NITROFURANTOIN BRISTOL LABORATORIES 100 MG CAPSULES HARD - summary of medicine characteristics

Nitrofurantoin Bristol Laboratories 100 mg Capsules, Hard

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 100 mg of Nitrofurantoin anhydrous in macrocrystalli­ne form.

Excipients with known effect: Also contains 137.26 mg of lactose monohydrate.

For a full list of excipients, see section 6.1.

Capsule, hard

Yellow/Yellow hard gelatin capsules of size “2” and imprinted with ‘BL’ on cap and ‘100’ on body, containing light yellow crystalline powder. The dimensions of the capsules are 17.6 ± 0.3 mm.

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 when due to susceptible microorganisms (see section 4.4 and 5.1)..

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

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.

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 (Section 4.8).

Method of administration

For oral use

This medicine should always be taken with food or milk. Taking Nitrofurantoin with a meal improves absorption and is important for optimal efficacy.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Patients suffering from renal dysfunction with an eGFR of less than 45 ml/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/min to treat resistant pathogens, when the benefits are expected to outweigh the risks. □ 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.

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.

For long-term treatment, monitor patients closely for evidence of hepatitis or pulmonary symptoms or other evidence of toxicity.

Discontinue treatment with Nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurological syndromes occur.

This medicinal product contains Lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicine.

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

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 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

Undesirable effects reported for nitrofurantoin are listed below according to system organ class.

Very common (> 1/10)

Common (> 1/100, < 1/10)

Uncommon (> 1/1000, < 1/100) Rare (> 1/10,000, < 1/1000)

Very rare (< 1/10,000), not known (cannot be estimated from the available data)

1

Treatment must be stopped when the blood count returns to normal.

Treatment must be stopped at the first sign of neurological and/or psychological reactions. 3 If any of the following respiratory reactions should occur, the use of this medicine must be stopped.

4 Acute pulmonary reactions usually occur within the first week of treatment, and are reversible once treatment is discontinued.

Diagnosed by X-ray.

Chronic pulmonary reactions may occur rarely in patients treated continuously for 6 months or more, and occur more frequently in elderly patients.

7 Fatalities have been reported. Cholestatic jaundice is generally associated with short-term treatment (usually up to 2 weeks). Chronic active hepatitis, occasionally resulting in necrosis, is generally associated with long-term treatment (usually 6 months). Treatment must be stopped at the first sign of hepatotoxicity (see Section 4.4).

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also

report side effects directly 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. By reporting side effects you can help provide more information on the safety of this medicine.

4.9 Overdose

Symptoms and signs of overdose include gastric irritation, nausea and vomiting. 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 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use, Nitrofuran derivatives

ATC Code: J01XE01

Mechanism of action

Nitrofurantoin is a nitrofuran. Therapeutically active concentrations are achieved only in the urine. Nitrofurantoin is most active in acidic urine, and if the pH value is lower than 8 the antibacterial activity is mostly lost. The precise mechanism of action is not known.

Several modes of action have been described. Nitrofurantoin inhibits a number of bacterial enzymes. It also inhibits bacterial ribosomal proteins, and hence results in complete inhibition of bacterial protein synthesis.

Nitrofurantoin may also cause damage to the DNA.

Mechanism of resistance

Resistance rarely develops during treatment with nitrofurantoin, possibly because nitrofurantoin has a number of different modes of action. Resistance may, however, occur with long-term treatment. Plasmid-encoded resistance has been reported in E. coli. Reduced sensitivity has been observed among ESBL-producing intestinal bacteria. Resistance may be due to a loss of nitrofuran reductases that produce the active intermediate products.

Breakpoints

The following breakpoints have been set by EUCAST:

Susceptibility

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable

Commonly susceptible species

Aerobic gram-positive micro-organisms

Aerobic gram-negative microorganisms

Anaerobic microorganisms

Other microorganisms

Species for which acquired resistance may be a problem Aerobic gram-positive micro-organisms

Aerobic gram-negative micro-organisms

Inherently resistant organisms

Aerobic gram-positive microorganisms

Aerobic gram-negative microorganisms

Other micro-organisms

5.2 Pharmacokinetic properties

The Nitrofurantoin macro crystals 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.

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 with an elimination half-life of about 30 minutes or less.

Maximum urinary excretion usually occurs 4–5 hours after administration of macrocrystalline Nitrofurantoin. Urinary drug dose recoveries of about 2530% 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 observations.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule Content

Lactose monohydrate

Maize starch Purified talc

Capsule Shell

Iron Oxide Yellow (E172)

Titanium dioxide (E171)

Gelatin

Printing ink

Shellac (E904)

Propylene glycol (E1520)

Strong ammonia solution (E527)

Black iron oxide (E172)

6.2 Incompatibilities

Not known.

6.3 Shelf life

24 months

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

White opaque 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

No special requirements for disposal

7 MARKETING AUTHORISATION HOLDER

Bristol Laboratories Limited

Unit 3, Canalside, Northbridge Road,

Berkhamsted, Hertfordshire, HP4 1 EG,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 17907/0521

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

23/07/2021