NIFURAN TABLETS

Indications

• Urinary tract infections (uncomplicated)
• Urinary tract infection prophylaxis
• Recurrent urinary tract infections

Dosage

Children: Child 3 months–11 years: 750 micrograms/kg 4 times a day for 3 days. Child 12–15 years: 50 mg 4 times a day for 3 days (7 days in pregnant women). Child 16–17 years: 50 mg 4 times a day for 3 days (7 days in males and pregnant women).

Adults: Adult: 50 mg 4 times a day for 3 days (7 days in males and pregnant women).

Mechanism of action

Nitrofurantoin is converted by bacterial nitroreductases to electrophilic intermediates that inhibit the citric acid cycle, as well as the synthesis of DNA, RNA, and proteins in bacteria. This mechanism disrupts vital processes necessary for bacterial survival and reproduction, leading to their death.

Pharmacodynamics

Nitrofurantoin exerts its antibacterial effects by interfering with multiple biological pathways in bacteria, ultimately leading to bacterial cell death. It achieves therapeutic concentrations quickly in the urine, which is essential for its efficacy in treating urinary infections. However, its rapid clearance from the body requires frequent dosing to maintain effective levels.

Pharmacokinetics

Nitrofurantoin is rapidly absorbed from the gastrointestinal tract and reaches peak plasma concentrations within 1 to 3 hours after oral administration. It is primarily excreted through the kidneys, with a significant portion being eliminated unchanged in the urine. The drug has a short half-life, which necessitates multiple doses throughout the day to maintain adequate therapeutic levels.

Contra-indications

• Gout
• Metabolic acidosis
• Severe dehydration
• Hepatic impairment
• Renal impairment (eGFR less than 10 mL/minute/1.73 m2)

Adverse effects

• Epigastric discomfort
• Skin reactions
• Agranulocytosis
• Alopecia
• Anaemia
• Angioedema
• Aplastic anaemia
• Appetite decreased
• Arthralgia
• Asthenia
• Chest pain
• Chills
• Circulatory collapse
• Confusion
• Cough
• Cyanosis
• Depression
• Diarrhoea
• Dizziness
• Drowsiness
• Dyspnoea
• Eosinophilia
• Euphoric mood
• Fever
• Granulocytopenia
• Haemolytic anaemia
• Headache
• Hepatic disorders
• Intracranial hypertension
• Increased risk of infection
• Leukopenia
• Lupus-like syndrome
• Nausea
• Nystagmus
• Pancreatitis
• Psychotic disorder
• Pulmonary reactions
• Respiratory disorders
• Skin reactions

Interactions

• Moderate interaction with topical prilocaine (increases risk of methaemoglobinaemia)
• Moderate interaction with topical anaesthetics (increases risk of methaemoglobinaemia)
• Moderate interaction with prilocaine (increases risk of methaemoglobinaemia)
• Unknown interaction with dapsone (increases risk of methaemoglobinaemia)

Precautions

• Avoid in patients with hepatic impairment
• Avoid in patients with renal impairment (eGFR less than 10 mL/minute/1.73 m2)
• Consider potential for false laboratory test results for urinary sepsis

Pregnancy

There is inadequate evidence of safety, but it has been in wide use for many years without apparent ill consequence, however, the

Mechanism of action

Nitrofurantoin is converted by bacterial nitroreductases to electrophilic intermediates which inhibit the citric acid cycle as well as synthesis of DNA, RNA, and protein. MICROSOMAL AND SOLUBLE FRACTIONS FROM BOTH RAT LIVER AND LUNG MEDIATED THE COVALENT BINDING OF (14)C-LABELED NITROFURANTOIN (I) TO TISSUE MACROMOLECULES IN VITRO. OXYGEN STRONGLY INHIBITED THE BINDING IN BOTH FRACTIONS, AND CARBON MONOXIDE FAILED TO INHIBIT THE BINDING IN MICROSOMAL PREPARATIONS, INDICATING ACTIVATION OF I IN BOTH SYSTEMS BY NITROREDUCTION RATHER THAN OXIDATION OF THE FURAN RING. MICROSOMAL NITROREDUCTION AND COVALENT BINDING OF I WERE INHIBITED BY AN ANTIBODY AGAINST NADPH-CYTOCHROME C REDUCTASE AND COVALENT BINDING WAS ENHANCED BY THE ADDITION OF FAD. IN SOLUBLE FRACTIONS, MAXIMUM RATES OF COVALENT BINDING WERE OBTAINED IN THE PRESENCE OF NADH AND HYPOXANTHINE, AND IT WAS INHIBITED BY ALLOPURINOL, A XANTHINE OXIDASE INHIBITOR. REDUCED GLUTATHIONE DECREASED COVALENT BINDING OF I IN BOTH MICROSOMAL AND SOLUBLE FRACTIONS OF LIVER AND LUNG, BUT THE RATE OF NITROREDUCTION WAS UNAFFECTED. THE HYPOTHESIS IS PRESENTED THAT THE TOXICITY OF NITROFURANS SUCH AS NITROFURANTOIN (I), WHICH ARE USED IN COMMERCIAL POULTRY PRODUCTION, IS DUE TO OXIDATIVE METABOLIC STRESS CAUSED BY THE O2- FREE RADICAL FORMED DURING METABOLISM OF THE COMPOUNDS.

Pharmacodynamics

Nitrofurantoin interferes with vital processes in bacteria, which leads to their death. Nitrofurantoin rapidly reaches therapeutic concentrations in the urine and is also cleared rapidly.