BUMETANIDE LIQUID 0.2 MG / ML ORAL SOLUTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Bumetanide Liquid 0.2 mg/ml oral solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 0.2 mg bumetanide.

Excipient(s) with known effect

Each ml of this medicine contains 275 mg sorbitol, 1.5 mg methyl parahydroxybenzoate and 0.15 mg propyl parahydroxyben­zoate.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral solution.

Bumetanide oral solution is a clear, green liquid with the flavour of peppermint.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Bumetanide Liquid 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

Posology

Adults, adolescents and children aged 12 years and older

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.

Elderly

Adjust dosage according to response: a dose of 0.5 mg bumetanide per day may be

sufficient in some elderly patients.

Paediatric population (children under 12 years)

Bumetanide Liquid should not be used for children under 12 years of age.

Method of administration

For oral administration.

4.3 Contraindi­cations

Hypersensitivity to the active substance or to any of the excipients listen in section 6.1.

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.

Bumetanide is contra-indicated in hepatic coma and care should be taken in states of severe electrolyte depletion.

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.

Excipients:

This medicine contains 1375 mg sorbitol in each spoonful (5 ml) which is equivalent to 275 mg/ml. Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.

This medicine contains methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reaction (possibly delayed).

This medicine contains less than 1 mmol sodium (23 mg) per spoonful (5 ml), that is to say essentially ‘sodium-free’

4.5 Interactions with other Medicaments and other forms of Interaction

In common with other diuretics, serum lithium levels may be increased when lithium is given concurrently with bumetanide.

This may result in increased lithium toxicity, including increased risk of cardiotoxic and neurotoxic effects of lithium. Therefore, it is recommended that lithium levels are carefully monitored and where necessary the lithium dosage is adjusted in patients receiving this combination.

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 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of Bumetanide Liquid 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.

Breast-feeding

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.

Thrombocytopenia, leukopenia, bone marrow failure, agranulocytosis

Hypersensitivity

Electrolyte imbalance, for example:

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

Headache, dizziness

Tinnitus, deafness

Orthostatic hypotension, hypotension

Gastrointestinal disorder, for example:

Nausea, vomiting, diarrhoea, abdominal pain

Cholestasis, jaundice

Rash*, urticaria, dermatitis, photosensitivity reaction, pruritus

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

Myalgia, muscle spasm, arthralgia

Renal failure acute

Gynaecomastia, breast pain

Fatigue

Blood creatinine increased

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 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: High-ceiling diuretics. Sulfonamides, plain

ATC code: C03CA02

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-para-hydroxybenzoate (E 218)

Propyl-para-hydroxybenzoate (E 216)

Sorbitol (E 420)

Xanthan gum

Sodium citrate

Patent blue V

Quinoline yellow

Peppermint flavour

Purified water.

6.2 Incompatibilities

Not applicable.

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

No special requirements.

7 MARKETING AUTHORISATION HOLDER

CHEMIDEX PHARMA LIMITED

T/A ESSENTIAL GENERICS

CHEMIDEX HOUSE,

7 EGHAM BUSINESS VILLAGE

CRABTREE ROAD

EGHAM

SURREY

TW20 8RB

UNITED KINGDOM

8 MARKETING AUTHORISATION NUMBER(S)

PL 17736/0118