This information is intended for use by health professionals

1. Name of the medicinal product

Nitrofurantoin 50 mg Tablets

Aratoin 50 mg Tablets

2. Qualitative and quantitative composition

Nitrofurantoin 50.00 mg

For the full list of excipients see section 6.1.

3. Pharmaceutical form

Tablet to be taken orally.

Flat yellow, bevelled and scored tablets.

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 due to susceptible strains of Escherichia coli, Enterococci, Staphylococci, Citrobacter, Klebsiella and Enterobacter.

4.2 Posology and method of administration

Posology

Adults

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

Severe Chronic Recurrence: 100mg four times a day for seven days.

Long Term Suppression: 50mg - 100mg once a day.

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

Paediatric population

Children and Infants over three months of age

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

Suppressive therapy: 1mg/kg/ once a day.

Elderly

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

Renal impairment

Nitrofurantoin is contraindicated in patients with renal dysfunction and in patients with an eGFR of less than 45 ml/minute (see sections 4.3 & 4.4).

Method of administration

For oral use. This medicine should be taken at meal times with food or milk.

4.3 Contraindications

Hypersensitivity to the active substance, other nitrofurans or to any of the excipients listed in section 6.1.

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

G6PD deficiency (see also section 4.6)

Acute porphyria.

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 newborn infant due to immature erythrocyte enzyme systems.

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.

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.

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 and susceptibility to 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 (paraesthesia).

Nitrofurantoin should be used in caution with patients with anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions and vitamin B (particularly folate) deficiency.

Acute, subacute and chronic pulmonary reactions have been observed in patients treated with nitrofurantoin. If these reactions occur, nitrofurantoin should be discontinued immediately.

Chronic pulmonary reactions (including pulmonary fibrosis and diffuse interstitial pneumonitis) can develop insidiously, and may occur commonly in elderly patients. Close monitoring of the pulmonary condition of patients receiving long-term therapy is warranted (especially in the elderly).

Hepatotoxicity

Hepatic reactions, including hepatitis, autoimmune hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. Fatalities have been reported. The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.

Patients on Nitrofurantoin are susceptible to false positive urinary glucose (if tested for reducing substances).

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.

Tablets contain lactose

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

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 sulfinpyrazone.

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.

7. As Nitrofurantoin belongs to the group of Antibacterials, it will have the following resulting interactions:

• Typhoid Vaccine (oral): Antibacterials inactivate oral typhoid vaccine.

4.6 Fertility, pregnancy and lactation

Pregnancy

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

Breastfeeding

Breast-feeding an infant known or suspected to have an erythrocyte enzyme deficiency (including G6PD deficiency), must be temporarily avoided, since Nitrofurantoin is detected in trace amounts in breast milk.

4.7 Effects on ability to drive and use machines

Nitrofurantoin may cause dizziness and drowsiness and the patient should not drive or operate machinery if affected this way.

4.8 Undesirable effects

A tabulated list of undesirable effects is outlined below:

The undesirable effects are listed according to organ systems and following frequencies:

Rare (≥1/10,000 to <1/1,000)

Not known (cannot be estimated from the available data)

System organ class

Frequency

Adverse reaction

Infections and infestations

Not known

Superinfections by fungi or resistant organisms such as Pseudomonas. However, these are limited to the genitourinary tract

Blood and Lymphatic system disorders

Rare

Not known

Aplastic anaemia

Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia,glucose¬6- phosphate dehydrogenase deficiency anaemia, megaloblastic anaemia and eosinophilia

Immune system disorders

Not known

Allergic skin reactions, angioneurotic oedema and anaphylaxis

Psychiatric disorders

Not known

Depression, euphoria, confusion, psychotic reactions

Nervous system disorders

Not known

Peripheral neuropathy including optic neuritis (sensory as well as motor involvement), nystagmus, vertigo, dizziness, headache and drowsiness.

Benign intracranial hypertension

Cardiac disorders

Rare

Collapse and cyanosis

Respiratory, thoracic and mediastinal disorders

Not known

Acute pulmonary reactions, Subacute pulmonary reactions*, Chronic pulmonary reactions, Cough, Dyspnoea, Pulmonary fibrosis; possible association with lupus-erythematous-like syndrome.

Gastrointestinal disorders

Not known

Sialadenitis, Pancreatitis, Nausea, Anorexia, Emesis, Abdominal pain and Diarrhea.

Hepatobiliary disorders

Not known

Cholestatic jaundice, Chronic active hepatitis (fatalities have been reported), Hepatic necrosis, autoimmune hepatitis

Skin and subcutaneous tissue disorders

Not known

Transient alopecia

Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome), maculopapular, erythematous or eczematous eruptions, urticaria, rash, and pruritus. Lupus-like syndrome associated with pulmonary reaction.

Drug Rash With Eosinophilia And Systemic Symptoms (DRESS syndrome), cutaneous vasculitis

Renal and urinary disorders

Not known

Yellow or brown discolouration of urine, interstitial nephritis

General disorders and administration site conditions

Not known

Asthenia, fever, chills, drug fever and arthralgia

Investigations

Not known

False positive urinary glucose

*Acute pulmonary reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration with consolidation or pleural effusion on chest x-ray, and eosinophilia. In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form.

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 in ECG have occurred, associated with 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 the MHRA yellow card scheme website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Symptoms and signs of overdose include gastric irritation, nausea and vomiting.

Management

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

Pharmacotherapeutic group: Antibacterials for systemic use, nitrofurantoin derivatives

ATC code: J01XE01

Mechanism of action

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

Absorption

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.

Elimination

Maximum urinary excretion usually occurs 2-4 hours after administration of nitrofurantoin. Urinary drug dose recoveries of about 40-45% are obtained. It has an elimination half-life of about 30 minutes.

5.3 Preclinical safety data

Carcinogenic effect of nitrofurantoin in animal studies was observed. However, human data and extensive use of nitrofurantoin over 50 years do not support such suggestion.

6. Pharmaceutical particulars
6.1 List of excipients

Lactose

Maize starch

Pregelatinised maize starch

Sodium starch glycollate

Magnesium stearate

Purified water

6.2 Incompatibilities

None stated.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Do not store above 25˚C. Store in the original package. Keep blister in the outer carton/keep container tightly closed.

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 & 1000

250 micron, pharmaceutical grade, green rigid PVC

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 & 1000

6.6 Special precautions for disposal and other handling

None

7. Marketing authorisation holder

Dr Reddy's Laboratories (UK) Limited,

6 Riverview Road,

Beverley,

East Yorkshire,

HU17 0LD

8. Marketing authorisation number(s)

08553/0087

9. Date of first authorisation/renewal of the authorisation

14/03/2011

10. Date of revision of the text

20/03/2019