Usage
- Nalidixic acid is prescribed for the treatment of uncomplicated urinary tract infections (UTIs) caused by susceptible gram-negative bacteria like E. coli, Proteus, Klebsiella, Enterobacter, Salmonella, and Shigella spp. It is also used to treat shigellosis (bacillary dysentery).
- Pharmacological Classification: Quinolone antibiotic.
- Mechanism of Action: Nalidixic acid inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication and repair. This inhibition leads to bacterial cell death.
Alternate Names
- International/Regional Variations: The name Nalidixic Acid itself is widely recognized.
- Brand Names: NegGram, WIN 18,320, Nadix, Dix, Negamet, Negadix KT, Abdogyl-N, Gramoneg.
How It Works
- Pharmacodynamics: Nalidixic acid exerts its bactericidal effect by inhibiting bacterial DNA synthesis. Its primary target is DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes crucial for bacterial DNA replication, transcription, and repair.
- Pharmacokinetics:
- Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 1-2 hours. Food can delay absorption but not bioavailability.
- Distribution: Distributed widely in the body and crosses the placenta. It also enters breast milk. 93% protein bound (nalidixic acid), 63% protein bound (hydroxynalidixic acid).
- Metabolism: Partially metabolized in the liver to its active metabolite, hydroxynalidixic acid, which accounts for a significant portion of the drug’s antibacterial activity in the urine.
- Elimination: Primarily eliminated via renal excretion (80-90% as inactive metabolites). A small amount is excreted in feces. Elimination half-life is 1-2.5 hours in individuals with normal renal function, but it can be prolonged in patients with renal impairment.
- Mode of Action: Nalidixic acid’s active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to bacterial DNA. This interaction interferes with the action of DNA gyrase and topoisomerase IV, ultimately blocking DNA replication and transcription, leading to bacterial cell death.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Nalidixic acid primarily acts through enzyme inhibition (DNA gyrase and topoisomerase IV).
- Elimination Pathways: Predominantly renal excretion, with some fecal excretion.
Dosage
Standard Dosage
Adults:
- Initial Therapy: 1 g orally four times daily for 1-2 weeks (total daily dose 4 g).
- Long-Term Therapy: 2 g orally daily (total daily dose) after the initial treatment period.
Children (over 3 months):
- Initial Therapy: 55 mg/kg/day orally in four divided doses for 1-2 weeks. Maximum dose not to exceed adult dose of 4g/day.
- Long-Term Therapy: 33 mg/kg/day orally in four divided doses after initial therapy. Maximum dose not to exceed adult dose of 2g/day.
- Prophylaxis: 15 mg/kg twice daily.
Special Cases:
- Elderly Patients: Dose reduction may be necessary due to age-related decline in renal function.
- Patients with Renal Impairment: Reduce dosage based on creatinine clearance. If creatinine clearance is greater than 20 mL/minute, use the standard dose. If less than 20 mL/minute, halve the standard dosage.
- Patients with Hepatic Dysfunction: Dose reduction may be considered.
Clinical Use Cases Dosage guidelines specifically for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations are not explicitly defined for Nalidixic Acid.
Dosage Adjustments
Dose adjustment should be based on renal function, hepatic function, and age.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea, abdominal pain
- Photosensitivity reactions (sunburn)
- Headache, dizziness, drowsiness
- Rash, pruritus, urticaria
Rare but Serious Side Effects
- Convulsions, intracranial hypertension (particularly in infants and young children)
- Toxic psychoses, hallucinations
- Peripheral neuropathy, muscular weakness, myalgia
- Cholestatic jaundice
- Thrombocytopenia, leukopenia, autoimmune hemolytic anemia
- Erythema multiforme, Stevens-Johnson syndrome, anaphylactoid reactions
- Tendon damage/rupture
Long-Term Effects
With prolonged use, the risk of some side effects like peripheral neuropathy might increase.
Contraindications
- Hypersensitivity to nalidixic acid or any quinolone antibiotic
- History of convulsive disorders
- Porphyria
- Infants under 3 months of age
- Severe renal impairment
Drug Interactions
- Antacids (containing calcium, magnesium, or aluminum), sucralfate, multivitamins with zinc, iron supplements: Reduce absorption of nalidixic acid. Administer 2 hours before or after these medications.
- Warfarin: Nalidixic acid can potentiate warfarin’s anticoagulant effects. Monitor INR closely.
