Nitrofurantoin 100mg capsules

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Public Assessment Report Public Assessment Report (PAR)

30-11--0001

Active ingredient:
Nitrofurantoin
Available from:
DE Pharmaceuticals
ATC code:
J01XE01
INN (International Name):
Nitrofurantoin
Dosage:
100mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 05011300
Authorization number:
; PL 12762/0049

1607482F

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

The name of your medicine is Nitrofurantoin 50mg or 100mg capsules, Hard. It will be referred to as Nitrofurantoin capsules for ease hereafter.

What is in this leaflet:

What Nitrofurantoin Capsules are and what they are used for

What you need to know before you take Nitrofurantoin Capsules

How to take Nitrofurantoin Capsules

Possible side effects

How to store Nitrofurantoin Capsules

Contents of the pack and other information

1. WHAT NITROFURANTOIN CAPSULES ARE AND WHAT THEY ARE USED FOR

Nitrofurantoin (the active substance in Nitrofurantoin Capsules) is an antibiotic.

It is used to prevent and treat infections of the bladder, kidney and other parts of the urinary tract.

You must talk to a doctor if you do not feel better or if you feel worse.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE NITROFURANTOIN CAPSULES

DO NOT TAKE Nitrofurantoin Capsules:

if you are allergic to nitrofurantoin, other medicines containing nitrofurantoin or to any of the other ingredients of this medicine (listed in Section 6)

if you have a disease of the kidneys which is severely affecting the way they work (ask your doctor if you are not sure)

if you are in the final stages of pregnancy (labour or delivery) as there is a risk that it might affect the baby

if you suffer from a blood disorder called porphyria

if you are deficient in an enzyme called G6PD (glucose-6-phosphate dehydrogenase)

if your child under three months of age

if you are breast feeding a baby with suspected or known deficiency in an enzyme called G6PD (glucose-6-phosphate dehydrogenase).

Tell your doctor if you are not sure about any of the above.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Nitrofurantoin Capsules:

if you have diabetes

if you are suffering from any illness causing severe weakness

if you have anaemia (a decrease in red blood cells causing pale skin, weakness and breathlessness); or a lack of vitamin B or abnormal levels of salts in your blood

(your doctor will be able to advise you)

if you have a history of allergic reactions.

if you have any problems with your kidneys

The above conditions may increase the chance of developing a side effect which results in damage to the nerves, causes altered sense of feeling, pins and needles.

if you lack an enzyme (body chemical) called glucose-6-phosphate dehydrogenase, which causes your red blood cells to be more easily damaged (this is more

common in black people and people of Mediterranean, Middle Eastern or Asian origin. Your doctor will know)

if you have any disease of the lungs, liver or nervous system. If you need to take Nitrofurantoin Capsules for a number of months, your doctor may want to regularly

check how your lungs and liver are working.

as this medicine may interfere with urine tests for glucose, causing the test to give a “false positive” result. That is, the test may say that glucose is present in the

urine even if it is not.

This medicine may also cause your urine to turn yellow or brown.

If you experience fatigue, yellowing of the skin or eyes, itching, skin rashes, joint pain, abdominal discomfort, nausea, vomiting, loss of appetite, dark urine, and pale

or gray-colored stools. It may be symptoms of liver disorder.

Other medicines and Nitrofurantoin Capsules

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

If they are taken with Nitrofurantoin Capsules their effect or the effect of Nitrofurantoin Capsules may be changed.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

Antacids for indigestion (e.g. magnesium trisilicate)

Medicines for gout (e.g. probenecid or sulfinpyrazone)

Medicines which slow the passage of food through the stomach (e.g. atropine, hyoscine)

Medicines for raised pressure in the eye (glaucoma), such as carbonic anhydrase inhibitors (e.g. acetazolamide)

Medicines which make the urine less acidic (e.g. potassium citrate mixture)

Medicines for infections, known as quinolones

Typhoid vaccine, which is given for the prevention of typhoid.

If you are in doubt about any of these medicines, ask your doctor or pharmacist.

Nitrofurantoin Capsules may interfere with the results of some tests for glucose in the urine.

Nitrofurantoin Capsules with food and drink:

Nitrofurantoin Capsules should always be taken with food or milk. Taking this medicine with food or milk makes it work more effectively. This will help to avoid stomach

upset and also to help the absorption.

Pregnancy, breast-feeding and fertility:

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

As far as it is known Nitrofurantoin Capsules may be used in pregnancy.

However, it should not be used during labour or delivery because there is a possibility that use at this stage may affect the baby. If you want to breast feed, please consult

your doctor first.

Driving and using machines:

Nitrofurantoin Capsules may cause dizziness and drowsiness. You should not drive or operate machinery if you are affected this way until such symptoms go away.

Nitrofurantoin Capsules contain lactose and sodium

This medicine contains lactose and sucrose (sugars). If you have been told by your doctor that you are intolerant to some sugars, contact your doctor before taking this

medicine.

This medicine contains less than 1 mmol sodium (23 mg) per dosage, that is to say essentially ‘sodium-free’.

3. HOW TO TAKE NITROFURANTOIN CAPSULES

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is:

PACKAGE LEAFLET: INFORMATION FOR THE USER

Nitrofurantoin 50mg and 100mg Capsules, Hard

Adults:

The normal dosage depends on the type of infection you have, and instructions should be written on the label provided by the pharmacist. Consult your pharmacist or

doctor if these instructions are not clear. The usual doses are:

For treatment of infections: Either one 50mg capsule or one 100mg capsule four times a day for seven days

For prevention of further infections: Either one 50mg capsule or one 100mg capsule at bedtime

For prevention of infections during surgery: One 50mg capsule four times a day on the day of the operation and three days thereafter.

Use in children and infants over three months of age:

The dose depends on the weight of the child and will be provided by your doctor. Follow your doctor’s instructions exactly.

