Furosemide

Registered South African indications:

• Cardiac oedema
• Ascites due to cirrhosis of the liver, mechanical obstruction or cardiac failure
• Renal oedema (in nephrotic syndrome, usually in conjunction with ACTH or corticosteroids)
• Pulmonary oedema
• Cerebral oedema
• Forced diuresis, e.g. management of barbiturate poisoning
• Burns, to reduce local oedema and to prevent oliguria from progressing to complete anuria
• Oliguria in acute or chronic renal failure, chronic renal insufficiency
• Conditions of fluid overloaded when IV therapy is indicated

Contraindications

Registered South African contraindications

20mg/2ml

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to sulphonamides
• Increased uraemia, azotaemia, and oliguria occurring during treatment of severe progressive renal disease
• Renal failure associated with hepatic coma, severe hypokalemia, severe hyponatremia, and in pre-comatose and comatose states associated with hepatic encephalopathy
• In states of electrolyte depletion, hypovolemia, dehydration, and hypotension
• Anuria or renal failure due to nephrotoxic or hepatotoxic medicines
• Pre-comatose states associated with hepatic cirrhosis
• Addison’s disease or pre-existing hypercalcemia
• Breastfeeding women

50mg/5ml

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to sulphonamides
• Anuria
• Renal failure due to nephrotoxic or hepatotoxic medicines
• Renal failure associated with hepatic coma
• Pre-comatose states associated with hepatic cirrhosis
• Breastfeeding

250mg/25ml

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to amiloride, sulphonamides, sulphonamide derivatives (cross-sensitivity exists between sulphonamides and furosemide)
• Hypovolaemia and dehydration (with or without accompanying hypotension)
• Severe hypokalaemia
• Severe hyponatraemia
• Comatose or pre-comatose states associated with hepatic cirrhosis
• Pregnancy
• Lactation
• Anuria or in renal failure due to nephrotoxic or hepatotoxic medicines nor in renal failure associated with hepatic coma
• Impaired renal function with a CrCl<30ml/min/1.73m² body surface area
• Patients with Addison’s disease or pre-existing hypercalcaemia
• Digoxin intoxication
• Porphyria

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to sulphonamides (possible cross-allergy with furosemide)
• Renal failure with anuria not responding to furosemide therapy
• Renal failure as a result of poisoning by nephrotoxic or hepatotoxic agents
• Renal failure associated with hepatic coma
• Coma and hepatic precoma associated with hepatic encephalopathy
• Severe hypokalemia
• Severe hyponatremia
• Hypovolemia or dehydration
• Breastfeeding women

Cautions

• Pregnancy  (20mg/2ml, 50mg/5ml) (South African recommendations)  
• Pregnancy (Recommendations in other jurisdictions)
• Renal impairment (20mg/2ml, 50mg/5ml) (South African recommendations)
• Renal impairment (CrCl≥30ml/min/1.73m²) (250mg/25ml) (South African recommendations)
• Renal impairment (eGFR<30ml/ml/1.73m²) (Recommendations in other jurisdictions)
• Hepatic impairment
• Elderly
• Hypovolaemia
• Electrolyte imbalances
• Hepatic cirrhosis
• Ascites 
• Hepato-renal syndrome
• Diabetes mellitus
• Prostatic hyperplasia
• Urinary stricture
• Gout
• Hypoproteinaemia
• Porphyria
• Premature infants

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

20mg/2ml

Cardiac oedema
- All forms of cardiac oedema in conjunction with adequate glycoside therapy
Ascites due to cirrhosis of the liver, mechanical obstruction or cardiac failure
Renal oedema (in nephrotic syndrome, usually in conjunction with ACTH or corticosteroids)
Cerebral oedema
Burns, to reduce local oedema and to prevent oliguria from progressing to complete anuria

• IV: 20-40mg, can be repeated after a minimum of 2hrs if necessary

Pulmonary oedema

• IV: Initial: 40mg; Repeated after 60-90min, if necessary

Forced diuresis, e.g. management of barbiturate poisoning

• IV: 20-40mg, in addition to electrolyte solution infusion; Further treatment varies based on urine elimination and must include substitution of the fluid and electrolyte losses

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Intravenous furosemide should be injected slowly. The rate of injection of 4mg/minute should not be exceeded

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IV/IM: Indicated where intestinal absorption is impaired or rapid diuresis/fluid elimination is necessary. The rapid and powerful effect produced by intravenous injection may result in a transitory fall in plasma volume

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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

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50mg/5ml

Cardiac oedema
Renal or hepatic oedema
Cerebral oedema
Conditions of fluid overloaded when IV therapy is indicated

