Nitrofurantoin

Nitrofurantoin is an oral urinary antiseptic used for uncomplicated lower urinary tract infection and for prophylaxis against recurrent cystitis. It reaches useful concentrations only in urine, so it is not used for pyelonephritis, prostatitis or systemic infection.

Classification. Nitrofuran.

Mechanism. Reduced inside bacterial cells to reactive intermediates that damage ribosomal proteins, DNA and metabolic enzymes; bactericidal in urine.

Spectrum. Escherichia coli (resistance remains low), Enterococcus faecalis, Staphylococcus saprophyticus and many Klebsiella and ESBL-producing Escherichia coli. Not active against Proteus, Pseudomonas, Serratia or Acinetobacter.

Pharmacokinetics. Rapid absorption, improved with food. Serum half-life under 1 hour. Concentrates in urine only. Excretion mainly renal; efficacy falls as clearance falls.

Maximum 400 mg daily (short courses); prophylaxis maximum 100 mg daily.

Adults, oral. - Uncomplicated cystitis, modified-release capsules: 100 mg every 12 hours for 3 to 5 days (3 days in women with uncomplicated infection). - Uncomplicated cystitis, immediate-release or macrocrystal form: 50 mg every 6 hours for 3 days, or 100 mg every 6 hours for 7 days in complicated lower infection when no other option exists. - Prophylaxis of recurrent urinary infection: 50 to 100 mg at night, reviewed after 6 months. - Pregnancy (second trimester or earlier): short courses after culture, only when other drugs are unsuitable.

Children over 3 months. Treatment 3 mg/kg/day in 4 divided doses (maximum 100 mg a dose) for 7 days. Prophylaxis 1 mg/kg at night (maximum 50 mg).

Alternatives. Trimethoprim, fosfomycin, pivmecillinam, cephalexin, amoxicillin clavulanate.

Contraindications. Estimated GFR under 45 mL/min (under 30 mL/min with caution only for short courses when no alternative exists); infants under 3 months; glucose 6-phosphate dehydrogenase deficiency; at term (38 to 42 weeks) and during labour; hepatic dysfunction from previous nitrofurantoin; previous pulmonary reaction; hypersensitivity.

Adverse effects. Nausea, vomiting, anorexia, headache, brown urine. Serious: acute pulmonary reaction (fever, cough, dyspnoea within days), chronic interstitial pulmonary fibrosis (months to years), hepatitis and cholestasis, peripheral neuropathy, haemolysis, drug fever, lupus-like syndrome.

Interactions. Magnesium trisilicate and other antacids (reduced absorption); probenecid and sulfinpyrazone (reduced urinary levels); fluoroquinolones (antagonism); norfloxacin; live oral typhoid vaccine.

Common prescribing errors. Using it in reduced kidney function, using it for pyelonephritis or prostatitis, continuous prophylaxis without liver and lung review, and giving it at term.

Special groups. - Pregnancy: acceptable after culture in the first and second trimesters when other options are unsuitable; avoid from 38 weeks and in labour (neonatal haemolysis).

Breastfeeding: avoid in infants under 1 month and in G6PD-deficient infants. - Older adults: avoid if estimated GFR is under 45 mL/min; higher pulmonary and neuropathy risk. - Kidney impairment: avoid when estimated GFR is under 45 mL/min. - Liver impairment: avoid in significant disease. - Region: used in East Africa as an oral option for uncomplicated cystitis where trimethoprim sulfamethoxazole resistance is high.

Administration. Take with food or milk. Swallow capsules whole; liquid forms are available for children.

Baseline and monitoring. - Baseline: estimated GFR, G6PD status where available, medication review, pregnancy gestation, urine culture. - During treatment: symptom review at 48 to 72 hours. - Long-term prophylaxis: liver tests, chest symptoms and chest imaging if unexplained cough or breathlessness, and neuropathy review every 6 months.

Stop rules. Stop for fever with cough or dyspnoea, jaundice, paraesthesia, severe rash or haemolysis.

Referral and escalation. Refer for pulmonary reaction, hepatotoxicity, neuropathy, treatment failure and recurrent infection needing prolonged prophylaxis.