Frusol 20mg / 5ml Oral Solution

1. Name Of The Medicinal Product

Frusol 20mg/5ml Oral Solution

2. Qualitative And Quantitative Composition

Furosemide Ph.Eur 20mg/5ml

3. Pharmaceutical Form

Oral Solution

4. Clinical Particulars

4.1 Therapeutic Indications

Furosemide is indicated in all conditions requiring prompt diuresis, including cardiac, pulmonary, hepatic and renal oedema, peripheral oedema due to mechanical obstruction or venous insufficiency and hypertension.

It is also indicated for the maintenance therapy of mild oedema of any origin.

4.2 Posology And Method Of Administration

This liquid should only be taken orally.

The medication should be administered in the morning to avoid nocturnal diuresis.

Adults: The usual initial daily dose is 40mg. This may be adjusted until an effective dose is achieved.

Children: 1 to 3mg/Kg body weight daily up to a maximum total dose of 40mg/day.

Elderly: In the elderly, Furosemide is generally eliminated more slowly. Dosage should be titrated until the required response is achieved.

4.3 Contraindications

Contra-indicated conditions	See also
Hypersensitivity to furosemide, amiloride, sulphonamides or sulphonamide derivatives, and/or any of the excipients of the product.
Hypovolaemia and dehydration (with or without accompanying hypotension)	Section 4.4
Severe hypokalaemia: severe hyponatraemia	Section 4.4
Comatose or pre-comatose states associated with hepatic cirrhosis	Section 4.4
Anuria or renal failure with anuria not responding to furosemide, renal failure as a result of poisoning by nephrotoxic or hepatotoxic agents
Impaired renal function with a creatinine clearance below 30ml/min per 1.73 m2 body surface area	Section 4.4
Addison's disease	Section 4.4
Digitalis intoxication	Section 4.5
Concomitant potassium supplements or potassium sparing diuretics	Section 4.5
Breast-feeding women	Section 4.6

4.4 Special Warnings And Precautions For Use

Conditions requiring correction before furosemide is started (see also section 4.3)

• Hypotension

• Hypovolaemia

• Severe electrolyte disturbances – particularly hypokalaemia, hyponatraemia and acid-base disturbances

Furosemide is not recommended

• In patients at high risk for radiocontrast nephropathy - it should not be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy.

• In elderly patients with dementia taking risperidone - Increased mortality (see below and section 4.5)

Particular caution and/or dose reduction required:

• elderly patients (lower initial dose as particularly susceptible to side-effects - see section 4.2).

• difficulty with micturition including prostatic hypertrophy (increased risk of urinary retention: consider lower dose). Closely monitor patients with partial occlusion of the urinary tract

• diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase: stop furosemide before a glucose tolerance test)

• pregnancy (see section 4.6)

• gout (furosemide may raise uric acid levels/precipitate gout)

• impaired hepatic function – hepatic failure and alcoholic cirrhosis particularly predispose to hypokalaemia and hypomagnesaemia (see section 4.3 and below – monitoring required)

• impaired renal function (see section 4.3 and below – monitoring required)

• adrenal disease (see section 4.3 – contraindication in Addison's disease)

• hypoproteinemia e.g. nephrotic syndrome (effect of furosemide may be impaired and its ototoxicity potentiated - cautious dose titration required).

• acute hypercalcaemia (dehydration results from vomiting and diuresis - correct before giving furosemide). Treatment of hypercalcaemia with a high dose of furosemide results in fluid and electrolyte depletion - meticulous fluid replacement and correction of electrolyte required

• premature infants – possible development of nephrocalcinosis/ nephrolithiasis (see below – monitoring of renal function required)

• some diuretics have been considered unsafe in acute porphyria

Avoidance with other medicines (see also section 4.5 for other interactions)

• concurrent NSAIDs should be avoided – if not possible diuretic effect of furosemide may be attenuated

• ACE-inhibitors & Angiotensin II receptor antagonists – severe hypotension may occur – dose of furosemide should be reduced/stopped (3 days) before starting or increasing the dose of these

• concurrent risperidone in elderly patients with dementia has resulted in increased mortality – no mechanism for and no consistent pattern of deaths identified (see section 4.5)

Laboratory and other monitoring requirements:

• Serum sodium

Particularly in the elderly or in patients liable to electrolyte deficiency

• Serum potassium

The possibility of hypokalaemia should be taken into account, in particular in patients with cirrhosis of the liver, those receiving concomitant treatment with corticosteroids, those with an unbalanced diet and those who abuse laxatives. Regular monitoring of the potassium, and if necessary treatment with a potassium supplement, is recommended in all cases, but is essential at higher doses and in patients with impaired renal function. It is especially important in the event of concomitant treatment with digoxin, as potassium deficiency can trigger or exacerbate the symptoms of digitalis intoxication (see section 4.5). A potassium-rich diet is recommended during long-term use.

Frequent checks of the serum potassium are necessary in patients with impaired renal function and creatinine clearance below 60ml/min per 1.73m2 body surface area as well as in cases where furosemide is taken in combination with certain other drugs which may lead to an increase in potassium levels (see section 4.5 & refer to section 4.8 for details of electrolyte and metabolic abnormalities)

• Renal function

Frequent BUN in first few months of treatment, periodically thereafter. Long-term/high-dose BUN should regularly be measured. Marked diuresis can cause reversible impairment of kidney function in patients with renal dysfunction. Adequate fluid intake is necessary in such patients. Serum creatinine and urea levels tend to rise during treatment. If used in premature infants there is a risk of nephrocalcinosis/nephrolithiasis so renal function must be monitored and renal ultrasonography performed

• Glucose

Adverse effect on carbohydrate metabolism - exacerbation of existing carbohydrate intolerance or diabetes mellitus. Regular monitoring of blood glucose levels is desirable.

• Other electrolytes

Patients with hepatic failure/alcoholic cirrhosis are particularly at risk of hypomagnesemia (as well as hypokalaemia). During long-term therapy (especially at high doses) magnesium, calcium, chloride, bicarbonate and uric acid should be regularly measured.

