Frusol 50mg / 5ml Oral Solution

Frusol 50mg/5ml Oral Solution

furosemide

Read all of this leaflet carefully before you start taking this medicine.

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


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


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


• If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet

• 1. What is Frusol 50mg/5ml Oral Solution and what is it used for


• 2. Before you take Frusol 50mg/5ml Oral Solution


• 3. How to take Frusol 50mg/5ml Oral Solution


• 4. Possible side effects


• 5. How to store Frusol 50mg/5ml Oral Solution


• 6. Further information

What is Frusol 50mg/5ml Oral Solution and what is it used for

The name of your medicine is Frusol 50mg/5ml Oral Solution (called Frusol in this leaflet). It contains furosemide. This belongs to a group of medicines called diuretics, or water tablets.

Furosemide can be used to remove the levels of excess water in the body caused by heart, lung, kidney, liver or blood vessel problems.

Before you take Frusol 50mg/5ml Oral Solution

Do not take Frusol and tell your doctor if:

• you are allergic (hypersensitive) to furosemide, sulphonamides or any other ingredients in this liquid (listed in Section 6). The signs of an allergic reaction include a rash, itching or shortness of breath


• you have symptoms of weakness, difficulty in breathing and light-headedness. This could be a sign of having too little water in the body


• you are dehydrated


• you are not passing water (urine) at all or only a small amount each day


• you have kidney failure or liver problems


• you have a severe change in blood salts, such as high potassium levels or low sodium levels. You may notice signs of this such as muscle cramps, weakness and tiredness.

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Frusol.

Take special care with Frusol

Before you take furosemide tell your doctor if:

• you have low blood pressure. The signs of this include dizziness, feeling less alert than usual, fainting and general weakness.


• you have difficulty in passing water (urine), particularly if you have an enlarged prostate gland


• you have gout


• you have low levels of protein in the blood. The signs of this may include swelling, feeling sick (nausea) or being sick (vomiting), diarrhoea and stomach pain


• you have brain disorders affecting your nervous system, or a condition called porphyria. This is a disorder that can cause skin blisters, pain in and around the stomach area (abdomen)


• you have diabetes


• you are going to give this medicine to a baby that was born too early.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Frusol.

Having tests whilst on Frusol

While you are taking this medicine, your doctor may give you regular blood tests. Your doctor will do this to monitor levels of salts and minerals in your blood and to check that your kidneys are working properly.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because furosemide, the main ingredient of this medicine, can affect the way some other medicines work. Also some medicines can affect the way furosemide works.

Tell your doctor if you are taking any of these medicines:

• medicines used to treat high blood pressure known as ACE-inhibitors or Angiotensin-II receptor antagonists, such as captopril and losartan


• medicines used to treat high blood pressure or prostate problems known as alpha-blockers, such as prazosin


• medicines used to treat high blood pressure, angina and heart failure known as beta blockers, such as propranolol, atenolol, sotalol


• digoxin used to treat heart failure and unusual heart rhythms


• medicines used to treat unusual heart beats, such as amiodarone, disopyramide, flecainide, lidocaine and mexiletine


• medicines used to treat pain and inflammation known as NSAIDs, such as indometacin or salicylates such as aspirin


• medicines used to treat infections caused by bacteria, such as lymecycline, vancomycin, gentamicin, ceftriaxone and colistin


• medicines used for depression, such as reboxetine, amitriptyline and phenelzine


• medicines used for mental problems called ‘psychoses’, such as amisulpride, sertindole, pimozide and chlorpromazine


• medicines used to treat epilepsy, such as carbamazepine, phenobarbital and phenytoin


• medicines used to treat infections caused by fungus, such as amphotericin


• medicines used to treat infections caused by a virus, such as nelfinavir, ritonavir and saquinavir


• atomoxetine used to treat Attention Deficit Hyperactivity Disorder (ADHD)


• drugs used after transplants, such as tacrolimus, ciclosporin


• medicines used to treat inflammation known as corticosteroids, such as prednisolone and dexamethasone


• medicines used to treat high blood pressure and other medicines used to remove water from the body known as diuretics, such as acetazolamide and metolazone


• lithium, used to treat extreme mood swings


• potassium salts used to treat low potassium in the blood


• medicines to treat asthma, such as salmeterol, salbutamol and theophylline. These medicines also treat chronic obstructive pulmonary disease


• medicines used to treat blocked noses, such as ephedrine and xylometazoline


• carbenoxolone used to treat mouth ulcers and problems with the digestive area of the stomach (the upper gastrointestinal area)


• laxatives that help you go to the toilet


• cisplatin, used to treat cancer


• clofibrate, used to treat high cholesterol


• warfarin, used to prevent atrial fibrillation, unwanted clotting and stroke


• anything that contains large amounts of liquorice


• sucralfate, used to treat stomach ulcers. Do not take sucralfate within two hours of taking Frusol. This is because the sucralfate can stop the Frusol from working properly.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Frusol.

Pregnancy and breast-feeding

Talk to your doctor before taking this medicine if you are pregnant or planning to become pregnant.

You should not take this medicine if you are breast-feeding.

Driving and using machines

While taking this medicine you may feel less alert than normal. If this happens, do not drive a car or use any tools or machines.

Important information about what is in Frusol

This medicine contains:

• liquid maltitol. If your doctor has told you that you cannot tolerate some sugars, see your doctor before taking this medicine


• ethanol (alcohol). Each dose contains up to 0.4g of alcohol. It may change or increase the effects of other medicines. It is harmful to those who suffer from alcoholism. You should be aware the product has alcohol in it if:
  
  
  • you are pregnant or breast-feeding
  • you have liver disease
  • you have epilepsy
  • you have had a brain injury or brain disease
  • you are going to give this medicine to a child.

How to take Frusol 50mg/5ml Oral Solution

Take this medicine as your doctor or pharmacist has told you. Look on the label and ask the doctor or pharmacist if you are not sure.

Taking this medicine

• this medicine contains 50mg of furosemide in each 5ml


• take this medicine by mouth


• it is best to take your dose in the morning


• plan your doses so that they do not affect your personal activities and sleep


• ask your doctor or pharmacist to help you plan the best time to take this medicine.

Adults

The usual dose for adults is:

• 40mg each day


• take the dose prescribed by your doctor.

Children

The usual dose for children is:

• 1mg to 3mg for each kilogram of the child’s body weight


• the correct dose will be worked out by the doctor


• children should not take more than 40mg each day.

Older People

If you are an older person, your doctor may start you on a lower dose and gradually raise this dose.

If you take more Frusol than you should

If you take more of the medicine than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you so the doctor knows what you have taken.

If you forget to take Frusol

• If you forget a dose, take it as soon as you remember it. However, if it is nearly time for the next dose, skip the missed dose


• Do not take a double dose (two doses at the same time) to make up for a forgotten dose.

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

Possible side effects

Like all medicines, Frusol can cause side effects, although not everybody gets them.

If you have an allergic reaction to Frusol, see a doctor straight away.

An allergic reaction may include:

• any kind of skin rash


• difficulty in breathing, fever and collapse


• more long-term allergic reactions including swelling of the kidneys and blood vessels and particular sensitivity of the skin to sunlight and other sources of light such as sun-beds.

