SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Genfura 100mg Tablets Nitrofurantoin 100mg Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Nitrofurantoin 100mg

Also contains lactose, for a full list of excipients see 6.1

3    PHARMACEUTICAL FORM

Tablet

Flat yellow bevelled tablets scored on one side and marked MP24 on the other side.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of and prophylaxis against acute or recurrent uncomplicated pyelitis or lower urinary tract infection - either spontaneous or following surgical procedures.

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

The drug should be used as a second line choice for acute attacks.

4.2    Posology and method of administration Adults:

•    Acute uncomplicated urinary tract infections: 50 mg four times daily, for 7 days.

•    Severe chronic recurrence: 100 mg four times a day, for 7 days.

•    Long term suppression: 50 mg - 100 mg once a day (at night)

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

Children and Infants over three months of age:

•    Acute uncomplicated urinary tract infections; 3 mg/kg/day in four divided doses for 7 days

•    Suppressive: 1 mg/kg, once a day (at night)

Elderly:

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

Route of administration: Oral, with food

4.3 Contraindications

•    Hypersensitivity to the drug or other nitrofurans

•    Patients suffering from renal dysfunction with an eGFR of less than 45 ml/min. 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.

•    Individuals with glucose 6-phosphate dehydrogenase (G-6-PD) deficiency, and mothers breast-feeding affected infants

•    Infants below 3 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 newborn infant due to immature erythrocyte enzyme systems

•    Patients with acute porphyrias

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 infections should be excluded in recurrent or severe cases.

Nitrofurantoin should be used with caution in renal dysfunction where creatinine clearance is between 60 ml and 90 ml, anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions, vitamin B (particularly folate) deficiency, or patients likely to have G-6-PD or other erythrocyte enzyme deficiency, pulmonary disease, hepatic dysfunctions, neurological disorders and allergic diathesis. Superinfection with fungal or non-susceptible organisms can occur in prolonged therapy.

Acute, subacute or chronic pulmonary reactions have been observed in patients treated with Nitrofurantoin. If these reactions occur, Nitrofurantoin should be discontinued and appropriate measures taken. Reports have cited pulmonary reactions as a contributing cause of death. Chronic pulmonary reactions (diffuse interstitial pneumonitis or pulmonary fibrosis, or other) can develop insidiously. These reactions occur rarely and generally in patients receiving therapy for six months or longer. Chronic pulmonary reactions can develop insidiously, and may occur more commonly in elderly patients. Close monitoring of the pulmonary condition of patients receiving long-term therapy is warranted and requires that the benefits of therapy be weighed against potential risks.

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 is generally associated with long-term therapy (usually after six months); the onset may be insidious, and patients should be monitored periodically for changes in liver function. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures taken.

Drug rashes, pyrexia and hepatitis associated with Nitrofurantoin therapy have been reported. The hepatitis is of an allergic type and may be associated with lymphocyte sensitisation. Bronchospasm and/or dyspnoea, cough and occasionally chest pain has been reported. These symptoms have sometimes been associated with pulmonary infiltration or pleural effusion which is usually transitory.

Ten percent of black patients and a variable percentage of ethnic groups of Mediterranean, Near Eastern and Asian origin, suffer from a deficiency of glucose-6-phosphate dehydrogenase in their blood cells. In such people, Nitrofurantoin, in common with many other therapeutic agents, may cause haemolysis. This enzyme deficiency is extremely rare in Caucasians. Any sign of haemolysis is an indication to discontinue the drug. Haemolysis ceases when the drug is withdrawn.

Discontinue treatment with Nitrofurantoin if otherwise unexplained pulmonary, hepatotoxic, haemolytic or neurologic symptoms occur. For long-term treatment beyond one month, monitor patient closely for appearance of haematological, hepatic, pulmonary or neurological symptoms and other evidence of toxicity.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine

4.5 Interaction with other medicinal products and other forms of interaction

•    Increased absorption with food and anticholinergic drugs

•    Decreased absorption with magnesium trisilicate

•    Increased metabolism of phenytoin

•    Decreased renal excretion of nitrofurantoin by probenecid and sulfinpyrazone

•    Decreased antibacterial activity by carbonic anhydrase inhibitors, urine alkalinisation and barbiturates

•    Antibacterial antagonism by quinolone antiinfectives

•    Interference with urinary estimations of glucose by clinitest (but not by clinistix) method

•    Nitrofurantoin may possibly reduce the contraceptive effect of oestrogens

4.6 Pregnancy and lactation

Based on animal reproduction studies and clinical experience in humans over many years, there is no evidence of any teratogenic effects of Nitrofurantoin on the foetus. However, the maternal side-effects may adversely affect the course of the pregnancy. The drug should be used at the lowest effective dose as appropriate for the specific indication only after careful assessment of benefits against potential risks.

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 whilst breast feeding an infant known or suspected to have any erythrocyte enzyme deficiency as Nitrofurantoin is detected in trace amounts in breast milk.

4.7. Effects on Ability to Drive and Use Machines

No or negligible influence.

4.8 Undesirable effects

Infections and infestation

As with other antimicrobial agents superinfections by resistant organisms such as Pseudomonas may occur. However, these are limited to the genitourinary tract because suppression of normal bacterial flora does not occur elsewhere in the body.