Clinical monitoring requirements (see also section 4.8):

Regular monitoring for

• blood dyscrasias. If these occur, stop furosemide immediately

• liver damage

• idiosyncratic reactions

Excipient Warnings

This product contains:

Ethanol 10%v/v (alcohol) – each dose contains up to 0.4g of alcohol.

It is harmful to those suffering from alcoholism. It should be taken into account in pregnant and lactating women, children and other high-risk groups (those suffering from liver disease, epilepsy, brain injury or disease). It may modify or increase the effect of other medicines.

Liquid maltitol – patients with a rare hereditary problem of fructose intolerance should not take this medicine.

Quinoline Yellow (E104) – can cause allergic-type reactions including asthma. The allergy is more common in people who are allergic to aspirin.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Antihypertensives – enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors or Angiotensin II receptor antagonists can result in marked falls in blood pressure, furosemide should be stopped or the dose reduced before starting an ACE-inhibitor or Angiotensin II receptor antagonists (see section 4.4). Increased risk of first dose hypotension with post-synaptic alpha-blockers (eg prazosin).

Antipsychotics – furosemide-induced hypokalaemia increases the risk of cardiac toxicity. Avoid concurrent use with pimozide. Increased risk of ventricular arrhythmias with pimozide (avoid concurrent use), amisulpride or sertindole. Enhanced hypotensive effect with phenothiazines.

In placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone. No consistent pattern for cause of death was observed but caution should be exercised and the risks and benefits of this combination considered prior to the decision to use.

Anti-arrhythmics (including amiodarone, disopyramide, flecainide and sotalol) - risk of cardiac toxicity (because of furosemide-induced hypokalaemia). The effects of lidocaine, tocainide or mexiletine may be antagonised by furosemide.

Cardiac glycosides – hypokalaemia and electrolyte disturbances (including hypomagnesemia) increase the risk of cardiac toxicity.

Drugs that prolong Q-T interval – increased risk of toxicity with furosemide induced electrolyte disturbances.

Vasodilators – enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine.

Other diuretics – profound diuresis possible when furosemide given with metolazone. Increased risk of hypokalaemia with thiazides. Contraindicated with potassium sparing diuretics (eg amiloride spironolactone) - increased risk of hyperkalaemia (see section 4.3). Concurrent use with tetracyclines may increase the risk of rising BUN (see section 4.4 – monitoring).

Renin inhibitors – aliskiren reduces plasma concentrations of furosemide.

Nitrates – enhanced hypotensive effect.

Lithium - furosemide reduces lithium excretion with increased plasma lithium concentrations (risk of cardio- and/or neuro-toxicity). Avoid concomitant administration unless plasma levels are monitored.

Chelating agents – sucralfate may decrease the gastro-intestinal absorption of furosemide – the 2 drugs should be taken at least 2 hours apart.

NSAIDs – increased risk of nephrotoxicity (especially with pre-existing hypovolaemia/dehydration. Indometacin and ketorolac may antagonise the effects of furosemide (avoid if possible see section 4.4).

Salicylates – effects may be potentiated by furosemide. Salicylic toxicity may be increased by furosemide.

Antibiotics – increased risk of ototoxicity with aminoglycosides, polymixins or vancomycin - only use concurrently if compelling reasons. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide can decrease vancomycin serum levels after cardiac surgery. Increased risk of hyponatraemia with trimethoprim.

Antiviral – plasma concentrations of diuretics may be increased by nelfinavir, ritonavir or saquinavir.

Antidepressants – enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Increased risk of hypokalaemia with reboxetine.

Antidiabetics – hypoglycaemic effects antagonised by furosemide.

Antiepileptics – increased risk of hyponatraemia with carbamazepine. Diuretic effect reduced by phenytoin.

Antihistamines – hypokalaemia with increased risk of cardiac toxicity.

Antifungals – increased risk of hypokalaemia and nephrotoxicity with amphotericin.

Anxiolytics and hypnotics – enhanced hypotensive effect. Chloral hydrate or triclofos may displace thyroid hormone from binding site.

CNS stimulants (drugs used for ADHD) – hypokalaemia increases the risk of ventricular arrhythmias.

Corticosteroids – diuretic effect anatgonised (sodium retention) and increased risk of hypokalaemia.

Cytotoxics – increased risk of nephrotoxicity and ototoxicity with platinum compounds/cisplatin.

Anti-metabolites – effects of furosemide may be reduced by methotrexate and furosemide may reduce renal clearance of methotrexate.

Potassium salts – contraindicated - increased risk of hyperkalaemia (see section 4.3).

Dopaminergics – enhanced hypotensive effect with levodopa.

Immunomodulators – enhanced hypotensive effect with aldesleukin. Increased risk of hyperkalaemia with ciclosprin and tacrolimus. Increased risk of gouty arthritis with ciclosporin.

Muscle relaxants – enhanced hypotensive effect with baclofen or tizanidine. Increased effect of curare-like muscle relaxants.

Oestrogens – diuretic effect antagonised.

Progestogens (drospirenone) – increased risk of hyperkalaemia.

Prostaglandins – enhanced hypotensive effect with alprostadil.

Sympathomimetics – increased risk of hypokalaemia with high doses of beta₂ sympathomimetics.

Theophylline – enhanced hypotensive effect.

Probenecid –effects of furosemide may be reduced by probenecid and furosemide may reduce renal clearance of probenecid.

Anaesthetic agents – general anaesthetic agents may enhance the hypotensive effects of furosemide. The effects of curare may be enhanced by furosemide.

Warfarin and clofibrate – compete with furosemide in binding to serum albumin – possibly significant if this is low (eg nephrotic syndrome).

Aminoglutethimide – concomitant use may increase the risk of hyponatraemia.

Alcohol – enhanced hypotensive effect.

Laxative abuse - increases the risk of potassium loss.

4.6 Pregnancy And Lactation

Frusol must not be given during pregnancy unless there are compelling medical reasons.

Furosemide may inhibit lactation and may pass into breast milk. Women must not breastfeed if they are treated with furosemide.

4.7 Effects On Ability To Drive And Use Machines

Mental alertness may be reduced and the ability to drive or operate machinery may be impaired.

4.8 Undesirable Effects

The side effects are generally minor and Furosemide is well tolerated.

