INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
BURINEX® 1 mg Tablets
BURINEX® 2 mg 0,5 mg/mL 4 mL Injection

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

BURINEX^® 1 mg Tablets
BURINEX^® 2 mg 0,5 mg/mL 4 mL Injection

COMPOSITION:
Tablets:        Each tablet contains 1 mg bumetanide.
Injection:        Each ampoule contains bumetanide 0,5 mg/mL in a neutral isotonic solution (phosphate buffer).

PHARMACOLOGICAL CLASSIFICATION:
A. 18.1 Diuretic

PHARMACOLOGICAL ACTION:
BURINEX^®(Bumetanide) is a potent high ceiling diuretic, with a rapid onset and a short duration of action.
After oral administration, diuresis begins within thirty minutes with a peak effect between one and two hours. The diuretic effect is virtually complete in four to six hours.
After intravenous injection, diuresis starts within a few minutes and generally ceases in about two hours. The diuretic effect produced by BURINEX^®is dose related so that patients who fail to respond to a low dose may respond as the dose is increased. BURINEX^®has been shown to exert its major effect in the ascending limb of the loop of Henle, but it may also have an additional action in the proximal tubule. BURINEX^®is a derivative of metanilamide and is chemically distinct from other available diuretics.
Investigations in healthy volunteers as well as in patients have revealed that BURINEX^® is excreted in the urine.

INDICATIONS:
BURINEX^® is indicated for the treatment of oedema, eg. that associated with congestive heart failure, renal disease, acute pulmonary oedema, hepatic ascites.
BURINEX^® injection may also be given intravenously or intramuscularly to those patients who are unable to take BURINEX^® tablets or who fail to respond satisfactorily to oral therapy.

CONTRA-INDICATIONS:
Anuria. Although BURINEX can be used to induce diuresis in renal insufficiency, any marked increase in blood urea or the development of oliguria during treatment of severe progressive renal disease is an indication for stopping treatment with BURINEX. BURINEX is contra-indicated in hepatic coma and in acute cases of moderately severe or severe liver failure. This does not preclude its use in treatment of ascites due to hepatic cirrhosis but such therapy is best initiated in hospital. BURINEX^®is contra-indicated in states of electrolyte depletion.