Blood and lymphatic system disorders

Eosinophilia, agranulocytosis, leucopenia, granulocytopenia, thrombocytopenia, haemolytic anaemia, megaloblastic anaemia, aplastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia Cessation of therapy has generally returned the blood picture to normal.

Immune system disorders Anaphylaxis

Metabolism and nutrition Anorexia

Psychiatric disorders

Depression, euphoria, confusion, psychotic reactions Nervous system disorders

Peripheral neuropathy (including optical neuritis), with symptoms of sensory as well as motor involvement, which may become severe or irreversible has occurred but has usually been associated with severe renal impairment and/or prolonged therapy

Nystagmus, dizziness, headache, drowsiness

Treatment should be discontinued at the first signs of neurological involvement

Ear and labyrinth disorders Vertigo

Vascular disorders

Benign intracranial hypertension

Respiratory, thoracic and mediastinal disorders

Cough, chest pain, dyspnoea, pulmonary infiltration with consolidation, altered pulmonary function

Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution is often dramatic.

Sub-acute reactions may take several months to resolve once the drug has been stopped. If the symptoms are not recognised as being drug-related and therapy is not stopped, they may become more severe.

Chronic pulmonary reactions may occur in patients who have received continuous therapy for six months or more. Chronic pulmonary reactions may occur more commonly in elderly patients. 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. Pulmonary function may be impaired permanently, even after cessation of therapy. The risk is greater when chronic pulmonary reactions are not recognised early. It is important to recognise symptoms as early as possible.

If any respiratory reactions occur the drug should be discontinued Gastrointestinal disorders

Nausea, emesis, abdominal pain, diarrhoea, sialadenitis, pancreatitis

These reactions may be minimised by taking the drug with food or milk or by

adjustment of dosage.

Hepato-biliary disorders

Cholestatic jaundice (generally associated with short-term therapy, usually up to two weeks), chronic active hepatitis, occasionally leading to hepatic necrosis, (generally associated with long-term therapy, usually after six months)

Treatment should be stopped at the first sign of hepatotoxicity.

Skin and subcutaneous tissue disorders

Exfoliative dermatitis, erythema multiforme (including Stevens-Johnson syndrome), allergic skin reactions; angioneurotic oedema, maculopapular, erythematous, eczematous eruptions, urticaria, rash, pruritus, Lupus-like syndrome associated with pulmonary reactions to Nitrofurantoin, transient alopecia

Musculoskeletal and connective tissue disorders Arthralgia

Renal and urinary disorders

Urine may become coloured yellow or brown

General disorders and administration site conditions Drug fever, fever, chills, chest pain, malaise, asthenia

Investigations

Pleural effusion on X-ray. Changes in ECG have occurred, associated with pulmonary reactions, radiological and histological findings of diffuse interstitial pneumonitis or fibrosis, or both are also common manifestations of the chronic pulmonary reactions.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme: www.mhra.gov.uk/yellowcard

4.9. Overdose

Symptoms and signs of overdosage include gastric irritation, nausea and vomiting. There is no known specific antidote. Nitrofurantoin can be haemodialysed. Treatment is by induction of emesis or by gastric lavage in recent ingestion. Full blood count, liver function tests and pulmonary function should be monitored. A high fluid intake should be maintained to promote urinary excretion of the drug.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Nitrofurantoin is bactericidal in vitro to most gram-positive and gram-negative urinary tract pathogens and minimum inhibitory concentrations have been reported to range from 4 to 100 micrograms per millilitre. It is most active in acid urine and when the pH exceeds 8 most of the anti-bacterial activity is lost.

Nitrofurantoin is thought to act by interfering with bacterial enzymes involved in carbohydrate metabolism.

5.2. Pharmacokinetic Properties

Nitrofurantoin is readily absorbed from the gastro-intestinal tract and from 25% to 60% is bound to plasma proteins. The plasma half-life is approximately 20 minutes.

Nitrofurantoin diffuses across the placenta and low concentrations appear in the foetal circulation and have been detected in milk.

About 40% of a dose is excreted in the urine as Nitrofurantoin.

Nitrofurantoin may colour the urine.

5.3. Preclinical Safety Data

No relevant information additional to that contained elsewhere in the SPC.

6.1 List of excipients

Lactose Maize starch

Pregelatinised maize starch Sodium starch glycollate Magnesium stearate Purified water

6.2. Incompatibilities

Not applicable.

6.3. Shelf Life

Containers: 36 months Blister packs: 36 months

6.4. Special Precautions for Storage

Containers: Do not store above 25°C. Keep the container tightly closed. Blister packs: Do not store above 25°C. Store in the original package.

6.5 Nature and contents of container

High density polystyrene containers with polythene lids and/or polypropylene containers with polypropylene or polythene lids.

Pack sizes: 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000.

250 micron white opaque rigid PVC pharmaceutical grade 20 micron hard-tempered aluminium foil, coated on the dull side with 6-7 gsm heat-seal lacquer and printed on the bright side.

Pack sizes: 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000.

6.6. Instruction for Use/Handling

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Metwest Pharmaceuticals Limited 15 Runnelfield Harrow on the Hill Middlesex HA1 3NY United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 17521/0024

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

03/02/2009

10 DATE OF REVISION OF THE TEXT

02/09/2014