General

Side effects of a minor nature such as nausea, malaise, gastric upset (vomiting or diarrhoea) may occur but are not usually severe enough to necessitate withdrawal of treatment.

Disturbance of electrolytes and water balance (see also section 4.4).

Furosemide leads to increased excretion of sodium, chloride, water and other electrolytes (in particular potassium, calcium and magnesium). Symptomatic electrolyte disturbances and metabolic acidosis may develop either gradually or acutely (with higher furosemide doses). Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment.

Signs of electrolyte disturbances include increased thirst, headache, hypotension, confusion, muscle cramps, tetany, muscle weakness, disorders of cardiac rhythm and gastrointestinal symptoms.

The diuretic action of furosemide may lead to or contribute to hypovolaemia and dehydration, especially in dehydrated patients. Severe fluid depletion may lead to haemoconcentration with a tendency for thrombosis to develop.

Furosemide may cause a reduction in blood pressure which if pronounced may cause signs and symptoms such as impairment of concentration and reactions, light-headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance.

Other blood biochemistry

Treatment with furosemide may lead to transitory increases in blood creatinine and urea levels and to an increase in cholesterol and triglyceride levels. Serum levels of uric acid may increase and attacks of gout may occur (see section 4.4).

Bladder outlet obstruction

Increased production of urine may provoke or aggravate any obstruction of urinary outflow (including prostatic hyperplasia or narrowing of the urethra) and acute retention of urine with possible secondary complications may occur.

Haematological

Aplastic anaemia and bone marrow depression has been reported as a rare complication and necessitate withdrawal of treatment.

Occasionally, thrombocytopenia may occur with rare cases of leucopenia and eosinophilia, and isolated cases of agranulocytosis and haemolytic anaemia.

Tetany and reduced serum calcium

Serum calcium levels may be reduced; in very rare cases tetany has been observed. Nephrocalcinosis/nephrolithiasis has been reported in premature infants.

Control of glucose

Glucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to deterioration of metabolic control; latent diabetes mellitus may become manifest.

Hearing disorders

Hearing disorders and tinnitus, although usually transitory, may occur in rare cases, particularly in patients with renal failure with hypoproteinemia (e.g. in nephrotic syndrome.) See also section 4.4.

Anaphylaxis and allergic reactions

Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely. The incidence of allergic reactions such as skin rash, photosensitivity, vasculitis, fever, interstitial nephritis, or shock is very low but treatment should be withdrawn when these occur.

Hepato-biliary disorders

Pure intra hepatic cholestasis, hepatic function abnormal, increase in liver transaminases. Isolated cases of acute pancreatitis and jaundice have been reported after long term diuretic therapy.

Skin and mucous membrane

Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, erythema multiforme, exfoliative dermatitis, purpura. Steven-Johnson's syndrome, toxic epidermal necrolysis may occasionally occur.

Nervous system disorders

Rarely, paraesthesia may occur. Psychiatric disorder NOC.

Premature infants

If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus. Risk of nephrocalcinosis/nephroliathiasis (see Tetany and reduced serum calcium and section 4.4 re monitoring).

Renal and urinary disorders

Reduced diuresis, urinary incontinence.

Hepatic encephalopathy in patients with hepatocellular insufficiency may occur.

4.9 Overdose

Overdosing may lead to dehydration and electrolyte depletion through excessive diuresis. Severe potassium loss may lead to serious cardiac arrhythmias.

Treatment of overdose consists of fluid replacement and electrolyte imbalance correction.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group:

High-Ceiling Diuretic Sulfonamide - CO3C A 01

Furosemide is a potent loop diuretic which inhibits sodium and chloride reabsorption at the Loop of Henlé. The drug eliminates both positive and negative free water production. Furosemide acts at the luminal face of the epithelial cells by inhibiting co-transport mechanisms for the entry of sodium and chloride. Furosemide gains access to its site of action by being transported through the secretory pathway for organic acids in the proximal tubule. It reduces the renal excretion of uric acid. Furosemide causes an increased loss of potassium in the urine and also increases the excretion of ammonia by the kidney.

5.2 Pharmacokinetic Properties

When oral doses of Furosemide are given to normal subjects the mean bioavailability of the drug is approximately 52% but the range is wide. In plasma, Furosemide is extensively bound to proteins mainly to albumin. The unbound fraction in plasma averages 2 - 4% at therapeutic concentrations. The volume of distribution ranges between 170 - 270ml/Kg. The half life of the ß phase ranges from 45 - 60 min. The total plasma clearance is about 200ml/min. Renal excretion of unchanged drug and elimination by metabolism plus faecal excretion contribute almost equally to the total plasma clearance. Furosemide is in part cleared by the kidneys in the form of the glucuronide conjugate.

5.3 Preclinical Safety Data

Furosemide is a widely used diuretic which has been available for over thirty years and its safety profile in man is well established.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Ethanol, sodium hydroxide, quinoline yellow (E104), cherry flavour (containing ethanol and propylene glycol), liquid maltitol (E965), disodium hydrogen phosphate (E339), citric acid monohydrate (E330) and purified water.

6.2 Incompatibilities

None known

6.3 Shelf Life

24 months

3 months once open

6.4 Special Precautions For Storage

Store at or below 25°C.

6.5 Nature And Contents Of Container

Bottles:	Amber (Type III) glass
Closures:	a) Aluminium, EPE wadded, Roll-On Pilfer Proof Closures (ROPP)
	b) HDPE, EPE wadded, tamper evident
	c) HDPE, EPE wadded, tamper evident, child resistant
Capacity:	150ml, 200ml or 300ml.

6.6 Special Precautions For Disposal And Other Handling

Keep out of the reach of children.

Administrative Data

7. Marketing Authorisation Holder

Rosemont Pharmaceuticals Ltd

Yorkdale Industrial Park

Braithwaite Street

Leeds

LS11 9XE

UK

8. Marketing Authorisation Number(S)

00427/0109

9. Date Of First Authorisation/Renewal Of The Authorisation

6 April 1998 / 31/03/2003

10. Date Of Revision Of The Text

11/08/2011

Fucidin Ointment

Fucidin Ointment

sodium fusidate

Please 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 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 become serious, or you notice any side effects not listed in this
  leaflet please tell your doctor or pharmacist.

