SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Nitrofurantoin 50 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 50 mg of Nitrofurantoin.

For excipients, see 6.1

3    PHARMACEUTICAL FORM

Tablet.

Yellow tablet, round, flat, bevel edged tablets. Engraving: ‘Biorex 838’ on one side and a scoreline on the reverse or ‘7N2’ on one side and a scoreline on reverse.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures.

Nitrofurantoin is specifically indicated for the treatment of infections, when due to susceptible strains of Escherichia coli, Enterococci, Staphylococci, Citrobacter, Kiebsiella and Enterobacter.

4.2 Posology and method of administration

For oral administration.

Dosage:

Adults

Acute Uncomplicated Urinary Tract Infections: 50 mg four times daily for seven days

Severe Chronic Recurrence: 100 mg four times a day for seven days Long Term Suppression: 50 mg-100 mg once a day.

Prophylaxis: 50 mg four times daily for the duration of procedure and 3 days thereafter.

Children and Infants over three months of age

Acute Urinary Tract Infections: 3 mg/kg/day in four divided doses for seven days.

Suppressive: 1 mg/kg, once a day.

For children under 25 kg body weight consideration should be given to the use of nitrofurantoin suspension.

Elderly

Provided there is no significant renal impairment, in which nitrofurantoin is contraindicated, the dosage should be that for any normal adult. See precaution and risks to elderly patients associated with long-term therapy (Section 4.8.)

4.3 Contraindications

Patients suffering from renal dysfunction with a creatinine clearance of less than 60 ml/minute or elevated serum creatinine.

Patients suffering from renal dysfunction with an eGFR of less than 45 ml/minute. Nitrofurantoin may be used with caution as short-course therapy only for the treatment of uncomplicated lower urinary tract infection in individual cases with an eGFR between 30-44 ml/min to treat resistant pathogens, when the benefits are expected to outweigh the risks.

In infants under three months of age as well as pregnant patients at term (during labour and delivery) because of the theoretical possibility of haemolytic anaemia in the foetus or in the new-born infant, due to immature erythrocyte enzyme systems.

Patients with known hypersensitivity to nitrofurantoin or other nitrofurans.

4.4 Special warnings and precautions for use

Nitrofurantoin is not effective for the treatment of parenchymal infections of unilaterally non-functioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases.

Since pre-existing conditions may mask adverse reactions, nitrofurantoin should be used with caution in patients with pulmonary disease, hepatic dysfunction, neurological disorders, and allergic diathesis.

Peripheral neuropathy, which may become severe or irreversible, has occurred and may be life threatening. Therefore, treatment should be stopped at the first signs of neural involvement (paraesthesiae). Nitrofurantoin should be used in caution with patients with anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions and vitamin B (particularly folate) deficiency.

Chronic pulmonary reactions can develop insidiously, and may occur commonly in elderly patients. Close monitoring of pulmonary conditions of patients receiving long-term therapy is warranted.

Nitrofurantoin should be discontinued at any sign of haemolysis in those with suspected glucose-6-phosphate dehydrogenase deficiency.

Gastrointestinal reactions may be minimised by taking the drug with food or milk, or by adjustment of dosage.

Discontinue treatment with Nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurological syndromes occur.

For long-term treatment, monitor patients closely for evidence of hepatitis or pulmonary symptoms or other evidence of toxicity.

4.5 Interaction with other medicinal products and other forms of interaction

1.    Increased absorption with food or agents delaying gastric emptying

2.    Decreased absorption with magnesium trisilicate.

3.    Decreased renal excretion of nitrofurantoin by probenecid and sulphinpyrazone.

4.    Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine alkalisation.

5.    Anti-bacterial antagonism by quinolone anti-infectives.

6.    Interference with some tests for glucose in urine.

4.6 Pregnancy and lactation

Animal studies with nitrofurantoin have shown no teratogenic effects. Nitrofurantoin has been in extensive use since 1952, and its suitability in human pregnancy has been well documented. However, as with all drugs, the maternal side effects may adversely affect the course of pregnancy. The drug should be used at the lowest dose as appropriate for specific indication, only after careful assessment.

Nitrofurantoin is however contraindicated in infants under three months of age and in pregnant women during labour and delivery, because of the possible risk of haemolysis of the infants immature red cells. Caution should be exercised while breast-feeding an infant known or suspected to have an erythrocyte enzyme deficiency, since nitrofurantoin is detected in trace amounts in breast milk.

4.7 Effects on ability to drive and use machines

Nitrofurantoin should not affect the ability of the patient to drive or use machinery.

4.8 Undesirable effects

Respiratory

If any of the following reactions occur the drug should be discontinued.

