Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Generics [UK] Ltd t/a Mylan, Station Close, Potters Bar, Herts, EN6 1TL
Sudden changes in cardiovascular pressure-flow relationships, leading to circulatory collapse, can occur particularly in the elderly if the oedema is eliminated too rapidly. It is important to remember this when bumetanide is given in high doses, either orally or intravenously.
Patients with chronic renal failure on high doses of bumetanide should remain under constant hospital supervision.
Patients on a low salt diet may suffer electrolyte imbalance. Serum electrolyte checks, in particular for sodium, potassium, chloride and bicarbonate, should be carried out on a regular basis and, where necessary, replacement therapy carried out.
Bumetanide may enhance the nephrotoxicity or ototoxicity of other drugs, particularly in patients with renal impairment.
Bumetanide may precipitate encephalopathy in patients with hepatic impairment.
Bumetanide may increase uric acid. Blood glucose and blood uric acid should be measured periodically, especially in diabetics and those suspected of latent diabetes and in patients with gout.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The following combinations with bumetanide are considered potentially hazardous:
Bumetanide should not be administered concurrently with lithium, as diuretics reduce the clearance rate of lithium leading to increased blood-lithium levels with signs of overdose (see section 4.3).
When bumetanide is used to treat oedema in hypertensive patients the dose of antihypertensive drug may need to be adjusted as bumetanide may potentiate its effects.
The dose of bumetanide may need to be adjusted when given in conjunction with cardiac glycosides, such as digitalis, since the increased potassium excretion resulting from bumetanide administration can cause an increased sensitivity of the myocardium to the toxic effects of glycosides.
Certain NSAIDS are known to have antagonistic effects on the action of diuretics.
Bumetanide should not be given concurrently with certain antibiotics and antifungals, such as cephaloridine or amphotericin as it could lead to increased toxic effects from these antibiotics and antifungals.
Although tests in animals have shown no teratogenic effects, there are no data on its effect on pregnant humans. Therefore it is advisable to avoid taking this drug during the first trimester.
There are no data on breast-feeding and therefore nursing mothers should stop bumetanide treatment during breast-feeding unless the drug is essential. In such cases, the infant should be observed for any adverse effects.
Bumetanide has no known effect on the ability to drive or operate machinery.
Adverse effects are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data):
Rare: Bone marrow depression associated with the use of bumetanide, but it has not been proven definitely to be attributed to the drug.
Not known: thrombocytopenia.
Common: dehydration.
Uncommon: fluid and electrolyte depletion.
Not known: hyperuricaemia, hyperglycaemia.
Common: dizziness, headache.
Not known: encephalopathy (in patients with pre-existing hepatic disease).
Uncommon: ear pain, vertigo.
Rare: Hearing disturbance after administration of bumetanide, which is reversible.
Common: hypotension.
Common: nausea.
Uncommon: diarrhoea.
Not known: stomach cramps, abdominal pain, vomiting, dyspepsia.
Common: pruritis (in patients with liver disease).
Uncommon: urticaria.
Not known: rash.
Not known: muscle cramps, arthralgia.
Uncommon: painful breasts.
Not known: gynaecomastia.
Common: fatigue.
Uncommon: chest discomfort.
Not known: raised blood urea and serum creatinine, abnormalities of serum levels of hepatic enzymes
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 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.
Not applicable.
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