Understanding Potential Risks: What Does Long-Term Pepcid Use Cause?

October 14, 2025 •

4 min read

Studies show that long-term use of acid-reducing medications like Pepcid can be linked to vitamin B12 deficiency [1.4.1, 1.4.2]. For the millions who rely on it for heartburn, a crucial question arises: what does long-term Pepcid use cause beyond this well-documented effect?

Quick Summary

An in-depth look at the potential health consequences of prolonged famotidine (Pepcid) use. This overview covers impacts on nutrient absorption, the nervous system, kidney and liver health, and how it compares to other acid reducers.

Key Points

Vitamin B12 Deficiency: The most significant documented long-term risk of famotidine is impaired absorption of vitamin B12 from food [1.2.2, 1.4.1].
Mechanism of Action: Famotidine is an H2 blocker that works by inhibiting histamine-stimulated gastric acid secretion [1.3.4].
Central Nervous System Effects: Rarely, long-term use can cause CNS side effects like confusion and agitation, especially in the elderly or those with kidney disease [1.2.1, 1.2.4].
Kidney Function is Key: Famotidine is cleared by the kidneys, so people with renal impairment require dose adjustments to prevent toxicity [1.6.5].
Bone Health: Unlike PPIs, famotidine has not been strongly linked to an increased risk of osteoporosis or bone fractures in adults [1.5.1, 1.5.4].
Comparison to PPIs: H2 blockers like famotidine are generally considered to have fewer long-term risks than proton pump inhibitors (PPIs) [1.7.3, 1.9.1].
Intended Use: Over-the-counter Pepcid is meant for short-term use (e.g., 14 days); long-term therapy should be supervised by a doctor [1.9.3].

How Pepcid (Famotidine) Works

Pepcid's active ingredient, famotidine, is a histamine H2-receptor antagonist, or H2 blocker [1.3.2, 1.3.4]. In the stomach, parietal cells are responsible for producing acid. This process is stimulated by several things, including histamine [1.7.2]. Famotidine works by competitively blocking the H2 receptors on these cells, which effectively inhibits gastric acid secretion [1.3.4, 1.3.6]. By reducing both the volume and concentration of stomach acid, famotidine helps treat conditions like gastroesophageal reflux disease (GERD), peptic ulcers, and other hypersecretory conditions [1.2.3, 1.3.4]. Its effect begins within an hour of oral administration and can last for 10 to 12 hours [1.3.5].

Defining 'Long-Term Use'

Over-the-counter (OTC) famotidine is intended for short-term use, typically not exceeding a 14-day course unless directed by a doctor [1.9.3]. Prescription famotidine might be prescribed for longer periods, but the term "long-term" in medical studies often refers to continuous use for a year or more [1.4.6]. Using acid-suppressing drugs for two or more years has been more strongly associated with certain deficiencies [1.4.4, 1.4.5]. It is crucial to have regular check-ins with a healthcare provider to re-evaluate the need for continued therapy [1.4.3].

Potential Long-Term Effects of Pepcid

While generally considered to have a good safety profile, especially compared to other classes of acid reducers, prolonged use of famotidine is not without potential risks. Most side effects that require weeks or months to become apparent are rare [1.2.2].

Vitamin B12 Deficiency

The most well-documented risk associated with long-term use of H2 blockers like famotidine is vitamin B12 deficiency [1.2.2]. Stomach acid plays a key role in separating vitamin B12 from the food it's attached to, allowing it to be absorbed by the body [1.4.1]. By suppressing stomach acid, famotidine can interfere with this process [1.4.1]. A 2013 study in The Journal of the American Medical Association found that using H2 blockers for two or more years was associated with an increased risk of B12 deficiency [1.4.2, 1.4.4]. Left untreated, this deficiency can lead to anemia, nerve damage, and even dementia [1.4.1, 1.4.2].

Central Nervous System (CNS) Effects

Though rare, long-term use of famotidine has been associated with CNS side effects, especially in older adults or those with pre-existing kidney disease [1.2.1, 1.2.4]. Because the drug is cleared by the kidneys, impaired function can lead to its accumulation in the blood, increasing the risk of side effects [1.2.2, 1.6.5]. Reported CNS effects include:

Confusion or delirium [1.2.1]
Agitation [1.2.1]
Hallucinations [1.2.1]
Seizures [1.2.1]
Anxiety and depression [1.2.3]

Kidney and Liver Function

Famotidine is primarily eliminated through the kidneys, so dosage adjustments are necessary for patients with moderate to severe renal impairment to avoid toxicity [1.6.4, 1.6.5]. While proton pump inhibitors (PPIs) have been more strongly linked to chronic kidney disease, caution is still advised with long-term H2 blocker use in those with compromised kidney function [1.6.2].

