NEGGRAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEGGRAM (NEGGRAM).
Nalidixic acid is a quinolone antibacterial agent that inhibits bacterial DNA gyrase (topoisomerase II), thereby interfering with DNA replication and repair.
| Metabolism | Hepatic metabolism: partial glucuronidation and oxidation; excreted renally (80% unchanged and metabolites). |
| Excretion | Renal: 85-90% (glomerular filtration and tubular secretion, 80% as unchanged drug, 5-10% as active metabolite 7-hydroxynalidixic acid); fecal: 4-5% |
| Half-life | 1-2 hours in normal renal function (terminal elimination half-life); prolonged to 6-12 hours in severe renal impairment (CrCl <20 mL/min) |
| Protein binding | 90-95% (primarily to albumin, with minor binding to alpha-1-acid glycoprotein) |
| Volume of Distribution | 0.3-0.5 L/kg (low Vd, indicating limited extravascular distribution, primarily confined to extracellular fluid and genitourinary tract; does not penetrate CSF or prostatic tissue well) |
| Bioavailability | 50-60% (oral, with food decreasing absorption; first-pass metabolism reduces systemic availability of parent drug; active metabolite contributes to efficacy) |
| Onset of Action | Oral: 1-2 hours (time to therapeutic plasma concentration for UTI); intravenous: not applicable (no parenteral formulation) |
| Duration of Action | 8-12 hours (bacteriostatic effect based on dosing interval of 4 times daily; clinical duration may extend to 24 hours post-dose for susceptible organisms) |
1 g orally four times daily for 7-14 days.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl 30-50 mL/min: 1 g every 12 hours; CrCl 15-29 mL/min: 1 g every 24 hours; CrCl <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class B or C: avoid use due to risk of hepatic toxicity. |
| Pediatric use | Children >1 year: 50 mg/kg/day divided every 6 hours; maximum 4 g/day. |
| Geriatric use | Reduce dose by 50% and monitor renal function; avoid in CrCl <30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEGGRAM (NEGGRAM).
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Discontinue nursing or drug due to potential serious adverse reactions (arthropathy). |
| Teratogenic Risk | Category C: Risk cannot be ruled out. First trimester: Associated with arthropathy and cartilage erosion in animal studies; avoid unless benefit outweighs risk. Second/third trimesters: Potential for fetal harm; use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
Not recommended for use in children under 3 months of age; risk of arthropathy in immature animals.
| Serious Effects |
["Hypersensitivity to nalidixic acid or any quinolone.","Children less than 3 months of age.","Patients with a history of tendinopathy associated with quinolones."]
| Precautions | ["Risk of peripheral neuropathy; discontinue if symptoms occur.","May cause photosensitivity reactions; avoid excessive sunlight.","Use caution in patients with CNS disorders (seizure threshold).","Not recommended for patients with known G6PD deficiency (risk of hemolytic anemia)."] |
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| Monitor for signs of arthropathy or cartilage damage in infant; observe for maternal gastrointestinal disturbances and CNS effects. |
| Fertility Effects | May impair fertility in males (sperm abnormalities) and females (menstrual irregularities); reversible upon discontinuation. |