Are there concerns with long-term use of Pepcid (Famotidine)?

From the Guidelines

Long-term use of Pepcid (famotidine) may raise concerns, but it is generally considered safe when used as directed, and the most recent evidence suggests that patients should have a regular review of ongoing indications for use and documentation of that indication 1.

Key Considerations

• Potential issues with extended use include vitamin B12 deficiency, increased risk of certain infections like pneumonia or C. difficile, reduced calcium absorption potentially affecting bone health, and kidney problems in those with pre-existing kidney disease.
• Some people may develop tolerance to the medication over time, making it less effective.
• If acid suppression is needed for more than a few weeks, it's essential to consult with a healthcare provider to evaluate the underlying cause of symptoms and discuss whether continued Pepcid use is appropriate.

Recommendations

• Regular monitoring of vitamin levels and kidney function may be necessary during long-term use, especially in older adults or those with other health conditions.
• Patients without a definitive indication for chronic PPI should be considered for a trial of de-prescribing 1.
• The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for potential adverse effects associated with PPI use 1.

Important Notes

• Pepcid is an H2 receptor antagonist, and while it has a different mechanism of action than proton pump inhibitors (PPIs), similar considerations regarding long-term use and potential side effects should be taken into account.
• The most recent and highest quality study on this topic emphasizes the importance of regular review and documentation of indications for PPI use, which can be applied to the use of H2 receptor antagonists like Pepcid as well 1.

From the FDA Drug Label

Longer treatment durations have not been studied in clinical trials [see Clinical Studies (14.1,14.2,14. 3)]. Reduction of the risk of DU recurrence 20mg once daily 1 year c or as clinically indicated

The main concern for taking long-term Pepcid (Famotidine) is that longer treatment durations have not been studied in clinical trials. However, for the reduction of the risk of duodenal ulcer recurrence, a dosage of 20mg once daily is recommended for up to 1 year.

• Key points:
  • No studies have been conducted on the effects of long-term use beyond 1 year for reduction of duodenal ulcer recurrence.
  • The maximum recommended duration for other conditions, such as active duodenal ulcer, active gastric ulcer, symptomatic non-erosive GERD, and erosive esophagitis, is up to 8 weeks or up to 12 weeks.
• Clinical decision: Given the lack of studies on long-term use, it is recommended to use the lowest effective dose and to monitor patients closely for any potential adverse effects 2.

From the Research

Concerns for Long-Term Pepcid Use

There are several concerns associated with long-term use of Pepcid (famotidine), a histamine 2 receptor antagonist (H2RA). Some of these concerns include:

• Vitamin B12 deficiency: Long-term use of H2RAs like Pepcid has been linked to an increased risk of vitamin B12 deficiency 3, 4, 5.
• Osteoporosis risk: Although the evidence is indirect, long-term use of proton pump inhibitors (PPIs) has been linked to an increased risk of osteoporosis, and it is possible that H2RAs like Pepcid may also have a similar effect 6.
• Elevated homocysteine levels: Some studies have found that PPI use is associated with elevated homocysteine levels, a marker of vitamin B12 deficiency, although the evidence is not consistent 7.

Vitamin B12 Deficiency

The association between long-term H2RA use and vitamin B12 deficiency is supported by several studies:

• A case-control study found that long-term use of H2RAs was associated with an increased risk of vitamin B12 deficiency, with an odds ratio of 1.25 (95% CI, 1.17-1.34) 3.
• A study of elderly patients found that nearly 50% of those on prolonged acid suppression therapy with H2RAs or PPIs had deficient or insufficient serum vitamin B12 levels 4.
• A review of the literature found that H2RAs can reduce serum vitamin B12 concentrations by inhibiting the absorption of the vitamin, although the clinical implications of this effect are not fully understood 5.

Other Potential Risks

Other potential risks associated with long-term Pepcid use include:

• Osteoporosis: A study found that pantoprazole, a PPI, can alter the bone remodeling process by affecting the TRPM7 channel, which may increase the risk of osteoporosis 6.
• Elevated homocysteine levels: A cross-sectional study found that PPI use was associated with higher homocysteine levels, although the difference was small and may not be clinically significant 7.