Furosemide 50mg/5ml Solution for Injection Taj Pharma

  1. Name of the medicinal product

Furosemide 20mg/2ml Solution for Injection Taj Pharma
Furosemide 50mg/5ml Solution for Injection Taj Pharma
Furosemide 250mg/25ml Solution for Injection Taj Pharma

  1. Qualitative and quantitative composition

a) Furosemide 20mg/2ml Solution for Injection.
Each ml contains:
Furosemide USP                          10mg
Water for injection  USP              q.s

b) Furosemide 50mg/5ml Solution for Injection.
Each ml contains:
Furosemide USP                          10mg
Water for injection  USP              q.s

c) Furosemide 250mg/25ml Solution for Injection
Each ml contains:
Furosemide USP                          10mg
Water for injection USP               q.s

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Colourless or almost colourless sterile solution intended for parenteral administration to human beings.

  1. Clinical particulars

4.1 Therapeutic indications

Furosemide is a potent diuretic and is recommended for use when prompt and effective diuresis is required.

Furosemide Injection 20mg/2ml and 50mg/5ml are appropriate for use in emergencies or where oral therapy is not feasible. The indications include cardiac, pulmonary, hepatic and renal oedema.

Furosemide Injection 250mg/25ml is for use in the management of oliguria due to acute or chronic renal insufficiency with a glomerular filtration rate below 20ml/minute.

4.2 Posology and method of administration

Posology:

Furosemide Injection 20mg/2ml and 50mg/5ml are for intramuscular or for intravenous administration and must always be given slowly. Furosemide Injection 250mg/25ml is for slow intravenous administration.

Furosemide Injection 20mg/2ml and 50mg/5ml

Adults: Initially, doses of 20 – 50mg may be administered by the intramuscular route, or by slow intravenous injection at a rate not exceeding 4mg/minute. The diuretic effect of furosemide is proportional to the dosage and, if larger doses are required, they should be given as a controlled infusion at a rate not exceeding 4mg/minute and titrated according to the response.

Elderly: Elimination of furosemide is generally slower in the elderly. Dosage should be titrated until the required effect is achieved.

Paediatric population: Dosages for children range from 0.5 – 1.5mg/kg weight daily up to a maximum total daily dose of 20mg.

Furosemide Injection 250mg/25ml

Adults: Furosemide Injection 250mg/25ml is for slow intravenous injection at a rate not exceeding 4mg/minute.

An initial dose of 250mg (one 25ml ampoule) may be added to about 225ml Sodium Chloride Injection B.P. or Ringer’s Solution for Injection, and infused over one hour at a drip rate of 80 drops/minute (4mg/minute).

If urine output within the next hour is insufficient, a dose of 500mg (two 25ml ampoules) in an appropriate infusion fluid, the total volume of which must be governed by the patient’s state of hydration, may be infused at a rate not exceeding 4mg/minute. If a satisfactory urine output has still not been achieved within one hour following the end of the second infusion, a third dose consisting of 1,000mg (four 25ml ampoules) in an appropriate infusion fluid may be given. The rate of infusion should never exceed 4mg/minute.

If the third infusion (1,000mg over 4 hours) is not effective, dialysis will probably be required.

In oliguric or anuric patients with significant fluid overload, it may not be practicable to use the aforementioned method of administration. In such cases, the use of a constant-rate infusion pump with a micrometer screw-gauge adjustment may be considered for direct administration of the injection into the vein. The rate of infusion should still never exceed 4mg/min.

If the response to either method of administration is satisfactory (urine output 40 – 50ml/hour), the effective dose (of up to 1,000mg) may be repeated every 24 hours. Alternatively, treatment may be maintained by oral administration of Furosemide Tablets, using 500mg by mouth for each 250mg required by injection. Appropriate adjustments to dosage may then be made according to the patient’s response.

Elderly: Elimination of furosemide is generally slower in the elderly. Dosage should be titrated until the required effect is achieved.

