Furosemide

Registered South African indications:

• Oedema
• Symptomatic hypercalcaemia
• Hypertension - mild to moderate
• Greatly reduced glomerular-filtration
• Oliguria due to acute or chronic renal insufficiency (GFR<20ml/min but >5ml/min)
• Acute renal failure (postoperative phase and in association with septic processes)
• Chronic renal insufficiency (predialytic stage in terminal renal failure)
• Fluid retention (associated with nephritis syndrome)
• Conditions where prolonged diuresis is required
• Ascites due to cirrhosis of the liver, mechanical obstruction or cardiac failure
• Barbiturate poisoning (using the principle of “forced diuresis”)
• Burns, to reduce local oedema and to prevent oliguria from progressing to complete anuria

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to sulphonamides
• Increasing azotaemia and oliguria during treatment of severe progressive renal disease
• Increasing uraemia and oliguria occur during treatment of severe progressive renal disease (500mg tab)
• Anuria
• Hypokalaemia
• Severe hypokalaemia (500mg tab)
• Hyponatraemia
• Severe hyponatraemia (500mg tab)
• Hypovolaemia with or without hypotension
• Hypotension (Ret cap)
• Dehydration
• Drug-induced renal failure (40mg cap)
• Renal failure associated with hepatic coma (40mg cap)
• Hepatic coma and states of electrolyte depletion (therapy should not be started until the basic condition is corrected or improved)
• Pre-comatose and comatose states associated with hepatic encephalopathy (500mg tab)
• Breastfeeding women

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Furosemide should be administered during pregnancy only if strictly indicated, and then only for short periods of time (20mg tab, 40mg tab, 80mg tab, sol, Ret cap)

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Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to sulphonamides, sulphonamide derivatives or amiloride 
• Anuria and impaired renal function (creatinine clearance below 30ml/min/1.73m² body surface area) and renal failure resulting from poisoning by nephrotoxic and/or hepatotoxic agents (tab)
• Anuria (sol)
• Renal failure with anuria not responding to furosemide, or as a result of poisoning by nephrotoxic or hepatotoxic agents, or associated with hepatic coma (sol)
• Electrolyte disturbances (severe hyponatremia, severe hypokalaemia, hypovolaemia)
• Dehydration
• Hypotension (tab)
• Concomitant use of potassium supplements or potassium-sparing diuretics (Potassium salts) (tab)
• Pre-coma/coma associated with hepatic cirrhosis or encephalopathy
• Addison's disease (tab)
• Digitalis intoxication (tab)
• Breastfeeding women

Cautions

• Pregnancy
• Renal impairment (South African recommendations)
• Severe renal impairment (eGFR<30ml/mi/1.73m²) (Recommendations in other jurisdictions)
• Hepatic impairment
• Elderly
• Hepatic cirrhosis
• Ascites 
• Hepato-renal syndrome
• Diabetes mellitus
• Prostatic hyperplasia
• Urinary stricture
• Gout
• Hypoproteinaemia
• Porphyria
• Premature infants
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption  
• Fructose intolerance

Forms avail. in SA and covered in this monograph: cap, retard cap (Ret cap), sol, tab

South African registered indications and dosages

Oedema
- Of cardiac origin
- Of hepatic origin
- Of renal origin
- In management of refractory oedema, used in conjunction with other types of diuretics, particularly potassium-sparing diuretics

• Oral (40mg cap): Initial: 40mg daily; May be increased to 80mg after 6hrs and then to 120mg after another 6hrs if no response; Daily doses over 120mg should be divided into 2-3 separate doses; Once oedema is controlled: Maintenance: 20-40mg daily
• Oral (40mg tab): Initial: 40mg daily; May be increased to 200mg daily if necessary; Daily doses over 120mg should be divided into 2-3 separate doses; Maintenance: 20-40mg daily

Oedema
- Cardiac oedema, in conjunction with adequate glycoside therapy
- Renal oedema in nephrotic syndrome
- Oedema during the last trimester of pregnancy (pre-eclamptic toxaemia and eclampsia)
- Cerebral oedema
- Burns, to reduce local oedema and to prevent oliguria from progressing to complete anuria
Ascites due to liver cirrhosis, mechanical obstruction or cardiac failure

• Oral (20mg tab, 80mg tab, sol): 20-80mg/day, preferably in the morning; May be increased to 80mg after 6 hours and then to 120mg after another 6 hours if no response; Daily doses over 120mg should be divided into 2-3 separate doses; Once oedema is controlled: Maintenance: 20-40mg/day

