Summary of Product Characteristics (SmPC) - Urantoin/nitrofurantoin 50 mg tablets
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
Poso
logy
Adu
lts
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 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).
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 always be taken with food or milk. Taking
Urantoin Tablets / Nitrofurantoin Tablets with a meal improves absorption and is important for optimal efficacy.
4.3 Contraindications
Hypersensitivity to the active substance, other
nitrofurans or to any of the excipients listed in
Patients suffering from renal dysfunction with a an eGFR of below
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
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 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).
Pulmonary adverse reactions
Acute, subacute and chronic pulmonary reactions have been observed in patients treated with nitrofurantoin. If these reactions occur, nitrofurantoin should be discontinued immediately. Signs of pulmonary damage include difficulty and or pain when breathing, shortness of breath and coughing up blood or mucus.
Chronic pulmonary reactions
Chronic pulmonary reactions (including pulmonary fibrosis and diffuse interstitial pneumonitis) can develop insidiously and can often occur in elderly patients. Close monitoring of the lung disease of patients receiving long-term therapy is indicated (especially in the elderly).
Acute pulmonary reactions
Pulmonary reactions may be acute and usually occur within the first week of treatment. Increased vigilance for respiratory symptoms in patients who have just started therapy is warranted (especially in the elderly).
Nitrofurantoin should be discontinued at any sign of haemolysis in those with suspected glucose-6-phosphate dehydrogenase deficiency.
Discontinue treatment with nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurological syndromes occur.
Tablets contains lactose and sodium
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicine contains less than 1mmol sodium (23mg) per 50mg or 100mg tablet, that is to say essentially ‘sodium free’.
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 sulfinyprazone.
- 4. Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine alkalinisation.
- 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 anti-bacterials, it will have the following resulting interactions:
- Typhoid Vaccine (oral): anti-bacterials 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.
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 infant’s immature red cells.
Breast-feeding
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, cutaneous vasculitis |
| 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 diarrhoea. |
| 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 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 Yellow Card Scheme: 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 overdosage include gastric irritation, nausea and vomiting.
Management
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: Anti-bacterials for systemic use, Nitrofuran derivatives ATC code: J01XE01
Mechanism of action
Nitrofurantoin is a broad-spectrum anti-bacterial 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. 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 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 25ºC 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
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
Boumpoulinas 11, 3rd Floor
NICOSIA
CYPRUS
P.C. 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
18/07/2023