Burinex 1 mg Tablets

Bumetanide Ph Eur 1 mg

Tablet

Burinex 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.

In oedema of cardiac or renal origin where high doses of a potent short acting diuretic are required, Burinex 5 mg tablets may be used.

For oral administration.

Most patients require a daily dose of 1 mg which can be given as a single morning or early evening dose. Depending on the patient's response, a second dose can be given six to eight hours later. In refractory cases, the dose can be increased until a satisfactory diuretic response is obtained, or infusions of Burinex can be given.

Children: Not recommended for children under 12 years of age.

Dosage in the elderly: Adjust dosage according to response. A dose of 0.5 mg bumetanide per day may be sufficient in some elderly patients.

Although Burinex 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 Burinex.

Hypersensitivity to Burinex. Burinex is contraindicated in hepatic coma and care should be taken in states of severe electrolyte depletion.

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

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 Burinex is given in high doses intravenously or orally. 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.

Encephalopathy may be precipitated in patients with pre-existing hepatic impairment.

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

Like other diuretics, Burinex 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.

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

As with other diuretics, Burinex 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.

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

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

Although tests in four animal species have shown no teratogenic effects, the ordinary precaution of avoiding use of Burinex in the first trimester of pregnancy should at present be observed. Since it is not known whether bumetanide is distributed into breast milk, a nursing mother should either stop breast feeding or observe the infant for any adverse effects if the drug is absolutely necessary for the mother.

None known.

Reported reactions include abdominal pain, vomiting, dyspepsia, diarrhoea, stomach and muscle cramps, arthralgia, dizziness, fatigue, hypotension, headache, nausea, encephalopathy (in patients with pre-existing hepatic disease), fluid and electrolyte depletion, dehydration, hyperuricaemia, raised blood urea and serum creatinine, hyperglycaemia, abnormalities of serum levels of hepatic enzymes, skin rashes, pruritus, urticaria, thrombocytopenia, gynaecomastia and painful breasts. Bone marrow depression associated with the use of Burinex has been reported rarely but it has not been proven definitely to be attributed to the drug. Hearing disturbance after administration of Burinex is rare and reversible.

High dose therapy:

In patients with severe chronic renal failure given high doses of Burinex, there have been reports of severe, generalised musculoskeletal pain sometimes associated with muscle spasm, occurring one to 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.

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.

Burinex is a potent, high ceiling loop diuretic with a rapid onset and a short duration of action. The primary site of action is the ascending limb of the Loop of Henle where it exerts inhibiting effects on electrolyte reabsorption causing the diuretic and natriuretic action observed.

After oral administration of 1 mg Burinex, 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.

Burinex is well absorbed after oral administration with the bioavailability reaching between 80 and 95%. The elimination half life ranges from between 0.75 to 2.6 hours. No active metabolites are known. Renal excretion accounts for approximately half the clearance with hepatic excretion responsible for the other half. There is an increase in half-life and a reduced plasma clearance in the presence of renal or hepatic disease. In patients with chronic renal failure the liver takes more importance as an excretory pathway although the duration of action is not markedly prolonged.

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

Maize starch

Lactose

Colloidal anhydrous silica

Povidone

Polysorbate 80

Agar powder

Talc

Magnesium stearate

None known.

3 years.

This medicinal product does not require any special temperature storage conditions.

Store in the original package. Keep the blisters or bottle in the outer carton in order to protect from light.

Blister packs of 14, 28 or 56 tablets; amber glass bottles containing 10, 100 or 1000 tablets.

Not all pack sizes may be marketed.

None.

LEO Laboratories Limited

Longwick Road

Princes Risborough

Bucks

HP27 9RR

UK

PL 00043/0021R

27 June 1996

December 2011