Summary of medicine characteristics - MACRODANTIN 50 MG CAPSULES, NITROFURANTOIN 50 MG CAPSULES HARD
Macrodantin 50mg Capsules
Nitrofurantoin 50mg Capsules, Hard
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Nitrofurantoin capsules, Hard containing 50 mg Nitrofurantoin Ph. Eur. in macrocrystalline form.
Excipients with known effect
Lactose – 175.60mg per capsule
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
The 50 mg hard gelatin capsule has an opaque yellow cap and opaque white body marked ‘Eaton 008’divided between the body and the cap.
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. It is indicated in adults, children and infants over 3 months old.
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
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 25 kg 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 (see 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 Macrodantin Capsules 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 section 6.1.
Patients suffering from renal dysfunction with an eGFR 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 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 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.
Excipients
Capsule 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 1 mmol sodium (23 mg) per dosage, 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 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 interaction:
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.
Fertility
No data available
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-phosphatedehydrogenase deficiency anaemia, megaloblastic anaemia and eosinophilia |
| Immune system disorders | Not known | Anaphylaxis, angioneurotic oedema and allergic skin reactions |
| Psychiatric disorders | Not known | Psychotic reactions, depression, euphoria, confusion, |
| Nervous system disorders | Not known | Benign intracranial hypertension, peripheral neuropathy including optic neuritis (sensory as well as motor involvement), nystagmus, vertigo, dizziness, headache and drowsiness. |
| Cardiac disorders | Rare | Collapse and cyanosis |
| Respiratory, thoracic and mediastinal disorders | Not known | Pulmonary fibrosis; possible association with lupus-erythematous-like syndrome. acute pulmonary reactions, * subacute pulmonary reactions, * chronic pulmonary reactions, * cough, dyspnoea |
| Gastrointestinal disorders | Not known | Sialadenitis., pancreatitis, , anorexia, emesis, abdominal pain, diarrhoea and nausea. |
| Hepatobiliary disorders | Not known | Chronic active hepatitis (fatalities have been reported), hepatic necrosis, autoimmune hepatitis, cholestatic jaundice |
| Skin and subcutaneous tissue disorders | Not known | Drug Rash With Eosinophilia And Systemic Symptoms (DRESS syndrome) Lupus-like syndrome associated with pulmonary reaction, exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome), maculopapular, erythematous or eczematous eruptions, cutaneous vasculitis, urticaria, rash, and pruritus. transient alopecia |
| Renal and urinary disorders | Not known | interstitial nephritis, yellow or brown discolouration of urine |
| 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 Yellow Card Scheme at: 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 haemodialyzed 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, 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 2530% are obtained. It has an elimination half-life of about 30 minutes or less.
5.3. Preclinical Safety Data
5.3. Preclinical Safety DataCarcinogenic 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 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
The capsule fill contains lactose monohydrate, maize starch and purified talc. The capsule shell contains quinoline yellow (E104), titanium dioxide (E171), gelatin, sodium lauryl sulphate. The printing ink contains shellac and black iron oxide (E172).
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 30°C. Store in the original package to protect from light and moisture.
6.5 Nature and contents of container
Nitrofurantoin 50 mg capsules, Hard are supplied in a PVC/aluminium foil blister pack of 30. Each pack comprises 3 blister cards containing 10 capsules on each card.
6.6 Special precautions for disposal
6.6 Special precautions for disposalAny unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Mercury Pharmaceuticals Ltd,
Capital House,
85 King William Street,
London EC4N 7BL, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 12762/0048