Reactions reported after oral administration of NegGram include the following.

Reversible subjective visual disturbances without objective findings have occurred infrequently (generally with each dose during the first few days of treatment). These reactions include overbrightness of lights, change in color perception, difficulty in focusing, decrease in visual acuity, and double vision.

Toxic psychosis or brief convulsions have been reported.

In infants and children receiving therapeutic doses of NegGram, increased intracranial pressure with bulging anterior fontanel, papilledema, and headache has been observed. A few cases of 6th cranial nerve palsy have been reported. 

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.

Central Nervous System (CNS) effects including convulsions, increased intracranial pressure, and toxic psychosis have been reported with nalidixic acid therapy. Convulsive seizures have been reported with other drugs in this class. Quinolones may also cause CNS stimulation which may lead to tremor, restlessness, lightheadedness, confusion, and hallucinations.

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching.

Nalidixic acid and other members of the quinolone drug class have been shown to cause arthropathy in juvenile animals. 

Toxicological studies have shown that nalidixic acid and related drugs can produce erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of most species tested.

Moderate to severe phototoxicity reactions have been observed in patients who are exposed to direct sunlight while receiving NegGram or other members of this drug class.

CNS effects: drowsiness, weakness, headache, and dizziness and vertigo.

Vision effects: Reversible subjective visual disturbances without objective findings have occurred infrequently (generally with each dose during the first few days of treatment). These reactions include overbrightness of lights, change in color perception, difficulty in focusing, decrease in visual acuity, and double vision.

Toxic psychosis or brief convulsions have been reported.

In infants and children receiving therapeutic doses of NegGram, increased intracranial pressure with bulging anterior fontanel, papilledema, and headache has been observed. A few cases of 6th cranial nerve palsy have been reported. 

Gastrointestinal: abdominal pain, nausea, vomiting, and diarrhea.

Allergic: rash, pruritus, urticaria, angioedema, eosinophilia, arthralgia with joint stiffness and swelling, and anaphylactoid reaction. Erythema Multiforme and Stevens-Johnson syndrome have been reported with nalidixic acid and other drugs in this class. Rash and photosensitivity reactions consisting of erythema and bullae on exposed skin surfaces usually resolve completely in 2 weeks to 2 months after NegGram is discontinued; however, bullae may continue to appear with successive exposures to sunlight or with mild skin trauma for up to 3 months after discontinuation of drug.

Other: cholestasis, paresthesia, metabolic acidosis, thrombocytopenia, leukopenia, or hemolytic anemia, sometimes associated with glucose 6-phosphate dehydrogenase deficiency.

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.

Central Nervous System (CNS) effects including convulsions, increased intracranial pressure, and toxic psychosis have been reported with nalidixic acid therapy. Convulsive seizures have been reported with other drugs in this class. Quinolones may also cause CNS stimulation which may lead to tremor, restlessness, lightheadedness, confusion, and hallucinations.

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching.

Nalidixic acid and other members of the quinolone drug class have been shown to cause arthropathy in juvenile animals. 

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including quinolones, and may range in severity from mild to life-threatening.

Blood counts and renal and liver function tests should be performed periodically.

Moderate to severe phototoxicity reactions have been observed in patients who are exposed to direct sunlight while receiving NegGram or other members of this drug class. Excessive sunlight should be avoided. Therapy should be discontinued if phototoxicity occurs.

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.

Toxicological studies have shown that nalidixic acid and related drugs can produce erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of most species tested.

Animal Pharmacology

NegGram (nalidixic acid) and related drugs have been shown to cause arthropathy in juvenile animals of most species tested.

Long-term administration of nalidixic acid to rats resulted in retinal degeneration and cataracts.

Hydroxynalidixic acid, the principal metabolite of NegGram, has been shown to have oculotoxic potential, namely in dogs and cats where it produced retinal degeneration upon prolonged administration leading, in some cases, to blindness.