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Nalidixic (Neggram) 500mg

Nalidixic acid: Side Effects

Nalidixic acid, the first quinolone, first introduced in 1962, is now only rarely used and has been supplanted by the fluoroquinolones. It is almost completely absorbed from the gastrointestinal tract and is rapidly eliminated by the kidneys, resulting in urinary concentrations 4-6 times higher than plasma concentrations. There are better drugs to treat urinary tract infections.

General adverse effects

The adverse effects of nalidixic acid tend to be toxic rather than allergic. Nervous system toxicity is predominant, including disturbances of sensory perception and benign intracranial hypertension, which is nearly exclusively found in babies and young children. Gastrointestinal toxicity and skin reactions also occur. Immunological and hypersensitivity reactions mainly affect the skin. Drug fever is rare. Hematological and hepatic reactions are very rare. Tumor-inducing effects have not been reported but require further study, since nalidixic acid, as a DNA gyrase inhibitor, damages DNA. Fluorinated derivatives, but not nalidixic acid, induced unscheduled DNA synthesis in vitro but not in vivo. While specific fluoroquinolones, such as CP-115,953, have cytotoxic effects on eukaryotic cancer cells, the fluoroquinolones designed specifically as antimicrobial agents have extremely low toxicity against eukaryotic cells. This is due to a marked reduction in the affinity for eukaryotic topoisomerases versus prokaryotic topoisomerases.

Organs and Systems

Nervous system

Benign intracranial hypertension (pseudotumor cerebri) mainly affects babies, especially during the first 3 months of life. Occasionally even older children can be affected, especially when inordinately high doses are used. Very rarely, it occurs in adults with renal insufficiency. In infancy, impaired nalidixic acid elimination (due to underdeveloped glucuronidation), overdosage, or prolonged treatment may be responsible. Metabolic acidosis is usually important in adults.

The syndrome includes headache, nausea and vomiting, dizziness, tinnitus, papilledema, and visual disturbances caused by scotoma or optic nerve damage. In babies, the first symptoms appear during the first 3 days of treatment; while in older children and adults symptoms may not appear before a second or even later exposure. In adults, peripheral paresis or severe pyramidal and extrapyramidal symptoms, occasionally followed by a transitory psychosis, have been observed.

After withdrawal, most symptoms usually subside quickly. Papillary edema and ocular palsy recede more slowly, the latter not always completely.

Functional short-lasting phenomena, such as sensations of over-bright lights, blurred vision, altered color perception, or difficulty in focusing, are dose-dependent and have been observed in about 7% of cases. They begin 30-60 minutes after drug intake and subside within 20 minutes to 3 hours.

Convulsions without benign intracranial hypertension have been reported. Affected patients usually had preexisting cerebral disease or had taken very high doses. Normal doses in otherwise healthy persons can exceptionally provoke convulsions.

Uncharacteristic general symptoms, such as headache, dizziness, drowsiness, insomnia, or restlessness, can occur.

Sensory systems

Occasional cases of tinnitus have been attributed to nalidixic acid.

Psychological, psychiatric

Disturbances of body perception, hallucinations, confusion, confabulation, and depression can rarely occur with nalidixic acid.


Hyperglycemia associated with convulsions has been observed after the use of high single doses of nalidixic acid.


Nalidixic acid can cause metabolic acidosis in infants. This has also been seen in older children and adults with renal insufficiency and can result from disturbed lactate metabolism. Extreme overdosage can cause metabolic acidosis in subjects with normal renal function.


Rarely, hemolytic anemia associated with glucoses-phosphate dehydrogenase deficiency has been precipitated by nalidixic acid.

Rarely hemolytic anemia in neonates has been attributed to nalidixic acid in breast milk.


Nausea, vomiting, and occasionally diarrhea or abdominal pain occur in about 8% of patients taking nalidixic acid.


Cholestatic hepatitis has been reported in patients taking nalidixic acid.


