Description

NITOIN is sustained release formulation of Nitrofurantoin. Nitrofurantoin is an antibacterial agent specific for urinary tract infections. It works by killing bacteria or preventing their growth. However, Nitrofurantoin will not work for colds, flu, or other virus infections.

The mechanism of action of Nitrofurantoin is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive. This is made possible by the rapid reduction of Nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA, respiration, pyruvate metabolism and other macromolecules within the cell. It is not known which of the actions of Nitrofurantoin is primarily responsible for its bacteriocidal activity.

Composition

NITOIN is film coated sustained release formulation of Nitrofurantoin 100mg.

Pharmacology

Organisms are said to be susceptible to Nitrofurantoin if their Minimum inhibitory concentration (MIC) is 32 µg/ml or less. The peak blood concentration of Nitrofurantoin following an oral dose of Nitrofurantoin 100 mg, is less than 1 µg/ml and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 µg/ml or more. For this reason, Nitrofurantoin cannot be used to treat anything other than simple cystitis.

At the concentrations achieved in urine, Nitrofurantoin is bacteriocidal. Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided. Resistance to Nitrofurantoin may be chromosomal or plasmid mediated and involves inhibition of nitrofuran reductase.[5] Acquired resistance in E. coli continues to be rare. Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be sub therapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60 ml/min or less. However a retrospective chart review may suggest that Nitrofurantoin is not contraindicated in this population.

Indications

Nitrofurantoin is indicated only for the treatment of acute uncomplicated urinary tract infections (acute cystitis) caused by susceptible strains of Escherichia coli or Staphylococcus saprophyticus.

Nitrofurantoin is not indicated for the treatment of pyelonephritis or perinephric abscesses. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nitrofurantoin and other antibacterial drugs, Nitrofurantoin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Nitrofurantoin lack the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with Nitrofurantoin are predisposed to persistence or reappearance of bacteriuria. Urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy. If persistence or reappearance of bacteriuria occurs after treatment with Nitrofurantoin, other therapeutic agents with broader tissue distribution should be selected. In considering the use of Nitrofurantoin, lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antimicrobial resistance when agents with broader tissue distribution are utilized.

Contraindications

Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug.

Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. For the same reason, the drug is contraindicated in neonates under one month of age.

NITOIN is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with Nitrofurantoin.

NITOIN is also contraindicated in those patients with known hypersensitivity to Nitrofurantoin.

Warnings

Nitrofurantoin can cause nausea and vomiting, fever, rash, hypersensitivity pneumonitis. It can also cause pulmonary fibrosis.[10] All these side effects are much more common in the elderly.

Patients should be informed that Nitrofurantoin colours urine a dark orange-brown; this is completely harmless.

Neonates (babies up to the age of one month) have immature enzyme systems in their red blood cells (glutathione instability) and Nitrofurantoin must therefore not be used because it can cause haemolytic anaemia. For the same reason, Nitrofurantoin should not be given to pregnant women after 38 weeks of pregnancy, or who are about to give birth.

Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60ml/min) due to systemic accumulation and sub therapeutic levels reached in the urinary tract. However a retrospective chart review may suggest that Nitrofurantoin is not contraindicated in this population.[11]

Precautions

Nitrofurantoin must be taken with food and can cause bleeding in the stomach, vomiting and other gastrointestinal disruptions if these warnings are not adhered to. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of risk of extravascular hemolysis resulting in anemia.

Side Effects and Adverse Reactions

The most frequent clinical adverse events that were reported as possibly or probably drug-related were nausea (8%), headache (6%), and flatulence (1.5%). Additional clinical adverse events reported as possibly or probably drug-related occurred in less than 1% of patients studied and are listed below within each body system in order of decreasing frequency:

Gastrointestinal: Diarrhea, dyspepsia, abdominal pain, constipation, emesis

Neurologic: Dizziness, drowsiness, amblyopia

Respiratory: Acute pulmonary hypersensitivity reaction

Allergic: Pruritus, urticaria

Dermatologic: Alopecia

Miscellaneous: Fever, chills, malaise

Dosage and Administration

NITOIN should be taken with food. Adults and Pediatric Patients over 12 Years: One 100 mg tablet every 12 hours for seven days.

Overdosage

Occasional incidents of acute overdosage of Nitrofurantoin have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended. There is no specific antidote, but a high fluid intake should be maintained to promote urinary excretion of the drug. Nitrofurantoin is dialyzable

Storage

Store in a cool, dry place. Protect from light and moisture.

Presentation

NITOIN is available as film coated sustained release formulation of Nitrofurantoin 100mg tablets supplied in blister strips of 10 tablets and 10 such strips in a box.