If you get any of the following side effects, see your doctor as soon as possible:

• changes in the amounts of water, salts or minerals in your body. The signs of this you may feel are thirst, headache, feeling dizzy particularly when standing up, feeling confused, muscle twitching and unusual heart beats. These may happen quickly but also over time. If you have liver problems you may be more at risk of these symptoms


• difficulty in passing water (urine)


• a change in the amount of blood cells. The signs you may feel are feeling weak, unexplained bruises or bleeding, getting more infections and sores or ulcers in the mouth


• difficulty in controlling your blood sugar levels if you have diabetes.


• developing diabetes. The signs you may feel are thirst, needing to go to the toilet a lot more and weight loss


• loss of hearing and/or ringing in the ears. If you have kidney problems you may be more at risk


• skin problems such as rash, itching and a serious illness with blistering of the skin, mouth, eyes and genitals


• swelling of the pancreas. This may show as severe pain in the back and/or in the area in and around the stomach (the abdomen) and jaundice which shows as yellowing of the skin and the whites of the eyes caused by liver or blood problems


• tingling or numbness in the hands and feet


• sudden severe joint pains linked to increased amounts of uric acid in the blood. This is known as gout


• blood clots forming when you are severely dehydrated


• low blood pressure. The signs you may feel are being unable to concentrate, feeling light-headed, a feeling of pressure in the head, headache, feeling drowsy, feeling weak, changes in vision, dry mouth and feeling dizzy when standing up.

This medicine may raise cholesterol and lipid (fat) levels in the blood.

If this medicine is used in babies born too soon (prematurely), this medicine can cause:

• persistence of a blood channel that normally closes at or around birth. This may cause heart failure, failure to grow, shortness of breath and rapid pulse


• kidney stones and/or calcium deposits in the body.

Tell your doctor if you get any of these side effects:

• feeling sick (nausea) or being sick (vomiting)


• generally feeling unwell.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Frusol 50mg/5ml Oral Solution

• keep out of the reach and sight of children.


• do not store above 25°C.


• after you open the bottle, this medicine expires after 3 months. Take this medicine back to the pharmacy three months after you first open it.


• do not use after the expiry date which is stated on the label and carton (exp: month, year)


• the expiry date refers to the last day of that month


• do not use Frusol if you notice that the appearance or smell of your medicine has changed. Talk to your pharmacist


• 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.

Further information

What Frusol 50mg/5ml Oral Solution contains

• The active ingredient is furosemide.


• The other ingredients are ethanol, sodium hydroxide, cherry flavour (containing ethanol and propylene glycol), liquid maltitol (E965), disodium hydrogen phosphate (E339), citric acid monohydrate (E330) and purified water.

What Frusol 50mg/5ml Oral Solution looks like and contents of the pack

A clear yellow liquid that smells like cherry.

It comes in a brown glass bottle holding 150ml of solution.

Marketing Authorisation Holder and Manufacturer

Rosemont Pharmaceuticals Ltd

Yorkdale Industrial Park

Braithwaite Street

Leeds

LS11 9XE

UK

This leaflet was last approved in April 2009.

P0454

FYBOGEL PLAIN

1. Name Of The Medicinal Product

Fybogel.

2. Qualitative And Quantitative Composition

Each single dose sachet contains 3.5g ispaghula husk BP.

3. Pharmaceutical Form

Effervescent granules for preparation of an oral suspension

4. Clinical Particulars

4.1 Therapeutic Indications

The treatment of patients requiring a high fibre regimen: for example, for the relief of constipation including constipation in pregnancy and the maintenance of regularity; for the management of bowel function in patients with colostomy, ileostomy, haemorrhoids, anal fissure, chronic diarrhoea associated with diverticular disease, irritable bowel syndrome and ulcerative colitis.

4.2 Posology And Method Of Administration

Fybogel should be stirred into a glass of water and taken as soon as effervescent subsides, preferably after meals.

Adults and children over 12 years:	One sachet morning and evening.
Elderly:	There is no indication the dosage need be modified for the elderly.
Children 6-12 years:	Half to one level 5ml spoonful depending on size and age morning and evening.
Children under 6 years:	To be taken only when prescribed by a doctor. Half to one level 5ml spoonful depending on size and age morning and evening.

4.3 Contraindications

Fybogel is contra-indicated in cases of intestinal obstruction, faecal impaction and colonic atony such as senile mega-colon.

4.4 Special Warnings And Precautions For Use

Due to its aspartame content, Fybogel should not be given to patients with phenylketonuria.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known

4.6 Pregnancy And Lactation

Fybogel may be used during pregnancy and lactation since the ispaghula husk is not absorbed from the gastrointestinal tract.

4.7 Effects On Ability To Drive And Use Machines

Not applicable in view of physical mode of action.

4.8 Undesirable Effects

None known

4.9 Overdose

In the event of overdosage conservative measures should be taken. The patient may notice abdominal discomfort and flatulence and attention should be paid to maintaining an adequate fluid intake, particularly if the granules have been taken without water, contrary to administration instructions.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Ispaghula husk is capable of absorbing up to 40 times it own weight of water in vitro and part of its activity can be attributed to its action as a simple bulking agent. In addition colonic bacteria are believed to use the hydrated material as a metabolic substrate. This results in an increase in the bacterial cell mass with a consequent softening of the faeces.

5.2 Pharmacokinetic Properties

The mode of action of Fybogel is physical and does not depend on absorption into the systemic circulation.

5.3 Preclinical Safety Data

No preclinical findings relevant to the prescriber have been reported.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Potassium bicarbonate	USP
Sodium bicarbonate	Ph Eur
Citric acid	Ph Eur
Riboflavin sodium phosphate	Ph Eur
Beta-caotene 10 % (E160a)	HSE
Aspartame	Ph Eur
Saccharin sodium	Ph Eur
Polysorbate 80	Ph Eur
Silica, colloidal anhydrous	Ph Eur

6.2 Incompatibilities

None known

6.3 Shelf Life

Three years

6.4 Special Precautions For Storage

Store below 30°C in a dry place.

6.5 Nature And Contents Of Container

Sachets of paper/aluminium foil/polythene laminate enclosed in a cardboard outer carton.

Pack size(s): Ten or thirty sachets (pack size printed in bold is currently sold).

6.6 Special Precautions For Disposal And Other Handling

No special instructions.

7. Marketing Authorisation Holder

Reckitt Benckiser Healthcare (UK) Limited

Dansom Lane

Hull

HU8 7DS

United Kingdom

8. Marketing Authorisation Number(S)

PL 00063/0023

9. Date Of First Authorisation/Renewal Of The Authorisation

15/01/1990 / 09/06/2003

10. Date Of Revision Of The Text

17/01/2007

Furadantin 25mg / 5ml Oral Suspension

1. Name Of The Medicinal Product

Furadantin® 25mg/5ml Oral Suspension OR Nitrofurantoin 25mg/5ml Oral Suspension

2. Qualitative And Quantitative Composition

Contains 25mg Nitrofurantoin Ph. Eur per 5ml

3. Pharmaceutical Form

An opaque yellow liquid with a lemon/apricot charateristic odour.