Rarely, liver-related side effects such as elevated liver enzymes, hepatitis, and jaundice have been reported with famotidine use, although these are not exclusively linked to long-term use [1.2.1, 1.2.5].

Bone Health

Concerns about acid-suppressing medications and bone health have primarily focused on PPIs, which have been linked to an increased risk of osteoporosis-related fractures [1.5.1, 1.9.3]. The evidence linking famotidine (an H2 blocker) to decreased bone mineral density is much weaker and often inconsistent [1.5.2, 1.5.4]. Most studies suggest that H2 blockers like famotidine have little to no significant impact on bone density or fracture risk in adults [1.5.1, 1.5.4].


Feature	H2 Blockers (e.g., Pepcid/Famotidine)	Proton Pump Inhibitors (PPIs) (e.g., Prilosec/Omeprazole)
Mechanism	Blocks histamine at H2 receptors to reduce stomach acid secretion [1.3.4].	Blocks the final step in acid production by inhibiting the proton pump [1.7.2].
Speed & Duration	Starts working within 1 hour; effects last 10-12 hours [1.3.5, 1.7.5].	Can take 1-4 days for full effect, but effects last longer (up to 72 hours) [1.7.3, 1.7.5].
Effectiveness	Effective for mild, infrequent heartburn and GERD [1.7.4].	Generally considered more effective for chronic GERD and healing the esophagus [1.7.5, 1.9.1].
Long-Term Risks	Main risk is Vitamin B12 deficiency. CNS effects are rare, mainly in the elderly or those with kidney issues [1.2.2, 1.2.4]. Considered safer for long-term use than PPIs [1.7.3].	Associated with a higher risk of B12, magnesium, and calcium deficiencies, kidney disease, pneumonia, and bone fractures [1.9.3, 1.9.5].

Managing Long-Term Use and Alternatives

For those who need long-term acid suppression, it is vital to work with a healthcare provider to use the lowest effective dose and to monitor for potential side effects [1.4.5]. Lifestyle changes can also significantly reduce the need for medication. These include:

Maintaining a healthy weight [1.7.5]
Avoiding trigger foods like spicy, fatty, or acidic items [1.7.4, 1.7.5]
Elevating the head of the bed while sleeping [1.7.5]
Stopping smoking and limiting alcohol [1.8.5]

If medication is still necessary, alternatives include PPIs, which are more potent but carry different long-term risks, or other non-prescription options like antacids for immediate, short-term relief [1.7.1, 1.7.2]. In some cases, surgical procedures like fundoplication or the LINX device may be considered to avoid long-term medication use [1.7.1].

Conclusion

While Pepcid is a safe and effective medication for many, long-term use is not without potential consequences. The primary concern is an increased risk of vitamin B12 deficiency due to the suppression of stomach acid. Other rare but serious effects on the central nervous system and liver can occur, particularly in vulnerable populations. Compared to PPIs, H2 blockers like famotidine generally have fewer associated long-term risks [1.9.1, 1.9.2]. Anyone considering or currently on long-term Pepcid therapy should maintain an open dialogue with their healthcare provider to weigh the benefits against the risks and explore all management options.

For more information on H2 Blockers, you can visit the National Library of Medicine.

Frequently Asked Questions

The most well-documented long-term side effect is vitamin B12 deficiency, which can occur because the reduction in stomach acid interferes with the body's ability to absorb this vitamin from food [1.2.2, 1.4.1].

Famotidine is cleared by the kidneys, so individuals with pre-existing kidney disease need a reduced dose to avoid accumulation and potential toxicity, such as central nervous system side effects. While not strongly linked to causing kidney disease, monitoring is important for those on long-term therapy [1.2.2, 1.6.5].

Unlike proton pump inhibitors (PPIs), famotidine (an H2 blocker) is not thought to raise the risk of osteoporosis or decreased bone density in adults. Studies have not reported this as a significant side effect [1.5.1, 1.5.4].

While many people take it long-term under a doctor's supervision, it's associated with risks like vitamin B12 deficiency. It's best to use the lowest effective dose for the shortest possible duration and have regular medical reviews to assess the ongoing need for the medication [1.4.5].

Rarely, long-term use can lead to central nervous system (CNS) side effects like confusion, delirium, agitation, and seizures. This risk is higher in older adults and those with impaired kidney function [1.2.1, 1.2.4].

Generally, H2 blockers like Pepcid (famotidine) are considered to have fewer long-term risks than PPIs like Prilosec (omeprazole). PPIs have been associated with a higher risk of fractures, kidney issues, and multiple nutrient deficiencies [1.7.3, 1.9.3].

Pepcid reduces the amount of acid in your stomach. This acid is necessary to separate vitamin B12 from the protein in food so it can be absorbed. By lowering acid levels, Pepcid can hinder this process, leading to a deficiency over time [1.4.1].