Paediatric population: Dosages for children must be determined on the basis of the severity of the renal insufficiency and on the clinical response to initial doses.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Hypersensitivity to amiloride, sulphonamides or sulphonamide derivatives

Hypovolaemia and dehydration (with or without accompanying hypotension) (see section 4.4)

Severe hypokalaemia: severe hyponatraemia (see section 4.4).

Comatose or pre-comatose states associated with hepatic cirrhosis (see section 4.4).

Anuria or renal failure with anuria not responding to furosemide, renal failure as a result of poisoning by nephrotoxic or hepatotoxic agents, renal failure associated with hepatic coma

Impaired renal function with a creatinine clearance below 30ml/min per 1.73 m2 body surface area (see section 4.4).

Addison’s disease (see section 4.4). Digitalis intoxication (see section 4.5).

Porphyria

Breast-feeding women (see section 4.6).

4.4 Special warnings and precautions for use

Conditions requiring correction before furosemide is started (see also section 4.3)

Hypotension.

Hypovolaemia.

Severe electrolyte disturbances – particularly hypokalaemia, hyponatraemia and acid-base disturbances.

Furosemide is not recommended

In patients at high risk for radiocontrast nephropathy – it should not be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy.

In patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Particular caution and/or dose reduction required:

Symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with furosemide, particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension.

Elderly people (lower initial dose as particularly susceptible to side-effects – see section 4.2)

difficulty with micturition including prostatic hypertrophy (increased risk of urinary retention: consider lower dose). Closely monitor patients with partial occlusion of the urinary tract

diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase: stop furosemide before a glucose tolerance test)

pregnancy (see section 4.6)

gout (furosemide may raise uric acid levels/precipitate gout)

patients with hepatorenal syndrome

impaired hepatic function (see section 4.3 and below – monitoring required)

impaired renal function (see section 4.3 and below – monitoring required)

adrenal disease (see section 4.3 – contraindication in Addison’s disease)

hypoproteinaemia e.g. nephritic syndrome (effect of furosemide may be impaired and its ototoxicity potentiated – cautious dose titration required).

acute hypercalcaemia (dehydration results from vomiting and diuresis – correct before giving furosemide). Treatment of hypercalcaemia with a high dose of furosemide results in fluid and electrolyte depletion – meticulous fluid replacement and correction of electrolyte required.

Patients who are at risk from a pronounced fall in blood pressure

premature infants (possible development nephrocalcinosis/nephrolithiasis; renal function must be monitored and renal ultrasonography performed).

Avoidance with other medicines (see also section 4.5 for other interactions)

concurrent NSAIDs should be avoided – if not possible diuretic effect of furosemide may be attenuated

ACE-inhibitors & Angiotensin II receptor antagonists – severe hypotension may occur – dose of furosemide should be reduced/stopped (3 days) before starting or increasing the dose of these

Laboratory monitoring requirements:

Serum sodium

Particularly in the elderly people or in patients liable to electrolyte deficiency

Serum potassium

The possibility of hypokalaemia should be taken into account, in particular in patients with cirrhosis of the liver, those receiving concomitant treatment with corticosteroids, those with an unbalanced diet and those who abuse laxatives. Regular monitoring of the potassium, and if necessary treatment with a potassium supplement, is recommended in all cases, but is essential at higher doses and in patients with impaired renal function. It is especially important in the event of concomitant treatment with digoxin, as potassium deficiency can trigger or exacerbate the symptoms of digitalis intoxication (see section 4.5). A potassium-rich diet is recommended during long-term use.

Frequent checks of the serum potassium are necessary in patients with impaired renal function and creatinine clearance below 60ml/min per 1.73m2 body surface area as well as in cases where furosemide is taken in combination with certain other drugs which may lead to an increase in potassium levels (see section 4.5 & refer to section 4.8 for details of electrolyte and metabolic abnormalities).

Renal function

Frequent BUN in first few months of treatment, periodically thereafter. Long-term/high-dose BUN should regularly be measured. Marked diuresis can cause reversible impairment of kidney function in patients with renal dysfunction. Adequate fluid intake is necessary in such patients. Serum creatinine and urea levels tend to rise during treatment.

