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) |
| Molecular Weight | 232.23 |
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 | Avoid. Associated with arthropathy in animal studies and theoretical risk of fetal harm; use only if no alternative. |
| 2nd trimester | Avoid. Same risks as trimester 1; potential for joint/cartilage damage in fetus. |
| 3rd trimester | Avoid. Risk of fetal harm including arthropathy; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for NEGGRAM (NEGGRAM).
| Placental transfer | Nalidixic acid crosses the placenta; detected in fetal serum at concentrations approximately 50-70% of maternal serum levels. |
| Breastfeeding | Nalidixic acid is excreted into breast milk in small amounts. Avoid in nursing mothers due to potential for arthropathy and gastrointestinal disturbances in the infant. Use only if benefit outweighs risk. |
■ 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 quinoloneInfants less than 3 months of ageHistory of tendon disorders related to quinolone usePorphyriaSevere renal impairment (CrCl <20 mL/min)
| 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). |
| Food/Dietary | Avoid high-calcium foods (dairy, calcium-fortified juices) within 2 hours of dosing as they may chelate and reduce absorption. No other significant food interactions. |
Loading safety data…
| Lactation Rating |
| L4 - Possibly Hazardous |
| 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 | 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. |
| Clinical Pearls | NEGGRAM (nalidixic acid) is a first-generation quinolone, effective primarily against Gram-negative bacteria. Avoid in patients with glucose-6-phosphate dehydrogenase deficiency due to risk of hemolytic anemia. Use caution in renal impairment (CrCl <20 mL/min). May cause photosensitivity; avoid sun exposure. CNS stimulation possible; avoid in seizure disorders. |
| Patient Advice | Take with a full glass of water to prevent crystalluria. · Do not take with antacids containing magnesium, aluminum, or sucralfate; separate by at least 2 hours. · Avoid excessive sun exposure and use sunscreen to prevent photosensitivity reactions. · Report any signs of hemolytic anemia (pale skin, dark urine) if you have G6PD deficiency. · May cause dizziness; avoid driving or operating machinery until you know how you react. |