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures.

Nitrofurantoin is specifically indicated for the treatment of infections when due to susceptible strains of Escherichia coli, Enterococci, Staphylococci, Citrobacter, Klebsiella and Enterobacter.

4.2 Posology And Method Of Administration

Dosage:

Adults

Acute Uncomplicated Urinary Tract Infections: 50mg four times daily for seven days

Severe Chronic Recurrence: 100mg four times day for seven days

Long Term Suppression: 50mg - 100mg once a day.

Prophylaxis: 50mg four times daily for the duration of procedure and 3 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.

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).

4.3 Contraindications

Patients suffering from renal dysfunction with a creatinine clearance of less than 60ml/minute or elevated serum creatinine.

G6PD deficiency (including pregnancy at term, and breast-feeding of affected infants, Third trimester: May produce neonatal haemolysis if used at term, only small amounts are present in milk but could be enough to produce haemolysis in G6PD deficient infants), 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.

Patients with known hypersensitivity to nitrofurantoin or other nitrofurans.

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 with caution in 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).

Patients should be monitored closely for signs of hepatitis (particularly in long terms 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.

Gastrointestinal reactions may be minimised by taking the drug with food or milk, or by adjustment of dosage.

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.

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 resulting interactions:

Oestrogens: Antibacterials that do not induce liver enzymes possibly reduce contraceptive effect of oestrogens (risk probably small, Interactions of combined oral contraceptives may also apply to combined contraceptive patches).

Typhoid Vaccine (oral): Antibacterials inactivate oral typhoid vaccine.

4.6 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 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. Caution should be exercised while breast-feeding an infant known or suspected to have an erythrocyte enzyme deficiency, 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. Patients should be advised not to drive or operate machinery if affected in this way until such symptoms go away.

4.8 Undesirable Effects

Respiratory

If any of the following respiratory 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 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.

Minor symptoms such as fever, chills, cough and dyspnoea may be 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.

Hepatic

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. Treatment should be stopped at the first sign of hepatotoxicity.

Neurological

Peripheral neuropathy (including optical neuritis) with symptoms of sensory as well as motor involvement, which may become severe or irreversible, has been reported infrequently. Less frequent reactions of unknown causal relationship are depression, euphoria, confusion, psychotic reactions, nystagmus, vertigo, dizziness, asthenia, headache and drowsiness. Treatment should be stopped at the first sign of neurological involvement.

Gastrointestinal

Nausea and anorexia have been reported. Emesis, abdominal pain and diarrhoea are less common gastrointestinal reactions.

Haematological

Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia, megaloblastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia, and eosinophilia have been reported. Aplastic anaemia has been reported rarely. Cessation of therapy has generally returned the blood picture to normal.

Hypersensitivity

Allergic skin reactions manifesting as angioneurotic oedema, maculopapular, erythematous or eczematous eruptions, urticaria, rash, and pruritis have occurred. Lupus-like syndrome associated with pulmonary reactions to Nitrofurantoin has been reported. Exfoliative dermatitis and erythema multiforme (including Stevens- Johnson Syndrome) have been reported rarely. Other hypersensitivity reactions include anaphylaxis, sialadenitis, pancreatitis, drug fever and arthralgia.

Miscellaneous

Transient alopecia and benign intracranial hypertension. 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.

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

Furadantin 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

Orally administered Nitrofurantoin is readily absorbed in the upper gastrointestinal tract and is rapidly excreted in the urine. Blood concentrations at therapeutic dosages are usually low with an elimination half-life of about 30 minutes.

Maximum urinary excretion usually occurs 2-4 hours after administration of Nitrofurantoin. Urinary drug dose recoveries of about 40-45% are obtained.

5.3 Preclinical Safety Data

A carcinogenic effect of Nitrofurantoin in animal studies was observed. However, human data and extensive use of Nitrofurantoin over 50 years do not support such observation.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Furadantin Suspension contains glycerol, polysorbate-20, Carbomer, Saccharin sodium, Methyl parahydroxybenzoate (E218), Propyl parahydroxybenzoate (E216), Sodium Hydroxide, Sodium Hydroxide, flavourings (Lemon Essence F31874 and Apricot Flavour F31191) and purified water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Three years

6.4 Special Precautions For Storage

Furadantin Suspension should be protected from light and freezing. It should be stored at a temperature not exceeding 25°.

6.5 Nature And Contents Of Container

Furadantin Suspension is supplied in 300ml amber glass bottles.

6.6 Special Precautions For Disposal And Other Handling

Used as directed by physician. A Patient Information Leaflet is provided with details of use and handling of the product.

Furadantin suspension should be protected from light, as exposure will cause darkening of the active principle. Because of this, amber bottles should be used in dispensing.

7. Marketing Authorisation Holder

Goldshield Pharmaceuticals Limited

NLA Tower

12-16 Addiscombe Road

Croydon

CR0 0XT

United Kingdom

8. Marketing Authorisation Number(S)

PL 12762/0055

9. Date Of First Authorisation/Renewal Of The Authorisation

31/03/2000

10. Date Of Revision Of The Text

06/10/2010

Fersaday 100mg Tablets

1. Name Of The Medicinal Product

Fersaday 100mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 322.0mg Ferrous Fumarate BP

3. Pharmaceutical Form

Film-coated Tablets

4. Clinical Particulars

4.1 Therapeutic Indications

Prophylaxis and treatment of iron deficiency states.

4.2 Posology And Method Of Administration

Adults and the elderly: One tablet daily (the foil enclosing the tablet is printed with days of the week in sequence).

In severe or refractory iron deficiency, one tablet may be given twice a day.

Children: Fersaday tablets are not intended for the treatment of children.

Method of administration: Oral

4.3 Contraindications

Known hypersensitivity to any of the ingredients of the product.

Paroxysmal nocturnal haemoglobinuria, haemosiderosis, haemochromatosis, active peptic ulcer, repeated blood transfusions, regional enteritis, and ulcerative colitis. Ferasday tablets must not be used in anaemias other than those due to iron deficiency.

4.4 Special Warnings And Precautions For Use

Some post gastrectomy patients show poor absorption of iron. Care is needed when treating patients with iron deficiency anaemia in patients with treated or controlled peptic ulceration. Duration of treatment of uncomplicated iron deficiency anaemia should not usually exceed 6 months (or 3 months after reversal of the anaemia has been achieved).

Since anaemia due to combined iron and vitamin B12 or folate deficiencies may be microcytic in type, patients with microytic anaemia resistant to therapy with iron alone should be screened for vitamin B12 or folate deficiency. Fersaday tablets should be kept out of the reach of children.

The label will state:

Important Warning: Contains Iron.

Keep out of the reach and sight of children, as overdose may be fatal.

This will appear on the front of the pack within a rectangle, in which there is no other information.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Iron reduces the absorption of penicillamine. Absorption of both iron antibiotic may be reduced if Fersaday is given with tetracycline. Concurrent administration of antacids may reduce absorption of iron. Chloramphenicol delays plasma iron clearance, incorporation of iron into red blood cells and interferes with erythropoiesis. Some inhibition of iron absorption may occur if it is taken with cholestyramine, tea, eggs or milk.