Glucose

Adverse effect on carbohydrate metabolism – exacerbation of existing carbohydrate intolerance or diabetes mellitus. Regular monitoring of blood glucose levels is desirable.

Other electrolytes

Patients with hepatic failure/alcoholic cirrhosis are particularly at risk of hypomagnesia (as well as hypokalaemia). During long-term therapy (especially at high doses) magnesium, calcium, chloride, bicarbonate and uric acid should be regularly measured.

Clinical monitoring requirements (see also section 4.8):

Regular monitoring for blood dyscrasias. If these occur, stop furosemide immediately

liver damage

idiosyncratic reactions.

Other alterations in lab values

Serum cholesterol and triglycerides may rise but usually return to normal within 6 months of starting furosemide.

Concomitant use with risperidone

In risperidone placebo-controlled trials in elderly people with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97 years) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.

No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be avoided in elderly patients with dementia (see section 4.3 Contraindications).

4.5 Interaction with other medicinal products and other forms of interaction

General- The dosage of concurrently administered cardiac glycosides, diuretics, anti-hypertensive agents, or other drugs with blood-pressure-lowering potential may require adjustment as a more pronounced fall in blood pressure must be anticipated if given concomitantly with furosemide.

The toxic effects of nephrotoxic drugs may be increased by concomitant administration of potent diuretics such as furosemide.

Some electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia) may increase the toxicity of certain other drugs (e.g. digitalis preparations and drugs inducing QT interval prolongation syndrome).

Antihypertensives – enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors or Angiotensin II receptor antagonists can result in marked falls in blood pressure, furosemide should be stopped or the dose reduced before starting an ACE-inhibitor or Angiotensin II receptor antagonists (see section 4.4)

Antipsychotics – furosemide-induced hypokalaemia increases the risk of cardiac toxicity. Avoid concurrent use with pimozide. Increased risk of ventricular arrhythmias with amisulpride or sertindole. Enhanced hypotensive effect with phenothiazines.

When administering risperidone, caution should be exercised and the risks and benefits of the combination or co-treatment with furosemide or with other potent diuretics should be considered prior to the decision to use. See section 4.4 Special warnings and precautions for use regarding increased mortality in elderly patients with dementia concomitantly receiving risperidone

Anti-arrhythmics (including amiodarone, disopyramide, flecanaide and sotalol) – risk of cardiac toxicity (because of furosemide-induced hypokalaemia). The effects of lidocaine, tocainide or mexiletine may be antagonised by furosemide.

Cardiac glycosides – hypokalaemia and electrolyte disturbances (including hypomagnesia) increase the risk of cardiac toxicity.

Drugs that prolong Q-T interval – increased risk of toxicity with furosemide-induced electrolyte disturbances

Vasodilators – enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine

Other diuretics – profound diures is possible when furosemide given with metolazone.

Increased risk of hypokalaemia with thiazides.

Renin inhibitors – aliskiren reduces plasma concentrations of furosemide

Nitrates – enhanced hypotensive effect

Lithium – In common with other diuretics, serum lithium levels may be increased when lithium is given concomitantly with furosemide, resulting in increased lithium toxicity, including increased risk of cardiotoxic and neurotoxic effects of lithium. Therefore, it is recommended that lithium levels are carefully monitored and where necessary the lithium dosage is adjusted in patients receiving this combination.

Chelating agents – sucralfate may decrease the gastro-intestinal absorption of furosemide – the 2 drugs should be taken at least 2 hours apart

NSAIDs – increased risk of nephrotoxicity. Indometacin and ketorolac may antagonise the effects of furosemide (avoid if possible see section 4.4). NSAIDs may attenuate the action of furosemide and may cause acute renal failure in cases of pre-existing hypovolaemia or dehydration.

Salicylates – effects may be potentiated by furosemide. Salycylic toxicity may be increased by furosemide

Antibiotics – increased risk of ototoxicity with aminoglycosides, polymixins or vancomycin – only use concurrently if compelling reasons. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide can decrease vancomycin serum levels after cardiac surgery. Increased risk of hyponatraemia with trimethoprim. Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins.

