SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Diuresal¹ Tablets 40mg or Frusemide Tablets 40mg

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains frusemide BP 40mg.

3    PHARMACEUTICAL FORM

Tablet

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Furosemide is a diuretic for the management of oedema of cardiac, renal or hepatic origin, pulmonary oedema, toxaemia of pregnancy, and mild or moderate hypertension.

4.2 Posology and method of administration

Initial dosage 1 tablet daily. This is then adjusted to the minimum effective dose which can range from % tablet (20mg) on alternate days to 2 tablets (80mg) or more in resistant oedema.

Children

1mg to 3mg per kilogram body weight daily up to a maximum of 40mg/day. Elderly:

Furosemide is eliminated more slowly in the elderly. Dosage should be adjusted according to the observed clinical response.

Method of administration: Oral.

4.3 Contraindications

Hypersensitivity to Furosemide, any of the other ingredients in this medicine, sulphonamides, sulphonamide derivatives/amiloride.

Furosemide tablets are contraindicated in electrolyte disturbances (severe hyponatraemia: severe hypokalaemia, hypovolaemia), dehydration and/ or hypotension.

Concomitant potassium supplements or potassium sparing diuretics (see section 4.5). Anuria and impaired renal function (creatinine clearance below 30mL/min per 1.73 m2 body surface area) and renal failure resulting from poisoning by nephrotoxic and/or hepatotoxic agents.

Digitalis intoxication (see also section 4.5).

Pre comatose states associated with hepatic cirrhosis or encephalopathy.

Addison's disease

Breast-feeding women (see section 4.6).

4.4 Special Warnings and Precautions for Use

Hypotension and/or hypovolaemia (see also section 4.3).

These and any acid-base disturbances should be corrected before furosemide is started.

Dose titration/adjustment (see section 4.2)

•    Patients with hypoproteinaemia (such as that associated with the nephotic syndrome) require careful dose titration (reduced furosemide effect: increased risk of ototoxicity)

•    In moderate liver congestion dosage adjustment may be needed.

Caution required:

Caution needed in the following circumstances

•    impaired hepatic function (see sections 4.2 & 4.3 and below - monitoring required)

•    impaired renal function and hepato-renal syndrome (see section 4.3 and below -monitoring required)

•    diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase)

•    elderly patients ¹

•    gout (increased risk of hyperuricaemia)

•    patients at risk of pronounced falls in blood pressure.

Clinical monitoring requirements (see also section 4.8):

Regular monitoring for

•    blood dyscrasias. If these occur, stop furosemide immediately

•    liver damage

•    idiosyncratic reactions.

In premature infants there is a risk of development of nephrocalcinosis/nephrolithiasis. Renal function must be monitored and renal ultrasonography performed.

Laboratory monitoring requirements:

•    frequent BUN (blood urea nitrogen test) in first few months of treatment, periodically thereafter

•    serum electrolytes with replacement as appropriate.

Other alterations in lab values

•    Serum creatinine and urea levels tend to rise during treatment

•    Serum cholesterol and triglycerides may rise but usually return to normal within 6 months of starting furosemide

•    Furosemide should be discontinued before a glucose tolerance test.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Toxic effects of nephrotoxic antibiotics may be increased by concomitant administration of potent diuretics such as furosemide. Interactions have also been reported with ototoxic antibiotics.

Dosage of concurrently administrated cardiac glycosides or anti-hypertensive agents may require adjustment.

If ACE inhibitors are given with furosemide treatment a fall in blood pressure may occur. The furosemide dosage should be reduced or stopped before giving an ACE inhibitor.

Latent diabetes may become manifest or the insulin requirements of diabetic patients may increase.

Certain NSAIDs have been shown to attenuate the action of furosemide and may cause renal failure in cases of pre-existing hypovolaemia.

Furosemide attenuates the action of some drugs (e.g. the effects of antidiabetics) and-necessitate increased dosage of insulin for diabetic patients. Furosemide may potentiate the effects of theophylline, salicylates and curare-type muscle relaxants.

Glucocorticoids may cause sodium retention and exacerbate potassium loss.

In common with other diuretics serum lithium levels may be increased when lithium is administered concomitantly, necessitating adjustment of the lithium dose.

Acute pancreatitis has been reported with high-dose parenteral furosemide.