4.6 Pregnancy And Lactation

Administration of Fersaday tablets during the first trimester of pregnancy may be undesirable.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Gastro-intestinal disorders have been reported including gastro-intestinal discomfort, anorexia, nausea, vomiting, constipation, diarrhoea, darkening of the stools may occur.

4.9 Overdose

Acute overdosage with oral iron requires emergency treatment. In young children 200-250mg ferrous fumerate is considered to be extremely dangerous. Symptoms and signs of abdominal pain, vomiting and diarrhoea appear within 60 minutes. Cardiovascular collapse with coma may follow. Some improvement may occur after this phase in some patients, and may be followed by recovery. In other patients, after about 16 hours, deterioration may occur with diffuse vascular congestion, pulmonary oedema, convulsions, anuria, hypothermia, severe shock, metabolic acidosis, coagulation abnormalities or hypoglycaemia.

Vomiting should be induced immediately, followed by parenteral injection of desferrioxamine mesylate and then gastric lavage. In the meantime it is useful to give milk and/or 5% sodium bicarbonate solution by mouth.

Dissolve 2 grams of desferrioxamine mesylate in 2 or 3ml of water for injections and give intramuscularly. A solution of 5 grams desferrioxamine mesylate in 50 to 100ml of fluid may be left in the stomach. If desferrioxamine is not available, leave 300ml of 1% to 5% sodium bicarbonate in the standard. Fluid replacement is essential.

Recovery may be complicate by long term sequelae, such as hepatic necrosis, pyloric sterosis, or acute toxic encephalitis which may cause CNS damage.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Iron is an essential constituent of the body, and is necessary for haemoglobin formation and the oxidative processes of living tissues. Iron and iron salts should be given for the treatment or prophylaxis of iron deficiency anaemias. Preparations of iron are administered by mouth, by intramuscular or intravenous injection.

Soluble ferrous salts are most effective by mouth. Ferrous fumarate is an easily absorbed source of iron for replacement therapy. It is a salt of ferrous iron with an organic acid and is less irritant to the gastro-intestinal tract than salts with inorganic acids.

5.2 Pharmacokinetic Properties

Once in the stomach, the acid conditions of the gastric contents cause the dissociation of ferrous fumerate and ferrous ions are liberated. These ions are absorbed through the proximal portion of the duodenum.

The ferrous iron absorbed by the mucosal cells of the duodenum is oxidised to the ferric form, and this is bound to protein to form Ferritin.

Ferritin in the mucosal cells releases iron into the blood, where it is bound to transferrin and is passed onto the iron stores in the liver, spleen, and bone marrow.

These stores constitute a reserve of iron for synthesis of haemoglobin, myoglobin, and iron containing enzymes.

Iron is lost from the body through loss of cells i.e, urine, faeces, hair, skin, sputum, nails, sloughing of mucosal cells, and through blood loss.

Ferrous fumarate has the same pattern of absorption and excretion as dietary iron.

5.3 Preclinical Safety Data

No further data

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet Core

Maize Starch BP

Sodium Lauryl Sulphate BP

Gelatin BP

Paraffin Liquid BP

Purified Water BP

Film Coating

Hydroxypropyl Methylcellulose USP

Acetylated Monoglyceride

Opaspray Buff K1-3618

Dichloromethane

Industrial Methylated Spirit BP

Purified Water BP

6.2 Incompatibilities

None

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Protect from light.

Do not store above 30^oC.

6.5 Nature And Contents Of Container

Cartons containing two blister packs of 14 tablets, prepared from opaque PVC film and tempered aluminium foil. 28 tablets in each carton and dispensing pack of 1000 tablets in Polypropylene container with tamper evident low density polyethylene cap.

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

Goldshield Group Plc

Trading as Goldshield Pharmaceuticals,

NLA Tower,

Croydon,

Surrey CR0 OXT

8. Marketing Authorisation Number(S)

PL 10972/0041

9. Date Of First Authorisation/Renewal Of The Authorisation

07/01/2009

10. Date Of Revision Of The Text

24/02/2009

Fematrix 40 transdermal patch

Fematrix


40

transdermal patch

What you should know about Fematrix 40

Please read this leaflet before you take your medicine, and keep it safe because you may want to read it again. If you have any questions or are not sure about anything, ask your doctor or a pharmacist.

What is in Fematrix 40?

Fematrix belongs to a group of medicines known as Hormone Replacement Therapy or HRT.

Fematrix 40 is a self-adhesive transdermal patch containing 1.25 mg of estradiol. Each patch delivers approximately 40 micrograms of estradiol in 24 hours. The patch is rectangular in shape with rounded corners and comes in a sachet. Each box contains 8 sachets, each containing one patch.

The estradiol in Fematrix 40 is made from plant materials. The patch also contains: diethyltoluamide, acrylic adhesive (Dow Corning MG-0560) and acrylic thickener (Acrysol 33).

The marketing authorisation holder is

Solvay Healthcare Limited

Southampton

SO18 3JD

UK

Fematrix 40 patches are manufactured by

LTS Lohmann Therapie Systeme AG

D-56626 Andernach

Germany

What is Fematrix 40 for?

Fematrix is an estrogen only HRT for peri and postmenopausal women, used to treat the symptoms of the menopause (change of life). These symptoms vary from woman to woman, and can include hot flushes, night sweats, sleeping difficulties, dryness of the vagina and urinary problems.

Fematrix is suitable for peri and postmenopausal women who may or may not still be having their periods and women switching from standard (cyclic or sequential) HRT on the advice of their doctor.

Fematrix 40 is not a contraceptive. If you need contraception you should use a non-hormonal method.

How does Fematrix 40 work?

Fematrix contains estradiol. This hormone replaces the estradiol you produce in your ovaries from puberty until the menopause. Your body's natural estrogen is also called estradiol.

Estradiol replaces your body's natural estrogen, controlling your menopausal symptoms. Women who still have a womb should normally take some form of progesterone (a progestagen), because estrogen alone can cause problems due to a build up of the womb lining. When needed, a progestagen such as dydrogesterone 10 mg should normally be added to Fematrix for 12 - 14 days each month. Taking dydrogesterone for part of each monthly cycle (with Fematrix) helps prevent a build up of the womb lining by inducing a regular monthly bleed (see ‘endometrial cancer’).

Before taking Fematrix 40

Before you take your medicine, you should make sure that it is safe for you to do so. If you answer yes to any of the following questions, do not take Fematrix:

• Do you have, have you had, or does your doctor think you might have, breast cancer?


• Have you had or does your doctor think that you might have, a tumour which is made worse by estrogens (e.g., endometrial cancer)?


• Do you have or are you being treated for a blood clot in an artery or in a vein in your leg or anywhere else (a deep vein thrombosis), or a blood clot that has travelled to your lung or other parts of your body (an embolus)? Have you had one of these conditions in the past?


• Do you have angina, or have you ever had a heart attack or stroke?


• Has your doctor told you that you have porphyria (a metabolic disorder)?


• Are you allergic to any of the substances in the patch?