Antidepressants – enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Increased risk of hypokalaemia with reboxetine

Antidiabetics – hypoglycaemic effects antagonised by furosemide

Antiepileptics – increased risk of hyponatraemia with carbamazepine. Diuretic effect reduced by phenytoin.

Antihistamines – hypokalaemia with increased risk of cardiac toxicity

Antifungals – increased risk of hypokalaemia and nephrotoxicity with amphotericin

Anxiolytics and hypnotics – enhanced hypotensive effect. Chloral or triclorfos may displace thyroid hormone from binding site.

CNS stimulants (drugs used for ADHD) – hypokalaemia increases the risk of ventricular arrhythmias

Corticosteroids – diuretic effect anatgonised (sodium retention) and increased risk of hypokalaemia

Glychyrrizin -(contained in liquorice) may and increase the risk of developing hypokalaemia.

Cytotoxics – increased risk of nephrotoxicity and ototoxicity with platinum compounds/cisplatin. Nephrotoxicity of cisplatin may be enhanced if furosemide is not given in low doses (e.g. 40 mg in patients with normal renal function) and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.

Anti-metabolites – effects of furosemide may be reduced by methotrexate and furosemide may reduce renal clearance of methotrexate

Dopaminergics – enhanced hypotensive effect with levodopa.

Immunomodulators – enhanced hypotensive effect with aldesleukin. Increased risk of hyperkalaemia with ciclosprin and tacrolimus. Increased risk of gouty arthritis with ciclosporin

Muscle relaxants – enhanced hypotensive effect with baclofen or tizanidine. Increased effect of curare-like muscle relaxants

Oestrogens – diuretic effect antagonised

Progestogens (drosperidone) – increased risk of hyperkalaemia

Prostaglandins – enhanced hypotensive effect with alprostadil

Sympathomimetics – increased risk of hypokalaemia with high doses of beta2 sympathomimetics

Theophylline – enhanced hypotensive effect

Probenecid – effects of furosemide may be reduced by probenecid and furosemide may reduce renal clearance of probenecid.

Anaesthetic agents – general anaesthetic agents may enhance the hypotensive effects of furosemide. The effects of curare may be enhanced by furosemide.

Alcohol – enhanced hypotensive effect

Laxative abuse – increases the risk of potassium loss

Others: Concomitant administration of aminoglutethimide may increase the risk of hyponatraemia.

4.6 Fertility, pregnancy and lactation

Pregnancy

Furosemide crosses the placental barrier and should not be given during pregnancy unless there are compelling medical reasons. It should only be used for the pathological causes of oedema which are not directly or indirectly linked to the pregnancy. The treatment with diuretics of oedema and hypertension caused by pregnancy is undesirable because placental perfusion can be reduced, so, if used, monitoring of fetal growth is required. However, furosemide has been given after the first trimester of pregnancy for oedema, hypertension and toxaemia of pregnancy without causing fetal or newborn adverse effects.

Breast-feeding (see section 4.3)

Furosemide is contraindicated as it passes into breast milk and may inhibit lactation.

4.7 Effects on ability to drive and use machines

Reduced mental alertness, dizziness and blurred vision have been reported, particularly at the start of treatment, with dose changes and in combination with alcohol. Patients should be advised that if affected, they should not drive, operate machinery or take part in activities where these effects could put themselves or others at risk.

4.8 Undesirable effects

Undesirable effects can occur with the following frequencies: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000, including isolated reports), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders:

Uncommon:

thrombocytopenia

Rare: Eosinophilia, Leukopenia, Bone marrow depression (necessitates withdrawal of treatment). The haemopoietic status should be therefore be regularly monitored.

Very Rare:

aplastic anaemia or haemolytic anaemia

agranulocytosis

Nervous system disorders

Rare:

paraesthesia, hyperosmolar coma

Not known:

Dizziness, fainting and loss of consciousness (caused by symptomatic hypotension).

Endocrine disorder

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. Insulin requirements of diabetic patients may increase.

Eye disorders

Uncommon: visual disturbance

Ear and labyrinth disorders

Hearing disorders and tinnitus, although usually transitory, may occur in rare cases, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephritic syndrome) and/or when intravenons furosemide has been given too rapidly.