Children below 3 months of age should not take Nitrofurantoin Capsules. Nitrofurantoin Capsules should be taken with food or milk.

Medical Checks:

Your doctor will watch carefully for any effects on the liver, lungs, blood or nervous system.

Nitrofurantoin Capsules may interfere with the results of some tests for glucose in the urine.

Method of administration

Nitrofurantoin Capsules should always be taken with food or milk. Taking this medicine with food or milk makes it work more effectively.

If you take more Nitrofurantoin Capsules than you should:

Consult your doctor or pharmacist immediately or go to the emergency department of the nearest hospital. Always take any leftover capsules with you, as well as the

container and label, so that the medical staff knows what you have taken.

If you forget to take Nitrofurantoin Capsules:

Do not worry. If you remember later on that day, take that day’s dose as usual. If you miss a whole day’s dose take the normal dose on the next day. Do not take a

double dose to make up for a forgotten capsule. If you are not sure ask your doctor or pharmacist.

If you stop taking Nitrofurantoin Capsules:

Your doctor will tell you how long to take the treatment. Do not stop earlier than you are told, even if you feel better.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most of them are mild and disappear when you stop taking Nitrofurantoin Capsules.

All medicines can cause allergic reactions although serious allergic reactions are rare. If you notice any sudden wheeziness, difficulty in breathing, swelling of

the eyelids, face or lips, rash or itching (especially affecting your whole body) STOP TAKING your medicine and go to a doctor immediately.

If you experience any of the side effects detailed below stop taking Nitrofurantoin Capsules and consult your doctor.

Your lungs may react to Nitrofurantoin Capsules. This may develop quickly, within a week of starting treatment or very slowly, especially in elderly patients. This

may produce fever, chills, cough and shortness of breath

Jaundice (inflammation of the liver causing yellowing of the skin or whites of the eyes)

The nerves outside the spinal cord may be affected causing changes to the sense of feeling and the use of muscles. In addition headache, extreme changes of mood

or mental state, confusion, weakness, blurred vision may occur. These effects may be severe and in some instances permanent

Raised pressure in the skull (causing severe headaches).

Severe reduction in blood cells which can cause weakness, bruising or make infections more likely

Blue or purple coloration of the skin due to low oxygen levels. A condition known as cyanosis.

Symptoms of fever, flu, abdominal pain, diarrhea, blood in your stool and weakness. These could be signs of a condition known as cutaneous vasculitis.

Symptoms of jaundice, fatigue, abdominal pain, joint pain and swelling. These could be signs of a condition known as autoimmune hepatitis.

Please note that while taking Nitrofurantoin Capsules your urine may become dark yellow or brown coloured. This is quite normal and not a reason to stop taking the

medicine.

Other side effects include:

Rare (may affect up to 1 in 1,000 people)

Loss of consciousness (collapse)

Not known (frequency cannot be estimated from the available data)

Feeling sick (nausea) and headache

Loose stools

Loss of appetite, stomachache, and being sick (vomiting)

Dizziness, drowsiness

Blood cells have been affected in some patients. This may result in bruising, delayed clotting of the blood, sore throat, fever, anaemia, and a susceptibility to colds

or persistent cold

A variety of skin rashes or reactions have occurred in some patients. These may appear as flaking skin, a red rash or fever accompanied by rapid heart rate and

severe rash with blistering. Other reactions may include inflammation of salivary glands (causing facial pains), inflammation of the pancreas (causing severe

abdominal pain) and joint pains

Short-term hair loss

Urinary infection by germs which are not sensitive to Nitrofurantoin Capsules.

Inflammation of small blood vessel walls, causing skin lesions

Liver inflammation due to turn of immune system against liver cells

Inflammation of kidney tissue surrounding tubules, causing renal impairment

Reporting of side effects

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

5. HOW TO STORE NITROFURANTOIN CAPSULES

Keep this medicine out of the sight and reach of children.

Do not store above 30°C. Store in the original package to protect from light and moisture.

Do not use Nitrofurantoin Capsules after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required.

These measures will help to protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Nitrofurantoin Capsules contains:

The active substance is Nitrofurantoin. Nitrofurantoin Capsules are available in two strengths, containing either 50mg or 100mg nitrofurantoin.

The other ingredients are talc, maize starch, lactose monohydrate. The capsule shell contains gelatin, sodium lauryl sulphate, quinoline yellow (E104) and titanium

dioxide (E171). The printing ink contains shellac and black iron oxide (E172).

What Nitrofurantoin Capsules looks like and contents of the pack:

Nitrofurantoin 50mg capsule is a no. 3 size hard gelatin capsule with an opaque yellow cap and white opaque body. The capsules are printed in edible black ink and

bears the monogram “Eaton 008”.

Nitrofurantoin 100mg capsule is a no. 2 size hard gelatin capsule with an opaque yellow cap and yellow opaque body. The capsules are printed in edible black ink and

bears the monogram “Eaton 009”.

The capsules are available in blister packs of 30.

Marketing Authorisation Holder: Mercury Pharmaceuticals Ltd., Capital House, 85 King William Street, London EC4N 7BL, UK

Manufacturer

Lusomedicamenta S.A., Sociedade Técnica Farmacêutica, Estrada Consiglieri Pedroso, 69-B, Queluz de Baixo, 2730-055 Barcarena, Portugal.

This leaflet was last revised in October 2019.

LF-117279-01

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

The name of your medicine is Nitrofurantoin 50mg or 100mg capsules, Hard. It will be referred to as Nitrofurantoin capsules for ease hereafter.

What is in this leaflet:

1. What Nitrofurantoin Capsules are and what they are used for

2. What you need to know before you take Nitrofurantoin Capsules

3. How to take Nitrofurantoin Capsules

4. Possible side effects

5. How to store Nitrofurantoin Capsules

6. Contents of the pack and other information

1. WHAT NITROFURANTOIN CAPSULES ARE AND WHAT THEY ARE USED FOR

Nitrofurantoin (the active substance in Nitrofurantoin Capsules) is an antibiotic.

