This information is intended for use by health professionals
Conditions requiring correction before furosemide is started (see also section 4.3)• Hypotension.• Hypovolaemia.• Severe electrolyte disturbances particularly hypokalaemia, hyponatraemia and acid-base disturbances.
Furosemide is not recommended• In patients at high risk for radiocontrast nephropathy - it should not be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy.• In patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.Particular caution and/or dose reduction required:• elderly patients (lower initial dose as particularly susceptible to side-effects - see section 4.2)• difficulty with micturition including prostatic hypertrophy (increased risk of urinary retention: consider lower dose). Closely monitor patients with partial occlusion of the urinary tract• diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase: stop furosemide before a glucose tolerance test)• pregnancy (see section 4.6)• gout (furosemide may raise uric acid levels/precipitate gout)• patients with hepatorenal syndrome• impaired hepatic function (see section 4.3 and below monitoring required)• impaired renal function (see section 4.3 and below monitoring required)• adrenal disease (see section 4.3 contraindication in Addison's disease)• hypoproteinaemia e.g. nephrotic syndrome (effect of furosemide may be impaired and its ototoxicity potentiated - cautious dose titration required).• acute hypercalcaemia (dehydration results from vomiting and diuresis - correct before giving furosemide). Treatment of hypercalcaemia with a high dose of furosemide results in fluid and electrolyte depletion - meticulous fluid replacement and correction of electrolyte required.• Patients who are at risk from a pronounced fall in blood pressure• premature infants (possible development nephrocalcinosis/nephrolithiasis; renal function must be monitored and renal ultrasonography performed).• Symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with furosemide, particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension
Avoidance with other medicines (see also section 4.5 for other interactions)• concurrent NSAIDs should be avoided if not possible diuretic effect of furosemide may be attenuated• ACE-inhibitors & Angiotensin II receptor antagonists severe hypotension may occur dose of furosemide should be reduced/stopped (3 days) before starting or increasing the dose of theseLaboratory monitoring requirements:• Serum sodiumParticularly in the elderly or in patients liable to electrolyte deficiency• Serum potassiumThe possibility of hypokalaemia should be taken into account, in particular in patients with cirrhosis of the liver, those receiving concomitant treatment with corticosteroids, those with an unbalanced diet and those who abuse laxatives. Regular monitoring of the potassium, and if necessary treatment with a potassium supplement, is recommended in all cases, but is essential at higher doses and in patients with impaired renal function. It is especially important in the event of concomitant treatment with digoxin, as potassium deficiency can trigger or exacerbate the symptoms of digitalis intoxication (see section 4.5). A potassium-rich diet is recommended during long-term use.Frequent checks of the serum potassium are necessary in patients with impaired renal function and creatinine clearance below 60ml/min per 1.73m2 body surface area as well as in cases where furosemide is taken in combination with certain other drugs which may lead to an increase in potassium levels (see section 4.5 & refer to section 4.8 for details of electrolyte and metabolic abnormalities)• Renal functionFrequent BUN in first few months of treatment, periodically thereafter. Long-term/high-dose BUN should regularly be measured. Marked diuresis can cause reversible impairment of kidney function in patients with renal dysfunction. Adequate fluid intake is necessary in such patients. Serum creatinine and urea levels tend to rise during treatment• GlucoseAdverse effect on carbohydrate metabolism - exacerbation of existing carbohydrate intolerance or diabetes mellitus. Regular monitoring of blood glucose levels is desirable.• Other electrolytesPatients with hepatic failure/alcoholic cirrhosis are particularly at risk of hypomagnesia (as well as hypokalaemia). During long-term therapy (especially at high doses) magnesium, calcium, chloride, bicarbonate and uric acid should be regularly measured.Clinical monitoring requirements (see also section 4.8):Regular monitoring for• blood dyscrasias. If these occur, stop furosemide immediately • liver damage• idiosyncratic reactions
Other alterations in lab values• Serum cholesterol and triglycerides may rise but usually return to normal within 6 months of starting furosemide
Concomitant use with risperidoneIn risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97 years) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be avoided in elderly patients with dementia (see section 4.3 Contraindications).
PregnancyThere is clinical evidence of safety of the drug in the third trimester of human pregnancy & furosemide has been given after the first trimester of pregnancy for oedema, hypertension and toxaemia of pregnancy without causing fetal or newborn adverse effects. However, furosemide crosses the placental barrier and should not be given during pregnancy unless there are compelling medical reasons. It should only be used for the pathological causes of oedema which are not directly or indirectly linked to the pregnancy. The treatment with diuretics of oedema and hypertension caused by pregnancy is undesirable because placental perfusion can be reduced, so, if used, monitoring of fetal growth is required.
Lactation (see section 4.3)Furosemide is contraindicated as it passes into breast milk and may inhibit lactation.
Blood and lymphatic system disorders:
Rare:• Eosinophilia • Leukopenia• Bone marrow depression (necessitates withdrawal of treatment). The haemopoietic status should be therefore be regularly monitored.
Very Rare:• aplastic anaemia or haemolytic anaemia• agranulocytosis
Nervous system disorders
Rare:• paraesthesia• hyperosmolar comaNot known :Dizziness, fainting and loss of consciousness (caused by symptomatic hypotension)."
