Bumetanide Tablets 1mg
Bumetanide Tablets 1mg
Each tablet contains 1mg of bumetanide.
Excipient with known effect: Contains 50.6 mg of lactose monohydrate For the full list of excipients,see section6.1.
White to off-white normal convex uncoated tablet, plain on one side. On the other side is a breakline with a ‘1’ centrally above ‘BMT’.
The tablet can be divided into equal doses.
Bumetanide Tablets 1mg are indicated whenever diuretic therapy is required in the treatment of oedema, for example 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, Bumetanide Tablets 5mg may be used.
The dose should be carefully titrated in each patient according to the patient’s response and the required therapeutic activity.
Most patients require a daily dose of 1mg 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 Bumetanide can be given.
The maximum daily dosage is 10mg.
Not recommended for children under 12 years of age.
Adjust dosage according to response; a dose of 0.5mg of bumetanide per day may be sufficient in some elderly patients.
Method of administration For oral administration.
• Hypersensitivity to the active substance, sulfonylureas or any of the excipients listed in section 6.1.
• Oliguria or anuria during treatment of severe progressing renal disease, (although Bumetanide can be used to induce diuresis in renal insufficiency)
• Comatose or precomatose states associated with liver cirrhosis
• Severe electrolyte depletion
• Renal failure associated with hepatic coma or caused by poisoning by hepatotoxic agents.
• In combination with lithium salts; Bumetanide 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 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 (see section 4.3).
Patients with chronic renal failure on high doses of Bumetanide should remain under constant hospital supervision. Bumetanide should be used with caution in patients already receiving nephrotoxic drugs. In these patents close monitoring of fluid status and renal function is required (see section 4.3, 4.5).
Increased risk of ototoxicity when bumetanide is used in renal impairment, excessive doses, and concurrent use of other ototoxic drugs (see section 4.5).
Bumetanide should be used with caution in patients with hypotension and those on antihypertensive drugs (see section 4.5).
As with other diuretics, bumetanide may cause an increase in blood uric acid. Asymptomatic hyperuricemia has been reported with use.
Periodic checks on urine and blood glucose should be made in diabetics and in patients suspected of latent diabetes (see section 4.5 and 4.8).
Encephalopathy may be precipitated in patients with pre-existing hepatic impairment (see section 4.3).
Bumetanide Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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 (see section 4.3).
The toxic effects of nephrotoxic drugs may be increased by concomitant administration of potent diuretics such as bumetanide. Impairment of renal function may develop in patients receiving treatment with bumetanide and high doses of certain cephalosporins.
Bumetanide may potentiate the ototoxicity of aminoglycosides and other ototoxic drugs.
Since this may lead to irreversible damage, these drugs must not be used with Bumetanide unless there are compelling medical reasons. In such situations, careful medical supervision is required.
Like other loop diuretics, bumetanide shows a tendency to increase the excretion of potassium causing hypokalaemia. There is increased risk of hypokalaemia when loop diuretics are given with acetazolamide, amphotericin, corticosteroids, thiazides and related diuretics, high doses of beta2 sympathomimetics, theophylline and reboxetine. Thus the dose may need adjustment when given in conjunction with these drugs.
Hypokalaemia caused by loop diuretics can lead to an increase in the sensitivity of the myocardium to the toxic effects of digitalis, amiodarone, disopyramide, flecainide, and increases the risk of ventricular arrhythmias with sotalol, amisulpride, sertindole, atomoxetine and pimozide.
Bumetanide may potentiate the effect of antihypertensive agents and drugs inducing postural hypotension such as tricyclic antidepressants.
Certain non-steroidal anti-inflammatory drugs have been shown to antagonise the action of diuretics and increase the risk of nephrotoxicity and increase the risk of hyperkalaemia.
Bumetanide may antagonise hypoglycaemic effect of antidiabetic drugs. Adjustment of the dose of antidiabetic drugs may be needed in concomitant use (see section 4.4).
For bumetanide no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / foetal development, parturition or post natal development (see section 5.3).
The use of bumetanide in the first trimester of pregnancy should be avoided with caution exercised when prescribing to pregnant women in the remaining two trimesters.
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.
This medicine may have a small or moderate influence on the ability to drive or use machines. Bumetanide may cause fatigue and hypotension which may result in dizziness, light-headedness and blurred vision. Patients should not drive or use machines if they feel affected.
The following side effects, listed below by system organ class, have been reported to be associated with bumetanide or other loop diuretics. Since this information is mainly based on post marketing data, the frequency for these side effects is unknown.
Blood and lymphatic system disorders:
Thrombocytopenia, leukopenia, bone marrow depression, agranulocytosis,
Immune system disorders:
Metabolism and nutrition disorders:
Electrolyte imbalance, for example: Hypokalaemia, hyponatraemia, dehydration, hypomagnesaemia, gout, hyperuricaemia, alkalosis hypochloraemic, hyperglycaemia, hypocalcaemia, hyperlipidaemia.
Nervous system disorders:
Headache, dizziness, encephalopathy (in patients with pre-existing hepatic disease), paraesthesia
Ear and labyrinth disorders:
Tinnitus, hearing impairment, deafness, vertigo
Orthostatic hypotension, hypotension
Abdominal pain, nausea, vomiting, dyspepsia, diarrhoea, stomach cramps
Hepatobiliary system disorders:
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:
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.
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.
Pharmacotherapeutic group: Diuretics, high-ceiling diuretics, sulfonamides, plain ATC Code CO3 CA02
Mechanism of action
Bumetanide 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 a 1mg dose of 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 1mg dose.
Bumetanide 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 or hepatic impairment
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.
Chronic renal impairment
In patients with chronic renal failure the liver takes more importance as an excretory pathway although the duration of action is not markedly prolonged.
Bumetanide was shown to be devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system.
An 18-month study showed an increase in mammary adenomas of questionable significance in female rats receiving oral doses of 60mg/kg/day (2000 times a 2mg human dose). A repeat study at the same doses failed to duplicate this finding. Reproduction studies were performed to evaluate general reproductive performance and fertility in rats at oral dose levels of 10, 30, 60 or 100 mg/kg/day. The pregnancy rate was slightly decreased in the treated animals; however, the differences were small and not statistically significant.
Microcrystalline cellulose Lactose monohydrate Magnesium stearate Maize starch Sodium lauryl sulfate
AL/AL 39months AL/PVC/PVdC 48 months
Do not store above 25°C.
Bumetanide Tablets 1mg are packed in:
Aluminium/Aluminium or Aluminium/PVC/PVDC blisters in a carton box. The box may contain pack sizes of 20, 28, 30, 56, 60, 84 and 120 tablets.
Not all pack sizes may be marketed.
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Niche Generics Limited 1 The Cam Centre Wilbury Way
Hitchin Hertfordshire SG4 0TW United Kingdom
Date of first authorisation: 6th July 1999 Date of latest renewal: 31st March 2005