It is used to prevent and treat infections of the bladder, kidney and other parts of the urinary tract.

You must talk to a doctor if you do not feel better or if you feel worse.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE NITROFURANTOIN CAPSULES

DO NOT TAKE Nitrofurantoin Capsules:

if you are allergic to nitrofurantoin, other medicines containing nitrofurantoin or to any of the other ingredients of this medicine (listed in Section 6)

if you have a disease of the kidneys which is severely affecting the way they work (ask your doctor if you are not sure)

if you are in the final stages of pregnancy (labour or delivery) as there is a risk that it might affect the baby

if you suffer from a blood disorder called porphyria

if you are deficient in an enzyme called G6PD (glucose-6-phosphate dehydrogenase)

if your child under three months of age

if you are breast feeding a baby with suspected or known deficiency in an enzyme called G6PD (glucose-6-phosphate dehydrogenase).

Tell your doctor if you are not sure about any of the above.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Nitrofurantoin Capsules:

if you have diabetes

if you are suffering from any illness causing severe weakness

if you have anaemia (a decrease in red blood cells causing pale skin, weakness and breathlessness); or a lack of vitamin B or abnormal levels of salts in your blood

(your doctor will be able to advise you)

if you have a history of allergic reactions.

if you have any problems with your kidneys

The above conditions may increase the chance of developing a side effect which results in damage to the nerves, causes altered sense of feeling, pins and needles.

if you lack an enzyme (body chemical) called glucose-6-phosphate dehydrogenase, which causes your red blood cells to be more easily damaged (this is more

common in black people and people of Mediterranean, Middle Eastern or Asian origin. Your doctor will know)

if you have any disease of the lungs, liver or nervous system. If you need to take Nitrofurantoin Capsules for a number of months, your doctor may want to regularly

check how your lungs and liver are working.

as this medicine may interfere with urine tests for glucose, causing the test to give a “false positive” result. That is, the test may say that glucose is present in the

urine even if it is not.

This medicine may also cause your urine to turn yellow or brown.

If you experience fatigue, yellowing of the skin or eyes, itching, skin rashes, joint pain, abdominal discomfort, nausea, vomiting, loss of appetite, dark urine, and pale

or gray-colored stools. It may be symptoms of liver disorder.

Other medicines and Nitrofurantoin Capsules

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

If they are taken with Nitrofurantoin Capsules their effect or the effect of Nitrofurantoin Capsules may be changed.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

Antacids for indigestion (e.g. magnesium trisilicate)

Medicines for gout (e.g. probenecid or sulfinpyrazone)

Medicines which slow the passage of food through the stomach (e.g. atropine, hyoscine)

Medicines for raised pressure in the eye (glaucoma), such as carbonic anhydrase inhibitors (e.g. acetazolamide)

Medicines which make the urine less acidic (e.g. potassium citrate mixture)

Medicines for infections, known as quinolones

Typhoid vaccine, which is given for the prevention of typhoid.

If you are in doubt about any of these medicines, ask your doctor or pharmacist.

Nitrofurantoin Capsules may interfere with the results of some tests for glucose in the urine.

Nitrofurantoin Capsules with food and drink:

Nitrofurantoin Capsules should always be taken with food or milk. Taking this medicine with food or milk makes it work more effectively. This will help to avoid stomach

upset and also to help the absorption.

Pregnancy, breast-feeding and fertility:

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

As far as it is known Nitrofurantoin Capsules may be used in pregnancy.

However, it should not be used during labour or delivery because there is a possibility that use at this stage may affect the baby. If you want to breast feed, please consult

your doctor first.

Driving and using machines:

Nitrofurantoin Capsules may cause dizziness and drowsiness. You should not drive or operate machinery if you are affected this way until such symptoms go away.

Nitrofurantoin Capsules contain lactose and sodium

This medicine contains lactose and sucrose (sugars). If you have been told by your doctor that you are intolerant to some sugars, contact your doctor before taking this

medicine.

This medicine contains less than 1 mmol sodium (23 mg) per dosage, that is to say essentially ‘sodium-free’.

3. HOW TO TAKE NITROFURANTOIN CAPSULES

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is:

Adults:

The normal dosage depends on the type of infection you have, and instructions should be written on the label provided by the pharmacist. Consult your pharmacist or

doctor if these instructions are not clear. The usual doses are:

For treatment of infections: Either one 50mg capsule or one 100mg capsule four times a day for seven days

For prevention of further infections: Either one 50mg capsule or one 100mg capsule at bedtime

For prevention of infections during surgery: One 50mg capsule four times a day on the day of the operation and three days thereafter.

Use in children and infants over three months of age:

The dose depends on the weight of the child and will be provided by your doctor. Follow your doctor’s instructions exactly.

Children below 3 months of age should not take Nitrofurantoin Capsules. Nitrofurantoin Capsules should be taken with food or milk.

Medical Checks:

Your doctor will watch carefully for any effects on the liver, lungs, blood or nervous system.

Nitrofurantoin Capsules may interfere with the results of some tests for glucose in the urine.

Method of administration

Nitrofurantoin Capsules should always be taken with food or milk. Taking this medicine with food or milk makes it work more effectively.

If you take more Nitrofurantoin Capsules than you should:

Consult your doctor or pharmacist immediately or go to the emergency department of the nearest hospital. Always take any leftover capsules with you, as well as the

container and label, so that the medical staff knows what you have taken.

If you forget to take Nitrofurantoin Capsules:

Do not worry. If you remember later on that day, take that day’s dose as usual. If you miss a whole day’s dose take the normal dose on the next day. Do not take a

double dose to make up for a forgotten capsule. If you are not sure ask your doctor or pharmacist.

