Each 2mL contains Furosemide 20mg.
Pharmacology: Pharmacodynamics: Furosemide is a potent diuretic with a rapid action. Furosemide inhibits the reabsorption of electrolytes mainly in the thick ascending limb of the loop of Henle and also in the distal renal tubules. It may also have a direct effect in the proximal tubules. 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 exchanged 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 possibility that furosemide may also act at a more proximal site.
In addition to its diuretic actions, furosemide has been shown to increase peripheral venous capacitance and reduce forearm blood flow. It also reduces renal vascular resistance with a resultant increase in renal blood flow the degree of which is proportional to the initial resistance.
Furosemide has been shown to increase plasma-renin activity plasma-noradrenaline concentrations, and plasma-arginine-vasopressin concentrations. Alterations in the renin-angiotensin-aldosterone system may play a part in the development of acute tolerance. Furosemide increases renal-prostaglandin concentrations but it is unknown whether this is due to increased synthesis or inhibition of degradation or both. Prostaglandins appear to mediate the diuretic/natriuretic action. The primary effects appear to be alterations in renal haemodynamics with subsequent increases in electrolyte and fluid excretion.
The diuretic response to furosemide is related to the concentration in the urine, not to that in the plasma. Furosemide is delivered to the renal tubules by a non-specific organic acid pump in the proximal tubules.
In some cases sodium intake may be sufficient to overcome the diuretic effect and limiting sodium intake could restore responsiveness.
Pharmacokinetics: Furosemide is fairly rapidly absorbed from the gastrointestinal tract; bioavailability has been reported to be about 60-70% but absorption is variable and erratic. The half life of furosemide is up to about 2 hours although it is prolonged in neonates and in patients with renal and hepatic impairment. Furosemide is up to 99% bound to plasma albumin and is mainly excreted in the urine, largely unchanged. There is also some excretion via the bile and non-renal elimination is considerably increased in renal impairment. Furosemide crosses the placental barrier and is distributed into breast milk. The clearance of furosemide is not increased by haemodialysis.
The efficacy of furosemide as a diuretic depends upon its reaching site of action, the renal tubules, unchanged. About one-half to two-thirds of an intravenous dose or one-quarter to one-third of an oral 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 oedema associated with heart failure including pulmonary oedema, and with renal and hepatic disorders and may be effective in patients unresponsive to thiazide diuretics.
It is also used in high doses in the management of oliguria due to renal failure or insufficiency. Furosemide also used in the treatment of hypertension either alone or with other hypertensives.
Route of administration: intramuscular or intravenous.
Intravenous furosemide must be injected or infused slowly; a rate of 4mg per minute must not be exceeded. In patients with severe impairment of renal function (serum creatinine >5mg/dl), it is recommended that an infusion rate of 2.5mg per minute is not exceeded.
Intramuscular administration must be restricted to exceptional cases where neither oral nor intravenous administration are feasible. It must be noted that intramuscular injection is not suitable for the treatment of acute conditions such as pulmonary oedema.
To achieve optimum efficacy and suppress counter-regulation, a continuous furosemide infusion is generally to be preferred to repeated bolus injections. Where continuous furosemide infusion is not feasible for follow-up treatment after one or several acute bolus doses, a follow-up regimen with low doses given at short intervals (approx. 4 hours) is to be preferred to a regimen with higher bolus doses at longer intervals.
Doses of 20 to 50mg intramuscularly or intravenously may be given initially. If larger doses are required, they should be given increasing by 20mg increments and not given more often than every two hours. If doses greater than 50mg are required it is recommended that they be given by slow intravenous infusion. The recommended maximum daily dose of furosemide administration is 1,500mg.
Elderly: The dosage recommendations for adults apply, but in the elderly furosemide is generally eliminated more slowly. Dosage should be titrated until the required response is achieved.
Children: Parenteral doses for children range from 0.5 to 1.5mg/kg body weight daily up to a maximum total daily dose of 20mg.
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.
Treatment should therefore be aimed at fluid replacement and correction of the electrolyte imbalance. Together with the prevention and treatment of serious complications resulting from such disturbances and of other effects on the body, this corrective action may necessitate general and specic intensive medical monitoring and therapeutic measures.
No specific antidote to furosemide is known. If ingestion has only just taken place, attempts may be made to limit further systemic absorption of the active ingredient by measures such as gastric lavage or those designated to reduce absorption (e.g. activated charcoal).
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 cirrhosis. It should be used with care in patients with prostatic hyperplasia or impairment of micturition since it can precipitate acute urinary retention.
To reduce the risk of ototoxicity, furosemide should not be injected intravenously at a rate exceeding 4mg/minute.
Hypersensitivity: Furosemide is a sulfur-containing diuretic and hypersensitivity reactions may occur, although they are rare; cross-reactivity with other sulfur-containing drugs is also possible.
Furosemide should be used with care in patients with prostatic hyperplasia or impairment or micturition since it can precipitate acute urinary retention. It 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.
Hepatic impairment: In patients with chronic heart failure and moderate liver congestion, high-dose furosemide therapy could produce increases in liver enzymes suggestive of hepatitis. Special care should be taken in such patients to avoid severe ischaemic liver damage caused by a drop in systemic blood pressure.
As with the thiazides, furosemide should be avoided in patients with severe hepatic impairment.
There is clinical evidence of safety of the drug 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 foetal growth.
Furosemide passes into breast milk and may inhibit lactation. Women must not breast-feed if they are treated with furosemide.
Most adverse effects of furosemide occur with high doses, and serious effects are uncommon. The most common adverse effect 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. The risk of hypokalaemia may be less with loop diuretics such as furosemide, which have a short duration of action, than with thiazide diuretics. Unlike the thiazides, furosemide increase 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. 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.
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 increase the risk of arrhythmias with drugs that prolong the QT interval, such as astemizol, terfenadine, halofantrine, pimozide, and sotalol. Furosemide may also 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, corticotrophin, beta2 agonists such as salbutamol, carbenoxolone, amphotericin B, or reboxetine.
Furosemide can 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 antagonized by drugs that cause fluid retention, such as corticosteroids, NSAIDs, or carbenoxolone; the neprotoxicity of NSAIDs may also be enhanced.
Furosemide may enhance the nephrotoxicity of cephalosporin antibacterials such as cefalotin and can enhance the ototoxicity of aminoglycoside antibacterials and other ototoxic drugs.
Furosemide 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 furosemide include allopurinol and tetracyclines. Furosemide may alter the requirements for hypoglycaemics in diabetic patients.
There has been report of symptomatic hyponatraemia associated with the use of hydrochlorothiazide or furosemide and carbamazepine.
User Instructions and Pharmaceutical Precautions: Caution: Do not use if solution contains particles, growth, turbidity or if there is any change of appearance.
Store below 30ºC. Protect from light.
Shelf-Life: 3 years from date of manufacture.
C03CA01 - furosemide ; Belongs to the class of high-ceiling sulfonamide diuretics.
Inj 20 mg/2 mL (clear, colourless solution in amp) x 10's.