Furosemide Injection 10mg In 1ml
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Furosemide Injection 10mg in 1ml
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Furosemide Ph. Eur. 1% w/v
3 PHARMACEUTICAL FORM
A hypotonic sterile solution for injection
4. CLINICAL PARTICULARS
4.1. Therapeutic Indications
Furosemide is a diuretic indicated for use when a prompt and effective diuresis is required. The intravenous formulation is appropriate for use in emergencies or when oral therapy is precluded. Indications include cardiac, pulmonary, hepatic and renal oedema.
4.2. Posology and Method of Administration
Route of administration is by intravenous injection.
Adults
Furosemide injection must always be given slowly. The diuretic effect is proportional to the dose. An infusion rate of 4mg/minute should not be exceeded. In patients with severe impairment of renal function it is recommended that an infusion rate of 2.5mg per minute is not exceeded.
Doses of 20mg to 50mg intravenously may be given initially. If larger doses are required, they should be given increasing by 20mg increments and not given more than every two hours. If doses greater than 50mg are required it is recommended that they are given by slow intravenous infusion. The recommended maximum daily dose of furosemide administration is 1,500mg.
To achieve optimum efficacy and suppress counter-regulation, a continous Furosemide infusion is generally to be preferred to repeat 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.
Elderly
The dose recommendations for adults apply. Furosemide is generally eliminated more slowly in the elderly. Dosage should be titrated until the required response is achieved.
Children
Dosage ranges from 0.5 to 1.5mg/kg body weight daily up to a maximum total daily dose of 20mg.
4.3. Contra-Indications
Furosemide Injection is contra-indicated in patients with hypovolaemia or dehydration, anuria or renal failure with anuria not responding to furosemide, renal failure as a result of poisoning by nephrotoxic or hepatotoxic agents or renal failure associated with hepatic coma, severe hypokalaemia, severe hyponatraemia, pre-comatose and comatose states associated with hepatic encephalopathy and breast-feeding women.
Hypersensitivity to Furosemide or any of the excipients of Furoemide Injection. Patients allergic to sulphonamides may show cross-sensitivity to Furosemide.
4.4. Special Warnings and Special Precautions for Use
Furosemide Injection 10 mg in 1 ml is a hypotonic solution. The recommended rate of infusion should not be exceeded. (See section 4.2 Posology and Administration). Caution should be observed in patients liable to electrolyte deficiency. Regular monitoring of serum sodium, potassium and creatinine is recommended; particularly close monitoring is required in patients at high risk of developing electrolyte imbalances or in case of significant additional fluid loss. Hypovolaemia or dehydration as well as any significant electrolyte and acid-base disturbances must be corrected. This may require temporary discontinuation of furosemide.
Special warnings for the use of Furosemide include that latent diabetes may become manifest or the insulin requirements of diabetic patients may increase.
Patients with prostatic hypertrophy or impairment of micturition haven an increased risk of developing acute retention.
Where indicated, steps should be taken to correct hypotension or hypovolaemia before commencing therapy.
Caution should be observed in patients liable to electrolyte deficiency.
Care should be taken when administering to premature infants as they may develop nephrocalcinosis nephrolithiasis; renal function must be monitored and renal ultrasonography performed.
Particularly careful monitoring is necessary in patients with hypotension and those who are at risk from a pronounced fall in blood pressure. Care should also be taken in patients with gout or hepatorenal syndrome.
Cautious dose titration is required in patients suffering from hypoproteinaemia as the effect of Furosemide is weakened and its ototoxicity potentiated.
4.5 Interaction with other medicinal products and other forms of interaction
The dosage of concurrently administered cardiac glycosides or antihypertensive agents may require adjustment.
The toxic effects of nephrotoxic antibiotics may be increased by concomitant administration of potent diuretics such as furosemide.
As with other diuretics, serum lithium levels may be increased when lithium is given concomitantly, necessitating adjustment of lithium dosage.
Certain non-steroidal anti inflammatory agents have been shown to antagonise the action of diuretics such as Furosemide and may cause renal failure in cases of pre-existing hypovolaemia or dehydration.
Furosemide may potentiate the ototoxicity of aminoglycosides and other ototoxic drugs. Since this may lead to irreversible damage, these drugs must only be used with furosemide if there are compelling medical reasons. Interactions have been reported with ototoxic antibiotics and parenteral cisplatin.
Corticosteroids administered concurrently may cause sodium retention and exacerbate potassium loss.
A marked fall in blood pressure may be seen when ACE inhibitors are added to furosemide therapy. The dose of furosemide should be reduced, or the drug stopped, before initiating the ACE inhibitor.
Impairment of renal function may develop in patients receiving treatment with furosemide and high doses of certain cephalosporins.
Concomitant administration of carbamazepine or aminoglutethimide may increase the risk of hyponatraemia.
