Nitrofurantoin 100 mg capsules

Yellow coloured free flowing granules filled in hard gelatine capsule with white body printed with “100” in black and yellow cap printed with “NTF” in black.

4.1 Therapeutic indications Nitrofurantoin is indicated for the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures. It is indicated in adults, children and infants over 3 months old. 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 (UTIs): 50 mg four times daily for seven days. Severe chronic recurrence (UTIs): 100 mg four times daily for seven days. Long term suppression: 50-100 mg once a day. Prophylaxis: 50 mg four times daily for the duration of procedure and for three 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 other formulations of nitrofurantoin should be considered 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 Nitrofurantoin Capsules with a meal improves absorption and is important for optimal efficacy4.3 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 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 Nitrofurantoin is not effective for the treatment of parenchymal infections of unilaterally nonfunctioning 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 (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 conditions of patients receiving long-term therapy is warranted (especially in the elderly). Patient 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 dehydrogenase deficiency. Discontinue treatment with Nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurological syndromes occur. **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. **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). Capsules contain lactose and sodium: Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicine contains less than 1 mmol sodium (23 mg) per capsule, 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 sulphinpyrazone.
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 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 course of 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 infants' 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 until such symptoms go away.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: The ADRs derived from clinical studies and post-marketing surveillance with nitrofurantoin, sorted by MedDRA System Organ Class are listed below. The following terminologies have been used in order to classify the occurrence of undesirable effects. Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) 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- phosphatedehydrogenase 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 | 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 the national reporting system, the 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.

5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antibacterials for systemic use, Nitrofuran 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 The nitrofurantoin macrocrystals are specially formulated. The controlled crystal size is designed to control the speed of absorption and thus reduce the incidence of nausea. Clinical and animal studies indicate that Nitrofurantoin therapy decreases the likelihood of nausea in patients who might experience these symptoms on Nitrofurantoin therapy. This special formulation of Nitrofurantoin had not caused any decrease in antibacterial efficacy. Absorption Orally administered Nitrofurantoin is readily absorbed in the upper gastrointestinal tract at a slower rate and to reduced extent when compared to microcrystalline Nitrofurantoin. Blood concentrations at therapeutic dosage are usually low. Elimination Maximum urinary excretion usually occurs 4-5 hours after administration of macrocrystalline Nitrofurantoin. Urinary drug dose recoveries of about 25-30% are obtained. It has an elimination half-life of about 30 minutes or less.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 observations.

6.1 List of excipients Lactose monohydrate Maize starch Purified talc Capsule Shell Gelatin Sodium lauryl sulphate Iron oxide yellow (E172) Titanium dioxide (E171)6.2 Incompatibilities Not known.6.3 Shelf life 30 months.6.4 Special precautions for storage Store in the original container in order to protect from light.6.5 Nature and contents of container PVC /aluminium blisters of 10, 14, 15, 20, 28, 30 and 100 capsules. Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling Nitrofurantoin Capsules should be used as directed by physician. A patient information leaflet is provided with details of use and handling of the product.