• IV/IM: 20-50mg, can be repeated after a minimum of 2hrs if necessary

Acute pulmonary oedema

• IV: Initial: 40mg, given slowly; Repeated after 60min, if necessary; Increase to 80mg, as needed

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Intravenous injection should be given slowly. The rate of injection of 4mg/minute should not be exceeded. Intravenous or intramuscular administration of furosemide injection is indicated where intestinal absorption is impaired or prompt diuresis is required

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Furosemide is an anthranilic acid derivative and dissolves in alkaline media with salt formation

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The solution for parenteral application contains the sodium salt of the carboxylic acid without a solubiliser. The solution has a pH of about 9 but no buffer capacity, which means that the medicine may precipitate at pH values below 7. If the ready-to-use solution has a pH ranging from weakly alkaline to neutral, the mixture may be used for up to 24 hours

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Furosemide must not be mixed with other medicines in the same injection syringe. The duration of treatment is at the physician’s discretion

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250mg/25ml

Oliguria in acute or chronic renal failure, chronic renal insufficiency

• IV: Effective dose (up to 1g), may be given as a slow infusion daily; Adjust dose according to patient's response​​​​​: 250mg diluted to 250ml in a suitable diluent infused over 1hr; If urine output is insufficient within an hour, this dose may be followed by 500mg added to an infusion fluid, the volume of which must be governed by the patient’s state of hydration, and infused over 2hrs; If urine output is still not satisfactory within 1hr of the end of the second infusion, a third dose of 1g may be infused over 4hrs

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Patients not responding to 1g furosemide 250mg/25ml probably require dialysis

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Method of administration
250mg (furosemide 250mg/25ml) diluted to 250ml in a suitable diluent infused over one hour
Suitable diluents include dextrose 5%; ringers lactate; sodium chloride 0.9% or dextrose 10% or 20% in water
In oliguria or anuric patients with significant fluid overload, the injection may be given directly into the vein at an administration rate never to exceed 4mg/minute

Paed. forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

20mg/2ml

Cardiac oedema
- All forms of cardiac oedema in conjunction with adequate glycoside therapy
Ascites due to cirrhosis of the liver, mechanical obstruction or cardiac failure
Renal oedema (in nephrotic syndrome, usually in conjunction with ACTH or corticosteroids)
Cerebral oedema
Burns, to reduce local oedema and to prevent oliguria from progressing to complete anuria
Pulmonary oedema
Forced diuresis, e.g. management of barbiturate poisoning

Infants and children below 15 years

• IV: 1mg/kg body mass per day; Up to a max. of 20mg per day

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50mg/5ml

Cardiac oedema
Renal or hepatic oedema
Acute pulmonary oedema
Cerebral oedema
Conditions of fluid overloaded when IV therapy is indicated

Infants and children below 15 years

• IV: 0.5-1.5mg/kg body mass per day; Up to a max. of 20mg per day

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Intravenous injection should be given slowly. The rate of injection of 4mg/minute should not be exceeded. Should be used parenterally (if necessary, continuous drip infusion) only in life-threatening situations

---

Intravenous or intramuscular administration of furosemide injection is indicated where intestinal absorption is impaired or prompt diuresis is required

---

Furosemide is an anthranilic acid derivative and dissolves in alkaline media with salt formation

---

The solution for parenteral application contains the sodium salt of the carboxylic acid without a solubiliser. The solution has a pH of about 9 but no buffer capacity, which means that the medicine may precipitate at pH values below 7. If the ready-to-use solution has a pH ranging from weakly alkaline to neutral, the mixture may be used for up to 24 hours

---

Furosemide must not be mixed with other medicines in the same injection syringe. The duration of treatment is at the physician’s discretion

---

250mg/25ml

• No specific paediatric recommendations provided

---

Parenteral administration (if necessary, continuous drip infusion) is indicated only in life threatening conditions

---

Intravenous furosemide should be injected slowly. The rate of injection of 4mg/minute should not be exceeded

---

IV/IM: Indicated where intestinal absorption is impaired or rapid diuresis/fluid elimination is necessary. The rapid and powerful effect produced by intravenous injection may result in a transitory fall in plasma volume

---

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

20mg/2ml, 50mg/5ml

• Caution
• Safety in pregnancy has not been established
• Animal data indicate that furosemide may cause foetal abnormalities
• Furosemide crosses the placental barrier. As furosemide is a potent diuretic, reduction in maternal blood volume following administration could compromise placental perfusion
• It should not be given during pregnancy unless there are compelling medical reasons
• Treatment during pregnancy requires monitoring of foetal growth

250mg/25ml

• Contraindicated
• The safety of furosemide in pregnancy has not been established
• Furosemide should not be used during pregnancy since it crosses the placenta. Furosemide may compromise placental perfusion by reducing maternal blood volume

