Urantoin/Nitrofurantoin 50mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
URANTOIN/Nitrofurantoin 50mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Nitrofurantoin BP 50.00 mg
3 PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of and prophylaxis against acute or recurrent uncomplicated pyelitis or lower urinary tract infection proven to be due to E. coli, Staph. aureus or Strep. faecalis - either spontaneous or following surgical procedures. The drug should be used as a second line choice for acute attacks.
4.2 Posology and method of administration
Adults: Uncomplicated acute urinary tract infections:
50 mg t.i.d. for 3 days.
Severe chronic recurrence: 100 mg t.i.d. for 7 days.
Long term suppression: 100mg once a day or 2.4 mg/kg/day if
Treatment duration less than 3 months and 50 mg once a day or 1.2 mg/kg/day if treatment duration more than 3 months.
For prophylaxis: 50 mg t.i.d. for duration of procedure and 3 days thereafter.
Special groups (uncomplicated acute lower UTI):
Children: 1.2-2.4 mg/kg/day
Elderly: 50 mg b.i.d.
Route of administration: Oral
4.3 Contraindications
o Hypersensitivity to the drug or other nitrofurans.
o Renal dysfunction with an eGFR of less than 45ml/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/minute to treat resistant pathogens, when the benefits are expected to outweigh the risks.
o Patients with porphyria.
o Infants below 3 months of age.
o Pregnant patients at term.
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, 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 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.
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 sulfinyprazone. Decreased antibacterial activity by carbonic anhydrase inhibitors, urine alkalinisation and barbiturates. Antibacterial antagonism by quinolone anti-infectives. Interference with urinary estimations of glucose by clinitest (but not by clinistix) method.
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. 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. 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.
4.7 Effects on ability to drive and use machines
None stated
4.8 Undesirable effects
Respiratory: Acute, subacute or chronic pulmonary reactions may occur. Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration with consolidation or pleural effusion on X-ray and eosinophilia. Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy.
Resolution is often dramatic.
In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. Upon cessation of therapy, recovery may require several months. 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. Malaise, dyspnoea on exertion, cough and altered pulmonary function are common manifestations which can occur insidiously. Radiological and histological findings of diffuse interstitial pneumonitis or fibrosis, or both, are also common manifestations of the chronic pulmonary reactions. Fever is rarely prominent. 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.
Gastrointestinal: Nausea and anorexia have been reported. Emesis, abdominal pain and diarrhoea are less common gastrointestinal reactions. These reactions may be minimised by taking the drug with food or milk or by adjustment of dosage. Hepatic reactions including cholestatic jaundice and chronic active hepatitis occur rarely.
Hypersensitivity: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely.
Allergic skin reactions manifesting as angioneurotic oedema, maculopapular, erythematous or eczematous eruptions, urticaria, rash, pruritus have occurred. Lupuslike syndrome associated with pulmonary reactions to nitrofurantoin has been reported.
Other hypersensitivity reactions include anaphylaxis, sialadenitis, pancreatitis, drug fever and arthralgia.
Haematological: Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, megaloblastic anaemia and eosinophilia have occurred. Cessation of therapy has generally returned the blood picture to normal. Aplastic anaemia has been reported rarely.
Neurological: Peripheral neuropathy, which may become severe or irreversible has occurred but has usually been associated with severed renal impairment and/or prolonged therapy. Less frequent reactions, of unknown causal relationship are nystagmus, vertigo, dizziness, asthenia, headache and drowsiness. Should numbness or tingling occur in any part of the body, treatment should be discontinued.
Miscellaneous: Transient alopecia has been reported.
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.
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.
5.3 Preclinical safety data
Not applicable.
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
Special precautions for disposal
6.6
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
02/09/2014