluminum hydroxide	Levothyroxine	Absorption of levothyroxine is delayed or impaired.	Separate doses by at least 4 hours.
	Tetracyclines	Absorption of antibiotic is decreased.	Separate doses by at least 4 hours.
	Fluoroquinolones	Absorption of antibiotic is decreased.	Take antibiotic 2 hours before or 6 hours after taking antacid.
Magnesium hydroxide, aluminum hydroxide	Azithromycin	Absorption of antibiotic is decreased.	Separate doses by at least 2 hours.
Sodium bicarbonate	Quinidine	Increased urinary pH may decrease renal excretion of quinidine.	Avoid concurrent use or monitor response to therapy.
	Salicylates	Increased urinary pH may increase renal excretion of salicylates.	Avoid concurrent use or monitor for decreased response to salicylates.
Antacids, H2RAs, PPIs	Erlotinib, dasatinib, gefitinib, other tyrosine kinase inhibitors, rilpivirine, ledipasvir/sofosbuvir	Increased gastric pH decreases absorption.	Avoid concurrent use of PPI or H2RA; separate from antacids by several hours.
H2RAs, PPIs	Itraconazole, ketoconazole, atazanavir, iron sulfate, calcium carbonate	Increased gastric pH may decrease disintegration, dissolution, or ionization of drug, leading to decreased absorption.	Avoid concurrent use or monitor response to therapy.
Cimetidine	Phenytoin, warfarin, amiodarone, clopidogrel, nifedipine, theophylline, tricyclic antidepressants, others	Cimetidine inhibits CYP450 1A2, 2C19, and to a lesser extent, 2D6, 3A4.	Avoid use of cimetidine in patients taking medications metabolized by these CYP enzymes.
Cimetidine, esomeprazole, lansoprazole, omeprazole	Citalopram	Inhibition of CYP450 2C19 increases citalopram concentrations and dose-dependent risk of QT prolongation.	Citalopram dose should not exceed 20 mg per day if used concomitantly.
PPIs	Warfarin, theophylline, tacrolimus, mycophenolate mofetil	PPI inhibition of CYP2C19 may result in increased concentrations of target drugs.	Avoid concurrent use or check with prescriber.
	Digoxin	PPIs may increase digoxin absorption.	Check with prescriber before use.
	Methotrexate	Concurrent use increases risk of toxicity of methotrexate.	Avoid concurrent use of high-dose methotrexate. Clinically significant toxicity is unlikely with lower weekly doses.
Omeprazole, esomeprazole	Clopidogrel	Inhibition of variants of CYP2C19 reduces conversion of clopidogrel to its active form.	Avoid concurrent use or check with prescriber. Clinically significant interaction is unlikely.
	Cilostazol, diazepam	Inhibited metabolism may result in increased concentration of target drug.	Avoid concurrent use. Lansoprazole may be a safer alternative.

Source: Chapter 13, APhA's Handbook of Nonprescription Drugs.