In cases of laxative abuse the risk of an increased potassium loss should be borne in mind.

| 4.6 Pregnancy and lactation    Deleted: n

The teratogenic and embryotoxic potential of furosemide in humans is unknown.

There is little evidence of safety of high-dose furosemide in human pregnancy, although the results of animal work, in general, show no hazardous effects.

The drug should not be used in pregnant women unless the benefits to the patient outweigh the possible risk to the foetus which includes persistence of patent ductus arteriosus (section 4.8).

Furosemide may inhibit lactation or may pass into the breast milk, it should therefore be used with caution in nursing mothers.

4.7 Effects on ability to drive and use machines

Nausea has been reported to occur with Furosemide.

Reduced alertness may impair ability to drive or operate machinery.

4.8 Undesirable Effects

Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).

		concentration and reactions, lightheadedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance).
	Uncommon:	hypotension, hypovolaemia
	Rare:	vasculitis, thrombosis, shock
Gastrointestinal disorders:	Uncommon:	dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhoea, constipation
	Rare:	acute pancreatitis (in long-term diuretic treatment, including furosemide).
Hepatobiliary disorders:	Rare:	pure intrahepatic cholestasis (jaundice), hepatic function abnormal.
Skin and subcutaneous tissue disorders:	Rare:	rash, pruritus, photosensitivity, toxic epidermal necrolysis.
	Frequency not known:	urticaria, erythema multiforme, purpura, exfoliative dermatitis, itching, allergic reactions, such as skin rashes, various forms of dermatitis including urticaria, bullous lesions. When these occur treatment should be withdrawn.
Musculoskeletal and connective tissue disorders:	Uncommon:	muscle cramps, muscle weakness.
Renal and urinary disorders:	Uncommon:	reduced diuresis, urinary incontinence, urinary obstruction (in patients with hyperplasia of the prostate, bladder inability to empty, urethral stricture unspecified).
	Rare:	nephrocalcinosis (in pre-term infants treated with Furosemide), interstitial nephritis, acute renal failure.
Congenital, familial and genetic disorders:	Rare:	patent ductus arteriosus
General disorders and administration site conditions:	Uncommon:	Fatigue
	Rare:	malaise, fever, severe anaphylactoid or anaphylactic reactions (e.g. with

		shock).
	Frequency not known:	hypovolaemia,
Investigations:	Common:	creatinine increased, blood urea increased
	Rare:	Transaminases increased, blood

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

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4.9 Overdosage

Symptoms include dehydration and electrolyte depletion due to excessive diuresis. In cirrhotic patients, overdosage may precipitate hepatic coma.

Treatment should be aimed at fluid replacement and correction of the electrolyte imbalance. The drug should be discontinued and electrolyte and water replacement instituted immediately; adjustment should be on the basis of careful monitoring.

5.1 Pharmacodynamic properties

ATC code: CO3C A01

The evidence from many experimental studies suggests that furosemide acts along the entire nephron with the exception of the distal exchange site. The main effect is on the ascending limb of the loop of Henley with a complex effect on renal circulation. Blood-flow is diverted from the juxta-medullary region to the outer cortex.

The principle renal action of furosemide is to inhibit active chloride transport in the thick ascending limb. Re-absorption of sodium chloride from the nephron is reduced and a hypotonic or isotonic urine produced.

It has been established that prostaglandin (PG) biosynthesis and the renin-angiotensin system are affected by furosemide administration and that furosemide alters the renal | permeability of the glomerulus to serum proteins.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to | that already included in other sections of the SPC.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose Maize starch Pregelatinised starch Talc

Magnesium stearate Microcrystalline cellulose.

6.2 Incompatibilities

Not known.

6.3 Shelf life

Blister pack: 36 months

6.4    Special precautions for storage

Blister pack: Do not store above 25°C. Store in the original package.

6.5    Nature and contents of container

Blister pack (opaque blister strips: 250pm PVC with 60gsm PVDC coating, with 20 pm aluminium foil backing): Pack size 28

6.6    Special precautions for disposal

Not applicable.

7 MARKETING AUTHORISATION HOLDER

Ennogen Pharma Limited Unit G4,

Riverside Industrial Estate,

Riverside Way, Dartford DA1 5BS UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 40147/0039

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/08/2012

10 DATE OF REVISION OF THE TEXT

16/04/2014

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   difficulty with micturition/potential obstruction in the urinary tract including prostatic hypertrophy (increased risk of acute retention)