Urantoin/Nitrofurantoin 50mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
URANTOIN/Nitrofurantoin 50mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Nitrofurantoin tablets contain 50mg of Nitrofurantoin BP
Excipients with known effect: Each tablet also contains 80.000 mg of lactose.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
Nitrofurantoin tablets are 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, when due to susceptible strains of Escherichia coli, Enterococci, Staphylococci, Citrobacter, Klebsiella and Enterobacter.
4.2 Posology and method of administration
Posology
Adult
Acute uncomplicated urinary tract infections: 50 mg four times daily for 7
days
Severe chronic recurrence: 100 mg four times day for 7 days Long term suppression: 50mg-100 mg once a day
Prophylaxis: 50 mg 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: 1mg/kg, once a day.
For children under 25kg body weight consideration should be given to the use of
Nitrofurantoin.
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).
Method of administration: Oral
4.3 Contraindications
o Patients with known hypersensitivity to nitrofurantoin or other nitrofurans or to any of the excipients listed in section 6.1.
o Patients suffering from renal dysfunction with a an eGFR of less than 45-ml/minute or 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/minute to treat resistant pathogens, when the benefits are expected to outweigh the risks.
o G6PD deficiency (see also Section 4.6)
o Acute porphyria
o 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 infections 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 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 (paraesthesiae).
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).
Patients should be monitored closely for signs of hepatitis (particularly in long-term use). Urine may be coloured yellow or brown after taking Nitrofurantoin. 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 dehydogenase deficiency. Gastrointestinal reactions may be minimised by taking the drug with food or milk, or by adjustment of dosage.
For long-term treatment, monitor patient closely for evidence of hepatitis or pulmonary symptoms or other evidence of toxicity.
Discontinue treatment with nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurologic symptoms occur.
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 or agents delaying gastric emptying.
Decreased absorption with magnesium trisilicate.
Decreased renal excretion of nitrofurantoin by probenecid and sulphinyprazone.
Decreased antibacterial activity by carbonic anhydrase inhibitors and urine alkalinisation.
Antibacterial antagonism by quinolone anti- infectives.
Interference with some tests for glucose-in urine.
As Nitrofurantoin belongs to the group of Antibacterials, it will have the following resulting interactions:
• Oestrogens: In common with other antibiotics, nitrofurantoin may
affect
the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of oestrogen-containing contraceptive products. Therefore, patients should be warned appropriately and extra contraceptive precautions taken.
• 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, the maternal side-effects may adversely affect the course of the pregnancy.
The drug should be used at the lowest dose as appropriate for a specific indication only after careful assessment.
Breast-feeding
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. 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
Respiratory:
If any of the following respiratory 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. 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.
Minor symptoms such as fever, chills, cough and dyspnoea may be significant. Collapse and cyanosis have been reported rarely. 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.
Gastrointestinal: Nausea and anorexia have been reported. Emesis, abdominal pain and diarrhoea are less common gastrointestinal reactions.
Hypersensitivity:
Allergic skin reactions manifesting as angioneurotic oedema, maculopapular, erythematous or eczematous eruptions, urticaria, rash and pruritus have occurred. Lupuslike syndrome associated with pulmonary reactions to nitrofurantoin has been reported.
Exfoliative dermatitis and erythema multiforme (including Stevens- Johnson Syndrome) have been reported rarely.
Other hypersensitivity reactions include anaphylaxis, sialadenitis, pancreatitis, drug fever and arthralgia.
Haematological: Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia, megaloblastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia, and eosinophilia have been reported. Aplastic anaemia has been reported rarely. Cessation of therapy has generally returned the blood picture to normal.
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.
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 bacterial flora does not occur elsewhere in the body.
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. Standard treatment is by induction of emesis or by gastric lavage in cases of recent ingestion. 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, Nitrofuran
derivatives
ATC code: J01XE01
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 gastro-intestinal tract and is rapidly excreted in the urine.
Elimination
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
Carcinogenic effect of Nitrofurantoin in animal studies was observed. However, human data and extensive use of Nitrofurantoin over 50 years do not support such observation.
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
Store below 25°C in a dry place in well closed containers. Protect from light.
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 green 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 & 1000
6.6 Special precautions for disposal
Not applicable
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
Boumpoulinas 11, 3 rd Floor
NICOSIA
CYPRUS
PC. 1060
CYPRUS
8 MARKETING AUTHORISATION NUMBER(S)
PL 33414/0069
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
21/11/2008
10 DATE OF REVISION OF THE TEXT
12/10/2016