In this leaflet:

• 1. What Fucidin Ointment is and what it is used for


• 2. Before you use Fucidin Ointment


• 3. How to use Fucidin Ointment


• 4. Possible side effects


• 5. How to store Fucidin Ointment


• 6. Further information

What Fucidin Ointment Is And What It Is Used For

Fucidin Ointment contains sodium fusidate. It is a type of antibiotic.

Fucidin Ointment works by killing germs (bacteria) that cause infections.

Fucidin Ointment is used to treat conditions where the skin is infected by germs (bacteria), such as:

• Impetigo (a weeping, crusty and swollen patch of skin)


• Infected dermatitis (inflammation of the skin) and spots


• Infected cuts and grazes.

Before You Use Fucidin Ointment

Do not use Fucidin Ointment

• If you are allergic (hypersensitive) to fusidic acid or sodium fusidate.


• If you are allergic (hypersensitive) to any of the other ingredients in your medicine. You can find a list of these ingredients in section 6 of this leaflet.

Take special care with Fucidin Ointment

• Take special care if you are going to use this medicine near your eyes or the eyes of a child.


• If you use the ointment over a long time or in large amounts it may make the chance of getting any side effects higher. Also your skin may get more sensitive to this medicine.

Taking other medicines

Please tell your doctor or pharmacist if you are taking, or have recently taken any other medicines. This includes any medicines which you have bought without a prescription.

Pregnancy and breast-feeding

Please ask your doctor or pharmacist for advice before using Fucidin Ointment:

• If you are pregnant, or think you are pregnant. You must not use your medicine for a long time or in large amounts. You must ask your doctor for advice.


• If you are breast-feeding.

Tell your doctor if you become pregnant while using this medicine.

Driving and using machines

Usually your medicine will have very little effect on your ability to drive or use machines. Check with your doctor if you feel any side effect that may stop you from driving or using machines.

Important information about some of the ingredients of Fucidin Ointment

Fucidin Ointment contains:

• Lanolin (wool fat). This may give you an itchy rash and inflammation on your skin where your medicine is used.


• Cetyl alcohol. This may give you an itchy rash and inflammation on your skin where your medicine is used.

Please ask your doctor if you are worried about any of the ingredients in this medicine.

How To Use Fucidin Ointment

Always use Fucidin Ointment exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

How to put on Fucidin Ointment

This medicine is only for using on your skin or the skin of a child. Do not swallow it. Do not put it inside your body.

Remove the cap. Check the seal is not broken before you first use the ointment. Then push the spike in the cap through the seal on the tube.

Always wash your hands before using Fucidin Ointment. Rub the medicine gently on the skin. If you use it on your face be careful to avoid your eyes.

Unless you are using the ointment to treat your hands, always wash your hands after using Fucidin Ointment.

If you accidentally get any medicine in your eye, wash it out with cold water straight away. Then bathe your eye with eyewash if possible. Your eye may sting. If you start to have any problems with your sight or your eye is sore, contact your doctor immediately.

How much Fucidin Ointment to use

Your doctor will tell you how much Fucidin Ointment to use.

Usually, you should use this medicine three or four times each day.

If you have been told to cover the skin with any dressings or bandages you may not need to use the medicine so often. A nappy on a baby may act as a dressing. Follow the advice of your doctor.

If you forget to use Fucidin Ointment

If you forget to use this medicine, use it as soon as you remember. Then next use this medicine at the usual time.

If you have any further questions about using this medicine, please ask your doctor or pharmacist.

Fucidin Ointment Side Effects

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

Important side effects to look out for:

You must get urgent medical help if you have any of the following symptoms. You may be having an allergic reaction:

• You have difficulty breathing


• Your face or throat swell


• Your skin develops a severe rash.

Other possible side effects:

Skin problems

• Rash


• Stinging and irritation


• Itchy rash and skin inflammation in the area where the medicine is used.

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

How To Store Fucidin Ointment

• Keep out of the reach and the sight of children.


• Do not use Fucidin Ointment after the expiry date on the carton. The expiry date is the last day of that month.

Medicines should not be thrown away in waste water or in household waste. Please ask your pharmacist how to throw away any medicine you do not need any more. If you do this you will help protect the environment.

Further Information

What Fucidin Ointment contains

• The active ingredient is sodium fusidate 2%.


• The other ingredients are cetyl alcohol, lanolin (wool fat), liquid paraffin and white soft paraffin.

You can find important information about some of the ingredients in your medicine near the end of section 2 of this leaflet.

What Fucidin Ointment looks like and contents of the pack

Fucidin Ointment is an off white ointment.

Fucidin Ointment comes in tubes of 15 g and 30 g.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

LEO Laboratories Limited

Princes Risborough

Bucks.

HP27 9RR

UK

Manufacturer:

LEO Laboratories Limited

Dublin 12

Ireland

This leaflet was last revised in March 2008.

Registered Trade Mark

LEO

014156-03

Fosamax

1. Name Of The Medicinal Product

FOSAMAX® 10 mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 13.05 mg of alendronate sodium, which is the molar equivalent to 10 mg of alendronic acid.

Excipients:

Each tablet contains 103.95 mg lactose anhydrous.

For a full list of excipients see section 6.1

3. Pharmaceutical Form

Tablets

Oval white tablets marked with '936' on one side, and plain on the other.

4. Clinical Particulars

4.1 Therapeutic Indications

'Fosamax' is indicated for the treatment of osteoporosis in post-menopausal women to prevent fractures.

'Fosamax' is indicated for the treatment of osteoporosis in men to prevent fractures.

'Fosamax' is indicated for the treatment of glucocorticoid-induced osteoporosis and prevention of bone loss in post-menopausal women considered at risk of developing the disease.

Risk factors often associated with the development of osteoporosis include thin body build, family history of osteoporosis, early menopause, moderately low bone mass and long-term glucocorticoid therapy, especially with high doses (

4.2 Posology And Method Of Administration

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of ‘Fosamax’ on an individual patient basis, particularly after 5 or more years of use.

Treatment of osteoporosis in post-menopausal women: The recommended dosage is 10 mg once a day.