Symptomatic hypercalcaemia

• Oral (40mg tab): Initial: 40mg daily; May be increased to 200mg daily if necessary; Daily doses over 120mg, divided into 2-3 separate doses; Maintenance: 20-40mg daily

Hypertension - mild to moderate

• Oral (20mg tab, 40mg tab, 80mg tab, sol): 40-80mg, daily preferably in the morning; Lower doses may be sufficient if used in combination with other antihypertensive agents

Greatly reduced glomerular-filtration
Oliguria due to acute or chronic renal insufficiency (GFR<20ml/min but >5ml/min)
Acute renal failure (postoperative phase and in association with septic processes)
Fluid retention (associated with nephritis syndrome)

• Oral (500mg tab): Initial: 250mg; May be increased to 1500mg/24hrs; Titration: If no adequate response in 4-6hrs, increase initial dose by 250-500mg (half to one tab); In exceptional cases, up to 2000mg/24hrs

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Transition: Oral administration suitable for continuing treatment after initiating parenterally

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Chronic renal insufficiency (predialytic stage in terminal renal failure)

• Oral (500mg tab): Initial: 250mg; If no adequate response in 4-6hrs, increase by 250mg every 4-6hrs until effective dose is reached, usually between 250-2000mg (half to 4 tab)

Conditions where prolonged diuresis is required
- Oedema (cardiac, hepatic, renal, due to burns) particularly in elderly patients
- Other conditions in which diuretic therapy is indicated, such as toxaemia of pregnancy
- Oedema due to venous insufficiency and after thrombosis

• Oral (Ret cap): Initial: 60mg daily; In mild cases: 60mg on alternative days

- Management of mild to moderate hypertension, either alone or as an adjuvant

• Oral (Ret cap): Initial: 60mg daily; In exceptional cases: 60-120mg or more depending on individuals' response

Barbiturate poisoning (forced diuresis)

• Oral (20mg tab, 80mg tab, sol): 20-40mg, in addition to infusion with electrolyte solution; Further treatment varies based on urine elimination and must include substitution of the fluid and electrolyte losses

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In poisoning with acid or basic substances the elimination rate can be further increased by alkalisation or acidification of the urine, respectively

Paed. forms avail. in SA and covered in this monograph: cap, sol, tab

South African registered indications and dosages

Oedema
- Of cardiac origin
- Of hepatic origin
- Of renal origin
- In management of refractory oedema, used in conjunction with potassium-sparing diuretics

• Oral (40mg cap, 40mg tab): Initial: 1mg/kg body weight daily; May be increased up to a max. of 3mg/kg body weight per day; Max dose: 120mg/24hrs

Symptomatic hypercalcaemia
Hypertension - mild to moderate

• Oral (40mg tab): Initial: 1mg/kg body weight daily; May be increased up to a max. of 3mg/kg body weight per day; Max dose: 120mg/24hrs

Oedema
- Cardiac oedema, in conjunction with adequate glycoside therapy
- Renal oedema in nephrotic syndrome
- Cerebral oedema
- Burns, to reduce local oedema and to prevent oliguria from progressing to complete anuria
Ascites due to liver cirrhosis, mechanical obstruction or cardiac failure
Hypertension - mild to moderate
Barbiturate poisoning (forced diuresis)

Infants and children below 15 years

• Oral (20mg tab, 80mg tab, sol): 2mg/kg/day in divided doses, up to a maximum of 6mg/kg

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Furosemide 500mg tablets are not suitable for children
Furosemide 60mg retard capsules are not suitable for children

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In poisoning with acid or basic substances the elimination rate can be further increased by alkalisation or acidification of the urine, respectively

Pregnancy

South African recommendations

40mg capsule

• First trimester: Caution not recommended
• Second and third trimester: Caution
• Not to be used in the first trimester of pregnancy
• There is little evidence of safety of high-dose furosemide in human pregnancy, although the results of animal work, in general, show no hazardous effects

Retard capsule

• First trimester and last 3 months of pregnancy: Caution; not recommended
• Second trimester: Caution
• Animal experiments show no teratogenic effects, but the safety of furosemide in pregnancy in humans has not been established
• Furosemide retard capsules are therefore not recommended for use during the first and last three months of pregnancy and should only be used during pregnancy if strictly indicated (conditions in which diuretic therapy is indicated, such as toxaemia of pregnancy) and then for a short period only

