Can long-term use of nitrofurantoin cause neurological damage?

From the Guidelines

Long-term use of nitrofurantoin can potentially cause neurological damage, and patients should be closely monitored for symptoms of peripheral neuropathy, particularly if they have underlying conditions such as renal impairment, anemia, diabetes, vitamin B deficiency, or electrolyte abnormalities. The risk of neurological damage from nitrofurantoin is a concern due to its potential to interfere with cellular energy production in nerve cells 1. Symptoms of peripheral neuropathy may include numbness, tingling, pain in the extremities, muscle weakness, and in some cases, difficulty walking. If patients experience any neurological symptoms while taking nitrofurantoin long-term, they should contact their healthcare provider immediately, as these effects can sometimes be irreversible if the medication isn't discontinued promptly 1. For patients requiring long-term urinary tract infection prophylaxis, healthcare providers should consider alternative medications or lower doses of nitrofurantoin with regular monitoring for neurological symptoms. Some studies suggest that the risk of adverse events, including neurological effects, increases with prolonged use of nitrofurantoin, typically beyond 6 months 1. However, the most recent and highest quality study on this topic is from 2024, which emphasizes the importance of monitoring patients for adverse events, including neurological symptoms, when using nitrofurantoin for extended periods 1. Key points to consider include:

• Nitrofurantoin can cause peripheral neuropathy with long-term use
• Patients with underlying conditions are at higher risk
• Regular monitoring for neurological symptoms is essential
• Alternative medications or lower doses of nitrofurantoin may be considered for long-term prophylaxis
• Healthcare providers should discuss the potential risks and benefits of nitrofurantoin with patients before prescribing it for extended periods 1.

From the FDA Drug Label

Neuropathy: Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating disease may enhance the occurrence of peripheral neuropathy. Neurologic: Peripheral neuropathy, which may become severe or irreversible, has occurred Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the possibility of peripheral neuropathy

Long-term use of nitrofurantoin may cause neurological damage, specifically peripheral neuropathy, which can be severe or irreversible. Factors such as renal impairment, anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the risk of peripheral neuropathy. 2 2

From the Research

Neurological Damage from Long-Term Nitrofurantoin Use

• There is limited direct evidence on the long-term neurological effects of nitrofurantoin use 3, 4, 5, 6, 7.
• A study from 2021 found that patients taking nitrofurantoin reported gastrointestinal and central nervous system symptoms as side effects, but the frequency and severity of these symptoms were not specified 7.
• Another study from 2021 reported that perimenopausal and menopausal women on prolonged daily prophylaxis with nitrofurantoin did not have a high incidence of neurological adverse events, with no cases of neurological damage reported 4.
• A 1998 study found that older patients (> 65 years) did not report more adverse events, including neurological symptoms, than younger patients during long-term prophylaxis with nitrofurantoin 5.
• Overall, while there is some evidence of central nervous system symptoms as a side effect of nitrofurantoin use, there is no clear indication of long-term neurological damage from the available studies 3, 4, 5, 6, 7.

Adverse Events and Long-Term Use

• The available studies suggest that long-term use of nitrofurantoin can be associated with adverse events, including gastrointestinal and central nervous system symptoms 4, 5, 7.
• However, the frequency and severity of these adverse events are not well characterized, and more research is needed to fully understand the risks of long-term nitrofurantoin use 3, 4, 5, 6, 7.
• Clinicians should weigh the risks and benefits of chronic nitrofurantoin therapy and monitor patients for signs and symptoms of potential adverse events while on treatment 4.