NALIDIXIC ACID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NALIDIXIC ACID (NALIDIXIC ACID).
Nalidixic acid is a first-generation quinolone antibiotic that inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, thereby interfering with DNA replication, transcription, and repair. It exhibits bactericidal activity primarily against Gram-negative bacteria.
| Metabolism | Nalidixic acid is extensively metabolized in the liver. The major metabolic pathway involves oxidation of the methyl group to form a carboxylic acid metabolite, 7-hydroxynalidixic acid, which retains antibacterial activity. Minor pathways include glucuronidation. It induces its own metabolism with repeated doses. |
| Excretion | Primarily renal (80-90% as unchanged drug and active metabolites, including hydroxynalidixic acid and dicarboxylic acid derivative); minimal biliary (<5%) and fecal (<5%) excretion. |
| Half-life | Terminal half-life is approximately 1-2.5 hours in adults with normal renal function. In patients with renal impairment (CrCl <20 mL/min), half-life may be prolonged to 6-21 hours, requiring dose adjustment. |
| Protein binding | Highly protein bound (90-95%), primarily to albumin. Binding is concentration-dependent and saturable. |
| Volume of Distribution | Vd is approximately 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid and tissues, with limited penetration into CSF unless meninges are inflamed. |
| Bioavailability | Oral bioavailability is >90% when administered as the sodium salt (tablets or suspension); absorption is rapid and nearly complete after oral administration. |
| Onset of Action | Oral: Clinical effect (antibacterial) begins within 1-2 hours following a single dose, corresponding to peak serum concentrations. |
| Duration of Action | Duration of antibacterial action is approximately 6-8 hours based on serum levels above MIC for susceptible organisms. Given short half-life, dosing every 6 hours is required for continuous effect. |
| Molecular Weight | 232.23 |
1 g orally every 6 hours for 7-14 days. For uncomplicated urinary tract infections, 1 g orally every 12 hours may be sufficient.
| Dosage form | TABLET |
| Renal impairment | GFR > 50 mL/min: No adjustment. GFR 10-50 mL/min: 1 g every 8-12 hours. GFR < 10 mL/min: 1 g every 24 hours or avoid use. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Caution, reduce dose by 50%. Child-Pugh C: Avoid use due to risk of hepatotoxicity. |
| Pediatric use | Children 3 months to 12 years: 55 mg/kg/day orally divided every 6 hours. Maximum 4 g/day. Not recommended for infants < 3 months due to risk of intracranial hypertension. |
| Geriatric use | Start at lower end of dosing range (e.g., 1 g every 8 hours). Monitor for CNS effects and renal function. Adjust based on creatinine clearance. |
| 1st trimester | Use is contraindicated due to arthropathy risk from animal studies; avoid unless no alternative. |
| 2nd trimester | Use is contraindicated; potential fetal cartilage damage and other toxicity. |
| 3rd trimester | Use is contraindicated; avoid near term due to risk of neonatal hemolysis and intracranial hypertension. |
Clinical note
Comprehensive clinical and safety monograph for NALIDIXIC ACID (NALIDIXIC ACID).
| Placental transfer | Crosses placenta; animal studies show fetal cartilage damage. |
| Breastfeeding | Excreted into breast milk in small amounts; risk of arthropathy and hemolysis in nursing infants. Use caution, avoid if possible. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to nalidixic acid or other quinolonesPorphyriaInfants less than 3 months of agePregnancy and breastfeeding (contraindicated)
| Precautions | Central nervous system effects (seizures, increased intracranial pressure, confusion, hallucinations), photosensitivity reactions (severe sunburn), tendon rupture (rare), peripheral neuropathy, hepatotoxicity, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency, and interactions with warfarin (increased anticoagulant effect). Avoid use in children, pregnant women, and nursing mothers due to arthropathy risk. |
| Food/Dietary | Take on an empty stomach (1 hour before or 2 hours after meals) for best absorption. Avoid concomitant intake of antacids, iron, zinc, or calcium supplements; these chelate and reduce absorption. No specific food interactions; however, avoid alcohol as it may increase CNS side effects. |
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| L4 |
| Teratogenic Risk | Animal studies have shown fetal toxicity at high doses. Human data are limited; however, nalidixic acid is generally considered low risk during the first trimester. In the second and third trimesters, concern for neonatal hemolytic anemia and kernicterus due to displacement of bilirubin from albumin binding sites exists, particularly in G6PD-deficient neonates. Avoid near term. |
| Fetal Monitoring | Monitor maternal renal function and blood counts. In newborns exposed near term, monitor for signs of hemolytic anemia and bilirubin levels. |
| Fertility Effects | No clinically significant effects on human fertility have been reported. Animal studies at high doses showed some impairment of spermatogenesis, but relevance is unclear. |
| Clinical Pearls | Nalidixic acid is a first-generation quinolone used primarily for urinary tract infections caused by Gram-negative bacteria (e.g., E. coli, Proteus, Klebsiella). It has poor systemic absorption and is concentrated in urine. It is rarely used today due to resistance and availability of safer alternatives (e.g., fluoroquinolones). Avoid in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolytic anemia. May cause photosensitivity reactions; advise sun avoidance. Watch for increased intracranial pressure in infants and children. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop early. · Drink plenty of fluids while taking this medication unless otherwise instructed. · Avoid sun exposure and use sunscreen; photosensitivity reactions may occur. · Report any signs of hemolytic anemia (pale skin, dark urine, shortness of breath) especially if you have G6PD deficiency. · This medication may cause dizziness or visual disturbances; avoid driving or operating machinery until effects are known. |