If any of the following apply to you, you should check with your doctor before you start taking Fematrix:

• you have or have had serious liver disease; or


• you have irregular or unusually heavy periods; or


• you have or have had endometrial hyperplasia; or


• you are pregnant.

Medical check-ups

Before you start taking HRT, your doctor should ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen, and may do an internal examination - but only if these examinations are necessary for you, or if you have any special concerns.

Once you’ve started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.

Be sure to:

• 
  go for regular breast screening and cervical smear tests


• 
  regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.

If you have (or had in the past, or are at risk of getting) any of the following conditions, your doctor may want to see you more often for check-ups:

• fibroids or endometriosis


• blood clots in the legs or lungs


• tumours related to estrogens


• high blood pressure


• liver complaints


• sugar diabetes


• gall stones


• migraine or severe headache


• systemic lupus erythematosus (SLE) (a disease which affects the skin and major organs)


• epilepsy (fits)


• asthma


• otosclerosis (a type of deafness)

Safety of HRT

As well as benefits, HRT has some risks which you need to consider when you’re deciding whether to take it, or whether to carry on taking it.

Effects on your heart or circulation

Heart disease

HRT is not recommended for women who have heart disease, or have had heart disease recently. If you have had heart disease, talk to your doctor to see if you should take HRT.

HRT will not help to prevent heart disease.

Studies with one type of HRT (containing conjugated estrogen plus the progestagen MPA), have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.

If you get:

• a pain in your chest that spreads to your arm or neck

• 
  See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

Stroke

Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:

• getting older


• high blood pressure


• smoking


• drinking too much alcohol


• an irregular heartbeat

If you are worried about any of these things,
or if you have had a stroke in the past, talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT - on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.

For women in their 50s who are taking HRT, the figure would be 4 in 1000.

Looking at women in their 60s who are not taking HRT - on average, over a 5-year period, 11 in 1000 would be expected to have a stroke.

For women in their 60s who are taking HRT, the figure would be 15 in 1000.

If you get:

• unexplained migraine-type headaches, with or without disturbed vision

• 
  See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood clots

HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.

These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE.

DVT and PE are examples of a condition called venous thromboembolism, or VTE.

You are more likely to get a blood clot:

• if you are seriously overweight


• if you have had a blood clot before


• if any of your close family have had blood clots


• if you have had one or more miscarriages


• if you have any blood clotting problem that needs treatment with a medicine such as warfarin


• if you’re off your feet for a long time because of major surgery, injury or illness


• if you have a rare condition called SLE

If any of these things apply to you,
talk to your doctor to see if you should take HRT.

Compare

Looking at women in their 50s who are not taking HRT — on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.

For women in their 50s who are taking HRT, the figure would be 7 in 1000.

Looking at women in their 60s who are not taking HRT — on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.

For women in their 60s who are taking HRT, the figure would be 17 in 1000.

If you get:

• painful swelling in your leg


• sudden chest pain


• difficulty breathing

• 
  See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot.

If you’re going to have surgery,
make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.

Effects on your risk of developing cancer

Breast cancer

Women who have breast cancer, or have had breast cancer in the past, should not take HRT. Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking estrogen-only HRT for 5 years is about the same as for a woman of the same age who’s still having periods over that time and not taking HRT. The risk for a woman who is taking estrogen plus progestagen HRT is higher than for estrogen-only HRT (but estrogen plus progestagen HRT is beneficial for the endometrium, see ‘Endometrial cancer’ below).

For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping.

Your risk of breast cancer is also higher:

• if you have a close relative (mother, sister or grandmother) who has had breast cancer


• if you are seriously overweight

Compare

Looking at women aged 50 who are not taking HRT — on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.

For women who start taking estrogen-only HRT at age 50 and take it for 5 years, the figure will be 33 and 34 in 1000 (ie an extra 1-2 cases).

If they take estrogen-only HRT for 10 years, the figure will be 37 in 1000 (an extra 5 cases).

For women who start taking estrogen plus progestagen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (ie an extra 6 cases).

If they take estrogen plus progestagen HRT for 10 years, the figure will be 51 in 1000 (ie an extra 19 cases).

If you notice
any changes in your breast, such as:

• dimpling of the skin


• changes in the nipple


• any lumps you can see or feel

• 
  Make an appointment to see your doctor as soon as possible.

Endometrial cancer (cancer of the lining of the womb)

Taking estrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestagen as well as the estrogen helps to lower the extra risk.

If you still have your womb, your doctor may prescribe a progestagen as well as estrogen. If so, these may be prescribed separately, or as a combined HRT product.

If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take estrogen without a progestagen.

If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestagen as well as an estrogen.

Your product, Fematrix is an estrogen-only product

Compare

Looking at women who still have a uterus and who are not taking HRT – on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.

For women who take estrogen-only HRT the number will be 2 to 12 times higher, depending on the dose and how long you take it.

The addition of a progestagen to estrogen-only HRT substantially reduces the risk of endometrial cancer.

If you get
breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.

But if the bleeding or spotting:

• carries on for more than the first few months


• starts after you’ve been on HRT for a while


• carries on even after you’ve stopped taking HRT

• 
  Make an appointment to see your doctor. It could be a sign that your endometrium has become thicker.

Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.

Some studies have indicated that taking estrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

Are you taking any of these other medicines?

If you are taking anticonvulsants (eg. phenobarbital, phenytoin, carbamazepine), anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz), ritonavir, nelfinavir or herbal preparations containing St John’s wort (Hypericum perforatum), talk to your doctor or a pharmacist. These other medicines may stop Fematrix working properly.

How to use Fematrix 40

Generally your doctor will start you on Fematrix 40. Your doctor will aim to give you the lowest dose for the shortest time to treat your symptoms. The dose can then be increased, by your doctor, if necessary. One Fematrix patch should be applied twice weekly on a continuous basis. Each patch should be removed after 3 to 4 days and replaced with a new patch applied to a slightly different site. Patches should be applied to clean, dry and intact areas of skin below the waist on the lower back or buttocks. Fematrix should not be applied on or near the breasts.

In women with a uterus, a progestagen such as dydrogesterone 10 mg should normally be added to Fematrix for 12-14 days each month.

If you are having regular periods you should apply the first patch within five days of the start of bleeding. If you are not having regular periods and are not taking any other HRT preparations, or you are switching from a combined continuous HRT product, you can apply the patch on any convenient day.

If you are currently using a 'cyclic’ or ‘sequential' HRT preparation (which involves taking an estrogen tablet or patch for part of the month, followed by both estrogen and progestagen tablet or patch for up to 14 days) you should apply the first Fematrix patch the day after you finish the pack i.e. at the end of the progestagen phase.

If you forget to change your patch at the right time you should change it as soon as possible. But remember to follow your normal schedule for sticking on the next one. If you normally change your patch on a Monday and Thursday and you forget to change your Monday patch until Tuesday or Wednesday, then you must still change your next patch on Thursday. If a patch is missed or applied late, it is more likely that you will have irregular bleeds.

If your patch comes off before the day when you regularly change it and you cannot stick it back on, put a new patch on. You should then change this patch on your normal change day and carry on as usual.

How to put on a patch

You should stick the patch on dry, unbroken areas of your skin below the waistline such as your lower back or buttocks. Do not put the patch on or near the breasts.