If you stop taking Nitrofurantoin Capsules:

Your doctor will tell you how long to take the treatment. Do not stop earlier than you are told, even if you feel better.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most of them are mild and disappear when you stop taking Nitrofurantoin Capsules.

All medicines can cause allergic reactions although serious allergic reactions are rare. If you notice any sudden wheeziness, difficulty in breathing, swelling of

the eyelids, face or lips, rash or itching (especially affecting your whole body) STOP TAKING your medicine and go to a doctor immediately.

If you experience any of the side effects detailed below stop taking Nitrofurantoin Capsules and consult your doctor.

Your lungs may react to Nitrofurantoin Capsules. This may develop quickly, within a week of starting treatment or very slowly, especially in elderly patients. This

may produce fever, chills, cough and shortness of breath

Jaundice (inflammation of the liver causing yellowing of the skin or whites of the eyes)

The nerves outside the spinal cord may be affected causing changes to the sense of feeling and the use of muscles. In addition headache, extreme changes of mood

or mental state, confusion, weakness, blurred vision may occur. These effects may be severe and in some instances permanent

Raised pressure in the skull (causing severe headaches).

Severe reduction in blood cells which can cause weakness, bruising or make infections more likely

Blue or purple coloration of the skin due to low oxygen levels. A condition known as cyanosis.

Symptoms of fever, flu, abdominal pain, diarrhea, blood in your stool and weakness. These could be signs of a condition known as cutaneous vasculitis.

Symptoms of jaundice, fatigue, abdominal pain, joint pain and swelling. These could be signs of a condition known as autoimmune hepatitis.

Please note that while taking Nitrofurantoin Capsules your urine may become dark yellow or brown coloured. This is quite normal and not a reason to stop taking the

medicine.

Other side effects include:

Rare (may affect up to 1 in 1,000 people)

Loss of consciousness (collapse)

Not known (frequency cannot be estimated from the available data)

Feeling sick (nausea) and headache

Loose stools

Loss of appetite, stomachache, and being sick (vomiting)

Dizziness, drowsiness

Blood cells have been affected in some patients. This may result in bruising, delayed clotting of the blood, sore throat, fever, anaemia, and a susceptibility to colds

or persistent cold

A variety of skin rashes or reactions have occurred in some patients. These may appear as flaking skin, a red rash or fever accompanied by rapid heart rate and

severe rash with blistering. Other reactions may include inflammation of salivary glands (causing facial pains), inflammation of the pancreas (causing severe

abdominal pain) and joint pains

Short-term hair loss

Urinary infection by germs which are not sensitive to Nitrofurantoin Capsules.

Inflammation of small blood vessel walls, causing skin lesions

Liver inflammation due to turn of immune system against liver cells

Inflammation of kidney tissue surrounding tubules, causing renal impairment

Reporting of side effects

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

5. HOW TO STORE NITROFURANTOIN CAPSULES

Keep this medicine out of the sight and reach of children.

Do not store above 30°C. Store in the original package to protect from light and moisture.

Do not use Nitrofurantoin Capsules after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required.

These measures will help to protect the environment.

6.

CONTENTS OF THE PACK AND OTHER INFORMATION

What Nitrofurantoin Capsules contains:

The active substance is Nitrofurantoin. Nitrofurantoin Capsules are available in two strengths, containing either 50mg or 100mg nitrofurantoin.

The other ingredients are talc, maize starch, lactose monohydrate. The capsule shell contains gelatin, sodium lauryl sulphate, quinoline yellow (E104) and titanium

dioxide (E171). The printing ink contains shellac and black iron oxide (E172).

What Nitrofurantoin Capsules looks like and contents of the pack:

Nitrofurantoin 50mg capsule is a no. 3 size hard gelatin capsule with an opaque yellow cap and white opaque body. The capsules are printed in edible black ink and

bears the monogram “Eaton 008”.

Nitrofurantoin 100mg capsule is a no. 2 size hard gelatin capsule with an opaque yellow cap and yellow opaque body. The capsules are printed in edible black ink and

bears the monogram “Eaton 009”.

The capsules are available in blister packs of 30.

Marketing Authorisation Holder: Mercury Pharmaceuticals Ltd., Capital House, 85 King William Street, London EC4N 7BL, UK

Manufacturer

Lusomedicamenta S.A., Sociedade Técnica Farmacêutica, Estrada Consiglieri Pedroso, 69-B, Queluz de Baixo, 2730-055 Barcarena, Portugal.

This leaflet was last revised in October 2019.

LF-117279-01

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Nitrofurantoin 100mg Capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 100 mg of Nitrofurantoin Ph Eur in macrocrystalline form.

Excipient with known effect:

Each capsule contains 162mg lactose monohydrate.

For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

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

CLINICAL PARTICULARS

4.1

Therapeutic indications

Nitrofurantoin is indicated for the treatment of and prophylaxis against acute or

recurrent, uncomplicated lower urinary tract infections when due to susceptible

micro-organisms (see section 4.4 and 5.1)

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

antibacterial agents.

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.

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 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 of below 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 below 45 ml/minute 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 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.

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.

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.

Capsules contain lactose and sodium:

This medicine contains lactose. Patients with rare hereditary problems of galactose

intolerance, the Lapp 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

Increased absorption with food or agents delaying gastric emptying.

Decreased absorption with magnesium trisilicate.

Decreased renal excretion of Nitrofurantoin by probenecid and

sulphinpyrazone.

Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine

alkalisation.

Anti-bacterial antagonism by quinolone anti-infectives.

Interference with some tests for glucose in urine.