Treatment of osteoporosis in men: The recommended dosage is 10 mg once a day.

Treatment and prevention of glucocorticoid-induced osteoporosis: For post-menopausal women not receiving hormone replacement therapy (HRT) with an oestrogen, the recommended dosage is 10 mg once a day.

To permit adequate absorption of 'Fosamax':

'Fosamax' must be taken at least 30 minutes before the first food, beverage, or medication of the day with plain water only. Other beverages (including mineral water), food and some medications are likely to reduce the absorption of 'Fosamax' (see 4.5 'Interaction with other medicinal products and other forms of interaction').

To facilitate delivery to the stomach and thus reduce the potential for local and oesophageal irritation/adverse experiences (see 4.4 'Special warnings and precautions for use'):

• 'Fosamax' should only be swallowed upon arising for the day with a full glass of water (not less than 200 mls or 7 fl.oz.).

• Patients should only swallow 'Fosamax' whole. Patients should not crush or chew the tablet or allow the tablet to dissolve in their mouths because of a potential for oropharyngeal ulceration.

• Patients should not lie down until after their first food of the day which should be at least 30 minutes after taking the tablet.

• Patients should not lie down for at least 30 minutes after taking 'Fosamax'.

• 'Fosamax' should not be taken at bedtime or before arising for the day.

Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see 4.4 'Special warnings and precautions for use').

Use in the elderly: In clinical studies there was no age-related difference in the efficacy or safety profiles of 'Fosamax'. Therefore no dosage adjustment is necessary for the elderly.

Use in renal impairment: No dosage adjustment is necessary for patients with GFR greater than 35 ml/min. 'Fosamax' is not recommended for patients with renal impairment where GFR is less than 35 ml/min, due to lack of experience.

Use in children (under 18 years): Alendronate has been studied in a small number of patients with osteogenesis imperfecta under 18 years of age. Results are insufficient to support its use in children.

4.3 Contraindications

• Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.

• Inability to stand or sit upright for at least 30 minutes.

• Hypersensitivity to any component of this product.

• Hypocalcaemia (see 4.4 'Special warnings and precautions for use').

4.4 Special Warnings And Precautions For Use

'Fosamax' can cause local irritation of the upper gastro-intestinal mucosa. Because there is a potential for worsening of the underlying disease, caution should be used when 'Fosamax' is given to patients with active upper gastro-intestinal problems, such as dysphagia, oesophageal disease, gastritis, duodenitis or ulcers or with a recent history (within the previous year) of major gastro-intestinal disease such as peptic ulcer, or active gastro-intestinal bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty (see 4.3 'Contraindications'). In patients with known Barrett's oesophagus prescribers should consider the benefits and potential risks of alendronate on an individual patient basis.

Oesophageal reactions (sometimes severe and requiring hospitalisation), such as oesophagitis, oesophageal ulcers and oesophageal erosions, rarely followed by oesophageal stricture or perforation, have been reported in patients receiving 'Fosamax'. Physicians should therefore be alert to any signs or symptoms signalling a possible oesophageal reaction and patients should be instructed to discontinue 'Fosamax' and seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing or retrosternal pain, new or worsening heartburn.

The risk of severe oesophageal adverse experiences appears to be greater in patients who fail to take 'Fosamax' properly and/or who continue to take 'Fosamax' after developing symptoms suggestive of oesophageal irritation. It is very important that the full dosing instructions are provided to, and understood by the patient (see 4.2 'Posology and method of administration'). Patients should be informed that failure to follow these instructions may increase their risk of oesophageal problems.

While no increased risk was observed in extensive clinical trials, there have been rare (post-marketing) reports of gastric and duodenal ulcers, some severe and with complications.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.

The following risk factors should be considered when evaluating an individual's risk of developing osteonecrosis of the jaw:

• potency of the bisphosphonate (highest for zoledronic acid), route of administration (see above) and cumulative dose

• cancer, chemotherapy, radiotherapy, corticosteroids, smoking

• a history of dental disease, poor oral hygiene, periodontal disease, invasive dental procedures and poorly fitting dentures.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with poor dental status.

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

During bisphosphonate treatment, all patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain or swelling.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique, fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilaterial; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bishphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment. During bishphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

Bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. In post-marketing experience, these symptoms have rarely been severe and/or incapacitating (see '4.8 Undesirable effects'). The time to onset of symptoms varied from one day to several months after starting treatment. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.

'Fosamax' is not recommended for patients with renal impairment where GFR is less than 35 ml/min, (see 4.2 'Posology and method of administration').

Causes of osteoporosis other than oestrogen deficiency, ageing and glucocorticoid use should be considered.

Hypocalcaemia must be corrected before initiating therapy with alendronate (see 4.3 'Contra-indications'). Other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be effectively treated. In patients with these conditions, serum calcium and symptoms of hypocalcaemia should be monitored during therapy with 'Fosamax'.

Due to the positive effects of alendronate in increasing bone mineral, decreases in serum calcium and phosphate may occur especially in patients taking glucocorticoids in whom calcium absorption may be decreased. These are usually small and asymptomatic. However, there have been rare reports of symptomatic hypocalcaemia, which have occasionally been severe and often occurred in patients with predisposing conditions (e.g. hypoparathyroidism, vitamin D deficiency and calcium malabsorption). Ensuring adequate calcium and vitamin D intake is particularly important in patients receiving glucocorticoids.

Excipients

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of 'Fosamax'. Therefore, patients must wait at least 30 minutes after taking 'Fosamax' before taking any other oral medicinal product (see 4.2 'Posology and method of administration' and 5.2 'Pharmacokinetic properties')...

No other drug interactions of clinical significance are anticipated. Concomitant use of HRT (oestrogen ± progestin) and 'Fosamax' was assessed in two clinical studies of one or two years duration in post-menopausal osteoporotic women (5.1 'Pharmacodynamic properties, concomitant use with oestrogen/hormone replacement therapy (HRT)'). Combined use of 'Fosamax' and HRT resulted in greater increases in bone mass, together with greater decreases in bone turnover, than seen with either treatment alone. In these studies, the safety and tolerability profile of the combination was consistent with those of the individual treatments.

