Each mL contains: Furosemide 10 mg.
Pharmacology: Pharmacodynamics: Mechanism of Action: It appears to act primarily by inhibiting active reabsorption of chloride ions in the ascending limb of the loop of Henle. Urinary excretion of sodium, chloride, potassium, hydrogen, calcium, magnesium, ammonium, bicarbonate, and possibly phosphate is increased; the chloride excretion exceeds that of sodium and there is an enhanced exchange of sodium for potassium leading to greater excretion of potassium. The resulting low osmolality of the medulla inhibits the reabsorption of water by the kidney. There is a possibility that furosemide may also act at a more proximal site.
Pharmacokinetics: Furosemide is highly bound to plasma proteins, almost exclusively to albumin. The proportion of free (unbound) furosemide is higher in patients with heart disease, renal impairment, and cirrhosis of the liver. Patients with liver disease also have an increased apparent volume of distribution which is proportionally greater than the observed decrease in protein binding. Patients with nephrotic syndrome have significant proteinuria and secondary hypoalbuminaemia. This results in reduced protein binding in the blood, particularly at higher blood concentrations, and binding to proteins present in the urine, which may account for the resistance to furosemide therapy reported in these patients. A glucuronide metabolite of furosemide is produced in varying amounts. The site of metabolism is unknown at present. There is debate over another potential metabolite, 4-chloro-5-sulfamoyl anthranilic acid (CSA). It has been argued that it is an artifact produced during the extraction procedures although there is some evidence to refute this. A half-life for furosemide in healthy subjects has generally been reported in the range of 30 to 120 minutes. In patients with endstage renal disease the average half-life is 9.7 hours. The half-life may be slightly longer in patients with hepatic dysfunction and a range of 50 to 327 minutes has been reported in patients with heart failure. In severe multi-organ failure the half-life may range from 20 to 24 hours. Furosemide clearance is influenced by age, underlying disease state, and drug interactions. Clearance reduces with increasing age, probably due to declining renal function. Renal impairment in renal or cardiac disease reduces renal clearance, although this may be compensated for by increases in non-renal clearance. Hepatic impairment has little impact on clearance. Renal and nonrenal clearance may be reduced by probenecid and indometacin.
The effectiveness of furosemide as a diuretic depends upon it reaching its site of action, the renal tubules, unchanged. About one-half to two-thirds of an intravenous dose are excreted unchanged, the difference being largely due to the poor bioavailability from the oral route. The effect of furosemide is more closely related to its urinary excretion than to the plasma concentration. Urinary excretion may be reduced in renal impairment due to reduced renal blood flow and reduced tubular secretion.
Furosemide is used in the treatment of edema associated with heart failure including pulmonary edema, and with renal and hepatic disorders and may be effective in patients unresponsive to thiazide diuretics.
20 to 50 mg of furosemide may be given by slow intravenous injection; intramuscular injection may be given in exceptional cases but is not suitable for acute conditions. If necessary further doses may be given, increasing by 20-mg increments and not given more often than every 2 hours. If doses above 50 mg are required they should be given by slow intravenous infusion.
For pulmonary edema, if an initial slow intravenous injection of 40 mg does not produce a satisfactory response within one hour, a further 80 mg may be given slowly intravenously.
For children, the usual oral dose is 1 to 3 mg/kg daily up to a maximum of 40 mg daily; doses by injection are 0.5 to 1.5 mg/kg daily up to a maximum of 20 mg daily.
High-dose therapy. In the management of oliguria in acute or chronic renal failure where the glomerular filtration rate is less than 20 mL/minute but greater than 5 mL/minute, furosemide 250 mg diluted to 250 mL in a suitable diluent is infused over one hour. If urine output is insufficient within the next hour, this dose may be followed by 500 mg added to an appropriate infusion fluid, the total volume of which must be governed by the patient's state of hydration, and infused over about 2 hours. If a satisfactory urine output has still not been achieved within one hour of the end of the second infusion then a third dose of 1 g may be infused over about 4 hours. The rate of infusion should never exceed 4 mg/minute. In oliguric patients with significant fluid overload, the injection may be given without dilution directly into the vein, using a constant rate infusion pump with a micrometer screw-gauge adjustment; the rate should still never exceed 4 mg/minute. Patients who do not respond to a dose of 1 g probably require dialysis. If the response to either dosage method is satisfactory, the effective dose (of up to 1 g) may then be repeated every 24 hours. Dosage adjustments should subsequently be made according to the patient's response.
Single dose. Discard any remaining portion.
It should not be given in anuria or in renal failure caused by nephrotoxic or hepatotoxic drugs nor in renal failure associated with hepatic coma. Furosemide should not be given in pre-comatose states associated with hepatic cirrhosis. It should be used with care in patients with prostatic hyperplesia or impairment of micturition that furosemide should not be injected intravenously at a rate exceeding 4 mg/minute although the BNF advises that a single dose of up to 800 mg may be given more rapidly.