Furosemide may sometimes attenuate the effects of other drugs (eg antidiabetes and pressor amines) and sometimes potentiate them (eg salicylates, theophylline, lithium, phenytoin and curare type muscle relaxants).
4.6. Pregnancy and Lactation
Pregnancy
Data from animal studies indicate furosemide has no hazardous effect on pregnancy. There is also clinical evidence of safety of furosemide in the third trimester of pregnancy; however, furosemide should only be used in pregnancy when strictly indicated and for short term treatment.
Lactation
As furosemide may inhibit lactation or be excreted in breast milk, it should be used with caution in nursing mothers.
4.7. Effects on Ability to Drive and Use Machines
Reduced mental alertness may impair ability to drive or operate dangerous machinery.
4.8 Undesirable effects
Furosemide is generally well tolerated.
Eosinophilia is rare.
Nausea, malaise or gastric upset may occur but are not usually severe enough to necessitate withdrawal of treatment.
As 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 water. In addition excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased. Symptomatic electrolyte disturbance and metabolic alkalosis may develop in the form of gradually increasing electrolyte deficit or, e.g. where higher Furosemide doses are adminstered to patients with normal renal function, acute severe electrolyte losses. Warning signs of electrolyte disturbances include increased thirst, headache, hypotension, confusion, muscle cramps, tetany, muscle weakness, disorders of cardiac rhythm, and gastrointestinal symptoms. Pre-existing metabolic alkalosis (e.g. in decompenstaed cirrhosis of the liver) may be aggravated by Furosemide treatment.
Calcium depletion may occur; in very rare cases tetany has been observed. Nephrocalcinosis/ has been reported in premature infants.
The incidence of allergic reactions, such as skin rashes, or interstitial nephritis or shock, is very low but treatment should be withdrawn when these occur. Standard measures for the treatment of shock should be taken.
Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, erythema multiforme, exfoliative dermatitis, purpura.
Auditory disorders and acute pancreatitis have been reported with high dose parenteral furosemide.
A transient rise in creatinine and urea levels have been reported with furosemide, as with other diuretics.
In common with other sulphonamide based diuretics, hyperuricaemia may occur and, in rare cases, clinical gout has been precipitated.
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.
Increased production of urine may provoke or aggravate complaints in patients with an obstruction of urinary outflow. Thus acute retention of urine with possible secondary complications may occur, for example in patients with bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra.
If furosemide is administered to premature infants in the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.
Severe anaphylactoid reactions (e.g. with shock) occur rarely.
Bone marrow depression has been reported as a rare complication and necessitates withdrawal of treatment.
Occasionally, thrombocytopenia may occur. In rare cases, leucopenia, and in isolated cases, agranulocytosis, aplastic anaemia or haemolytic anaemia may develop.
Rarely, paraesthesiae may occur.
There may be aggravation of metabolic alkalosis.
Serum cholesterol and triglyceride levels may rise during furosemide treatment but will usually return to normal within 6 months.
Glucose 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.
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.
4.9. Overdose
In case of overdose there is danger of dehydration and electrolyte depletion due to excessive diuresis. 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 specific 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).
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Furosemide inhibits the re-absorption of electrolytes primarily in the thick ascending limb of the loop of Henle and also have a direct effect in the distal renal tubules. It may also have a direct in the proximal tubules. Excretion of sodium, potassium, calcium and chloride ions is increased and water excretion enhanced. It has no clinically significant effect on carbonic anhydrase.
5.2. Pharmacokinetic Properties
The half life of furosemide is up to about 2 hours although it is prolonged in neonates and in patients with renal and hepatic insufficiency. It is up to about 99% bound to plasma albumin and is mainly excreted in the urine, largely unchanged. Furosemide crosses the placental barrier and is excreted in milk. The clearance of furosemide is not increased by haemodialysis.
5.3. Preclinical Safety Data
There is no pre-clinical data of relevance to the prescriber which is additional to that already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Sodium chloride Sodium hydroxide Water Nitrogen
6.2. Incompatibilities
Solutions should not be mixed with Glucose injection or other acidic solutions
Furosemide may precipitate out of solution in fluids of low pH (e.g. dextrose solutions).
6.3. Shelf Life
24 months
6.4. Special Precautions for Storage
Do not store above 25°C. Do not refrigerate. Store in the original container.
6.5.
Nature and Contents of Container
8ml of a sterile solution for injection presented in a Glass (Type I) 10ml prefilled syringe, Rubber piston PH 701/50/C Black and Tip cap rubber W1883.
6.6. Instruction for Use, Handling and Disposal
Use once and discard any remaining solution.
No needle is provided with this syringe.
Do not use the product if the packaging is damaged.
7. MARKETING AUTHORISATION HOLDER
Aurum Pharmaceuticals Ltd Bampton Road Harold Hill Romford
Essex RM3 8UG United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PL 12064/0076
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
23/02/2009
10 DATE OF REVISION OF THE TEXT
17/04/2004