Skin reactions occur in about 5% of patients taking nalidixic acid, including urticaria, erythematous or maculopapular rashes, isolated pruritus, purpura, lesions resembling pityriasis rosea, erythema multiforme, or exfoliative dermatitis. Except for the latter, they usually run a benign course.

Phototoxic reactions occur in animals given nalidixic acid after exposure to light and have been reported in patients taking nalidixic acid, with blistering. Sometimes the lesions develop only several days after nalidixic acid withdrawal. The eruptions can persist for several months after withdrawal.


Large doses of nalidixic acid cause degenerative inflammatory damage in the large weight-bearing joints in animals, and occasionally arthritis, arthralgia, or myalgia occur in humans. However, three retrospective controlled studies showed no evidence of nalidixic acid-associated arthropathy in children.

Long-Term Effects

Drug tolerance

Salmonella typhimurium DT104 is usually resistant to ampicillin, chloramphenicol, streptomycin, sulfona-mides, and tetracycline. An outbreak of 25 culture-confirmed cases of multidrug-resistant S. typhimurium DT104 has been identified in Denmark. The strain was resistant to the above-mentioned antibiotics and nalidixic acid and had reduced susceptibility to fluoroquinolones. A swineherd was identified as the primary source. The DT104 strain was also found in cases of salmonellosis in Washington State, and soft cheese made with unpasteurized milk was identified as an important vehicle of its transmission.


The genotoxic effects of nalidixic acid (400 mg bd for 10 days) and metronidazole (250 mg tds for 10 days) have been investigated in a prospective randomized study in 20 patients with Trichomonas vaginalis infections. Evaluation was by the sister-chromatid exchange test, in which an increased number of exchanges in lymphocytes reflects mutagenic action. Metronidazole had no effect but there was a significant increase with nalidixic acid.

Second-Generation Effects Teratogenicity

In a case-control surveillance of congenital abnormalities in 22 865 women who had neonates or fetuses with congenital abnormalities, and 38 151 pregnant women who had neonates without any defects, treatment with nalidixic acid during pregnancy was associated with an increased risk of pyloric stenosis. Nalidixic acid should be avoided during pregnancy.


Very small amounts of nalidixic acid pass into the breast milk. Use during lactation should therefore also be avoided. Rare cases of hemolytic anemia in the newborn have been related to nalidixic acid ingested through breast milk.

Drug Administration

Drug overdose

In 18 children with nalidixic acid intoxication, most of whom were aged under 1 year, the clinical effects were neurological disorders of alertness, hypertensive cranial syndrome, and neuronal damage; some had a metabolic acidosis. Treatment included gastric lavage, correction of acid-base balance, and control of convulsions.

A woman survived ingestion of nalidixic acid 32 g despite developing lactic acidosis, hyperglycemia, convulsions, and abnormal behavior. The maximum recorded plasma concentration of nalidixic acid was 185 µg/ml and the half-life was 3.2 hours. Carboxynalidixic acid was demonstrated in the plasma.

A woman developed a severe metabolic acidosis and coma after taking nalidixic acid 28 g. She was given sodium bicarbonate 600 mmol and developed a respiratory alkalosis with secondary tetany. She recovered consciousness 9 hours later and the acid-base disturbance resolved after 60 hours.

Drug-Drug Interactions

Urine alkalinizing compounds

Alkalinization of the urine increases the excretion of nalidixic acid.


Nalidixic acid can displace warfarin from its plasma albumin binding sites, briefly enhancing its anticoagulant effect.

Interference with Diagnostic Tests

Glucose measurements

If reducing agents are given with nalidixic acid, glycosuria and hyperglycemia can be mimicked by the presence of nalidixic and glucuronic acid compounds in blood and urine.


Urine concentrations of C17-ketosteroids (but not of C17-hydroxysteroids) can be falsely raised by nalidixic acid.

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