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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NALIDIXIC ACID (NALIDIXIC ACID).
| Breastfeeding | Nalidixic acid is excreted into breast milk in low quantities; the milk-to-plasma ratio is approximately 0.21. Considered compatible with breastfeeding, but caution in infants with G6PD deficiency or jaundice. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to nalidixic acid or other quinolones, history of tendon disorders related to fluoroquinolones, concurrent use with tizanidine (CYP1A2 inhibitor interaction), children and adolescents (risk of arthropathy), pregnancy (teratogenic effects in animal studies), and breastfeeding.
| 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. |
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| 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. |