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Nalidixic acid, is a quinolone antibacterial agent for oral administration.
Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Unchanged nalidixic acid appears in the urine along with an active metabolite, hydroxynalidixic acid, which has antibacterial activity similar to that of nalidixic acid. The hydroxy metabolite represents 30 percent of the biologically active drug in the blood and 85 percent in the urine. Peak serum levels of active drug average approximately 20 mcg to 40 mcg per mL (90 percent protein bound), one to two hours after administration of a 1 g dose to a fasting normal individual, with a half-life of about 90 minutes. Peak urine levels of active drug average approximately 150 mcg to 200 mcg per mL, three to four hours after administration, with a half-life of about six hours.
Microbiology: 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.
WARNINGS:
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. Therefore, nalidixic acid should be used with caution in patients with known or suspected CNS disorders, such as, cerebral arteriosclerosis or epilepsy, or other factors which predispose seizures. If these reactions occur in patients receiving nalidixic acid, the drug should be discontinued and appropriate measures instituted.
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.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including quinolones.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis".
PRECAUTIONS:
General: blood counts and renal and liver function tests should be performed periodically if treatment is continued for more than two weeks. nalidixic acid should be used with caution in patients with liver disease, epilepsy, or severe cerebral arteriosclerosis. Caution should be used in patients with severe renal failure.
Moderate to severe phototoxicity reactions have been observed in patients who are exposed to direct sunlight while receiving nalidixic acid.
Pregnancy: Pregnancy Category C.
Nursing Mothers: a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
Pediatric Use: safety and effectiveness in infants below the age of three months have not been established.
Geriatric Use: caution should therefore be observed in using nalidixic acid in elderly patients.
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.
Quinolones have been shown to interfere with the metabolism of caffeine.
Quinolones, including nalidixic acid, may enhance the effects of the oral anticoagulant warfarin or its derivatives.
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 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.
Drug laboratory test iInteractions: a false-positive reaction for glucose may be obtained, due to the liberation of glucuronic acid from the metabolites excreted.
Incorrect values may be obtained for urinary 17-keto and ketogenic steroids in patients receiving nalidixic acid, because of an interaction between the drug and the m -dinitrobenzene used in the usual assay method.
SIDE EFFECTS:
Reactions reported after oral administration of Nalidixic acid include the following.
CNS effects: drowsiness, weakness, headache, and dizziness and vertigo. 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. They usually disappeared promptly when dosage was reduced or therapy was discontinued. Toxic psychosis or brief convulsions have been reported rarely, usually following excessive doses. In general, the convulsions have occurred in patients with predisposing factors such as epilepsy or cerebral arteriosclerosis. In infants and children receiving therapeutic doses of Nalidixic acid, increased intracranial pressure with bulging anterior fontanel, papilledema, and headache has occasionally been observed. A few cases of 6th cranial nerve palsy have been reported. Although the mechanisms of these reactions are unknown, the signs and symptoms usually disappeared rapidly with no sequelae when treatment was discontinued.
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 was the most frequently reported adverse reaction. Photosensitivity reactions consisting of erythema and bullae on exposed skin surfaces usually resolve completely in 2 weeks to 2 months after Nalidixic acid 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: rarely, cholestasis, paresthesia, metabolic acidosis, thrombocytopenia, leukopenia, or hemolytic anemia, sometimes associated with glucose 6-phosphate dehydrogenase deficiency.
DOSAGE AND ADMINISTRATION:
Antacids containing calcium, magnesium, or aluminum; sucralfate; divalent or trivalent cations such as iron; multivitamins contaning zinc; or didanosine, chewable/buffered tablets of the pediatric powder for oral solution should not be taken within the two-hour period before or within the two-hour period after taking nalidixic acid.
Adults: the recommended dosage for initial therapy in adults is 1 g administered four times daily for one or two weeks (total daily dose, 4 g). For prolonged therapy, the total daily dose may be reduced to 2 g after the initial treatment period. Underdosage during initial treatment may predispose to emergence of bacterial resistance.
Pediatric patients. Nalidixic acid should not be administered to infants younger than three months. Dosage in Pediatric Patients 12 years of age and under should be calculated on the basis of body weight. The recommended total daily dosage for initial therapy is 55 mg/kg/day, administered in four equally divided doses. For prolonged therapy, the total daily dose may be reduced to 33 mg/kg/day.
How Supplied: Each pack of Ruz-Nalidixic Acid 500 mg tablets contains 100 tablets, in 10 blisters.
storage: Store tablets at room temperature, up to 30°C.
For more information please refer to:
PDR 2000, page 2748-50