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

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)

Infections and infestations

Overgrowth of non-susceptible

organisms

Not known

Blood and lymphatic system disorders

Agranulocytosis

Not known

Leucopenia

Not known

Granulocytopenia

Not known

Haemolytic anaemia

Not known

Thrombocytopenia

Not known

Megaloblastic anaemia

Not known

Glucose-6-phosphate dehydrogenase

deficiency anaemia

Not known

Eosinophilia

Not known

Aplastic anaemia

Rare

Immune system disorders

Anaphylaxis

Not known

Allergic skin reactions

Not known

Angioneurotic oedema

Not known

Cutaneous vasculitis

Not known

Psychiatric disorders

Depression

Not known

Euphoria

Not known

Confusion

Not known

Psychotic reactions

Not known

Nervous system disorders

Dizziness

Not known

Peripheral neuropathy (including optical

neuritis)

Not known

Nystagmus

Not known

Vertigo

Not known

Headache

Not known

Drowsiness

Not known

Benign intracranial hypertension

Not known

Cardiac disorders

Collapse

Rare

Cyanosis

Rare

Gastrointestinal disorders

Diarrhoea

Not known

Nausea

Not known

Anorexia

Not known

Emesis

Not known

Abdominal pain

Not known

Sialadenitis

Not known

Pancreatitis

Not known

Hepatobiliary disorders

Cholestatic jaundice

Not known

Chronic active hepatitis

Not known

Hepatic necrosis

Not known

Autoimmune hepatitis

Not known

Skin and subcutaneous tissue disorders

Pruritus

Not known

Maculopapular

Not known

Rash

Not known

Erythematous or eczematous eruptions

Not known

Urticaria

Not known

Stevens-Johnson syndrome

Rare

Exfoliative dermatitis

Rare

Drug Rash with Eosinophilia And

Systemic Symptoms (DRESS syndrome)

Not known

Erythema multiforme

Rare

Lupus-like syndrome associated with

pulmonary reaction to nitrofurantoin

Not known

Transient alopecia

Not known

Cutaneous vasculitis

Not known

Respiratory, thoracic and mediastinal disorders

Acute pulmonary disorder

Not known

Chronic pulmonary disorder

Not known

Cough, dyspnoea

Not known

Pulmonary fibrosis; possible association

with lupus-erythematous-like syndrome

Not known

Renal and urinary disorders

Interstitial nephritis

Not known

General disorders and administration site conditions

Chills

Not known

Asthenia

Not known

fever

Not known

Drug fever and arthralgia

Not known

Investigations

False positive urinary glucose

Not known

As with other antimicrobial agents, superinfections by fungi or resistant

organisms such as Pseudomonas may occur. However, these are limited to the

genito-urinary tract because suppression of normal bacterial flora does not

occur elsewhere in the body.

Cessation of therapy has generally returned the blood picture to normal

Treatment should be stopped at the first sign of neurological involvement

With symptoms of sensory as well as motor involvement, which may

become severe or irreversible has been reported infrequently

Treatment should be stopped at the first sign of hepatotoxicity

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, occasionally leading to hepatic necrosis is generally associated with

long-term therapy (usually after six months). The onset may be insidious

If any of the following reactions occur the drug should be discontinued.

Acute pulmonary reactions usually occur within the first week of treatment

and are reversible with cessation of therapy. Acute pulmonary reactions are

commonly

manifested

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

have

occurred,

associated

with

pulmonary

reactions.

Minor

symptoms

such

fever,

chills,

cough

dyspnoea

significant. Collapse and cyanosis have been reported rarely. 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. It is

important to recognise symptoms as early as possible. Pulmonary function

may be impaired permanently, even after cessation of therapy.

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

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use, Nitrofuran derivatives

ATC Code: J01XE01

Mechanism of action

Nitrofurantoin is bactericidal in urine at therapeutic doses. The mechanism of the

antimicrobial action of nitrofurantoin is unusual among antibacterials.

Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which

inactivate or alter bacterial ribosomal proteins and other macromolecules. As a result

of such inactivations, the vital biochemical processes of protein synthesis, aerobic

energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are

inhibited.

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

Public Assessment Report

National Procedure

Nitrofurantoin 100mg Capsules

(nitrofurantoin)

PRODUCT LICENCE NUMBER:

PL 20117/0227

Morningside Healthcare Limited

PAR Nitrofurantoin 100mg Capsules

PL 20117/0227

2

LAY SUMMARY

Nitrofurantoin 100mg Capsules

(Nitrofurantoin Ph Eur in macrocrystalline form)

This is a summary of the Public Assessment Report (PAR) for Nitrofurantoin 100mg Capsules.

It explains how this product was assessed and its authorisation recommended, as well as its

conditions of use. It is not intended to provide practical advice on how to use this product.

This product will be referred to as Nitrofurantoin Capsules in this lay summary for ease of

reading.

For practical information about using Nitrofurantoin Capsules, patients should read the

package leaflet or contact their doctor or pharmacist.

What are Nitrofurantoin Capsules and what are they used for?

This application is for a generic medicine. This means that medicine is the same as, and

considered interchangeable with, a reference medicine already authorised in the European

Union (EU) called Macrodantin Capsules 100 mg.

Nitrofurantoin Capsules

are used to prevent and treat infections of the bladder, kidney and

other parts of the urinary tract.

How do Nitrofurantoin Capsules work?

Nitrofurantoin Capsules contain an active ingredient called nitrofurantoin (macrocrystalline

form), which is an antibiotic. Antibiotics are used to treat infections caused by bacteria.

Nitrofurantoin works by killing the bacteria that cause infections of the urinary tract.

How are Nitrofurantoin Capsules used?

The pharmaceutical form of this medicine is a capsule and the route of administration is oral.

The capsules should be swallowed whole and be taken with food or milk.

Adults:

The normal dosage depends on the type of infection the patient has and instructions should be

written on the label provided by the pharmacist. Consult the pharmacist or doctor if these

instructions are not clear. The usual doses are:

For treatment of infections: Either one 50mg capsule or one 100mg capsule four times a

day for seven days.