- Probenecid: May reduce renal clearance of nalidixic acid, increasing the risk of toxicity.
- Didanosine: Chewable/buffered tablets and pediatric powders for oral solution reduce nalidixic acid absorption. Co-administration is contraindicated.
- Other drugs metabolized by the liver: Potential for altered metabolism.
Pregnancy and Breastfeeding
- Pregnancy: Should be avoided, especially during the first trimester. There is a potential risk of cartilage damage.
- Breastfeeding: Nalidixic acid is excreted in breast milk. The risk-benefit ratio should be carefully considered before use in lactating mothers.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV, disrupting bacterial DNA replication and repair.
- Side Effects: Nausea, vomiting, diarrhea, photosensitivity, headache, dizziness, rash. Rare but serious: convulsions, psychoses, peripheral neuropathy, blood dyscrasias, severe skin reactions.
- Contraindications: Hypersensitivity, convulsive disorders, porphyria, infants <3 months, severe renal impairment.
- Drug Interactions: Antacids, sucralfate, metal ions (calcium, magnesium, aluminum, iron, zinc), warfarin, probenecid, didanosine.
- Pregnancy & Breastfeeding: Avoid in pregnancy, especially first trimester; use with caution during breastfeeding.
- Dosage: Adults: Initially 1 g four times daily for 1-2 weeks; long-term: 2 g daily. Children (>3 months): Initially 55 mg/kg/day in four divided doses; long-term: 33 mg/kg/day in four divided doses.
- Monitoring Parameters: Renal function, liver function, complete blood count for long-term therapy.
Popular Combinations
Specific, routinely prescribed combinations with nalidixic acid are not typically recommended or commonly utilized in current clinical practice.
Precautions
- General Precautions: Renal and hepatic function tests, and complete blood count monitoring recommended for long-term therapy.
- Pregnant Women: Avoid, particularly in the first trimester.
- Breastfeeding Mothers: Use with caution.
- Children & Elderly: Age-specific dosing adjustments needed. Infants < 3 months should not receive nalidixic acid.
- Lifestyle Considerations: Avoid prolonged sun exposure, alcohol may worsen side effects, and driving or operating machinery should be avoided if experiencing dizziness or drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nalidixic Acid?
A: Adults: 1 g four times daily for 1-2 weeks initially, then 2 g daily for long-term therapy. Children (>3 months): 55 mg/kg/day in four divided doses initially, then 33 mg/kg/day in four divided doses for prolonged treatment. Adjustments needed for renal/hepatic impairment.
Q2: What are the common side effects of Nalidixic Acid?
A: Nausea, vomiting, diarrhea, abdominal pain, photosensitivity reactions, headache, dizziness, drowsiness, rash, itching, hives.
Q3: What are the serious side effects of Nalidixic Acid?
A: Seizures, hallucinations, toxic psychosis, peripheral neuropathy, cholestatic jaundice, thrombocytopenia, leukopenia, hemolytic anemia, erythema multiforme, Stevens-Johnson syndrome, anaphylactoid reactions, tendon rupture.
Q4: What are the contraindications for Nalidixic Acid?
A: Hypersensitivity to nalidixic acid or quinolones, history of seizures, porphyria, infants under 3 months old, severe renal impairment.
Q5: Can Nalidixic Acid be used during pregnancy or breastfeeding?
A: Generally avoided during pregnancy, particularly the first trimester. Use cautiously during breastfeeding, weighing risks and benefits.
Q6: How does Nalidixic Acid interact with antacids?
A: Antacids reduce the absorption of nalidixic acid. Take nalidixic acid 2 hours before or after antacids.
Q7: What is the mechanism of action of Nalidixic Acid?
A: Inhibits bacterial DNA gyrase and topoisomerase IV, disrupting bacterial DNA replication and repair.
Q8: Can Nalidixic Acid be used to treat viral infections?
A: No, nalidixic acid is only effective against bacterial infections.
Q9: How long should a patient take Nalidixic Acid?
A: Typically 1-2 weeks for acute infections. Longer durations might be necessary for chronic or persistent infections, but at a reduced dosage.
Q10: What precautions should patients take while on Nalidixic Acid?
A: Avoid prolonged sun exposure, limit alcohol intake, and refrain from driving or operating machinery if experiencing dizziness or drowsiness.