Oral solution and tablet formulations

• Caution; not recommended
• Furosemide crosses the placental barrier and must not be given during pregnancy (40mg tab, 500mg tab)
• Treatment during pregnancy require monitoring of foetal growth (40mg tab, 500mg tab)
• Furosemide should be administered during pregnancy only if strictly indicated, and then only for short periods of time (20mg tab, 40mg tab, 80mg tab, sol)

Recommendations in other jurisdictions

• Caution; not recommended
• Results of animal work, in general, show no hazardous effect of furosemide in pregnancy
• There is clinical evidence of safety of furosemide in the third trimester of human pregnancy; however, furosemide crosses the placental barrier
• It must not be given during pregnancy unless there are compelling medical reasons. Treatment during pregnancy requires monitoring of fetal growth

Breastfeeding

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated
• Furosemide may inhibit lactation or may pass into the breast milk, it should therefore not be used during lactation

Fertility

South African recommendations

• No information available

Recommendations in other jurisdictions

• No information available
  No human data on the effect of furosemide on fertility are available
  In rats, there was no effect on mating or fertility with furosemide treatment

South African recommendations

40mg capsule

• Caution; no dose adjustment recommended
  Renal impairment has little effect on the elimination rate of furosemide, but less than 20% residual renal function increases the elimination time
• Renal failure associated with hepatic coma: Contraindicated
• Drug-induced renal failure: Contraindicated
• Increasing azotaemia and oliguria occurring during treatment of severe progressive renal disease, anuria, hypokalaemia, hyponatraemia, hypovolaemia with or without hypotension, dehydration: Contraindicated

Retard capsules, oral solution and tablet formulations

• Caution; no dose adjustment recommended
  Furosemide should be used with caution in patients with antibiotic-induced renal impairment
• Increasing azotaemia and oliguria occur during treatment of severe progressive renal disease, anuria, hypokalaemia, hyponatraemia, hypovolaemia with or without hypotension, dehydration: Contraindicated
• Anuric renal failure: Contraindicated (500mg tab)
• Increasing uraemia and oliguria occurring during treatment of severe progressive renal disease: Contraindicated (500mg tab)

Recommendations in other jurisdictions

• eGFR≥30ml/min/1.73m²: No dose adjustment recommended
• eGFR<30ml/min/1.73m²: Caution; dose adjustment recommended

Renal function status	Recommendation
eGFR≥30ml/min/1.73m2	No adjustment necessary
eGFR<30ml/min/1.73m2	Increased furosemide dosages might be necessary to obtain the intended diuretic response because of reduced drug release into the kidney tubules. Nonetheless, single doses exceeding 160-200mg are not expected to produce further diuretic benefits
Intermittent haemodialysis (thrice weekly): Not dialysable
Anuric patients	Contraindicated
Patients with residual kidney function	Same as eGFR<30ml/min/1.73m2 recommendations
Peritoneal dialysis: Not dialyzable
Anuric patients	Contraindicated
Patients with residual kidney function	Same as eGFR<30ml/min/1.73m2 recommendations Note: Limited information from single-dose studies indicates that a 500mg oral dose may be more successful in enhancing urine production compared to a 250mg dose, if needed
Continuous renal replacement therapy (CRRT)	Not recommended for use CRRT ultrafiltration tends to offer more efficient fluid control
Prolonged intermittent renal replacement therapy (PIRRT) (eg, sustained, low-efficiency diafiltration)
Anuric patients	Contraindicated
Patients with residual kidney function	Same as eGFR<30ml/min/1.73m2 recommendations

*Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins

South African recommendations

• Caution; no dose adjustment recommended (40mg cap)
  Where liver disease is present, biliary elimination is reduced up to 50% (40mg cap)
• Hepatic coma: Contraindicated
• Pre-comatose and comatose states associated with hepatic encephalopathy: Contraindicated (500mg tab)

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended 
  Patients with cirrhosis may experience reduced water-elimination effects along with an elevated risk for hypokalaemia and fluid loss. Pay special attention to monitoring these effects, especially when administering higher doses

South African recommendations

• Caution; no dose adjustment recommended
  The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present (40mg cap)
  In the elderly, furosemide is generally eliminated more slowly (500mg tab) 
  Excessive diuresis may result in dehydration and reduction of blood volume, with circulatory collapse and with the possibility of vascular thrombosis and embolism, particularly in elderly patients (60mg cap)
  Mainly at the start of the treatment, excessive diuresis, particularly in elderly patients, may give rise to circulatory disturbances, such as a feeling of pressure in the head, vertigo or visual impairment (20mg tab, 80mg tab, sol)