Acute pulmonary reactions usually occur within the first week of treatment and are reversible with cessation of therapy.

Subacute reactions may take several months to resolve once the drug has been stopped.

Chronic pulmonary reactions occur rarely in patients who have received continuous therapy for six months or longer and are more common in elderly patients. Changes to ECG have occurred, associated with pulmonary reactions. Minor symptoms such as fever, chills, cough and dyspnoea may be significant. Collapse and cyanosis have seldom been reported. The severity of chronic pulmonary reactions and their degree of resolution appear to be related to the duration of therapy after the first clinical signs appear. It is important to recognise symptoms as early as possible. Pulmonary function may be impaired permanently, even after cessation of therapy.

Hepatic

Hepatic reactions including cholestatic jaundice and chronic active hepatitis occur rarely. Fatalities have been reported. Cholestatic jaundice is generally associated with short-term therapy (usually up to two weeks). Chronic active

hepatitis, occasionally leading to hepatic necrosis is generally associated with long-term therapy (usually after six months). The onset may be insidious. Treatment should be stopped at the first sign of hepatotoxicity.

Neurological

Peripheral neuropathy (including optical neuritis) with symptoms of sensory as well as motor involvement, which may become severe or irreversible, has been reported infrequently. Less frequent reactions of unknown causal relationship are depression, euphoria, confusion, psychotic reactions, nystagmus, vertigo, dizziness, asthenia, headache and drowsiness. Treatment should be stopped at the first sign of neurological involvement.

Gastrointestinal

Nausea and anorexia have been reported. Emesis, abdominal pain and diarrhoea are less common gastrointestinal reactions.

Haematological

Agranulocytosis, leucopenia, granulocytopenia, haemolytic anemia, thrombocytopenia, megaloblastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia, and eosinophila have been reported. Aplastic anaemia have been reported rarely. Cessation of therapy has generally returned the blood picture to normal.

Hypersensitivity

Allergic skin reactions manifesting in angioneurotic oedema, maculopapular, erythematous or eczematous eruptions, urticaria, rash, and pruritus have occurred.

Lupus-like syndrome associated with pulmonary reactions to Nitrofurantoin has been reported.

Exfoliative dermatitis and erythema multiforme (including Steven-Johnson Syndrome) have been reported rarely.

Other hypersensitivity reactions include anaphylaxis, sialadenitis, pancreatitis, drug fever and arthralgia.

Miscellaneous

Transient alopecia and benign intracranial hypertension. As with other antimicrobial agents, superinfections by fungi or resistant organisms such as Pseudomonas may occur. However, these are limited to the genito-urinary tract because suppression of normal bacteria flora does not occur elsewhere in the body.

4.9 Overdose

Symptoms and signs of overdose include gastric irritation, nausea and vomiting. There is no known specific antidote. However, nitrofurantoin can be haemodialysed in cases of recent ingestion. Standard treatment is by induction of emesis or by gastric lavage. Monitoring of full blood count, liver function, and pulmonary function tests are recommended. A high fluid intake should be maintained to promote urinary excretion of the drug.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

ATC Code: G04A C (urinary antiseptics and antiinfectives, nitrofuran derivatives).

Nitrofurantoin is a broad-spectrum antibacterial agent, active against the majority of urinary pathogens. The wide range of organisms sensitive to the bactericidal activity include:

Escherichia coli Enterococcus Faecalis Klebsiella Species Enterobacter Species

Staphylococcus Species, e.g. S.Aureus, S.Saprophyticus, S.Epidermidis Citrobacter Species

Clinically most common urinary pathogens are sensitive to nitrofurantoin. Most strains of Proteus and Serratia are resistant. All pseudomonas strains are resistant.

5.2 Pharmacokinetic properties

Orally administered nitrofurantoin is readily absorbed in the upper gastrointestinal tract and is rapidly excreted in the urine. Blood concentrations at therapeutic dosages are usually low with an elimination half-life of about 30 minutes.

Maximum urinary excretion usually occurs 2-4 hours after administration of nitrofurantoin. Urinary drug dose recoveries of about 40-45% are obtained.

5.3 Preclinical safety data

Preclinical information has not been included because the safety profile of Nitrofurantoin has been established after many years of clinical use. Please refer to section 4.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maize Starch Lactose Alginic Acid

Magnesium Stearate (E572).

6.2 Incompatibilities

None known.

6.3 Shelf life

Three years.

6.4 Special precautions for storage

Store at a temperature not exceeding 25°C Protect from light

6.5 Nature and contents of container

Polypropylene 'Securitainer' fitted with polythene cap. Containers of 28, 50, 100 and 1,000 tablets.