DOSAGE AND DIRECTIONS FOR USE:
The following recommendations are based on clinical experience to date:
Most patients require a daily dose of 1 mg which can be given as a single morning 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.
The dose should be carefully titrated in each patient according to the patient's response and the required therapeutic activity. As a general rule, in patients not controlled on lower doses, dosage should be started at 5 mg daily and then increased by 5 mg increments every twelve to twenty-four hours until the required response is obtained or side-effects appear. Consideration should be given to twice daily dosage rather than once daily.
Pulmonary oedema: Initially 0,5-1 mg by intravenous injection. This can be repeated if necessary, twenty minutes later. In resistant oedemas associated with advanced renal insufficiency, doses up to 15 mg daily may be necessary to obtain the desired response and in exceptional circumstances 30-40 mg daily have been administered. It might be advantageous to divide the daily dosage in two single doses. When high intravenous dosage is required this may be given as continuous intravenous infusion up to 30 mg in twenty-four hours for up to two or three days.
Alternatively, BURINEX^®may be administered in doses of up to 5 mg by slow (3 minutes) intravenous injection at six hourly intervals. When intramuscular administration is considered appropriate, a dose of 0,5-1 mg should be given initially and the dose then adjusted according to diuretic response. Until further experience of paediatric use is accumulated,BURINEX^® should not be given to children.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Adverse reactions: Reported reactions include skin rashes and muscular cramps in the legs, abdominal discomfort, thrombocytopenia and gynaecomastia. When BURINEX^® has been used in high doses there have been reports of pancreatitis and of severe generalised musculoskeletal pain sometimes associated with muscle spasm.
Excessively rapid mobilisation of oedema, particularly in elderly patients, may give rise to sudden changes in cardiovascular pressure relationships with circulatory collapse. This should be borne in mind when BURINEX^® is given intravenously to susceptible subjects. BURINEX injection may aggravate pre-existing electrolyte imbalance and should be used with caution in these cases. Electrolyte disturbance is likely to occur in those patients treated with high doses or for prolonged periods, particularly in those patients taking a low salt diet.
Anti-hypertensive effects: BURINEX^® may potentiate the effects of anti-hypertensive drugs. The dose of the latter may require adjustment when BURINEX^®is used to treat oedema in hypertensive patients.
Uric acid metabolism: BURINEX^® may cause an increase in blood uric acid.
Effects on carbohydrate metabolism: Periodic checks on urine and blood glucose should be made in diabetics and patients suspected of latent diabetes.
Effects on hearing: High doses of BURINEX^® may cause disturbance of hearing, particularly in those patients with renal insufficiency.
Pregnancy: The use of BURINEX^® in the first trimester of pregnancy should be avoided.
Precautions: The precautions to be taken with BURINEX^® are mainly those associated with electrolyte disturbance. Electrolyte depletion may show itself by weakness, dizziness, lethargy, leg cramps, anorexia, vomiting or mental confusion. Patients in whom a risk of depletion is likely should undergo periodic serum electrolyte determinations.
BURINEX^®increases the excretion of potassium. This may cause the gradual development of low serum potassium levels. Patients on long term treatment should, therefore, be encouraged to take a high potassium diet. Potassium chloride supplements are indicated in those patients whose dietary potassium is possibly inadequate, the chloride tending to correct the hypochloraemia and metabolic alkalosis, which is occasionally associated with potassium depletion. Potassium sparing diuretics, such as spironolactone, have been used as an alternative approach. Studies have shown that continued daily administration of BURINEX^® for several months, supplemented with either potassium chloride or spironolactone produced an effective diuresis with minimal changes in serum electrolytes. Low serum potassium levels, it should be noted, increase the sensitivity of the myocardium to the toxic effects of digitalis.
It is also important to prevent hypokalaemia in patients with hepatic cirrhosis. Potassium supplements are also indicated in conditions associated with a particular tendency to potassium depletion, eg. long-term treatment with corticosteroids, ulcerative colitis, prolonged vomiting or diarrhoea.
For high dose therapy, treatment should be initiated at a low dose and gradually increased in 5 mg increments until the desired response is obtained.
Pharmaceutical precautions: When an intravenous infusion is required, BURINEX^® injection may be added to dextrose injection B.P., Sodium Chloride injection B.P., or Sodium Chloride and Dextrose injection B.P. When 12,5 mg Bumetanide (as BURINEX^® injection) was added to one litre of these infusion fluids, no evidence of precipitation was observed over a period of seventy two hours. Higher concentrations of BURINEX^® in these infusion fluids may cause precipitation. It is good practice to inspect all infusion fluids containing BURINEX^® from time to time. Should cloudiness appear the infusion should be discarded.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Generally, measures should be taken to restore blood volume, maintain blood pressure and correct electrolyte disturbance. No other specific treatment appears to be necessary.

IDENTIFICATION:

Tablets 1 mg:	A white, flat, circular, uncoated, bevelled-edged tablet marked with a score line and the number 133 on one face, and a lion logo imprinted on the other.
Injection:	Clear, colourless solution in an amber glass ampoule.

PRESENTATION:

Tablets 1 mg:	Bottles of 100 tablets.
	Cartons containing 10 blister packs of 10 tablets each.

Injections:
BURINEX^®2 mg 0,5 mg/mL 4 mL: 5 ampoules per unit carton.

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light. Keep out of reach of children.

REGISTRATION NUMBERS:
Tablets 1 mg: G/18.1/94
Injection: BURINEX^®2 mg 0,5 mg/mL 4 mL: P/18.1/145

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Adcock Ingram Limited
Adcock Ingram Park
17 Harrison Avenue
Bryanston
2152

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
January 1985

ADCOCK INGRAM PHARMACEUTICALS LTD LOGO
LEO PHARMACEUTICAL PRODUCTS LOGO

Under licence from:
Leo Pharmaceutical Products Ltd.
Ballerup, Denmark

New addition to this site: April 2004
Source: Pharmaceutical Industry
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