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Furosemide is generally eliminated more slowly. The dosage should be titrated until the required response is achieved

Central Nervous System Disorders

• Paraesthesia
• Confusion
• Headache
• Dizziness
• Fainting 
• Loss of consciousness
• Psychiatric disorder
• Fatigue
• Malaise

Cardiovascular Disorders

• Orthostatic intolerance
• Cardiac arrhythmias
• Patent ductus arteriosus (premature infants)
• Hypotension
• Vasculitis
• Thrombosis
• Shock

Gastrointestinal Disorders

• Dry mouth
• Nausea and vomiting
• Diarrhoea
• Constipation
• Acute pancreatitis 

Hepatobiliary Disorders

• Pure intrahepatic cholestasis
• Abnormal hepatic function

Genitourinary Disorders

• Nephrocalcinosis in infants
• Reduced diuresis
• Urinary incontinence
• Urinary obstruction 
• Acute renal failure
• Interstitial nephritis

Endocrine and Metabolic Disorders  

• Dehydration
• Hypokalaemia
• Hyponatraemia
• Hypochloremic metabolic alkalosis
• Hypocalcaemia
• Hypomagnesemia 
• Hypochloraemia
• Hypoproteinaemia
• Impaired glucose tolerance 
• Hyperuricaemia
• Reduction of serum HDL-cholesterol
• Elevation of serum LDL-cholesterol
• Elevation of serum triglycerides
• Tetany
• Aggravated pre-existing metabolic alkalosis 

Musculoskeletal Disorders

• Muscle cramps
• Muscle weakness

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Photosensitivity
• Toxic epidermal necrolysis
• Urticaria
• Erythema multiforme
• Purpura
• Exfoliative dermatitis
• Itching
• Dermatitis
• Acute generalised exanthematous pustulosis 

Immune, Blood and Lymphatic System Disorders

• Aplastic anaemia
• Bone marrow depression 
• Eosinophilia
• Leucopenia
• Haemolytic anaemia
• Agranulocytosis
• Thrombocytopenia
• Hypersensitivity reactions
• Severe anaphylactoid reactions 

Sensory Disorders

• Visual disturbance
• Yellow vision
• Tinnitus
• Hearing loss

Others

• Fever
• Increased perspiration
• Transient pain at the injection site

• Potassium sparing diuretics
• Potassium supplements
• Antihypertensives
• Antipsychotics 
• Antiarrhythmics
• QT prolonging agents
• Cardiac glycosides 
• Vasodilators 
• Renin inhibitors 
• Nitrates
• Lithium 
• Sucralfate 
• Bile acid sequestrants 
• Non-steroidal anti-inflammatory drugs
• Salicylates 
• Antibiotics 
• Antidepressants 
• Antidiabetics 
• Antiepileptics 
• Antihistamines 
• Amphotericin
• Anxiolytics
• Central nervous system stimulants
• Diuretics
• Hypnotics 
• Corticosteroids 
• Cytotoxics 
• Levodopa
• Aldesleukin
• Muscle relaxants
• Baclofen
• Oestrogens
• Progestogens 
• Alprostadil
• Sympathomimetics 
• Theophylline 
• Probenecid 
• Anaesthetic agents 
• Alcohol 
• Laxatives
• Liquorice

Specific cases may require

• Renal function
• Hepatic function
• Full blood count
• Serum electrolytes
• Fluid balance
• Audiometry

Furosemide is a potent loop diuretic which inhibits sodium and chloride reabsorption at the proximal and distal tubules and in the Loop of Henle, thus increasing the urinary excretion of sodium, chloride and water. Urinary excretion of potassium, calcium and magnesium are also increased, together with bicarbonate.

Tablet 20mg

• Austell-Furosemide (Austell)
• Lasix (Sanofi) originator

Tablet 40mg

• Austell-Furosemide (Austell)
• Dino-Retic (F.D.C. SA)
• Diuresix (Innovata)
• Furobe (Unimed Healthcare)
• Furosemide 40 Unimed (Unimed Healthcare)
• Lasix (Sanofi) originator
• Mylan Furosemide (Mylan)
• Puresis (Pharmacare)
• Sandoz Furosemide (Sandoz)

Tablet 80mg 

• Lasix (Sanofi) originator

Tablet 500mg 

• Lasix (Sanofi) originator

Capsule 40mg

• Aquarid (Alliance)

Capsule retard 60mg

• Lasix Retard (Sanofi) originator

Solution (per ml) 10mg

• Lasix Oral Solution (Sanofi) originator