For prevention of further infections: Either one 50mg capsule or one 100mg capsule at

bedtime.

For prevention of infections during surgery: One 50mg capsule four times a day on the

day of the operation and three days thereafter.

Children and infants over three months of age:

The dose depends on the weight of the child and will be provided by the doctor. Follow the

doctor’s instructions exactly.

Children below 3 months of age should not take this medicine.

Medical Checks:

PAR Nitrofurantoin 100mg Capsules

PL 20117/0227

3

The doctor will watch carefully for any effects on the liver, lungs, blood or nervous system.

This medicine may interfere with the results of some tests for glucose in the urine.

For further information on how Nitrofurantoin Capsules

is used, refer to the package leaflet

and Summaries of Product Characteristics available on the Medicines and Healthcare

products Regulatory Agency (MHRA) website.

This medicine can only be obtained with a prescription.

The patient should always take this medicine exactly as their doctor/pharmacist has told them.

The patient should check with their doctor or pharmacist if they are not sure.

What benefits of Nitrofurantoin Capsules have been shown in studies?

Because Nitrofurantoin Capsules

are a generic medicine, studies in healthy volunteers have

been limited to tests to determine that it is bioequivalent to the reference medicine. Two

medicines are bioequivalent when they produce the same levels of the active substance in the

body.

What are the possible side effects of Nitrofurantoin Capsules?

Because Nitrofurantoin Capsules

are a generic medicine and they are bioequivalent to the

reference medicine, its benefits and possible side effects are considered to be the same as the

reference medicine.

For the full list of all side effects reported with this medicine, see Section 4 of the package

leaflet or the Summaries of Product Characteristics (SmPC) available on the MHRA website.

Why was Nitrofurantoin Capsules approved?

It was concluded that, in accordance with EU requirements, Nitrofurantoin Capsules

have been

shown to be comparable to and to be bioequivalent to the reference medicine. Therefore, the

MHRA decided that, as for the reference medicine, the benefits are greater than the risks and

recommended that it can be approved for use.

What measures are being taken to ensure the safe and effective use of Nitrofurantoin

Capsules?

Safety information has been included in the Summaries of Product Characteristics and the

package leaflet for Nitrofurantoin Capsules, including the appropriate precautions to be

followed by healthcare professionals and patients.

Other information about Nitrofurantoin Capsules

A Marketing Authorisation for Nitrofurantoin Capsules was granted in the UK on 20 January

2014.

The full PAR for Nitrofurantoin Capsules follows this summary.

This summary was last updated in January 2020.

PAR Nitrofurantoin 100mg Capsules

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TABLE OF CONTENTS

Contents

INTRODUCTION

......................................................................................................... 5

QUALITY ASPECTS

................................................................................................... 6

NON-CLINICAL ASPECTS

........................................................................................ 8

CLINICAL ASPECTS

.................................................................................................. 8

USER CONSULTATION

.......................................................................................... 10

OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND

RECOMMENDATION

........................................................................................................... 10

TABLE OF CONTENT OF THE PAR UPDATE

............................................................... 11

PAR Nitrofurantoin 100mg Capsules

PL 20117/0227

5

I

INTRODUCTION

Please note that the below PAR consists of the original assessment of these product

licences, which includes the joint assessment for Nitrofurantoin 50 mg Capsules (PL

20117/0226) and Nitrofurantoin 100 mg capsules (PL 20117/0227). A summary of key post

approval changes can be found in the ‘table of PAR update section’ to improve the

accuracy of this Public Assessment Report.

Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare

products Regulatory Agency (MHRA) considered that the applications for Nitrofurantoin

50mg and 100mg Capsules (PL 20117/0226-7) could be approved.

The products are approved for for the treatment of and prophylaxis against acute or recurrent,

uncomplicated lower urinary tract infections, when due to susceptible micro-organisms.

These products contain the active ingredient nitrofurantoin (in macrocrystalline form), which

is an antibacterial agent. Nitrofurantoin is bactericidal in urine at therapeutic doses.

Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate

or alter bacterial ribosomal proteins and other macromolecules. As a result of this

inactivation, the vital biochemical processes of protein synthesis, aerobic energy metabolism,

DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited.

The applications were submitted according to Article 10(1) of Directive 2001/83/EC, as

amended, claiming to be generic medicinal products of the originator products Macrodantin

Capsules 100 mg (PL 00364/0006; Warner Chilcott Pharmaceuticals UK Limited), which

was initially granted a licence in the UK on 16 October 1989. The current Marketing

Authorisation Holder of the reference products is Mercury Pharmaceuticals Limited (PL

12762/0049), following a change of ownership that was concluded on 31 March 2000.

No new non-clinical studies were conducted, which is acceptable given that the applications

are based on being a generic medicinal products of a reference products that have been

licensed for over 10 years.

With the exception of the bioequivalence study, no new clinical studies were conducted,

which is acceptable given that the application is based on being a generic medicinal product

of a reference product that has been in clinical use for over 10 years. The bioequivalence

study was conducted in-line with current Good Clinical Practice (GCP).

The MHRA has been assured that acceptable standards of Good Manufacturing Practice

(GMP) are in place for these products at all sites responsible for the manufacture, assembly

and batch release of these products.

Safety information has been included in the Summaries of Product Characteristics and the

package leaflets for 50mg and 100mg Capsules, including the appropriate precautions to be

followed by healthcare professionals and patients. A summary of the pharmacovigilance

system have been provided with these applications and are satisfactory.

Marketing authorisations were granted for these products on 20 January 2014.

PAR Nitrofurantoin 100mg Capsules

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6

II

QUALITY ASPECTS

II.1

Introduction

Each capsule contains either 50 mg or 100 mg Nitrofurantoin Ph Eur in macrocrystalline

form.