Recommendations in other jurisdictions

• Caution
• Furosemide should only be used in pregnancy for short periods and only after a particularly careful review of the indication for its use, as furosemide crosses the placental barrier
• Diuretics are not suitable for the routine treatment of hypertension and oedemas in pregnancy, as they impair placental perfusion and thus intrauterine growth
• If it is necessary to administer furosemide to pregnant women with heart failure or renal impairment, electrolytes and haematocrit, as well as foetal growth, must be closely monitored
• Displacement of bilirubin from its albumin-binding sites and hence an increased risk of kernicterus in the presence of hyperbilirubinaemia has been discussed for furosemide
• Furosemide crosses the placenta and reaches 100% of maternal serum concentrations in umbilical cord blood
• No malformations in humans have been reported to date, which might be associated with furosemide exposure
• However, there is limited experience to allow a conclusive evaluation of any potential harmful effect on the embryo/foetus
• Foetal urine production may be stimulated in utero. In the treatment of preterm infants with furosemide, urolithiasis has been observed to occur

Breastfeeding

South African recommendations

• Contraindicated
• Furosemide passes into breast milk and may inhibit lactation
• Women must not breastfeed if they are treated with furosemide

Recommendations in other jurisdictions

• Contraindicated
• Furosemide is excreted in human milk and inhibits lactation. Women must therefore not be treated with furosemide if they are breastfeeding. If applicable, breastfeeding should be discontinued

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No information available

South African recommendations

20mg/2ml

• Caution; no dose adjustment recommended
• Increased uraemia, azotaemia and oliguria occurring during treatment of severe progressive renal disease: Contraindicated
• Renal failure associated with hepatic coma, severe hypokalaemia, severe hyponatraemia and in pre-comatose and comatose states associated with hepatic encephalopathy: Contraindicated
• Anuria, or renal failure due to nephrotoxic or hepatotoxic medicines: Contraindicated

50mg/5ml

• Caution; no dose adjustment recommended
  Should be used with caution in patients with antibiotic- induced renal impairment
• Renal failure due to nephrotoxic or hepatotoxic medicines: Contraindicated
• Renal failure associated with hepatic coma: Contraindicated

250mg/25ml

• CrCl≥30ml/min/1.73m²: 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
• CrCl<30ml/min/1.73m²: Contraindicated
• Anuria or renal failure due to nephrotoxic or hepatotoxic medicines: Contraindicated
• Renal failure associated with hepatic coma: Contraindicated

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
Hemodialysis, intermittent (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

*In patients with advanced renal failure (serum creatinine >442micromol/l [>5mg/dl]), the injection/infusion rate should not exceed 0.25ml solution per minute (equivalent to 2.5mg furosemide per minute)

South African recommendations

• Caution; no dose adjustment recommended (20mg/2ml, 250mg/25ml)
  Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment (250mg/25ml)
  Where liver disease is present, biliary elimination is reduced up to 50% (250mg/25ml)
• Caution; no information available (50mg/5ml)
• Comatose or pre-comatose states associated with hepatic cirrhosis: Contraindicated (20mg/2ml, 50mg/5ml, 250mg/25ml)
• Pre-comatose and comatose states associated with hepatic encephalopathy: Contraindicated (20mg/2ml)

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
• Coma and hepatic precoma associated with hepatic encephalopathy: Contraindicated

South African recommendations

20mg/2ml

• Caution; no dose adjustment recommended
  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
  Caution should be observed in patients liable to electrolyte deficiency, such as the elderly

50mg/5ml

• Caution; no information available

250mg/25ml

• Caution; dose adjustment recommended
  Lower initial dose as elderly patients are particularly susceptible to side effects
  The diuretic effect can result in hypovolaemia and dehydration, especially in the elderly. There is an increased risk of thrombosis
  The elimination of furosemide is delayed in elderly patients where a certain degree of renal impairment is present

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  The recommended initial dose is 20mg daily, increasing gradually 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 
• Abdominal pain and cramping

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
• Thrombophlebitis

• 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.

Solution (per ml) 10mg

• Lasix Oral Solution (Sanofi) originator

Injection (per 2ml) 20mg

• A-Lennon Furosemide (Pharmacare)
• Furosemide Fresenius (Fresenius)
• Lasix (Sanofi) originator
• Litha Furosemide injection 20mg/2ml (Litha Pharma)
• Pharma-Q Furosemide (Pharma-Q)
• Sabax Furosemide (Adcock)

Injection (per 5ml) 50mg

• Furosemide Fresenius (Fresenius)
• Pharma-Q Furosemide (Pharma-Q)

Injection (per 25ml) 250mg

• Furosemide Fresenius (Fresenius)