SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Bumetanide 0.2 mg/ml Oral Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 0.2 mg bumetanide.

3    PHARMACEUTICAL FORM

Oral solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Bumetanide is indicated whenever diuretic therapy is required in the treatment of oedema, e.g. that associated with congestive heart failure, cirrhosis of the liver and renal disease including the nephrotic syndrome.

4.2 Posology and method of administration

For oral administration.

Adults:    Usually 1 mg (5 ml) as a single oral dose given morning or

early evening.The dosage should be adjusted according to the patient's response.

Not recommended for children under 12 years of age.

Elderly:    Adjust dosage according to response: a dose of 0.5 mg

bumetanide per day may be sufficient in some elderly patients.

4.3 Contraindications

Although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea or the development of oliguria or anuria during treatment of severe progressing renal disease are indications for stopping treatment with bumetanide.

Hypersensitivity to any of the ingredients. Bumetanide is contra-indicated in hepatic coma and care should be taken in states of severe electrolyte depletion.

As with other diuretics, bumetanide should not be administered concurrently with lithium salts. Diuretics can reduce lithium clearance resulting in high serum levels of lithium.

4.4 Special warnings and precautions for use

Excessively rapid mobilisation of oedema particularly in elderly patients may give rise to sudden changes in cardiovascular pressure flow relationships with circulatory collapse. This should be borne in mind when bumetanide is given in high doses. Electrolyte disturbances may occur, particularly in those patients taking a low salt diet. Regular checks of serum electrolytes, in particular sodium, potassium, chloride and bicarbonate should be performed and replacement therapy instituted where indicated.

As with other diuretics, bumetanide may cause an increase in blood uric acid. Periodic checks on urine and blood glucose should be made in diabetics and patients suspected of latent diabetes (see section 4.5).

Patients with chronic renal failure on high doses of bumetanide should remain under constant hospital supervision.

Caution is advised when used in patients with hypotension and in patients with porphyria.

Caution should be exercised when used in patients with hepatic impairment as there may be increased risk of encephalopathy.

Bumetanide should be used with caution in patients already receiving nephrotoxic or ototoxic drugs.

In patients with known hypersensitivity to sulfonamides or thiazides there may be a potential risk of hypersensitivity to bumetanide.

Bumetanide found in urine by doping test is cause for disqualification of athletes.

4.5 Interaction with other medicinal products and other forms of interaction

Like other diuretics, bumetanide shows a tendency to increase the excretion of potassium which can lead to an increase in the sensitivity of the myocardium to the toxic effects of digitalis. Thus the dose may need adjustment when given in conjunction with cardiac glycosides.

Bumetanide may potentiate the effects of antihypertensive drugs. Therefore, the dose of the latter may need adjustment when bumetanide is used to treat oedema in hypertensive patients.

Certain non-steroidal anti-inflammatory drugs have been shown to antagonise the action of diuretics.

4.6 Pregnancy and lactation

Pregnancy: There are no adequate data from the use of Bumetanide in pregnant women. Bumetanide should not be used during pregnancy unless clearly necessary. It may be used only when the potential benefit justifies the potential risk to the foetus.

Lactation: There is insufficient information on the excretion of Bumetanide in human or animal breast milk. Therefore Bumetanide should not be taken by nursing mothers.

4.7 Effects on ability to drive and use machines

Patients who experience dizziness or fatigue should not drive or operate machinery.

4.8 Undesirable effects

The following side effects, listed below by system organ class, have been reported to be associated with bumetanide use. Since only post marketing data are available, the frequency for these side effects is unknown.

Blood and lymphatic system disorders

Thrombocytopenia, leukopenia, bone marrow failure, agranulocytosis

Immune system disorders

Hypersensitivity

Metabolism and nutrition disorders

Electrolyte imbalance, for example:

Hypokalaemia, hyponatraemia, dehydration, hypomagnesaemia, gout, hyperuricaemia, alkalosis hypochloraemic, hyperglycaemia, hypocalcaemia, hyperlipidaemia

Nervous system disorders

Headache, dizziness

Ear and labyrinth disorders

Tinnitus, deafness

Vascular disorders

Orthostatic hypotension, hypotension

Gastrointestinal disorders

Gastrointestinal disorder, for example:

Nausea, vomiting, diarrhoea, abdominal pain

Hepatobiliary system disorders

Cholestasis, jaundice

Skin and subcutaneous tissue disorders

Rash*, urticaria, dermatitis, photosensitivity reaction, pruritus

*Various types of rash reactions such as erythematous, maculo-papular and pustular have been reported.

Musculoskeletal, connective tissue and bone disorders

Myalgia, muscle spasm, arthralgia

Renal and urinary disorders

Renal failure acute

Reproductive system and breast disorders

Gynaecomastia, breast pain

General disorders and administrative site conditions

Fatigue

Investigations

Blood creatinine increased

High Dose Therapy

In patients with severe chronic renal failure given high doses of bumetanide, there have been reports of severe, generalised, musculoskeletal pain sometimes associated with muscle spasm, occurring one or two hours after administration and lasting up to 12 hours. The lowest reported dose causing this type of adverse reaction was 5 mg by intravenous injection and the highest was 75 mg orally in a single dose. All patients recovered fully and there was no deterioration in their renal function. The cause of this pain is uncertain but it may be a result of varying electrolyte gradients at the cell membrane level.

Experience suggests that the incidence of such reactions is reduced by initiating treatment at 5-10 mg daily and titrating upwards using a twice daily dosage regimen at doses of 20 mg per day or more.

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.

4.9 Overdose

Symptoms would be those caused by excessive diuresis. Empty stomach by gastric lavage or emesis. General measures should be taken to restore blood volume, maintain blood pressure and correct electrolyte disturbance.

Pharmacodynamic properties

Bumetanide is a potent, high ceiling diuretic with a rapid onset and a short duration of action.

5.2 Pharmacokinetic properties

After oral administration of 1 mg bumetanide, diuresis begins within 30 minutes with a peak effect between one and two hours. The diuretic effect is virtually complete in three hours after a 1 mg dose.

In most patients 1 mg of bumetanide produces a similar diuretic effect to 40 mg of furosemide.

Bumetanide is well absorbed after oral administration. Bumetanide excretion in the urine shows a good correlation with the diuretic response. In patients with chronic renal failure, the liver takes more importance as an excretory pathway, although the duration of action in such patients is not markedly prolonged.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Methyl parahydroxybenzoate, propyl parahydroxybenzoate, sorbitol, xanthan gum, sodium citrate, patent blue V, quinoline yellow, peppermint flavour, purified water.

6.2 Incompatibilities

None known.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

Amber glass bottles, with plastic screw caps, of 5, 10, 25 and 150 ml. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

None.

7    MARKETING AUTHORISATION HOLDER

CHEMIDEX PHARMA LTD T/A ESSENTIAL GENERICS 7 EGHAM BUSINESS VILLAGE CRABTREE ROAD EGHAM

SURREY, TW20 8RB UNITED KINGDOM

8    MARKETING AUTHORISATION NUMBER(S)

PL 17736/0132

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/05/2012

10    DATE OF REVISION OF THE TEXT

20/04/2016