What are the long-term risks of taking Pepcid (Famotidine)?

From the Guidelines

Long-term use of Pepcid (famotidine) is generally considered safe, but it's essential to be aware of potential risks, including vitamin B12 deficiency, increased risk of infections, and interactions with other medications, as noted in studies such as 1. When considering the long-term use of Pepcid, it's crucial to weigh the benefits against the potential risks. The main concerns with long-term acid suppression therapy include:

• Vitamin B12 deficiency
• Increased risk of certain infections like pneumonia and C. difficile
• Potential increased risk of bone fractures
• Kidney problems in those with pre-existing kidney disease
• Possible interactions with other medications Famotidine works by reducing stomach acid production, which can affect nutrient absorption over time. For those requiring long-term acid suppression, it's advisable to use the lowest effective dose and periodically reassess the need for continued therapy. Some patients may benefit from intermittent use or alternative approaches to managing acid-related conditions. Regular monitoring by a healthcare provider is important during extended use, especially for elderly patients or those with other health conditions. As seen in 1, proton pump inhibitors (PPIs) have a higher risk of adverse effects, such as Clostridium difficile infection, hypomagnesaemia, and bone loss/fractures, making famotidine a reasonable option for many patients requiring ongoing acid suppression therapy. Additionally, studies like 1 suggest that H2 antagonists, such as famotidine, may be a safer alternative to PPIs in certain situations, like dual-antiplatelet therapy. Therefore, it's recommended to use the lowest effective dose of Pepcid and regularly monitor patients to minimize potential risks and optimize treatment outcomes, as supported by the most recent and highest quality study 1.

From the FDA Drug Label

While no direct fetotoxic effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased food intake were seen in some rabbits at oral doses of 200 mg/kg/day (about 49 times the recommended human dose of 80 mg per day, based on body surface area) or higher. Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of famotidine at least 600 times the usual human dose. In postmarketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving Famotidine [see Warnings and Precautions (5. 1)]. CNS adverse reactions and prolonged QT intervals have been reported in patients with moderate and severe renal impairment [see Warnings and Precautions (5.1)].

The long-term risks of Pepcid (famotidine) include:

• CNS adverse reactions in elderly patients with and without renal impairment
• Prolonged QT intervals in patients with moderate and severe renal impairment
• Potential renal impairment due to reduced clearance of famotidine in adults with moderate and severe renal impairment However, the FDA label does not provide direct information on long-term risks specific to Pepcid. 2

From the Research

Long-term Risks of Pepcid (Famotidine) and Proton Pump Inhibitors (PPIs)

• Long-term use of PPIs, such as Pepcid's alternative proton pump inhibitors, is associated with several adverse drug events, including:
  • Acute interstitial nephritis 3
  • Fractures 3, 4
  • Clostridium difficile-associated diarrhea (CDAD) 3
  • Vitamin B12 deficiency 5, 4
  • Magnesium deficiency 4, 6
• The American Gastroenterological Association provides best practice advice for long-term use of PPIs, including:
  • Patients with GERD and acid-related complications should take a PPI for short-term healing, maintenance of healing, and long-term symptom control 7
  • Patients with uncomplicated GERD who respond to short-term PPIs should attempt to stop or reduce them 7
  • The dose of long-term PPIs should be periodically reevaluated to prescribe the lowest effective dose 7
• Studies have shown that long-term acid suppression therapy with PPIs or H2 receptor blockers may result in serum vitamin B12 deficiency, but there is no class- or drug-based difference in the vitamin B12 deficiency caused 5
• The association between PPIs and adverse clinical effects, such as bone fracture, acute and chronic kidney disease, gastrointestinal infections, and deficiencies in vitamin B12 and magnesium, has been described in the literature 6
• Clinicians should be aware of the potential risks associated with long-term PPI use and consider greater vigilance, but higher-quality data is needed to better understand PPI-associated risks 6