Uncommon:

Deafness (sometimes irreversible)

Cardiac disorders

Uncommon: Cardiac arrhythmias

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. The diuretic effect of furosemide can result in hypovolaemia and dehydration, especially in the elderly. There is an increased risk of thrombosis.

Hepatobiliary disorders

In isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.

Hepatic encephalopathy in patients with hepatocellular insufficiency may occur (see Section 4.3).

Vascular Disorder:

Rare:

vasculitis

Skin and subcutaneous tissue disorders

Uncommon:

Photosensitivity

Rare:

Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, fever, hypersensitivity to light, exsudative erythema multiforme (Lyell’s syndrome and Stevens-Johnson syndrome), bullous exanthema, exfoliative dermatitis, purpura, AGEP (acute generalized exanthematous pustulosis) and DRESS (Drug rash with eosinophilia and systemic symptoms).

Not Known: Bullous Pemphigoid

Metabolism and nutrition disorders

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 increase excretion of water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased.

Metabolic acidosis can also occur. The risk of this abnormality increases at higher dosages and is influenced by the underlying disorder (e.g. cirrhosis of the liver, heart failure), concomitant medication (see section 4.5) and diet.

Symptomatic electrolyte disturbances and metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or e.g. where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses

Symptoms of electrolyte imbalance depend on the type of disturbance:

Sodium deficiency can occur; this can manifest itself in the form of confusion, muscle cramps, muscle weakness, loss of appetite, dizziness, drowsiness and vomiting.

Potassium deficiency manifests itself in neuromuscular symptoms (muscular weakness, paralysis), intestinal symptoms (vomiting, constipation, meterorism), renal symptoms (polyuria) or cardiac symptoms. Severe potassium depletion can result in paralytic ileus or confusion, which can result in coma.

Magnesium and calcium deficiency result very rarely in tetany and heart rhythm disturbances.

Serum calcium levels may be reduced; in very rare cases tetany has been observed.

Nephrocalcinosis/Nephrolithiasis has been reported in premature infants.

Serum cholesterol (reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol) and triglyceride levels may rise during furosemide treatment. During long term therapy they will usually return to normal within six months

As with other diuretics, treatment with furosemide may lead to transitory increase in blood creatinine and urea levels. Serum levels of uric acid may increase and attacks of gout may occur.

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.

Congenital, familial and genetic disorders

If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.

General disorders and administration site conditions

Uncommon: Fatigue

Rare:

Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occurs rarely.

fever

Malaise

Gastrointestinal disorders

Uncommon: dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhea, constipation.

Rare:

Acute Pancreatitis

Gastro-intestinal disorders such as nausea, malaise or gastric upset (vomiting or diarrhoea) and constipation may occur but not usually severe enough to necessitate withdrawal of treatment.

Renal and urinary disorders

Uncommon:

serum creatinine and urea levels can be temporarily elevated during treatment with furosemide.

Rare:

interstitial nephritis, acute renal failure.

Increased urine production, urinary incontinence, can be caused or symptoms can be exacerbated in patients with urinary tract obstruction. Acute urine retention, possibly accompanied by complications, can occur for example in patients with bladder disorders, prostatic hyperplasia or narrowing of the urethra.

Pregnancy, puerperium and perinatal conditions

In premature infants with respiratory distress syndrome, administration of Furosemide in the initial weeks after birth entails an increased risk of a persistent patent ductus arteriosus.

In premature infants, furosemide can be precipitated as nephrocalcinosis/kidney stones.

Rare complications may include minor psychiatric disturbances.

Special population:

Patients with hepatic impairment

Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

Features

Overdose can cause massive diuresis resulting in dehydration, volume depletion and electrolyte disturbances with consequent hypotension and cardiac toxicity. High doses have the potential to cause transient deafness and may precipitate gout (disturbed uric acid secretion).

Management

Benefits of gastric decontamination are uncertain. In patients presenting within 1 hour of ingestion, consider activated charcoal (50g for adults: 1g/kg for children)

Observe for a minimum of 4 hours – monitor pulse and blood pressure.