When you have chosen the area where you want to put the patch, make sure the area is not red or irritated. Before you apply the patch, wash and dry the area where you are going to put it. Do not put any powder, oil or cream on your skin before you stick the patch on as this might prevent it from sticking properly.

Take one sachet out of the box and carefully tear it open. Take out the patch, take off the smaller piece of shiny backing covering the sticky side (see Figure 1) and put the patch on the area of skin you have chosen.

Gently peel off the rest of the backing and flatten the surface of the patch with your other hand as you pull (Figure 2). This should give a smooth and wrinkle-free surface.

Pressing it for a few seconds will make it stick firmly (Figure 3). As long as you have stuck the patch on correctly, you can bathe or shower with little risk of it coming off.

When the time comes to change the patch, take off the old one. Place your new patch on a fresh area of skin.

After use, fold the Fematrix patch in two with the adhesive surface to the inside and dispose with the normal household waste. Do not flush the patch down the toilet.

Overdose

It is almost impossible to get an overdose of estradiol from Fematrix 40, but if you think you have, take off the patch(es) and tell a doctor.

Possible side effects

Some women may have side effects when taking Fematrix, but they usually disappear after the first few months. In the list of possible side effects given below, we give an indication of how likely it is that you will get these side effects: ‘common’ means less than one in ten patients may experience this side effect; ‘uncommon’ means less than one in a hundred; ‘rarely’ means less than one in a thousand; and ‘very rarely’ means less than one in ten thousand patients.

Some patients may experience a mild and brief local rash at the site of application with or without itching; this usually disappears rapidly on removal of the patch.

• Infections
  
  • symptoms of cystitis; thrush; (uncommon)
  
  


• Tumours
  
  • breast cancer; fibroids get bigger; (uncommon)
  
  


• Blood changes
  
  • anaemia (iron deficiency); (very rare)
  
  


• Mental problems
  
  • depression; change in sex drive; nervousness; (uncommon)
  
  


• Nervous system
  
  • headache; migraine; (common)
  
  
  • dizziness; (uncommon)
  
  
  • chorea (muscle twitches); (very rare)
  
  


• Eye changes
  
  • intolerance to contact lenses; change in the surface of the eye; (rare)
  
  


• Heart
  
  • heart attack; (very rare)
  
  


• Blood vessels
  
  • high blood pressure; peripheral vascular disease; varicose veins; venous thromboembolism (blood clots in the legs, pelvis or lungs); (uncommon)
  
  
  • stroke; (very rare)
  
  


• Gut complaints
  
  • nausea; abdominal pain; flatulence (wind); (common)
  
  
  • indigestion; (uncommon)
  
  
  • vomiting; (very rare)
  
  


• Liver complaints
  
  • gall bladder disease; (uncommon)
  
  
  • liver function changes (e.g. jaundice); (rare)
  
  


• Skin complaints
  
  • allergic skin reactions (including rash or itching); (uncommon)
  
  
  • skin discolouration; swelling or red patches on the skin; (very rare)
  
  


• Muscle and bone
  
  • leg cramps; (common)
  
  
  • back pain; (uncommon)
  
  


• Reproductive system
  
  • tender breasts; irregular bleeds and spotting; pelvic pain; (common)
  
  
  • vaginal discharge; painful periods; heavy or irregular periods; (uncommon)
  
  
  • swollen breasts; pre-menstrual tension (PMT); (rare)
  
  


• Inherited conditions
  
  • porphyria (a metabolic disorder) gets worse; (very rare)
  
  


• General complaints
  
  • asthenia (feeling weak); (common)
  
  
  • fluid retention; (uncommon)
  
  


• Investigations
  
  • weight changes (up or down); (common)
  
  

Tumours related to estrogens (both benign and malignant) have been associated with HRT (see ‘Effect on your risk of developing cancer’ above).

Dementia: HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.

Usually, side effects are not common and do not usually last long. If any of these side effects do last for a long time or you notice any other side effects and you are worried about them, please contact your doctor or a pharmacist for advice.

You should stop taking Fematrix 40 and contact your doctor if:

• you develop any of the conditions listed in the ‘Before taking Fematrix 40’ section; or


• you develop a blood clot (see ‘Blood clot’); or


• you get sudden problems with your vision, severe headaches or migraines (see ‘Stroke’); or


• you develop jaundice (yellowing of the skin); or


• you become pregnant; or


• your blood pressure increases.

How to store your medicine

Do not store above 25°C. Store in the original package. Do not use the patches after the expiry date shown on the pack. Store all medicines where children cannot see or reach them.

Take any unused patches back to a pharmacy (chemist).

This leaflet was revised in January 2006.

Remember

This medicine is for you. Please do not offer it to your family and friends, even if they have the same symptoms as you.

registered trade mark

Fabrazyme 35 mg, powder for concentrate for solution for infusion

Fabrazyme 35 mg powder for concentrate for solution for infusion

Agalsidase beta

Read all of this leaflet carefully before you start using this medicine.

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


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


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


• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Fabrazyme is and what it is used for


• 2. Before you use Fabrazyme


• 3. How to use Fabrazyme


• 4. Possible side effects


• 5. How to store Fabrazyme


• 6. Further information

What Fabrazyme Is And What It Is Used For

Fabrazyme is used as enzyme replacement therapy in Fabry disease, where the level of α-galactosidase enzyme activity is absent or lower than normal. If you suffer from Fabry disease a fat substance, called globotriaosylceramide (GL-3), is not removed from the cells of your body and starts to accumulate in the walls of the blood vessels of your organs.

Fabrazyme is indicated for use as long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease.

Before You Use Fabrazyme

Do not use Fabrazyme

If you have experienced an allergic anaphylactic reaction to agalsidase beta or if you are allergic (hypersensitive) to any of the other ingredients of Fabrazyme.

Take special care with Fabrazyme

If you are treated with Fabrazyme, you may develop infusion associated reactions. An infusion-associated reaction is any side effect occurring during the infusion or until the end of the infusion day (See 4 "Possible Side Effects"). If you experience a reaction like this, you should tell your doctor immediately. You may need to be given additional medicines to prevent such reactions from occurring.

Different groups of patients using Fabrazyme

The information in this leaflet applies to all patient groups including children, adolescents, adults and the elderly.

Using other medicines

There are no known interactions with other medicinal products. Fabrazyme should not be administered with chloroquine, amiodarone, benoquin or gentamicin due to a theoretical risk of decreased agalsidase beta activity. Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Using Fabrazyme with food and drink

Interactions with food and drink are unlikely.

Pregnancy and breast-feeding

Use of Fabrazyme during pregnancy is not recommended. There is no experience with the use of Fabrazyme in pregnant women. Fabrazyme may get into breast milk. Use of Fabrazyme during breast-feeding is not recommended. Ask your doctor or pharmacist for advice before taking this medicine.

How To Use Fabrazyme

Fabrazyme is given through a drip into a vein (by intravenous infusion). It is supplied as a powder which will be mixed with sterile water before it is given (see information for Health Care Professionals)

Fabrazyme is only used under the supervision of a doctor who is knowledgeable in the treatment of Fabry disease.

