“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Saturday, August 16, 2025

Nitrofurantoin


Introduction

Nitrofurantoin is an oral antibacterial agent widely used for the treatment and prevention of urinary tract infections (UTIs). Unlike broad-spectrum antibiotics, nitrofurantoin is primarily targeted against common urinary pathogens, particularly Escherichia coli and other susceptible Gram-negative and Gram-positive organisms. Its restricted spectrum and unique pharmacokinetics make it particularly valuable in urology and primary care settings, especially when managing uncomplicated cystitis in women.

This drug has been in clinical use since the mid-20th century and continues to be recommended in modern therapeutic guidelines as a first-line option for uncomplicated lower UTIs. Its efficacy is related to the ability to achieve high concentrations in urine while maintaining relatively low systemic plasma levels, thereby minimizing systemic toxicity but optimizing antimicrobial activity at the site of infection.

Pharmacological Classification

  • Class: Synthetic nitrofuran derivative, urinary tract antiseptic/antibiotic

  • ATC code: J01XE01

  • Formulations:

    • Immediate-release capsules (50 mg, 100 mg)

    • Oral suspension (25 mg/5 mL, mostly for pediatric use)

    • Macrocrystalline formulations (designed for better gastrointestinal tolerance)

    • Modified-release formulations (nitrofurantoin monohydrate/macrocrystals, e.g., 100 mg slow-release capsules)

Mechanism of Action

Nitrofurantoin exerts bactericidal activity by being reduced within bacterial cells by flavoproteins (nitrofuran reductase enzymes). This reduction generates highly reactive intermediates, including free radicals, which attack multiple bacterial targets:

  1. DNA damage: Disruption of DNA and RNA synthesis by inducing strand breakage.

  2. Protein synthesis inhibition: Inactivation of ribosomal proteins essential for bacterial growth.

  3. Metabolic interference: Alteration of bacterial carbohydrate metabolism and energy production.

  4. Cell wall synthesis disruption: Impairment of bacterial cell wall integrity.

Because the drug acts on multiple targets simultaneously, the risk of bacterial resistance is relatively low compared with other antibiotics. Resistance, when it occurs, usually involves reduced nitrofuran reductase activity within bacteria.

Pharmacokinetics

  • Absorption:
    Nitrofurantoin is rapidly absorbed from the gastrointestinal tract. Macrocrystalline formulations are absorbed more slowly, improving tolerability. Food enhances absorption and also reduces gastrointestinal irritation.

  • Distribution:
    Plasma concentrations remain low due to rapid elimination. Importantly, nitrofurantoin achieves very high urinary concentrations, which is essential for its therapeutic effect. Distribution into tissues outside the urinary tract is limited, which explains its ineffectiveness in systemic infections.

  • Metabolism:
    Metabolism occurs partially in the liver, but the drug largely remains unchanged until it reaches the kidneys.

  • Elimination:
    Excreted primarily via the kidneys into urine by glomerular filtration and tubular secretion.

    • Half-life: Approximately 20–60 minutes.

    • Urinary excretion: Produces antimicrobial levels in urine but not in blood or other tissues.

Clinical Indications

Nitrofurantoin is mainly reserved for the urinary tract due to its pharmacological profile.

  1. Uncomplicated cystitis (acute lower UTI)

    • First-line treatment in women, especially when resistance rates to trimethoprim-sulfamethoxazole or fluoroquinolones are high.

    • Effective against E. coli, Enterococcus faecalis, Klebsiella, and Staphylococcus saprophyticus.

  2. Prophylaxis of recurrent UTIs

    • Used as a low-dose, long-term therapy to prevent recurrence in patients with frequent UTIs.

    • Particularly recommended in women with ≥2 infections in 6 months or ≥3 in 12 months.

  3. Pediatric use

    • Suitable in children for both treatment and prophylaxis of UTIs when age >1 month.

  4. Pregnancy-related UTIs

    • Considered safe in most trimesters except near term (risk of hemolytic anemia in neonates due to immature red cell enzyme systems).

Contraindications

Nitrofurantoin must not be used in certain patient groups:

  • Renal impairment: Contraindicated when creatinine clearance <30 mL/min, as therapeutic urinary concentrations are not achieved and risk of systemic accumulation increases.

  • Late pregnancy (at term, 38–42 weeks): Risk of hemolytic anemia in neonates.