Treat hypotension and dehydration with appropriate IV fluids

Monitor urinary output and serum electrolytes (including chloride and bicarbonate). Correct electrolyte imbalances. Monitor 12 lead ECG in patients with significant electrolyte disturbances

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group: High-ceiling diuretic sulfonamides, loop diuretics;

Mechanism of action:

The principle renal action of furosemide is to inhibit active chloride transport in the thick ascending limb. Re-absorption of sodium, chloride from the nephron is reduced and a hypotonic or isotonic urine produced.

Pharmacodynamic effects:

The evidence from many experimental studies suggests that furosemide acts along the entire nephron with the exception of the distal exchange site. The main effect is on the ascending limb of the loop of Henley with a complex effect on renal circulation. Blood-flow is diverted from the juxta-medullary region to the outer cortex.

It has been established that prostaglandin (PG) biosynthesis and the renin-angiotensin system are affected by furosemide administration and that furosemide alters the renal permeability of the glomerulus to serum proteins.

5.2 Pharmacokinetic properties

Absorption:

Approximately 65% of the dose is absorbed after oral administration. The plasma half-life is biphasic with a terminal elimination phase of about 1½ hours.

Furosemide is a weak carboxylic acid which exists mainly in the dissociated form in the gastrointestinal tract. Furosemide is rapidly but incompletely absorbed (60-70%) on oral administration and its effect is largely over within 4 hours. The optimal absorption site is the upper duodenum at pH 5.0.

Distribution:

Furosemide is up to 99% bound to plasma proteins.

Biotransformation:

Furosemide is bound to plasma albumin and little biotransformation takes place

Elimination:

Regardless of route of administration 69-97% of activity from a radio-labelled dose is excreted in the first 4 hours after the drug is given. Furosemide is mainly eliminated via the kidneys (80-90%) mainly excreted in the urine, largely unchanged; but also excreted in the bile, non-renal elimination being considerably increased in renal failure. Furosemide crosses the placental barrier and is excreted in the milk.

A small fraction of the dose undergoes biliary elimination and 10-15% of the activity can be recovered from the faeces.

In renal/ hepatic impairment

Where liver disease is present, biliary elimination is reduced up to 50%. Renal impairment has little effect on the elimination rate of furosemide, but less than 20% residual renal function increases the elimination time.

The elderly

The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present.

New born

A sustained diuretic effect is seen in the newborn, possibly due to immature tubular function.

5.3 Preclinical safety data

No further information other than that which is contained in other sections of the Summary of Product Characteristics.

  1. Pharmaceutical particulars

6.1 List of excipients

Sodium Chloride B.P.

Sodium Hydroxide B.P.

Water for Injections B.P.

6.2 Incompatibilities

Furosemide may precipitate solutions of low pH, and therefore dextrose solutions are not suitable infusion fluids for furosemide injection. The injection solution should not be mixed with other drugs in infusion bottles.

6.3 Shelf life

3 years (36 months).

If only part used, discard the remaining solution.

6.4 Special precautions for storage

Keep in outer carton

Do not store above 25°C

Do not refrigerate or freeze.

6.5 Nature and contents of container

2ml, 5ml & 25ml One point cut (OPC) amber glass ampoules, glass type 1 Ph.Eur. packed in cardboard cartons to contain 10 x 2ml or 10 x 5ml or 10 x 25ml ampoules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

 

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Furosemide 20mg/2ml Solution for Injection Taj Pharma
Furosemide 50mg/5ml Solution for Injection Taj Pharma
Furosemide 250mg/25ml Solution for Injection Taj Pharma

Furosemide

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it
  • If you have further questions, ask your doctor or
  • If you get any side effects, talk to your doctor or This includes any possible side effects not listed in this leaflet. See section 4.

The product is known by the name above but will be referred to as Furosemide Injection throughout the rest of this leaflet.