Endocrine disorderGlucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to a deterioration of metabolic control; latent diabetes mellitus may become manifest. Insulin requirements of diabetic patients may increase.
Eye disordersUncommon: visual disturbance
Ear and labyrinth disordersHearing disorders and tinnitus, although usually transitory, may occur in rare cases, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephritic syndrome) and/or when intravenons furosemide has been given too rapidly.Uncommon:deafness (sometimes irreversible)"
Cardiac disordersUncommon: Cardiac arrhythmias Furosemide may cause a reduction in blood pressure which, if pronounced may cause signs and symptoms such as impairment of concentration and reactions, light headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance. Hepatobiliary disorders In isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.Hepatic encephalopathy in patients with hepatocellular insufficiency may occur (see Section 4.3).
Skin and subcutaneous tissue disorders
Rare:Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, fever, hypersensitivity to light, exsudative erythema multiforme (Lyell's syndrome and Stevens-Johnson syndrome), bullous exanthema, exfoliative dermatitis, purpura, AGEP (acute generalized exanthematous pustulosis) and DRESS (Drug rash with eosinophilia and systemic symptoms).Not Known:Acute generalised exanthematous pustulosis (AGEP)
Metabolism and nutrition disordersAs with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy. Furosemide leads to increased excretion of sodium and chloride and consequently increase excretion of water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased. Metabolic acidosis can also occur. The risk of this abnormality increases at higher dosages and is influenced by the underlying disorder (e.g. cirrhosis of the liver, heart failure), concomitant medication (see section 4.5) and diet.Symptomatic electrolyte disturbances and metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or e.g. where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses, Symptoms of electrolyte imbalance depend on the type of disturbance:Sodium deficiency can occur; this can manifest itself in the form of confusion, muscle cramps, muscle weakness, loss of appetite, dizziness, drowsiness and vomiting.Potassium deficiency manifests itself in neuromuscular symptoms (muscular weakness, paralysis), intestinal symptoms (vomiting, constipation, meterorism), renal symptoms (polyuria) or cardiac symptoms. Severe potassium depletion can result in paralytic ileus or confusion, which can result in coma.Magnesium and calcium deficiency result very rarely in tetany and heart rhythm disturbances.Serum calcium levels may be reduced; in very rare cases tetany has been observed.Nephrocalcinosis/Nephrolithiasis has been reported in premature infants.Serum cholesterol (reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol) and triglyceride levels may rise during furosemide treatment. During long term therapy they will usually return to normal within six months,As with other diuretics, treatment with furosemide may lead to transitory increase in blood creatinine and urea levels. Serum levels of uric acid may increase and attacks of gout may occur.The diuretic action of furosemide may lead to or contribute to hypovolaemia and dehydration, especially in elderly patients. Severe fluid depletion may lead to haemoconcentration with a tendency for thromboses to develop.
General disorders and administration site conditionsUncommon: FatigueRare:• Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely.• fever • Malaise
Gastrointestinal disordersUncommon: dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhea, constipation.Gastro-intestinal disorders such as nausea, malaise or gastric upset (vomiting or diarrhoea) and constipation may occur but not usually severe enough to necessitate withdrawal of treatment.
Renal and urinary disorders
Uncommon:• serum creatinine and urea levels can be temporarily elevated during treatment with furosemide.
Rare:• interstitial nephritis, acute renal failure.Increased urine production, urinary incontinence, can be caused or symptoms can be exacerbated in patients with urinary tract obstruction. Acute urine retention, possibly accompanied by complications, can occur for example in patients with bladder disorders, prostatic hyperplasia or narrowing of the urethra.
Pregnancy, puerperium and perinatal conditionsIn premature infants with respiratory distress syndrome, administration of Furosemide Accord Tablets in the initial weeks after birth entails an increased risk of a persistent patent ductus arteriosus. In premature infants, furosemide can be precipitated as nephrocalcinosis/kidney stones.Rare complications may include minor psychiatric disturbances.
Reporting of suspected adverse reactionsReporting 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 Yellow Card Scheme.Website: www.mhra.gov.uk/yellowcard.
FeaturesOverdose can cause massive diuresis resulting in dehydration, volume depletion and electrolyte disturbances with consequent hypotension and cardiac toxicity. The clinical picture in acute or chronic overdose depends primarily on the extent and consequences of electrolyte and fluid loss, e.g. hypovolaemia, dehydration, haemoconcentration, cardiac arrhythmias due to excessive diuresis. Symptoms of these disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion.High doses have the potential to cause transient deafness and may precipitate gout (disturbed uric acid secretion).
Management• Benefits of gastric decontamination are uncertain. In patients presenting within 1 hour of ingestion, consider activated charcoal (50g for adults: 1g/kg for children) • Observe for a minimum of 4 hours - monitor pulse and blood pressure.• Treat hypotension and dehydration with appropriate IV fluids• Monitor urinary output and serum electrolytes (including chloride and bicarbonate). Correct electrolyte imbalances. Monitor 12 lead ECG in patients with significant electrolyte disturbances