In addition to Nitrofurantoin Ph Eur in macrocrystalline form, these products also contain the

excipients lactose monohydrate, maize starch, purified talc. The capsule shell consists of

gelatin, sodium lauryl sulphate, iron oxide yellow (E172) and titanium dioxide (E171).

The finished products are packaged in PVC /aluminium blisters of 10, 14, 15, 20, 28, 30 and

100 capsules. Not all pack sizes may be marketed.

Satisfactory specifications and Certificates of Analysis have been provided for all packaging

components. All primary packaging complies with the current European regulations

concerning materials in contact with food.

II.2

ACTIVE SUBSTANCE

rINN: Nitrofurantoin Ph Eur in macrocrystalline

Chemical Name:

i) 1-[[(5-Nitro-2-furanyl)methylene]amino]2,4-imidazolidinedione

ii) N-(5-nitro-2-furfurylidene)-1-aminohydantoin and 1-(5-Nitro-2-

furfurylideneamino)hydantoin

Chemical Structure:

Molecular Weight:

238.16

Molecular formula:

Appearance:

Lemon-yellow crystals

Solubility:

Very

slightly

soluble

water

ethanol,

soluble

dimethylformamide

Nitrofurantoin Ph Eur in macrocrystalline is the subject of a European Pharmacopoeia

monograph.

Synthesis of the active substance from the designated starting materials has been adequately

described and appropriate in-process controls and intermediate specifications are applied.

Satisfactory specifications are in place for all starting materials and reagents, and these are

supported by relevant Certificates of Analysis.

Appropriate proof-of-structure data have been supplied for the active substance. All potential

known impurities have been identified and characterised.

An appropriate specification is provided for the active substance. Analytical methods have

been appropriately validated and are satisfactory for ensuring compliance with the relevant

specification. Batch analysis data are provided and comply with the proposed specification.

Satisfactory Certificates of Analysis have been provided for all working standards.

PAR Nitrofurantoin 100mg Capsules

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7

Suitable specifications have been provided for all packaging used. The primary packaging

complies with the current European regulations concerning materials in contact with food.

Appropriate stability data have been generated supporting a suitable retest period when stored

in the proposed packaging.

II.3

DRUG PRODUCTS

Pharmaceutical development

A satisfactory account of the pharmaceutical development has been provided.

Comparative

in vitro

dissolution and impurity profiles have been provided for the proposed

and reference products.

All excipients comply with either their respective European/national monographs, or a

suitable in-house specification. Satisfactory Certificates of Analysis have been provided for

all excipients.

With the exception of gelatin and lactose monohydrate, no excipients of animal or human

origin are used in the final products.

Suitable European Directorate for the Quality of Medicines and Healthcare (EDQM)

Certificates of Suitability have been provided by the suppliers of gelatin, showing that it is in

compliance with current European regulations concerning the minimisation of transmission

of TSE/BSE.

The supplier of lactose monohydrate has confirmed that it is sourced from healthy animals

under the same conditions as milk for human consumption.

The products do not contain or consist of genetically modified organisms (GMO).

Manufacture of the products

A description and flow-chart of the manufacturing method has been provided.

Satisfactory batch formulae has/have been provided for the manufacture of the products,

along with an appropriate account of the manufacturing process. The manufacturing process

has been validated and has shown satisfactory results.

Finished Product Specifications

The finished product specifications are satisfactory. The test methods have been described

and adequately validated. Batch data have been provided that comply with the release

specifications. Certificates of Analysis have been provided for any working standards used.

Stability

Finished product stability studies have been conducted in accordance with current guidelines,

using batches of the finished product stored in the packaging proposed for marketing. Based

on the results, a shelf-life of 30 months, with the storage conditions “Store in the original

container in order to protect from light”, is acceptable.

Suitable post approval stability commitments have been provided to continue stability testing

on batches of finished product.

PAR Nitrofurantoin 100mg Capsules

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8

II.4

Discussion on chemical, pharmaceutical and biological aspects

The grant of a marketing authorisations is recommended.

III

NON-CLINICAL ASPECTS

III.1

Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties nitrofurantoin

(macrocrystalline) are well-known, no new non-clinical studies are required, and none have

been provided. An overview based on the literature review is, thus, appropriate.

III.2

Pharmacology

No new pharmacology data were provided and none were required for these applications.

III.3

Pharmacokinetics

No new pharmacokinetic data were provided and none were required for these applications.

III.4

Toxicology

No new toxicology data were provided and none were required for these applications.

III.5

Ecotoxicity/Environmental Risk Assessment

Suitable justification has been provided for non-submission of an Environmental Risk

Assessment. As the applications are for generic versions of an already authorised products,

an increase in environmental exposure is not anticipated following approval of the Marketing

Authorisations for the proposed products.

III.6

Discussion on the non-clinical aspects

The grant of a marketing authorisations is recommended.

IV

CLINICAL ASPECTS

IV.1

Introduction

The clinical pharmacology, efficacy and safety of nitrofurantoin (macrocrystalline) are

well-known. With the exception of data from two bioequivalence studies, no new clinical

data are provided or are required for this type of application. An overview based on a

literature review and a review of these studies is, thus, satisfactory.

IV. 2

Pharmacokinetics

In support of these applications, the Marketing Authorisation Holder has submitted the

following bioequivalence studies:

Study 1: Fed conditions

A single-dose, randomised, open-label, balanced, two-treatment, two-sequence, two-

period, crossover bioequivalence study to compare the pharmacokinetic profile of the

applicant’s Nitrofurantoin 100mg Capsules with Macrodantin Capsules 100 mg

(Mercury Pharmaceuticals Limited)

in healthy adult subjects, under fed conditions.

