nalidixic acid
NegGram

Available forms
Available by prescription only
Suspension: 250 mg/5 ml
Tablets: 250 mg, 500 mg, 1 g

Indications and dosages
 Acute and chronic urinary tract infections caused by susceptible gram-negative organisms. Adults: 1 g P.O. q.i.d. for 7 to 14 days; 2 g P.O. daily for long-term use. Up to 6 g daily have been used for severe urinary tract infection.
Children older than age 3 months: 55 mg/kg P.O. daily divided q.i.d. for 7 to 14 days; 33 mg/kg P.O. daily divided q.i.d. for long-term use.

Pharmacodynamics
Antimicrobial action: Bactericidal. Inhibits microbial synthesis of DNA. Spectrum of action includes most gram-negative organisms except Pseudomonas species. (About 2% to 14% of patients develop nalidixic acid-resistant organisms during therapy.)

Pharmacokinetics
Absorption: Well absorbed from GI tract.
Distribution: Concentrates in renal tissue and seminal fluid. Doesn’t penetrate prostatic tissue. Only minimal amounts appear in CSF and placenta. Drug is highly protein-bound.
Metabolism: Metabolized to more active hydroxynalidixic acid and inactive conjugates in liver.
Excretion: 13% of drug metabolites and 2% to 3% of unchanged drug excreted via kidneys. In patients with normal renal function, plasma half-life is 1 to 2 1/2 hours. In anuric patients, half-life is prolonged up to 21 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, in those with seizure disorders, and in infants younger than age 3 months. Use cautiously in prepubertal children and patients with impaired renal or hepatic function, pulmonary disease, or severe cerebral arteriosclerosis.

Interactions
Drug-drug. Antacids: Decreases absorption of antibiotic. Give nalidixic acid 2 hours before or 6 hours after antacids.
Dicumarol, warfarin: Causes excessive anticoagulation. Monitor patient closely.
Photosensitizing drugs: May cause additive effects. Inform patient about increased sensitivity to sun exposure, and recommend precautions.
Drug-lifestyle. Sun exposure: Photosensitivity reactions may occur. Advise patient to take precautions.

Adverse reactions
CNS: drowsiness, weakness, headache, dizziness, vertigo, seizures, malaise, confusion, hallucinations, psychosis, increased intracranial pressure and bulging fontanelles in infants and children.
EENT: sensitivity to light, change in color perception, diplopia, blurred vision.
GI: abdominal pain, nausea, vomiting, diarrhea.
GU: renal impairment.
Hematologic: eosinophilia, leukopenia, thrombocytopenia, hemolytic anemia.
Hepatic: cholestatic jaundice, cholestasis.
Musculoskeletal: arthralgia, joint stiffness.
Skin: pruritus, photosensitivity, urticaria, rash.
Other: angioedema, anaphylactoid reaction.

Effects on lab test results
• May increase AST, BUN, and creatinine levels.
• May increase eosinophil count. May decrease hemoglobin, hematocrit, and platelet and WBC counts.

Overdose and treatment
Toxicity may cause psychosis, seizures, increased intracranial pressure, metabolic acidosis, lethargy, nausea, and vomiting. However, because nalidixic acid is rapidly excreted, such reactions usually resolve in 2 to 3 hours.

Special considerations
• Obtain culture and sensitivity tests before starting therapy and repeat as needed.
• Drug is ineffective against Pseudomonas infection or infection outside the urinary tract.
• Resistant bacteria may emerge after first 48 hours of therapy (especially if inadequate doses are given).
• Although CNS toxicity is rare, brief seizures, increased intracranial pressure, and toxic psychosis may occur in infants, children, and elderly patients.
• Use cautiously in days before delivery because of increased risk to neonate.
• False-positive reactions may occur in urine glucose tests using cupric sulfate reagents (such as Benedict’s test, Fehling’s solution, and Clinitest) from reaction between glucuronic acid (liberated by urinary metabolites of nalidixic acid) and cupric sulfate. Urine 17-ketosteroid and urine 17-ketogenic steroid levels may be falsely elevated because nalidixic acid interacts with m-dinitrobenzene, used to measure these urine metabolites. Urinary vanillylmandelic acid levels may also be falsely elevated.
• Obtain CBC and renal and liver function studies periodically during long-term therapy.
Pregnant patients
• Drug can be used during second and third trimesters of pregnancy; however, safety hasn’t been established for use in first trimester.
Breast-feeding patients
• Low levels of drug appear in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Don’t give drug to infants younger than age 3 months because safety hasn’t been established.
• Don’t give drug to prepubertal children because it can erode cartilage in weight-bearing joints.

Patient education
• Instruct patient to report visual disturbances; they usually disappear with dosage reduction.
• Warn patient about possible photosensitivity. Explain that photosensitivity reactions usually resolve 2 to 8 weeks after therapy ends, but that bullae may continue after exposure to sunlight or mild skin trauma for up to 3 months after therapy ends.
• Advise patient to take drug with food or milk to avoid GI upset.
• Warn patient to drive cautiously because drug may cause drowsiness or blurred vision.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use