Contraindicated are dependent on its effects on fluid and electrolyte balance are similar to those of the thiazide diuretics. Although furosemide is used in high doses for oliguria due to chronic or acute renal impairment it should not be given in anuria or in renal failure caused by nephrotoxic or hepatotoxic drugs nor in renal failure associated with hepatic coma. Furosemide should not be given in pre-comatose states associated with hepatic cirrhosis. It should be used with care in patients with prostatic hyperplasia or impairment of micturition since it can precipitate acute urinary retention.
Contains Sodium Sulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible persons.
Use in Pregnancy and Lactation: Furosemide should be used with caution during pregnancy and breast feeding since it crosses the placenta and also appears in breast milk. Furosemide may compromise placental perfusion by reducing maternal blood volume; it may also inhibit lactation.
Most adverse effects of furosemide occur with high doses, and serious effects are uncommon. The most common adverse effects is fluid and electrolyte imbalance including hyponatraemia, hypokalaemia, and hypochloraemic alkalosis, particularly after large doses or prolonged use. Signs of electrolyte imbalance include headache, hypotension, muscle cramps, dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, oliguria, cardiac arrhythmias, and gastrointestinal disturbances. Hypovolaemia and dehydration may occur, especially in the elderly. Because of their shorter duration of action, the risk of hypokalaemia may be less with loop diuretics such as furosemide than with thiazide diuretics. Unlike the thiazides, furosemide increases the urinary excretion of calcium and nephrocalcinosis has been reported in preterm infants.
Furosemide may cause hyperuricaemia and precipitate gout in some patients. It may provoke hyperglycaemia and glycosuria, but probably to a lesser extent than the thiazide diuretics. Pancreatitis and cholestatic jaundice seem to occur more often than with the thiazides. Other adverse effects include blurred vision, yellow vision, dizziness, headache, and orthostatic hypotension. Other adverse effects occur rarely. Skin rashes and photosensitivity reactions may be severe; hypersensitivity reactions include interstitial nephritis and vasculitis; fever has also been reported. Bone marrow depression may occur: there have been reports of agranulocytosis, thrombocytopenia, and leucopenia. Tinnitus and deafness may occur, in particular during rapid high-dose parenteral furosemide. Deafness may be permanent, especially in patients taking other ototoxic drugs.
Furosemide may enhance the nephrotoxicity of cephalosporin antibacterials such as cefalotin and can enhance the ototoxicity of aminoglycoside antibacterials and other ototoxic drugs.
Many of the interactions of furosemide are due to their effects on fluid and electrolyte balance. Diuretic-induced hypokalaemia may enhance the toxicity of digitalis glycosides and may also increase the risk of arrhythmias with drugs that prolong the QT interval, such as astemizole, terfenadine, halofantrine, pimozide, and sotalol. Furosemide may enhance the neuromuscular blocking action of competitive neuromuscular blockers, such as atracurium, probably by their hypokalaemic effect. The potassium-depleting effect of diuretics may be enhanced by corticosteroids, corticotropin, beta2 agonists such as salbutamol, carbenoxolone, amphotericin B, or reboxetine.
Diuretics may enhance the effect of other antihypertensives, particularly the first-dose hypotension that occurs with alpha blockers or ACE inhibitors. Orthostatic hypotension associated with diuretics may be enhanced by alcohol, barbiturates, or opioids. The antihypertensive effects of diuretics may be antagonised by drugs that cause fluid retention, such as corticosteriods, NSAIDs, or carbenoxolone; diuretics may enhance the nephrotoxicity of NSAIDs. Thiazides have been reported to diminish the response to pressors amines, such as noradrenaline, but the clinical significance of this effect is uncertain. Thiazides should not usually be used with lithium since the association may lead to toxic blood concentrations of lithium. Other drugs for which increased toxicity has been reported when given with thiazides include allopurinol and tetracyclines. Thiazides may alter the requirements for hypoglycaemics in diabetic patients.
Antibacterials: Severe hyponatraemia has been reported in patients taking trimethoprim with co-amilozide and hydrochlorothiazide.
Antiepileptics: There has been a report of symptomatic hyponatraemia associated with the use of hydrochlorothiazide of furosemide and carbamazepine.
Bile-acid binding resins: Gastrointestinal absorption of both chlorothiazide and hydrochlorothiazide has been reported to be reduced by colestipol and colestyramine. In a study in healthy subjects, colestyramine had the greatest effect on hydrochlorothiazide, decreasing absorption by 85% compared with a decrease of 43% with colestipol. Even when colestyramine was given 4 hours after hydrochlorothiazide reductions of absorption of at least 30 to 35% could be expected.
Calcium salts: The milk-alkali syndrome, characterized by hypercalcaemia, metabolic alkalosis, and renal failure, developed in a patient taking chlorothiazide and moderately large doses of calcium carbonate. Patients taking thiazides may be at increased risk of developing the syndrome because of their reduced ability to excrete excess calcium. Hypercalcaemia may also occur in patients taking thiazides with drugs that increase calcium levels.
Dopaminergics: For a report of increased amantadine toxicity associated with hydrochlorothiazide and triamterene.
Store at temperatures not exceeding 30°C. Protect from light.
C03CA01 - furosemide ; Belongs to the class of high-ceiling sulfonamide diuretics.
Soln for inj (amp) 10 mg/mL x 2 mL x 10's.