Naligram300 mg/5 ml

Nalidixic acid is a first-generation quinolone antibacterial used for the treatment of urinary tract infections caused by susceptible gram-negative organisms, including Proteus species, Klebsiella species, Enterobacter species, and Escherichia coli.

Contains Naligram 300 mg/5 ml as the active ingredient, available as oral tablets and as an oral suspension (commonly 250 mg per 5 mL).

Nalidixic acid was the first quinolone antibiotic developed and is used specifically for treating urinary tract infections caused by susceptible gram-negative bacteria. Unlike the later fluoroquinolones it paved the way for, Naligram 300 mg/5 ml has a narrower spectrum of activity, limited mainly to the urinary tract, and it is used less commonly today given the availability of broader-spectrum, better-tolerated alternatives. It has a distinctive risk profile, including the potential to trigger red blood cell breakdown (haemolysis) in patients with G6PD deficiency and a recognized risk of raised pressure inside the skull, particularly in infants.

Therapeutic Class: Urinary Antibacterial (First-generation Quinolone)

Nalidixic acid is rapidly and almost completely absorbed from the gastrointestinal tract, reaching peak blood concentrations within 2 to 4 hours. The parent drug and its active metabolite (hydroxyNaligram 300 mg/5 ml) are distributed to most tissues, with particularly high concentrations achieved in the kidney and urine, which is why it is effective for urinary tract infections but has limited use for infections elsewhere in the body. Approximately 80% of an administered dose is recovered in the urine at steady state, with a half-life of about 6 hours.

• Take with food to help reduce gastrointestinal upset
• Swallow tablets whole with water, or measure the oral suspension with the device provided
• Complete the full prescribed course, even if symptoms improve before the course is finished

The following should be assessed by a healthcare professional before combining with Naligram 300 mg/5 ml:

• Antacids, sucralfate, iron, and multivitamins containing zinc: can reduce Naligram 300 mg/5 ml absorption if taken too close together; separate dosing by at least 2 hours.
• Theophylline: Naligram 300 mg/5 ml can decrease theophylline blood levels; monitoring may be needed if used together.
• NSAIDs: combining with quinolone-class antibacterials, including Naligram 300 mg/5 ml, may increase the risk of central nervous system stimulation and seizures.
• Warfarin: Naligram 300 mg/5 ml may increase the anticoagulant effect of warfarin; closer INR monitoring is advisable.
• Melphalan: combined use has been associated with an increased incidence of severe haemorrhagic colitis.

Common side effects

• Nausea, vomiting, diarrhoea
• Drowsiness, weakness, headache, and dizziness (vertigo)
• Skin rash
• Photosensitivity (phototoxic skin reaction on sun exposure)

Serious side effects (seek urgent medical attention)

• Haemolysis (red blood cell breakdown) in patients with G6PD deficiency: pale skin, unusual fatigue, dark urine, jaundice - can occur even at standard doses in susceptible individuals.
• Raised intracranial pressure (pseudotumor cerebri), particularly in infants and young children: headache, nausea, vomiting, and, in infants, a bulging soft spot (fontanelle) - usually resolves after stopping the medicine, but requires prompt medical evaluation and monitoring to prevent lasting visual damage.
• Convulsions, particularly in patients with a seizure disorder or CNS lesion.
• Visual disturbances (double vision).
• Allergic reactions, including urticaria, fever, arthralgia, and eosinophilia.
• Jaundice, suggesting possible liver involvement.

Pregnancy

The risk-benefit of Naligram 300 mg/5 ml should be carefully considered during the first trimester of pregnancy, given limited safety data; use should only occur if a doctor determines it is necessary.

Breastfeeding

Nalidixic acid is excreted in breast milk, and there has been a report of haemolytic anaemia in a breastfed infant of a mother with impaired kidney function (azotaemia); risk-benefit should be carefully considered, and use during breastfeeding should be discussed with a healthcare professional.

• G6PD deficiency: Naligram 300 mg/5 ml can precipitate acute haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, a common inherited condition in many populations; use with caution and be alert for signs of haemolysis, particularly in regions or populations with higher G6PD deficiency prevalence.
• Raised intracranial pressure: a recognized, though uncommon, effect particularly in infants; monitor for headache, vomiting, or, in infants, a bulging fontanelle, and discontinue promptly if these occur.
• Photosensitivity: avoid excessive sun or UV light exposure during treatment, given the risk of a phototoxic skin reaction.
• Use with caution in patients with impaired hepatic or renal function; risk-benefit must be considered in these populations.
• May cause dizziness or drowsiness; use caution with driving or operating machinery until you know how it affects you.
• May cause false-positive urine glucose results with certain testing methods (such as Clinitest); enzymatic glucose oxidase-based tests are preferred if glucose monitoring is needed during treatment.

Overdose of Naligram 300 mg/5 ml may cause exaggerated central nervous system effects, including severe headache, drowsiness, confusion, visual disturbances, and, in significant overdose, convulsions or raised intracranial pressure, along with gastrointestinal symptoms. Suspected significant overdose requires prompt medical evaluation; treatment is generally supportive, provided in a medical facility.

Store below 30°C, away from light and moisture, as directed on the product label. Keep out of reach of children.

• Infants under 3 months: Contraindicated, given increased risk of raised intracranial pressure and limited safety data in this age group.
• Children: Used with weight-based dosing from 3 months of age; has been shown to cause cartilage degeneration in immature animals, so use should be limited to situations where clearly needed.
• G6PD deficiency: Use with caution and monitor for signs of haemolysis, given the recognized risk with this medicine.
• Renal or hepatic impairment: Dose reduction (commonly by half) is recommended in significant renal impairment (creatinine clearance ≤20 mL/min); use with caution in hepatic impairment.

Treatment typically begins with a higher initial dose for the first 1-2 weeks, and if a longer course is needed, continues at a reduced maintenance dose, as directed by the treating physician. The full prescribed course should be completed to reduce the risk of treatment failure and antibiotic resistance.

Drug Class: Quinolone antibacterial

Nalidixic acid works by inhibiting bacterial DNA synthesis. Its active metabolite, hydroxyNaligram 300 mg/5 ml, binds strongly but reversibly to bacterial DNA, interfering with the synthesis of RNA and, consequently, with bacterial protein synthesis, which stops the bacteria from multiplying and eventually kills them.

Nalidixic acid is used in children 3 months of age and older for urinary tract infections, with weight-based dosing (13.75 mg/kg every 6 hours initially, reducing to 8.25 mg/kg every 6 hours for longer courses). It is contraindicated in infants under 3 months, given increased risk of raised intracranial pressure in this age group. Caution regarding cartilage effects seen in immature animals is also relevant to pediatric use.