Study participants were given each treatment after a high fat, high-calorie breakfast, which

was consumed following an overnight fast of at least 10 hours. Blood samples were collected

for the measurement of pharmacokinetic parameters pre-dose and up to 24 hours post dose.

Each treatment regimen was separated by a washout period of 7 days.

The main pharmacokinetic results are presented in the table below:

PAR Nitrofurantoin 100mg Capsules

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Compared with the reference product, the 90 % confidence intervals for the test product are

within 80.00-125.00 % for AUC and C

. Nitrofurantoin 100mg Capsules can, therefore, be

considered to be bioequivalent with Macrodantin Capsules 100 mg, under fed conditions.

Study 2: Fasting conditions

A single-dose, randomised, open-label, balanced, two-treatment, two-sequence, two-

period, crossover bioequivalence study to compare the pharmacokinetic profile of the

applicant’s Nitrofurantoin 100mg Capsules with Macrodantin Capsules 100 mg

(Mercury Pharmaceuticals Limited)

in healthy adult subjects, under fasting conditions.

Study participants were given each treatment after an overnight fast of at least 10 hours.

Blood samples were collected for the measurement of pharmacokinetic parameters pre-dose

and up to 24 hours post dose. Each treatment regimen was separated by a washout period of 7

days.

The main pharmacokinetic results are presented in the table below:

Compared with the reference product, the 90 % confidence intervals for the test product are

within 80.00-125.00 % for AUC and C

. Nitrofurantoin 100mg Capsules can, therefore, be

considered to be bioequivalent with Macrodantin Capsules 100 mg, under fasting conditions.

As these products meet the bio-waiver criteria specified in the

Guideline on the Investigation

of Bioequivalence

(CPMP/EWP/QWP/1401/98 Rev.1/Corr**), the results and conclusions of

the bioequivalence study on the 100 mg strength can be extrapolated to the 50 mg strength

capsules.

IV.3

Pharmacodynamics

No new pharmacodynamic data have been submitted for these applications and none were

required.

PAR Nitrofurantoin 100mg Capsules

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IV.4

Clinical efficacy

No new efficacy data were submitted with these applications and none were required.

IV.5

Clinical safety

With the exception of the safety data submitted with the bioequivalence studies, no new

safety data were submitted with these applications.

The safety data from the bioequivalence studies showed that the test and reference products

were equally well tolerated. No new or unexpected safety issues were raised from the

bioequivalence study.

IV.6

Risk Management Plan (RMP)

The Pharmacovigilance System, as described by the applicant, fulfils the requirements and

provides adequate evidence that the applicant has the services of a qualified person

responsible for pharmacovigilance, and has the necessary means for the notification of any

adverse reaction suspected of occurring either in the Community or in a third country.

Suitable justification has been provided for not submitting a risk management plan for these

products. This is acceptable.

IV.7

Discussion on the clinical aspects

The grant of marketing authorisations is recommended for these applications.

V

USER CONSULTATION

The Patient Information Leaflet (PIL) has been evaluated via a user consultation study in

accordance with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The

results show that the PIL meets the criteria for readability as set out in the guideline on the

readability of the label and package leaflet of medicinal products for human use.

VI

OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND

RECOMMENDATION

The quality of the products is acceptable, and no new non-clinical or clinical safety concerns

have been identified. Extensive clinical experience with nitrofurantoin (macrocrystalline) is

considered to have demonstrated the therapeutic value of the compound. The benefit/risk is,

therefore, considered to be positive.

The Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and

labelling are satisfactory, in line with current guidelines and consistent with the reference

products.

In accordance with Directive 2012/84/EU, the current approved UK versions of the SmPCs

and PILs for these products are available on the MHRA website.

Representative copies of the current labelling for Nitrofurantoin 100 mg Capsules are

provided in Annex 1 (page 13 of this PAR).

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TABLE OF CONTENT OF THE PAR UPDATE

Steps taken after the initial procedure with an influence on the Public Assessment Report

(non-safety variations of clinical significance).

Please note that only non-safety variations of clinical significance are recorded below and in

the annexes to this PAR. The assessment of safety variations where significant changes are

made are recorded on the MHRA website or European Medicines Agency (EMA) website.

Minor changes to the marketing authorisation are recorded in the current SmPC and/or PIL

available on the MHRA website.

Application

type

Scope

Product

information

affected

Date of

grant

Outcome

Assessment

report

attached

Y/N

National Type

To register a

change in

address of the

marketing

authorisation

holder.

Consequently,

Section 7 of the

SmPC, the

patient

information

leaflet (PIL) and

labelling have

been updated.

Section 7 of

the SmPC,

the PIL and

labelling

20/08/2019

approved

National Type

To update

sections 4.2 and

4.4 of the SmPC

and PIL, to bring

it in line with the

agreed wording

as advised by the

Authority in

letter dated 5 of

July 2019.

Sections 4.2

and 4.4 of

the SmPC,

the PIL and

labelling

17/10/2019

approved

PAR Nitrofurantoin 100mg Capsules

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Annex 1

Reference:

PL 20117/0227-0021

Product:

Nitrofurantoin 100mg Capsules

Type of Procedure:

National

Submission category:

Type IB Variation

Reason

To update sections 4.2 and 4.4 of the SmPC and PIL to bring it in line with the agreed

wording as advised by the Authority in letter dated 5 of July 2019

.

Supporting evidence

The Company has submitted updated documents in support of the application:

MAA form

SmPC

Labelling

Evaluation

The updated documents are satisfactory.

Conclusion

The proposed changes are acceptable.

In accordance with Directive 2010/84/EU, the Summaries of Product Characteristics

(SmPCs) and Patient Information Leaflets (PILs) for products granted Marketing

Authorisations at a national level are available on the MHRA website.

Representative current labelling is presented below:

PAR Nitrofurantoin 100mg Capsules

PL 20117/0227

13

Decision:

Grant

Date:

17 October 2019

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