Nitrofurantoin is a prescription antibacterial medication specifically indicated for the treatment and prophylaxis of uncomplicated urinary tract infections (UTIs) caused by susceptible strains of Escherichia coli, Enterococcus faecalis, Staphylococcus saprophyticus, and certain strains of Klebsiella and Enterobacter species. It belongs to the nitrofuran antibiotic class and functions by damaging bacterial DNA and inhibiting vital enzymatic processes, leading to bacterial cell death. Its unique pharmacokinetic profile ensures high concentrations in the urine and renal tissues, while systemic absorption is limited, making it an ideal agent for lower urinary tract pathologies. This guide provides a comprehensive, expert-level overview for healthcare professionals and informed patients regarding its appropriate use, safety profile, and clinical considerations.

Features

• Active pharmaceutical ingredient: Nitrofurantoin (as macrocrystals or monohydrate/macrocrystals)
• Available formulations: Oral capsules (50 mg, 100 mg) and oral suspension
• Mechanism of action: Bacteriostatic and bactericidal; interferes with bacterial acetylcoenzyme A, disrupting carbohydrate metabolism, DNA, RNA, and cell wall synthesis
• Spectrum of activity: Primarily effective against common gram-positive and gram-negative uropathogens
• Specialized delivery: Macrocrystalline formulation is designed for slower dissolution and absorption, potentially reducing the incidence of gastrointestinal side effects

Benefits

• Provides highly concentrated antibacterial action directly in the urinary tract, precisely where the infection is located.
• Offers a first-line treatment option for acute, uncomplicated cystitis with a well-established efficacy and safety profile.
• Serves as an effective prophylactic agent for patients with recurrent UTIs, reducing the frequency of symptomatic episodes.
• Exhibits a low propensity for inducing bacterial resistance compared to some other antibiotic classes, helping preserve its long-term utility.
• Its limited systemic absorption minimizes the impact on gut flora and reduces the risk of systemic side effects like Clostridioides difficile-associated diarrhea.

Common use

Nitrofurantoin is exclusively used for urinary tract infections. Its primary indication is the treatment of acute, uncomplicated UTIs presenting as cystitis. It is not indicated for the treatment of pyelonephritis or perinephric abscesses due to inadequate tissue penetration in the renal parenchyma. A significant secondary use is for the long-term suppression (prophylaxis) of recurrent UTIs in appropriate patient populations, often administered as a single, low dose at bedtime.

Dosage and direction

Dosage is contingent upon the indication (treatment vs. prophylaxis), renal function, and the specific formulation. For the treatment of an acute UTI in adults with normal renal function (CrCl ≥ 60 mL/min), the typical dose is 100 mg orally twice daily for 5 days (macrocrystals) or 7 days (monohydrate/macrocrystals). For pediatric patients (≥ 12 years), dosing is based on body weight. For prophylaxis, a common regimen is 50 mg or 100 mg orally once daily at bedtime. The medication must be taken with food or milk to enhance absorption and minimize gastric upset. It is crucial to complete the entire prescribed course of therapy, even if symptoms subside earlier, to ensure eradication of the pathogen and prevent recurrence.

Precautions

• Renal Impairment: Contraindicated in patients with a creatinine clearance (CrCl) under 60 mL/min or significant renal impairment. Reduced renal function leads to subtherapeutic urinary drug levels and increased systemic exposure, elevating the risk of toxicity, including pulmonary reactions.
• Pulmonary Reactions: Acute, subacute, and chronic pulmonary reactions have been reported. Monitor for symptoms like dyspnea, cough, fever, and pulmonary infiltrates. These can occur hours to weeks after initiation and may become severe.
• Hepatic Reactions: Rare but severe hepatic reactions, including hepatitis and cholestatic jaundice, can occur. Monitor liver function in patients with pre-existing liver disease and discontinue use if hepatitis occurs.
• Peripheral Neuropathy: Potentially irreversible peripheral neuropathy has been reported. Risk factors include renal impairment, anemia, diabetes, electrolyte imbalance, vitamin B deficiency, and debilitating disease. Use with caution in these populations.
• Hemolytic Anemia: May cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Use with caution and discontinue if signs of hemolysis appear.

Contraindications

• Anuria, oliguria, or significant renal impairment (CrCl < 60 mL/min).
• Known hypersensitivity to nitrofurantoin or other nitrofuran derivatives.
• Patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior nitrofurantoin use.
• Pregnancy at term (38–42 weeks gestation) and during labor and delivery, due to the risk of hemolytic anemia in the neonate.
• Infants under one month of age, due to the risk of hemolytic anemia.

Possible side effect

Common side effects are often gastrointestinal and include nausea, vomiting, anorexia, and abdominal pain. Less common but more serious adverse reactions require medical attention:

• Pulmonary: Acute pulmonary sensitivity reactions (fever, chills, cough, chest pain, dyspnea, pulmonary infiltration), subacute reactions, and chronic pulmonary fibrosis.
• Hepatic: Hepatitis, cholestatic jaundice, chronic active hepatitis.
• Neurological: Peripheral neuropathy (paresthesia, numbness), headache, dizziness, drowsiness.
• Dermatological: Maculopapular or erythematous rash, pruritus, urticaria, angioedema.
• Hematological: Megaloblastic anemia, leukopenia, granulocytopenia, hemolytic anemia (especially in G6PD deficiency), thrombocytopenia.
• Other: Clostridioides difficile-associated diarrhea, superinfection, asthenia.

Drug interaction

• Antacids containing magnesium trisilicate: Concurrent administration can reduce the absorption and bioavailability of nitrofurantoin, leading to subtherapeutic urinary levels. Administer nitrofurantoin at least 1 hour before or 2 hours after such antacids.
• Probenecid and Sulfinpyrazone: These uricosuric agents can inhibit the renal tubular secretion of nitrofurantoin. This may result in increased serum levels and systemic toxicity, while simultaneously decreasing urinary concentrations and antimicrobial efficacy. Concomitant use is not recommended.
• Drugs with Neurotoxic Potential: Concomitant use with other medications known to cause neuropathy may increase the risk of peripheral neuropathy.
• Ulipristal: Nitrofurantoin may reduce the serum concentration of ulipristal, potentially diminishing its efficacy as an emergency contraceptive.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed one, as this increases the risk of adverse effects.

Overdose

Symptoms of overdose are primarily related to the gastrointestinal system, including nausea and vomiting. There is no specific antidote for nitrofurantoin overdose. Management is supportive and symptomatic. Due to its low solubility and rapid excretion, emesis is of limited value. Hemodialysis may be considered but is not particularly effective due to the drug’s high protein binding and rapid elimination.

Storage

Store at room temperature (20°–25°C or 68°–77°F) in a tightly closed container, protected from light, moisture, and excessive heat. Keep all medications out of the reach of children and pets. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard any expired or unused medication through a medicine take-back program.

Disclaimer

This information is intended for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision or for any adverse effects resulting from the use of information contained herein.

Reviews

• “As a urologist, nitrofurantoin remains a cornerstone of my practice for uncomplicated cystitis. Its targeted action and low resistance rates make it a reliable first-line choice.” – Medical Professional
• “Prescribed for recurrent UTIs, the prophylactic low dose has been life-changing. I’ve been infection-free for over a year with no noticeable side effects.” – Patient
• “While effective, the nausea was significant for me. Taking it with a full meal was absolutely mandatory to tolerate the treatment course.” – Patient
• “From an infectious disease perspective, its niche role in treating lower UTIs is valuable for antimicrobial stewardship, helping us reserve broader-spectrum agents for more serious infections.” – Medical Professional