1. Name Of The Medicinal Product
Bumetanide Injection 0.5 mg/ml, solution for injection.
2. Qualitative And Quantitative Composition
Bumetanide Ph Eur 0.5 mg/ml.
3. Pharmaceutical Form
Solution for injection.
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.
For those oedematous conditions where a prompt diuresis is required, Bumetanide Injection 0.5 mg/ml may be used, e.g. acute pulmonary oedema, acute and chronic renal failure. Bumetanide Injection 0.5 mg/ml can be given intravenously or intramuscularly to those patients who are unable to take Burinex Tablets or who fail to respond satisfactorily to oral therapy.
4.2 Posology And Method Of Administration
Route of administration: parenteral.
Pulmonary oedema : Initially 1 - 2 mg by intravenous injection. This can be repeated, if necessary, 20 minutes later.
In those conditions in which an infusion is appropriate, 2 - 5 mg may be given in 500 ml infusion fluid over 30 - 60 minutes. (See Section 4.4, special warnings and precautions for use).
When intramuscular administration is considered appropriate, a dose of 1 mg should be given initially and the dose then adjusted according to diuretic response.
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.
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 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.
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.
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.
Patients with chronic renal failure on high doses of bumetanide should remain under constant hospital supervision.
Pharmaceutical precautions
Bumetanide Injection 0.5 mg/ml is presented in amber glass containers to protect against deterioration due to exposure to light.
When an intravenous infusion is required, Bumetanide Injection 0.5 mg/ml may be added to Dextrose Injection BP, Sodium Chloride Injection BP or Sodium Chloride and Dextrose Injection BP.
When 25 mg bumetanide (as Bumetanide Injection 0.5 mg/ml) was added to 1 litre of these infusion fluids, no evidence of precipitation was observed over a period of 72 hours. Higher concentrations of bumetanide in these infusion fluids may cause precipitation. It is good practice to inspect all infusion fluids containing bumetanide from time to time. Should cloudiness appear, the infusion should be discarded.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
See Section 4.4 above.
4.6 Pregnancy And Lactation
Although tests in four animal species have shown no teratogenic effects, the ordinary precaution of avoiding use of bumetanide 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.
4.7 Effects On Ability To Drive And Use Machines
None known.
4.8 Undesirable Effects
Reported reactions include skin rashes and muscular cramps in the legs, abdominal discomfort, thrombocytopenia and gynaecomastia. Bone marrow depression associated with the use of bumetanide has been reported rarely, but it has not been proven definitely to be attributed to the drug. Hearing disturbance after administration of bumetanide is rare and reversible. The possibility of hearing disturbance must be considered, particularly when bumetanide is injected too quickly and in high doses.
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 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.
4.9 Overdose
Symptoms would be those caused by excessive diuresis. General measures should be taken to restore blood volume, maintain blood pressure and correct electrolyte disturbance.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Mode of action: bumetanide is a potent high ceiling diuretic with a rapid onset and a short duration of action.
5.2 Pharmacokinetic Properties
After intravenous injection, diuresis usually starts within a few minutes and ceases in about two hours.
In most patients, 1mg of bumetanide produces a similar diuretic effect to 40 mg furosemide. 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 pre-clinical 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
Xylitol, disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate and water for injections.
6.2 Incompatibilities
None known
6.3 Shelf Life
3 years.
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
5 x 4 ml amber glass ampoules (OP), each ampoule containing 2mg bumetanide.
6.6 Special Precautions For Disposal And Other Handling
None.
7. Marketing Authorisation Holder
Leo Laboratories Limited
Longwick Road
Princes Risborough
Bucks HP27 9RR
UK
8. Marketing Authorisation Number(S)
PL 0043/0060
9. Date Of First Authorisation/Renewal Of The Authorisation
24 November 1978/13 January 1995.
10. Date Of Revision Of The Text
November 2005
LEGAL CATEGORY
POM
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