Since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with alendronate.

Although specific interaction studies were not performed, in clinical studies 'Fosamax' was used concomitantly with a wide range of commonly prescribed drugs without evidence of clinical adverse interactions (see 5.1 'Pharmacodynamic properties' 'Concomitant use with oestrogen/hormone replacement therapy (HRT)').

4.6 Pregnancy And Lactation

Use during pregnancy

Alendronate should not be used during pregnancy. There are no adequate data from the use of alendronate in pregnant women. Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/fetal development, or postnatal development. Alendronate given during pregnancy in rats caused dystocia related to hypocalcemia (see 5.3 'Preclinical safety data').

Use during lactation

It is not known whether alendronate is excreted into human breast-milk. Alendronate should not be used by breast-feeding women.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines has been performed. However, certain adverse reactions that have been reported with 'Fosamax' may affect some patients' ability to drive or operate machinery. Individual responses to 'Fosamax' may vary (see section 4.8).

4.8 Undesirable Effects

'Fosamax' has been studied in nine major clinical studies (n=5,886). In the longest running trials in post-menopausal women up to five years experience has been collected. Two years safety data are available in both men with osteoporosis and men and women on glucocorticoids.

The following adverse experiences have been reported during clinical studies and/or post-marketing use:

[Common ()]

Immune system disorders:
Rare:	hypersensitivity reactions including urticaria and angioedema
Metabolism and nutrition disorders:
Rare:	symptomatic hypocalcaemia, often in association with predisposing conditions. (see section 4.4)
Nervous system disorders:
Common:	headache
Eye disorders:
Rare:	uveitis, scleritis, episcleritis
Gastrointestinal disorders:
Common:	abdominal pain, dyspepsia, constipation, diarrhoea, flatulence, oesophageal ulcer*, dysphagia*, abdominal distension, acid regurgitation
Uncommon:	nausea, vomiting, gastritis, oesophagitis*,oesophageal erosions*, melena
Rare:	oesophageal stricture*, oropharyngeal ulceration*, upper gastrointestinal PUBs (perforation, ulcers, bleeding)(see section 4.4)
*See sections 4.2 and 4.4
Skin and subcutaneous tissue disorders:
Uncommon:	rash, pruritus, erythema
Rare:	rash with photosensitivity
Very rare and isolated cases:	isolated cases of severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis
Musculoskeletal, connective tissue and bone disorders:
Common:	musculoskeletal (bone, muscle or joint) pain
Rare:	Osteonecrosis of the jaw (see section 4.4); severe musculoskeletal (bone, muscle or joint) pain (see 4.4 'Special warnings and precautions for use'); atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction)
General disorders and administration site conditions:
Rare:	transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically in association with initiation of treatment.
During post-marketing experience the following reactions have been reported (frequency unknown):
Nervous system disorders:	dizziness, dysgeusia
Ear and labyrinth disorders:	vertigo
Skin and subcutaneous tissue disorders:	alopecia
Musculoskeletal, connective tissue and bone disorders:
	joint swelling.
General disorders and administration site conditions:
	asthenia, peripheral oedema

Laboratory test findings

In clinical studies, asymptomatic, mild and transient decreases in serum calcium and phosphate were observed in approximately 18 and 10%, respectively, of patients taking 'Fosamax' versus approximately 12 and 3% of those taking placebo. However, the incidences of decreases in serum calcium to <8.0 mg/dl (2.0 mmol/l) and serum phosphate to

4.9 Overdose

No specific information is available on the treatment of overdosage with 'Fosamax'. Hypocalcaemia, hypophosphataemia and upper gastro-intestinal adverse events, such as upset stomach, heartburn, oesophagitis, gastritis, or ulcer, may result from oral overdosage. Milk or antacids should be given to bind alendronate. Owing to the risk of oesophageal irritation, vomiting should not be induced and the patient should remain fully upright.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

'Fosamax' is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation. The bone formed during treatment with 'Fosamax' is of normal quality.

Treatment of post-menopausal osteoporosis

The effects of 'Fosamax' on bone mass and fracture incidence in post-menopausal women were examined in two initial efficacy studies of identical design (n=994) as well as in the Fracture Intervention Trial (FIT: n=6,459).

In the initial efficacy studies, the mean bone mineral density (BMD) increases with 'Fosamax' 10 mg/day relative to placebo at three years were 8.8%, 5.9% and 7.8% at the spine, femoral neck and trochanter, respectively. Total body BMD also increased significantly. There was a 48% reduction in the proportion of patients treated with 'Fosamax' experiencing one or more vertebral fractures relative to those treated with placebo. In the two-year extension of these studies BMD at the spine and trochanter continued to increase and BMD at the femoral neck and total body were maintained.

FIT consisted of two placebo-controlled studies: a three-year study of 2,027 patients who had at least one baseline vertebral (compression) fracture and a four-year study of 4,432 patients with low bone mass but without a baseline vertebral fracture, 37% of whom had osteoporosis as defined by a baseline femoral neck BMD at least 2.5 standard deviations below the mean for young, adult women. In all FIT patients with osteoporosis from both studies, 'Fosamax' reduced the incidence of:

Overall these results demonstrate the consistent effect of 'Fosamax' to reduce the incidence of fractures, including those of the spine and hip, which are the sites of osteoporotic fracture associated with the greatest morbidity.

Prevention of post-menopausal osteoporosis

The effects of 'Fosamax' to prevent bone loss were examined in two studies of post-menopausal women aged

Concomitant use with oestrogen/hormone replacement therapy (HRT)

The effects on BMD of treatment with 'Fosamax' 10 mg once-daily and conjugated oestrogen (0.625 mg/day) either alone or in combination were assessed in a two-year study of hysterectomised, post-menopausal, osteoporotic women. At two years, the increases in lumbar spine BMD from baseline were significantly greater with the combination (8.3%) than with either oestrogen or 'Fosamax' alone (both 6.0%).

The effects on BMD when 'Fosamax' was added to stable doses (for at least one year) of HRT (oestrogen ± progestin) were assessed in a one-year study in post-menopausal, osteoporotic women. The addition of 'Fosamax' 10 mg once-daily to HRT produced, at one year, significantly greater increases in lumbar spine BMD (3.7%) vs. HRT alone (1.1%).