  • Neonates (<1 month old): Risk of hemolysis due to immature glutathione pathways.

  • Known hypersensitivity: Allergy to nitrofurantoin or excipients.

  • History of pulmonary toxicity or hepatotoxicity related to nitrofurantoin.

Precautions

  • Pulmonary toxicity: Both acute and chronic reactions may occur. Acute reactions often present with fever, cough, dyspnea, and eosinophilia; chronic use may cause interstitial lung disease or pulmonary fibrosis.

  • Hepatic toxicity: Rare but potentially severe hepatocellular, cholestatic, or autoimmune hepatitis-like reactions. Monitoring liver function during long-term therapy is recommended.

  • Peripheral neuropathy: May occur in prolonged use, particularly in patients with renal impairment, diabetes, or anemia.

  • Hemolysis in G6PD deficiency: Use with caution as oxidative stress can trigger hemolytic anemia.

  • Urine discoloration: May turn urine dark yellow or brown; this is harmless but important to counsel patients.

Adverse Effects

  1. Gastrointestinal: Nausea, vomiting, diarrhea, loss of appetite.

  2. Respiratory: Acute hypersensitivity pneumonitis, chronic pulmonary fibrosis.

  3. Hepatic: Cholestatic jaundice, hepatitis, hepatocellular necrosis (rare but severe).

  4. Neurological: Headache, dizziness, drowsiness, peripheral neuropathy.

  5. Hematological: Hemolytic anemia (especially in G6PD deficiency and neonates).

  6. Dermatological: Rash, pruritus, urticaria.

  7. Other: Benign urine discoloration.

Drug Interactions

  • Antacids (magnesium trisilicate): Reduce absorption and effectiveness.

  • Probenecid and sulfinpyrazone: Inhibit renal tubular secretion of nitrofurantoin, lowering urinary concentration and increasing serum toxicity risk.

  • Fluoroquinolones: Antagonistic effect when combined; avoid co-prescription.

  • Oral contraceptives: No significant interaction, but diarrhea or vomiting caused by nitrofurantoin may reduce contraceptive pill effectiveness.

Dosage

Adults

  • Acute uncomplicated cystitis:

    • 100 mg modified-release capsule twice daily for 5 days (preferred regimen).

    • Alternative: 50–100 mg immediate-release capsule four times daily for 5–7 days.

  • Prophylaxis of recurrent UTIs:

    • 50–100 mg immediate-release capsule once daily at bedtime.

Children (>1 month)

  • Therapeutic dose: 5–7 mg/kg/day orally, divided into four doses.

  • Prophylaxis: 1–2 mg/kg once daily at bedtime.

Elderly

  • Use with caution, especially if renal function is reduced. Avoid if creatinine clearance <30 mL/min.

Pregnancy

  • Safe in most trimesters.

  • Usual dose: 100 mg twice daily for 5 days.

  • Avoid at term (38–42 weeks gestation).

Special Clinical Considerations

  1. Uncomplicated vs. complicated UTIs
    Nitrofurantoin is effective only in uncomplicated infections confined to the lower urinary tract. It should not be used for pyelonephritis or systemic infections because adequate therapeutic levels in plasma, kidneys, or other tissues are not achieved.

  2. Long-term prophylaxis monitoring
    Patients on long-term prophylaxis (months to years) must be monitored for hepatic, pulmonary, and neurological adverse effects. Baseline and periodic assessment of liver enzymes, chest X-ray, and symptom review is recommended.

  3. Resistance patterns
    Resistance remains low for E. coli (generally <10% in many regions). However, some Klebsiella and Proteus species are intrinsically resistant.

Clinical Efficacy

Clinical studies and meta-analyses demonstrate nitrofurantoin’s strong efficacy in eradicating bacteriuria in uncomplicated cystitis. Cure rates often exceed 85–90% when the regimen is followed appropriately. Prophylactic use reduces recurrence rates significantly compared with placebo, making it a mainstay in recurrent UTI management strategies.

Patient Counseling Points

  • Take with food to improve absorption and reduce stomach upset.

  • Complete the full course even if symptoms improve earlier.

  • Urine may appear dark yellow or brown; this is harmless.

  • Report respiratory symptoms, skin rashes, persistent nausea, or yellowing of the eyes/skin immediately.

  • Maintain adequate hydration to promote urinary excretion.




on

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)