The recommended dose of Fabrazyme for adults and children 8 – 16 years is 1 mg/kg body weight, once every 2 weeks. No changes in dose are necessary for patients with kidney disease.

If you use more Fabrazyme than you should

There are no cases of overdose of Fabrazyme reported. Doses up to 3 mg/kg body weight have shown to be safe.

If you forget to use Fabrazyme

If you have missed an infusion of Fabrazyme, please contact your doctor.

Possible Side Effects

Like all medicines, Fabrazyme can cause side effects, although not everybody gets them.

In clinical studies side effects were mainly seen while patients were being given the medicine or shortly after. If you experience any serious side effect or side effects not listed, please tell your doctor immediately.

In clinical trials the following side effects were reported:

Very common (occurring in more than 1 in 10 patients):

• chills


• fever


• headache


• abnormal touch feeling (pins and needles)


• nausea


• vomiting


• feeling cold

Common (occurring in 1 in 100 to 1 in 10 patients):

• chest pain


• difficulty in breathing


• pallor


• itching


• abnormal tear secretion


• feeling weak


• tinnitus


• nasal congestion


• diarrhoea


• redness


• muscle pain


• increased blood pressure


• sudden swelling of the face or throat


• oedema in extremities


• vertigo


• stomach discomfort


• muscle spasms


• sleepiness


• increased heart beat


• abdominal pain


• back pain


• rash


• low heart rate


• lethargy


• syncope


• cough


• abdominal discomfort


• swelling face


• joint pain


• decreased blood pressure


• chest discomfort


• face oedema


• exacerbated difficulty in breathing


• muscle tightness


• fatigue


• flushing


• pain


• throat tightness


• dizziness


• palpitations


• decreased sensitivity to pain


• burning sensation


• wheezing


• urticaria


• pain at the extremities


• nasopharyngitis


• hot flush


• feeling hot


• hyperthermia


• decreased mouth sensitivity


• musculoskeletal stiffness

Uncommon (occurring in 1 in 1000 to 1 in 100 patients):

• tremor


• red eyes


• ear pain


• throat pain


• fast breathing


• itchy rash


• feeling hot and cold


• difficulty swallowing


• infusion site pain


• infusion site reaction


• itching eyes


• ear swelling


• bronchospasm


• runny nose


• heart burn


• skin discomfort


• musculoskeletal pain


• rhinitis


• influenza-like illness


• malaise


• low heart rate due to conduction disturbances


• increased sensitivity to pain


• upper respiratory tract congestion


• red rash


• (mottled purplish) skin discoloration


• coldness of the extremities


• injection site blood clotting


• skin discoloration


• oedema

Unknown frequency

• Serious allergic reactions


• serious inflammation of the vessels


• lower blood oxygen levels

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Fabrazyme

Keep out of the reach and sight of children.

Unopened vials

Store in a refrigerator (2 °C – 8 °C).

Do not use Fabrazyme after the expiry date which is stated on the labelling after the letters ‘EXP’.

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.

Further Information

What Fabrazyme contains

• The active substance is agalsidase beta, one vial contains 35 mg.


• Other ingredients are:
  
  • Mannitol
  • Sodium phosphate monobasic, monohydrate
  • Sodium phosphate dibasic, heptahydrate.

What Fabrazyme looks like and contents of the pack

Fabrazyme is supplied as a white to off-white, powder. After reconstitution it is a clear, colourless liquid, free from foreign matter. The reconstituted solution must be further diluted. Package sizes: 1, 5 and 10 vials per carton. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing authorisation holder

Genzyme Europe B.V.

Gooimeer 10

NL-1411DD Naarden

The Netherlands

Manufacturer

Genzyme Ltd.

37 Hollands Road

Haverhill

Suffolk

CB9 8PU

United Kingdom

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

United Kingdom/Ireland

Genzyme Therapeutics Ltd.

United Kingdom

Tel: +44 1865 405200

This leaflet was last approved in 01/2010

Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu. There are also links to other websites about rare diseases and treatments.

Flagyl 400mg Tablets

1. Name Of The Medicinal Product

Flagyl 400mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 400mg metronidazole.

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Film-coated tablets

White to off-white, circular biconvex, film coated tablets impressed 'FLAGYL 400' on one face, plain reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

Flagyl is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause.

Flagyl is active against a wide range of pathogenic micro-organisms notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis.

It is also active against Trichomonas, Entamoeba histolytica, Giardia lamblia and Balantidium coli.

Flagyl is indicated in adults and children for the following indications:

1. The prevention of post-operative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic streptococci.

2. The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, and post-operative wound infections from which pathogenic anaerobes have been isolated.

3. Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male.

4. Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis).

5. All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers).

6. Giardiasis.

7. Acute ulcerative gingivitis.

8. Anaerobically-infected leg ulcers and pressure sores.

9. Acute dental infections (e.g. acute pericoronitis and acute apical infections).

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

4.2 Posology And Method Of Administration

Oral route of administration.

Flagyl tablets should be swallowed with water (not chewed). It is recommended that the tablets be taken during or after a meal.

Prophylaxis against anaerobic infection: Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery.

Adults

400 mg 8 hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take tablets.

Children

Children < 12 years: 20-30mg/kg as a single dose given 1-2 hours before surgery

Newborns with a gestation age < 40 weeks: 10mg/kg body weight as a single dose before operation

Anaerobic infections: The duration of a course of Flagyl treatment is about 7 days but it will depend upon the seriousness of the patient's condition as assessed clinically and bacteriologically.

Treatment of established anaerobic infection:

Adults

800 mg followed by 400 mg 8 hourly.

Children

Children > 8 weeks to 12 years of age: The usual daily dose is 20-30mg/kg/day as a single dose or divided into 7.5mg/kg every 8 hours. The daily dose may be increased to 40mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days.

Children < 8 weeks of age: 15mg/kg as a single dose daily or divided into 7.5mg/kg every 12 hours. In newborns with a gestation age < 40 weeks, accumulation of metronidazole can occur during the first week of life, therefore the concentrations of metronidazole in serum should preferable be monitored after a few days therapy.

Protozoal and other infections:

Dosage is given in terms of metronidazole or metronidazole equivalent
	Duration of dosage in days	Adults and children over 10 years	Children
7 to 10 years	3 to 7 years	1 to 3 years
Urogenital trichomoniasis Where re-infection is likely, in adults the consort should receive a similar course of treatment concurrently	7    or	2000mg as a single dose or 200 mg three times daily or	40mg/kg orally as a single dose or 15-30 mg/kg/day divided in 2-3 doses; not to exceed 2000mg/dose
5-7	400mg twice daily
Bacterial vaginosis	5-7 or	400 mg twice daily
	1	2000mg as a single dose
Amoebiasis (a) Invasive intestinal disease in susceptible subjects	5	800 mg three times daily	400 mg three times daily	200 mg four times daily	200 mg three times daily
(b) Intestinal disease in less susceptible subjects and chronic amoebic hepatitis	5-10	400 mg three times daily	200 mg three times daily	100 mg four times daily	100 mg three times daily
(c) Amoebic liver abscess also other forms of extra-intestinal amoebiasis	5	400 mg three times daily	200 mg three times daily	100 mg four times daily	100 mg three times daily
(d) Symptomless cyst passers	5-10	400-800 mg three times daily	200-400 mg three times daily	100-200 mg four times daily	100-200 mg three times daily
Alternatively, doses may be expressed by body weight 35 to 50mg/kg daily in 3 divided doses for 5 to 10 days, not to exceed 2400mg/day
Giardiasis	3	2000mg once daily or	1000mg once daily	600-800 mg once daily	500 mg once daily
5	400mg three times daily or
7-10	500mg twice daily
Alternatively, as expressed in mg per kg of body weight: 15-40mg/kg/day divided in 2-3 doses.

