Medications That May Contribute to Heartburn

Rosemary R. Berardi, Pharm.D., F.C.C.P., F.A.S.H.P., F.A.P.H.A

Heartburn

Heartburn, the most common symptom of acid reflux, acid indigestion, or gastroesophageal reflux disease (GERD), is often mild and occasional (episodic), but may be frequent (occurs 2 or more days a week). For others, heartburn may be severe, frequent, and chronic. Heartburn occurs when the lower esophageal sphincter (LES), a specialized muscle at the end of the esophagus, does not open and close properly thereby permitting the backflow (reflux) of stomach juices into the esophagus. Other factors that influence the frequency and severity of heartburn include improper emptying of the stomach, impaired clearing action of the esophagus and decreased saliva.

Risk Factors

Certain factors can increase your risk (chances) of getting heartburn. These include diet (e.g., high-fat foods, citrus fruits and juices, alcohol), lifestyle (exercise, eating before bedtime, smoking), conditions such as hiatus hernia and pregnancy, and diseases such as diabetes. Prescription and over-the-counter medications may also contribute to heartburn. So, it is important to consider medications as a potential cause of heartburn.

What Is the Evidence?

Certain medications have been reported to cause or worsen heartburn. The list of medications includes those used to treat asthma and breathing difficulties, heart and blood pressure, arthritis and inflammation, osteoporosis, certain hormones, chemotherapy, and those that act on the nervous system. Numerous medications have been identified, but most concerns are theoretical as there is very little clinical evidence to support these claims. Although some medications are likely to worsen heartburn, most medications do not cause heartburn in a healthy individual. The medications most likely to contribute to heartburn are discussed below.

Which Medications are Most Likely to Contribute to Heartburn?

The following list includes prescription and nonprescription medications that may cause or worsen heartburn.

Medications used to treat asthma and breathing difficulties - Theophylline and other medications used for asthma and breathing difficulties weaken the LES, making it easier for stomach acid to reflux into the esophagus. Certain patients taking these medications, especially theophylline, e.g., (Theodur), may experience heartburn. Asthma medications administered by an inhaler, e.g., fluticasone (Flovent), beclomethasone (Vanceril), may be less problematic than oral theophylline.
Medications used to treat heart and blood pressure - Medications commonly used to treat heart and high blood pressure, such as calcium channel blockers, e.g., diltiazem (Cardizem), nifedipine (Procardia), beta-blockers, e.g., propranolol (Inderal), atenolol (Tenormin), alpha-blockers, e.g., prazosin (Minipress), and nitrates, e.g., isosorbide dinitrate (Isordil), nitroglycerin (Nitrostat), relax the LES and increase reflux of stomach juices into the esophagus, possibly contributing to heartburn.
Medications used to treat arthritis and inflammation - All nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin, Nuprin), naproxen (Aleve, Naprosyn), even those available over-the counter may cause or worsen heartburn. Cyclooxygenase-II (COX-2) inhibitors, e.g., celecoxib (Celebrex) are also associated with heartburn. Individuals who take an occasional or low-dose of aspirin or NSAID are not as likely to experience this side effect.
Medications used to treat osteoporosis - Bisphosphonates, such as alendronate (Fosamax), risedronate (Actonel), and other medications used to treat osteoporosis may injure the lining of the esophagus and lead to heartburn. Patients taking these medications should be sure to take them with a full glass of water and should not lie down for 30 to 60 minutes. Taking these precautions reduces the chance of these medications causing injury to the esophagus.
Medications used to treat anxiety, insomnia, depression, and pain - Some medications that act on the nervous system may contribute to heartburn. Antianxiety medications and agents used to treat insomnia, such as diazepam (Valium) or lorazepam (Ativan), antidepressants, including the tricyclic antidepressants such as amitriptyline (Elavil), and narcotics such as morphine and merpidine used to treat pain, may all cause or worsen heartburn by lowering the LES making it easier for stomach juices to reflux into the esophagus. One recent study reported a link between heartburn during sleep and benzodiazepines (e.g., diazepam, lorazepam) when used for sleep.¹
Medications used to treat Parkinson's disease and muscle spasms - Some antiparkinson medications containing levodopa (Sinemet) and antispasmotics, such as dicyclomine (Bentyl) or glycopyrrolate (Robinul), may increase reflux and heartburn by causing the LES to relax when it needs to be closed.
Medications used to treat cancer - Some medications used to treat cancer may cause heartburn, indigestion, and nausea. Patients receiving cancer chemotherapy may require medication to relieve heartburn and indigestion in addition to medication to treat nausea.
Hormones - Certain hormones, such as progesterone, a hormone contained in some birth control pills, may contribute to heartburn by decreasing LES pressure.

Steps to Take if You Feel That Medications are Contributing to Heartburn

Let your healthcare professional know if you experience heartburn or if your heartburn worsens when you begin a new prescription or nonprescription medication.
Keep a record of when you began to experience these symptoms in addition to when you started taking any new medication.
If a nonprescription medication causes or worsens heartburn, consult with your healthcare professional to determine whether you should stop the medication.
If a prescription medication seems to cause or worsen heartburn, contact your primary care provider as soon as possible. If the offending prescription medication cannot be stopped, other alternatives are available. These include switching the offending medication to another medication which is less likely to contribute to heartburn or treating the heartburn with either an antacid, H2-receptor antagonist or a proton pump inhibitor. The selection of a specific agent will depend on the frequency and severity of your heartburn.

Drugs Used to Combat Medication-Related Heartburn

All of the following medications may be used to combat medication-related heartburn. Onset and duration of heartburn relief as well as the frequency and severity of heartburn are important factors in selecting a product to treat medication-related heartburn.

Antacids - Antacids relieve heartburn quickly, but relief only lasts about 30 minutes on an empty stomach. If taken on a full stomach, antacids may provide relief for 2-3 hours. Antacids use should be limited to mild, infrequent heartburn and acid indigestion.
H2-receptor antagonists - The H2-receptor antagonists, e.g., famotidine (Pepcid, Pepcid AC, Pepcid AC Max), ranitidine (Zantac, Zantac 75, Zantac 150), cimetidine (Tagamet, Tagamet HB), and nizatidine (Axid, Axid AR) are available over-the counter and with a prescription. These agents relieve heartburn within an hour and provide a longer duration of relief (about 6 to 10 hours) than antacids. An over-the-counter product that contains an antacid plus famotidine (Pepcid Complete) is also available.
Proton pump inhibitors - Proton pump inhibitors are available over-the counter as omeprazole magnesium (Prilosec OTC) and with a prescription as omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix) and rabeprazole (Aciphex). These agents are intended for patients with frequent heartburn (2 or more days a week) or more severe heartburn.

¹Fass et al. Chest, May, 2005.

Additional References include:

American Phamaceutical Association, APhA Special Report: Strategies for the Self-treatment of Heartburn. Washingon DC: American Pharmaceutical Association; 2001:14.

Zweber A, Berardi RR. Heartburn and Dyspepsia. iN; Berardi RR, McDermitt JH, Newton GD, et al eds. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. 15th ed. Wasington, DC: American Pharmaceutical Assocation; 2006, in press.

Richter JE. Gastroesophageal reflux disease. In: Yamada T, Alpers DH, Kaplowitz N, et al., eds. Textbook of Gastroenterology. 4th ed. Philadelphia: Lippincott Williams & Williams; 2003:1196-1224.

Medications that may cause reflux and heartburn.
Accessed 7/8/2005.

- Reviewed by Jan Engle, Pharm.D.; and Robert S. Sandler, M.D., M.P.H.