In these studies, significant increases or favourable trends in BMD for combined therapy compared with HRT alone were seen at the total hip, femoral neck and trochanter. No significant effect was seen for total body BMD.

Treatment of osteoporosis in men

The efficacy of 'Fosamax' 10 mg once daily in men (ages 31 to 87; mean, 63) with osteoporosis was demonstrated in a two-year study. At two years, the mean increases relative to placebo in BMD in men receiving 'Fosamax' 10 mg/day were: lumbar spine, 5.3%; femoral neck, 2.6%; trochanter, 3.1%; and total body, 1.6%. 'Fosamax' was effective regardless of age, race, gonadal function, baseline rate of bone turnover, or baseline BMD. Consistent with much larger studies in post-menopausal women, in these 127 men, 'Fosamax' 10 mg/day reduced the incidence of new vertebral fracture (assessed by quantitative radiography) relative to placebo (0.8% vs. 7.1%) and, correspondingly, also reduced height loss (-0.6 vs. -2.4 mm).

Glucocorticoid-induced osteoporosis

The efficacy of 'Fosamax' 5 and 10 mg once-daily in men and women receiving at least 7.5 mg/day of prednisone (or equivalent) was demonstrated in two studies. At two years of treatment, spine BMD increased by 3.7% and 5.0% (relative to placebo) with 'Fosamax' 5 and 10 mg/day respectively. Significant increases in BMD were also observed at the femoral neck, trochanter, and total body. In post-menopausal women not receiving oestrogen, greater increases in lumbar spine and trochanter BMD were seen in those receiving 10 mg 'Fosamax' than those receiving 5 mg. 'Fosamax' was effective regardless of dose or duration of glucocorticoid use. Data pooled from three dosage groups (5 or 10 mg for two years or 2.5 mg for one year followed by 10 mg for one year) showed a significant reduction in the incidence of patients with a new vertebral fracture at two years ('Fosamax' 0.7% vs. placebo 6.8%).

5.2 Pharmacokinetic Properties

Absorption

Relative to an intravenous (IV) reference dose, the oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardised breakfast. Oral bioavailability in men (0.6%) was similar to that in women. Bioavailability was decreased similarly to an estimated 0.46% and 0.39% when alendronate was administered one hour or half an hour before a standardised breakfast. In osteoporosis studies, 'Fosamax' was effective when administered at least 30 minutes before the first food or beverage of the day.

Bioavailability was negligible whether alendronate was administered with, or up to two hours after, a standardised breakfast. Concomitant administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.

In healthy subjects, oral prednisone (20 mg three times daily for five days) did not produce a clinically meaningful change in oral bioavailability of alendronate (a mean increase ranging from 20% to 44%).

Distribution

Studies in rats show that alendronate transiently distributes to soft tissues following 1 mg/kg IV administration but is then rapidly redistributed to bone or excreted in the urine. The mean steady-state volume of distribution, exclusive of bone, is at least 28 litres in humans. Concentrations of drug in plasma following therapeutic oral doses are too low for analytical detection (<5 ng/ml). Protein binding in human plasma is approximately 78%.

Biotransformation

There is no evidence that alendronate is metabolised in animals or humans.

Elimination

Following a single IV dose of [¹⁴C] alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the faeces. Following a single 10 mg IV dose, the renal clearance of alendronate was 71 ml/min, and systemic clearance did not exceed 200 ml/min. Plasma concentrations fell by more than 95% within six hours following IV administration. The terminal half-life in humans is estimated to exceed ten years, reflecting release of alendronate from the skeleton. Alendronate is not excreted through the acidic or basic transport systems of the kidney in rats, and thus it is not anticipated to interfere with the excretion of other drugs by those systems in humans.

Characteristics in patients

Preclinical studies show that the drug that is not deposited in bone is rapidly excreted in the urine. No evidence of saturation of bone uptake was found after chronic dosing with cumulative IV doses up to 35 mg/kg in animals. Although no clinical information is available, it is likely that, as in animals, elimination of alendronate via the kidney will be reduced in patients with impaired renal function. Therefore, somewhat greater accumulation of alendronate in bone might be expected in patients with impaired renal function (see 4.2 'Posology and method of administration').

5.3 Preclinical Safety Data

In test animal species the main target organs for toxicity were kidneys and gastro-intestinal tract. Renal toxicity was seen only at doses >2 mg/kg/day orally (ten times the recommended dose) and was evident only on histological examination as small widely scattered foci of nephritis, with no evidence of effect on renal function. The gastro-intestinal toxicity, seen in rodents only, occurred at doses >2.5 mg/kg/day and appears to be due to a direct effect on the mucosa. There is no additional relevant information.

Significant lethality after single oral doses was seen in female rats and mice at 552 mg/kg (3,256 mg/m²) and 966 mg/kg (2,898 mg/m²) (equivalent to human oral doses* of 27,600 and 48,300 mg), respectively. In males, these values were slightly higher, 626 and 1,280 mg/kg, respectively. There was no lethality in dogs at oral doses up to 200 mg/kg (4,000 mg/m²) (equivalent to a human oral dose^* of 10,000 mg).

* Based on a patient weight of 50 kg.

6. Pharmaceutical Particulars

6.1 List Of Excipients

10 mg tablets: microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, magnesium stearate and carnauba wax.

6.2 Incompatibilities

None known.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

Blisters of opaque white PVC lidded with aluminium foil.

Pack size: 28 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Merck Sharp & Dohme Limited

Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK

8. Marketing Authorisation Number(S)

10 mg tablets: PL 0025/0326

9. Date Of First Authorisation/Renewal Of The Authorisation

10 mg tablets: 28 July 1995/ 3 June 2008

10. Date Of Revision Of The Text

October 2011

LEGAL CATEGORY

P.O.M.

© Merck Sharp & Dohme Limited 2011. All rights reserved.