Dosage is given in terms of metronidazole or metronidazole equivalent
	Duration of dosage in days	Adults and children over 10 years	Children
7 to 10 years	3 to 7 years	1 to 3 years
Acute ulcerative gingivitis	3	200 mg three times daily	100 mg three times daily	100 mg twice daily	50 mg three times daily
Acute dental infections	3-7	200 mg three times daily
Leg ulcers and pressure sores	7	400 mg three times daily
Children and infants weighing less than 10 kg should receive proportionally smaller dosages. Elderly: Flagyl is well tolerated by the elderly but a pharmacokinetic study suggests cautious use of high dosage regimens in this age group.

Eradication of Helicobacter pylori in paediatric patients:

As a part of a combination therapy, 20mg/kg/day not to exceed 500mg twice daily for 7-14 days. Official guidelines should be consulted before initiating therapy.

4.3 Contraindications

Known hypersensitivity to nitroimidazoles, metronidazole or any of the excipients.

4.4 Special Warnings And Precautions For Use

Regular clinical and laboratory monitoring (especially leucocyte count) are advised if administration of Flagyl for more than 10 days is considered to be necessary and patients should be monitored for adverse reactions, such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures).

Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system disease due to the risk of neurological aggravation.

There is a possibility that after Trichomonas vaginalis has been eliminated a gonococcal infection might persist.

The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present.

In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re-administered immediately after haemodialysis.

No routine adjustment in the dosage of Flagyl need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).

Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Flagyl should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily.

Patients should be warned that metronidazole may darken urine.

Due to inadequate evidence on the mutagenicity risk in humans (see section 5.3), the use of flagyl for longer treatment than usually required should be carefully considered.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction. Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.

Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anticoagulants. Dosage of the latter may require reducing. Prothrombin times should be monitored. There is no interaction with heparin.

Lithium retention accompanied by evidence of possible renal damage has been reported in patients treated simultaneously with lithium and metronidazole. Lithium treatment should be tapered or withdrawn before administering metronidazole. Plasma concentrations of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.

Patients receiving phenobarbital or phenytoin metabolise metronidazole at a much greater rate than normally, reducing the half-life to approximately 3 hours.

Metronidazole reduces the clearance of 5 fluorouracil and can therefore result in increased toxicity of 5 fluorouracil.

Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum ciclosporin and serum creatinine should be closely monitored when coadministration is necessary.

Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.

4.6 Pregnancy And Lactation

There is inadequate evidence of the safety of metronidazole in pregnancy but it has been in wide use for many years without apparent ill consequence. Nevertheless Flagyl, like other medicines, should not be given during pregnancy or during lactation unless the physician considers it essential; in these circumstances the short, high-dosage regimens are not recommended.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned about the potential for drowsiness, dizziness, confusion, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.

4.8 Undesirable Effects

The frequency of adverse events listed below is defined using the following convention:

very common (

Serious adverse reactions occur rarely with standard recommended regimens. Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy.

Blood and lymphatic system disorders:
	Very rare: agranulocytosis, neutropenia, thrombocytopenia, pancytopenia
	Not known: leucopenia.
Immune system disorders:
	Rare: anaphylaxis
	Not known: angiodema, urticaria, fever.
Metabolism and nutrition disorders:
	Not known: anorexia.
Psychiatric disorders:
	Very rare: psychotic disorders, including confusion and hallucinations.
	Not known: depressed mood
Nervous system disorders:
	Very rare:
	• encephalopathy (eg. confusion, fever, headache, hallucinations, paralysis, light sensitivity, disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (eg. ataxia, dysathria, gait impairment, nystagmus and tremor) which may resolve on discontinuation of the drug.
	• drowsiness, dizziness, convulsions, headaches
	Not known: during intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or transient epileptiform seizures have been reported. In most cases neuropathy disappeared after treatment was stopped or when dosage was reduced.
Eye disorders:
	Very rare: vision disorders such as diplopia and myopia, which, in most cases, is transient.
Gastrointestinal disorders:
	Not known: taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal disturbances such as epigastric pain and diarrhoea.
Hepatobiliary disorders:
	Very rare: abnormal liver function tests, cholestatic hepatitis, jaundice and pancreatitis which is reversible on drug withdrawal.
Skin and subcutaneous tissue disorders:
	Very rare: skin rashes, pustular eruptions, pruritis, flushing
	Not known: erythema multiforme.
Musculoskeletal, connective tissue and bone disorders:
	Very rare: myalgia, arthralgia.
Renal and urinary disorders:
	Very rare: darkening of urine (due to metronidazole metabolite).

4.9 Overdose

Single oral doses of metronidazole, up to 12g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for metronidazole overdosage. In cases of suspected massive overdose, symptomatic and supportive treatment should be instituted.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01X D01

Metronidazole has antiprotozoal and antibacterial actions and is effective against Trichomonas vaginalis and other protozoa including Entamoeba histolytica and Giardia lamblia and against anaerobic bacteria.

5.2 Pharmacokinetic Properties

Metronidazole is rapidly and almost completely absorbed on administration of Flagyl tablets; peak plasma concentrations occur after 20 min to 3 hours.

The half-life of metronidazole is 8.5 ± 2.9 hours. Metronidazole can be used in chronic renal failure; it is rapidly removed from the plasma by dialysis. Metronidazole is excreted in milk but the intake of a suckling infant of a mother receiving normal dosage would be considerably less than the therapeutic dosage for infants.

5.3 Preclinical Safety Data

Metronidazole has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results. Epidemiological studies have provided no clear evidence of an increased carcinogenic risk in humans.

Metronidazole has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent or humans in vivo, there was inadequate evidence of a mutagenic effect of metronidazole, with some studies reporting mutagenic effects, while other studies were negative.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Calcium hydrogen phosphate (E341),

Starch maize,

Povidone K30 (E1201),

Mmagnesium stearate (E572),

Tablet coat

Pharmacoat 615 (E464),

Macrogol 400 Ph. Eur.

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

5 years

6.4 Special Precautions For Storage

Store in the original package in order to protect from light.

6.5 Nature And Contents Of Container

Flagyl tablets 200 mg are available in aluminium/plastic blisters of 21 tablets and HDPE bottles of 100 and 250 tablets.

Not all pack sizes may be marketed

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

8. Marketing Authorisation Number(S)

PL 17780/0277

9. Date Of First Authorisation/Renewal Of The Authorisation

03 January 2007

10. Date Of Revision Of The Text

16.03.2011

LEGAL CATEGORY

POM