What is in this leaflet

  1. What Furosemide Injection is and what it is used for
  2. What you need to know before Furosemide Injection is given to you
  3. How Furosemide Injection is given to you
  4. Possible side effects
  5. How to store Furosemide Injection
  6. Contents of the pack and other information

 

  1. What furosemide injection is and what it is used for

Furosemide Injection is one of a group of medicines called diuretics. A diuretic helps get rid of excess fluid in the body by causing more urine to be passed.

Furosemide Injection is used to remove excess fluid from the body.

It may also be used when your kidneys are not functioning properly and not producing normal amounts of urine.

  1. What you need to know before furosemide injection is given to you
  • you are allergic to furosemide or any of the other ingredients of this medicine (listed in section 6).

Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue

  • you are allergic to amiloride, sulfonamides or sulphonamide derivatives, such as sulfadiazine or cotrimoxazole
  • you have a low blood volume or are dehydrated (with or without accompanying low blood pressure)
  • you have too little potassium or sodium in your blood (shown in blood test)
  • you have severe liver problems (cirrhosis)
  • you have already used furosemide in the past to treat failure to pass urine or kidney failure or if you have kidney failure that is due to medicines or chemicals that are prone to cause kidney or liver damage or if you have kidney failure due to underlying liver disorders
  • you are not passing any water (urine) or you have been told by a doctor that you have kidney failure. In some types of kidney failure, it is still okay to have this medicine. Your doctor will be able to decide
  • you have an illness called ‘Addison’s Disease’. This can make you feel tired and weak or if you are taking digitalis, used to treat heart problems
  • you have a disease called porphyria characterized by abdominal pain, vomiting or muscle weakness
  • you are breast feeding.

 

Warnings and precautions

Talk to your doctor or nurse before you are given Furosemide Injection:

  • if you are elderly, if you are on other medications which can cause drop in the blood pressure and if you have other medical conditions that are risks for the drop of blood pressure
  • if you have low blood pressure or feel dizzy when you stand up
  • if you feel dizzy or dehydrated. This can happen if you have lost a lot of water through being sick, having diarrhoea or passing water very often. It can also happen if you are having trouble drinking or eating
  • if you have low blood levels of essential minerals like sodium or potassium or you have acid base imbalance in the body identified by blood tests
  • if you have difficulty in passing water, for example because of an enlarged prostate gland (males only)
  • if you have diabetes
  • if you have gout (characterised by painful joints due to elevated uric acid levels)
  • if you have kidney or liver problems
  • if you have low blood protein levels (hypoproteinaemia) as this may reduce the effect of the drug and increase the risk of ear damage
  • if you have raised levels of calcium in the blood; careful monitoring of fluids and electrolyte levels are recommended
  • if you have a risk of fall in blood pressure; or in case of premature infants as they may be more prone to development of kidney stones
  • if you are already on medicines like NSAIDs (used for inflammation and pain) or ACE inhibitors (medicines used to lower blood pressure)
  • laboratory monitoring – It is recommended to undergo regular monitoring of blood levels for sodium, potassium, kidney function tests (blood urea nitrogen and creatinine levels), glucose, magnesium, calcium, chloride, bicarbonate and uric acid
  • regular monitoring is required to check for occurrence of blood dyscrasias (abnormal or imbalance in blood components), liver damage or any symptom that may occur particularly to you
  • if you are an elderly patient with dementia and are also taking risperidone.

Do not use Furosemide Injection if

  • you are planning to undergo procedure that includes the use of radiocontrast (as taking Furosemide Injection may increase the risk for kidney damage)
  • you cannot tolerate certain sugars like galactose or glucose.

Other medicines and Furosemide Injection

Tell your doctor if you are taking, have recently used or might use any other medicines

  • tell your doctor if you are taking the below medicines as the dose of these may need to be changed to avoid the risk of excessive lowering of blood pressure. Other blood pressure lowering agents (cardiac glycosides eg digoxin, other diuretics that help you pass more urine; or other blood pressure lowering agents)
  • if you are taking any drugs that can be harmful to your kidneys
  • if you have low levels of potassium or magnesium in your blood indicated by the blood counts.

