Brands, Medical Use, Clinical Data
Drug Category
- Anti-Infective Agents
- Enzyme Inhibitors
Dosage Forms
- Suspension (250 mg/5 mL tsp)
- Tablets (1000 mg, 500 mg, 250 mg)
Brands / Synonyms
Cybis; Dixiben; Dixinal; Eucistin; Innoxalon; Jicsron; naladixic acid
; Nalidic acid; Nalidixan; Nalidixate; Nalidixic acid USP27; Nalidixin; Nalidixinic acid; Nalitucsan; Nalix; Nalurin; Naxuril; Neggram; Negram; Nevigramon; Nogram; Sicmylon; Unaserus; Urisal; Uronidix; Wintomylon; Wintron
Indications
For the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species.
Pharmacology
Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.
Mechanism of Action
Evidence exists that the active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis.
Absorption
Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.
Toxicity
ORAL (LD50): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.
Biotrnasformation / Drug Metabolism
Hepatic. 30% of administered dose is metabolized to the active metabolite, hydroxynalidixic acid. Rapid conjugation of parent drug and active metabolite to inactive metabolites. Metabolism may vary widely among individuals. In the urine, hydroxynalidixic acid represents 80 to 85% of the antibacterial activity.
Contraindications
NegGram is contraindicated in patients with known hypersensitivity to nalidixic acid and in patients with a
history of convulsive disorders.
Drug Interactions
Elevated plasma levels of theophylline have been reported with concomitant quinolone use. There have been reports
of theophylline-related side effects in patients on concomitant therapy with quinolones and theophylline. Therefore,
monitoring of theophylline plasma levels should be considered and dosage of theophylline adjusted, as required.
Quinolones have been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of
caffeine and the prolongation of its plasma half-life.
Quinolones, including nalidixic acid, may enhance the effects of the oral anticoagulant warfarin or its
derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation test
should be closely monitored.
Nitrofurantoin interferes with the therapeutic action of nalidixic acid.
Antacids containing magnesium, aluminum, or calcium; sucralfate or divalent or trivalent cations such as iron;
multivitamins containing zinc; and Videx®, (Didanosine), chewable/buffered tablets or the pediatric powder for
oral solution may substantially interfere with the absorption of quinolones, resulting in systemic levels
considerably lower than desired. These agents should not be taken within the two hour period before or within the
two-hour period after nalidixic acid administration.
Elevated serum levels of cyclosporine have been reported with the concomitant use of some quinolones and
cyclosporine. Therefore, cyclosporine serum levels should be monitored and appropriate cyclosporine dosage
adjustments made when these drugs are used concomitantly.
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