Source: Health Products Regulatory Authority (IE) Revision Year: 2019 Publisher: KARO PHARMA AB, Box 16184, 103 24 Stockholm, Sweden
Caution is advised if bumetanide is to be administered to patients with severe hepatic impairment.
Caution should be exercised when bumetanide is used in patients with hypotension.
Electrolyte and fluid imbalance may occur and replacement therapy should be instituted where indicated. Serum potassium concentrations should be monitored regularly.
Administration of proton pump inhibitors has been associated with development of hypomagnesaemia. Hypomagnesaemia may be exacerbated with co-administration of bumetanide and particular attention to magnesium levels should be given when this combination is used.
As with other diuretics, bumetanide may cause an increase in blood uric acid.
Bumetanide should be used with caution in patients with potential obstruction of the urinary tract.
In patients with severe chronic renal failure treated with 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 for up to 12 hours. Occasionally analgesic medication has been required to treat the pain. All patients recovered fully and there was no deterioration in their renal function. The cause of this pain is uncertain but 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. When using more than 10 mg per day expert advice should be sought. Patients with chronic renal failure on high doses of bumetanide should remain under constant hospital supervision.
Caution is advised if bumetanide is to be administered to patients with severe or progressive renal impairment or with elevated urea/Blood Urea Nitrogen (BUN) or creatinine.
Periodic monitoring of urine and blood glucose should be made in diabetics and patients suspected of latent diabetes since this preparation may induce hyperglycaemia (see sections 4.5 and 4.8).
If known hypersensitivity to sulphonamides, there may be a potential risk of hypersensitivity to bumetanide.
Bumetanide found in urine by doping tests is a cause for disqualification of athletes.
Burinex tablets contain lactose as an excipient and patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Dose adjustment of hypoglycaemic agents may be necessary in patients with diabetes mellitus.
Hypokalaemia increases the sensitivity to digitalis glycosides which might result in digitalis toxicity (nausea, vomiting, and arrhythmias). Potassium level and signs for digitalis toxicity should be monitored. Potassium supplementation and lower digitalis glycoside dose should be considered.
Hypokalaemia increases the sensitivity to non-depolarising neuromuscular blocking agents.
Bumetanide reduces lithium clearance resulting in high serum levels of lithium, therefore concomitant therapy requires close monitoring of serum lithium levels. Lower lithium doses may be required.
Concomitant use of bumetanide and class III antiarrhythmic drugs may result in increased risk of electrolyte imbalance and subsequent cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest). Patients' electrolyte levels should be monitored as should symptoms of arrhythmias.
Non-steroidal anti-inflammatory drugs (NSAID) inhibit the effect of bumetanide. The effects of concurrent use should be monitored (e.g. blood pressure, signs of renal failure). Diuretics may enhance the nephrotoxicity of NSAIDs.
Bumetanide may potentiate the effect of antihypertensive agents including diuretics and drugs inducing postural hypotension (e.g. tricyclic antidepressants). First-dose hypotension may occur.
The potassium depleting effect of bumetanide may be increased by other potassium depleting agents.
The ototoxic effects of aminoglycosides may be increased by concomitant administration of potent diuretics such as bumetanide.
Probenecid inhibits the renal tubular secretion of bumetanide leading to a diminished natriuresis.
Bumetanide may cause harmful pharmacological effects during pregnancy, to the foetus or to the newborn child. Bumetanide should not be used during pregnancy unless the clinical condition of the woman requires treatment with bumetanide. It may be used only in case of heart failure when the potential benefit justifies the potential risk to the foetus.
Bumetanide should not be used during breast-feeding.
There are no clinical studies with bumetanide regarding fertility.
Bumetanide has no or negligible direct influence on the ability to drive and use machines. However, the patient should be informed that dizziness may occur during treatment and take this into account while driving or using machines.
The estimation of the frequencyof undesirable effects is based on a pooled analysis of data from clinical studies and spontaneous reporting.
Based on pooled data from clinical studies including more than 1000 patients who received bumetanide, approximately 12% of patients can be expected to experience an undesirable effect.
The most frequently reported adverse reactions during treatment are headache and electrolyte imbalance (including hypokalaemia, hyponatraemia, hypochloraemia and hyperkalaemia) occurring in approximately 4% ofthe patients, followed bydizziness (including orthostatic hypotension and vertigo) and fatigue occurring in approximately 3% of patients.
Electrolyte disturbances can occur especially during long term treatment.
Renal failure has been reported in post-marketing safety surveillance.
Undesirable effects are listed by Med DRA system organ class (SOC) and the individual undesirable effects arelisted starting with the most frequently reported. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Very common ≥1/10
Common ≥1/100 and <1/10
Uncommon ≥1/1,000 and <1/100
Rare ≥1/10,000 and <1/1,000
Very rare <1/10,000
Uncommon: Bone marrow failure and pancytopenia, Thrombocytopenia, Leukopenia including neutropenia, Anaemia
Common: Electrolyte imbalance (including hypokalaemia, hyponatraemia, hypochloraemia and hyperkalaemia)
Uncommon: Dehydration, Glucose metabolism disorder, Hyperuricaemia and gout
Common: Dizziness (including orthostatic hypotension and vertigo), Fatigue(including lethargy, somnolence, asthenia and malaise), Headache
Uncommon: Syncope
Uncommon: Hearing disturbances
Uncommon: Chest pain and discomfort
Uncommon: Hypotension
Uncommon: Dyspnoea, Cough
Common: Abdominal pain and discomfort, Nausea
Uncommon: Vomiting, Diarrhoea, Constipation, Drymouth and thirst
Uncommon: Rash*, Dermatitis and eczema, Urticaria Pruritus Photosensitivity
* Various types of rash reactions such as erythematous, maculo-papular and pustular have been reported
Common: Muscle spasms, Pain and myalgia
Common: Micturition disorder
Uncommon: Renal impairment (including renal failure)
Uncommon: Oedema peripheral
The safety profile of Bumetanide has not been established in the paediatric population.
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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL-Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Not applicable.
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