SPC.FSM.11.UK.3440

Frusol 40mg / 5ml Oral Solution

Frusol 40mg/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 40mg/5ml Oral Solution and what is it used for


• 2. Before you take Frusol 40mg/5ml Oral Solution


• 3. How to take Frusol 40mg/5ml Oral Solution


• 4. Possible side effects


• 5. How to store Frusol 40mg/5ml Oral Solution


• 6. Further information

What is Frusol 40mg/5ml Oral Solution and what is it used for

The name of your medicine is Frusol 40mg/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 40mg/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 40mg/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 40mg 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 (one 5ml spoonful) 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 40mg/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 40mg/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 40mg/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.

P0453

Folic Acid 5mg Tablets (Wockhardt UK Ltd)

FOLIC ACID 5MG TABLETS

Please read this leaflet carefully before you start to take this medicine. It gives an outline of the more important things you should know. If you want to know more about this medicine, or you are not sure about anything, ask your doctor or pharmacist. You should keep this leaflet throughout your course of treatment.

The Name Of Your Medicine Is Folic Acid 5Mg Tablets

Folic Acid 5mg Tablets contain the active ingredient folic acid. The tablet comes in one strength, 5mg.

Other ingredients in your tablet are lactose, maize starch, acacia spray-dried, magnesium stearate and stearic acid.

Folic Acid 5mg Tablets are plain yellow, biconvex tablets with breakline on one face and CP on the reverse.

Folic Acid 5mg Tablets are available in polypropylene or polyethylene tablet containers containing 100, 500 or 1000 tablets, glass bottles containing 100, 500 or 1000 tablets and blister packs containing 28 tablets.

Marketing Authorisation Holder:

Wockhardt UK Limited

Ash Road North

Wrexham

LL13 9UF

UK

Manufacturer:

CP Pharmaceuticals Limited

Ash Road North

Wrexham

LL13 9UF

UK

How Does Your Medicine Work?

Folic acid is a vitamin used to prevent or treat a deficiency (lack) of folic acid in the body.

What Are Folic Acid 5Mg Tablets For?

Folic Acid 5mg Tablets are used in adults and children for the treatment and prevention of folic acid deficiency which causes anaemia. This tends to occur in pregnancy, in patients on kidney dialysis and during treatment with some medicines.

Folic acid is also given to some women before and during pregnancy to prevent spina bifida (an abnormality of the spine) in babies, which can be caused by deficiency of this vitamin.

Before Taking This Medicine

You should not take Folic Acid 5mg Tablets if you have ever had a reaction to or been told that you are allergic to folic acid or any of the other ingredients in the tablet. Check by reading the list of ingredients above.

Before taking this medicine, you should let your doctor know if you are pregnant or breast-feeding or wish to become pregnant or start breast-feeding.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Taking another medicine while you are taking folic acid can affect how it or the other medicine works. Make sure that your doctor knows what other medicines you are taking. Do not take any other medicines while you are taking Folic Acid 5mg Tablets unless you have told your doctor or pharmacist and asked their advice. This includes medicines you may have bought yourself.

Examples of medicines that can affect Folic Acid 5mg Tablets are;

• Certain antibiotics (trimethoprim and sulphonamides, sometimes combined as co-trimoxazole).


• Some drugs used in the treatment of epilepsy (phenytoin, phenobarbital and primidone).


• Fluorouracil, a drug used to treat certain tumours.


• Some indigestion remedies (edible clay and antacids containing aluminium or magnesium). Allow at least a two hour gap between taking your Folic Acid Tablets and indigestion remedies.


• Preparations containing zinc such as vitamins or food supplements (this may be important in pregnancy).

If you have any doubts about whether you should take this medicine then talk to your doctor.

Advice When Taking Folic Acid 5Mg Tablets

• Patients with pernicious anaemia (or the possibility of pernicious anaemia) should be given Vitamin B12 as well as folic acid.


• Care needs to be taken in patients with certain tumours.

Taking This Medicine

In adults and children over one year, the usual dose of Folic Acid 5mg Tablets is one tablet a day for the treatment of anaemia or one tablet every one to seven days for the prevention of anaemia.

Children under one year should be given 500 micrograms per kilogram of body weight daily.

The usual dose for the prevention of spina bifida is one tablet a day, starting before conception and continuing for the first three months of pregnancy.

To obtain a tablet, press on the tablet from the blister (or bubble) side, pushing it through the foil. Do not remove the tablet from the blister until you are ready to take it.

Your doctor will decide the dose that is best for you. Always follow your doctor's instructions completely. Also, follow any instructions or warnings that appear on the label that the pharmacist may put on the pack. If you do not understand, or are in any doubt, ask your doctor or pharmacist.

Unless told otherwise, take your tablet with water.

You should take your medicine for as long as your doctor tells you to. If you forget to take a dose, take another as soon as you remember. If it is almost time for your next dose, then do not take the missed dose at all. Never double the next dose to make up for the one missed. Do not stop taking the medicine without talking to your doctor first.

If you accidentally take too many tablets you should contact your doctor, pharmacist or nearest hospital casualty department immediately. Take this leaflet and any tablets you have left to show the doctor or pharmacist.

Are There Any Side-Effects?

Like many medicines Folic Acid 5mg Tablets may cause side-effects in some patients, particularly when you first start taking them. The side-effects that some other patients have had with Folic Acid 5mg Tablets include loss of appetite, feeling sick, bloating of the stomach and wind. Allergic reactions are rare.

If you experience any other side-effects or feel that the medicine is affecting you badly, tell your doctor or pharmacist.

Safe Keeping For This Medicine

Do not take this medicine if the expiry date on the label has passed or if the tablets show signs of “going off” such as discoloration.

These tablets should not be stored above 25°C. Store in the original package in order to protect from light. Do not transfer Folic Acid 5mg Tablets to another container.

Keep Folic Acid 5mg Tablets out of the reach and sight of children.

Remember this medicine is for you only. Never give it to anyone else. It may harm them, even if their symptoms are the same as yours.

Unless your doctor tells you to, do not keep medicines that you no longer need. Give them back to your pharmacist.

Other formats:

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge:

0800 198 5000 (UK Only)

Please be ready to give the following information:

Product Name

Folic Acid 5mg Tablets

Reference Number

29831/0097

This is a service provided by the Royal National Institute of the Blind.

DATE OF REVISION September 2007

CP1

103583/1