A large number of drugs can interact with Furosemide which can significantly alter their effects. These drugs include:

  • medicines such as ramipril, enalapril, perindopril (called ‘ACE inhibitors’) or losartan, candesartan, irbesartan (called ‘angiotensin II receptor antagonists’)
  • anti-psychotics (medicines used to treat mental disorders) such as tricyclic antidepressants, hypnotics and anxiolytics (e.g pimozide, amisulpride, sertindole or phenothiazines), risperidone used to treat dementia
  • medicines for high blood pressure or heart problems (uneven heart beat) such as calcium channel blockers, beta blockers, clonidine, moxonidine, sodium nitroprusside, amiodarone, disopyramide, flecainide, minoxidil, lidocaine, prazosin, diazoxide, methyldopa, sotalol and mexiletine
  • thymoxamine or hydralazine used to lower blood pressure
  • metolazone – medicine used to pass more urine
  • nitrates – used to lower blood pressure
  • lithium – used for mental illness
  • sucralfate – this drug may decrease the absorption of furosemide
  • NSAIDs- drugs used to treat pain and inflammation (eg. indomethacin, ketorolac)
  • salicylates (eg aspirin)
  • – antibiotics belonging to class of aminoglycosides, polymixins or vancomycin; as there may be a risk of ear or kidney damage, low sodium levels with trimethoprim and cephalosporins e.g. cefalexin and ceftriaxone
  • – medicines used to treat depression (eg. TCA or MAOIs)
  • – medicines used to treat diabetics
  • – medicines used to treat epilepsy (eg carbamazepine, phenytoin)
  • – anti-histamines (medicines used to treat allergies)
  • – anti-fungals e.g. amphotericin (risk of potassium loss or renal damage indicated with furosemide)
  • – chloral hydrate or triclorfos (drugs used to treat anxiety)
  • – drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) like e.g. atomoxetine, amphetamines
  • – steroids (used to treat inflammation)
  • liquorice; increased risk of loss of potassium with furosemide
  • platinum containing compounds like cisplatin- used to treat cancers (increased risk of kidney damage with furosemide)
  • methotrexate- increase chance of furosemide toxicity
  • levodopa- used to treat parkinson’s disease (increased risk of lowering of blood pressure with furosemide)
  • medicines that modify immune system- (eg aldesleukin or ciclosprorin)
  • medicines used as muscle relaxants like baclofen, tizanidine or curare like drugs
  • birth control Pills or oestrogen containing drugs may block the effect of furosemide if taken concurrently
  • progesterone containing drugs (drosperidone) may lead to reduced blood potassium levels if taken with furosemide
  • medicines such as alprostadil, used to treat erectile dysfunction (impotency)
  • theophylline used for wheezing or difficulty in breathing
  • probenecid used for treatment of gout
  • medicines used as general anaesthetics to induce unconsciousness. If you are going to have an anaesthetic please ensure that the doctor or nurse knows you are taking furosemide
  • laxatives- drugs used to relieve constipation e.g. bisacodyl, senna
  • medicines for asthma when given in high doses such as salbutamol, terbutaline sulphate, salmeterol, formoterol or bambuterol
  • medicines used to treat blocked noses, such as ephedrine and xylometazoline
  • aminoglutethimide used to treat breast cancer.
  • Furosemide Injection with alcohol
  • avoid consumption of alcohol with Furosemide Injection as it may lead to excessive lowering of blood pressure.
  • Pregnancy, breast-feeding and fertility
  • Pregnancy
  • if you are pregnant or breast feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before taking this medicine. Furosemide passes through the placenta and hence should not be given during pregnancy unless doctor feels it extremely necessary. If it is given in cases of swelling or water retention, the growth of the baby must be regularly monitored.
  • furosemide passes into the milk and may inhibit secretion of milk. Hence it should be avoided in breast feeding women.
  • Driving and using machines
  • Furosemide may cause some patients to be less alert which could interfere with the ability to drive or to operate machines. If you notice that you are not as alert as usual, do not drive or operate machinery and ask your doctor for advice.
  • Important information about some of the ingredients of Furosemide Injection This medicine contains less than 1mmol sodium (23mg) per dose, i.e. is essentially ‘Sodium free’.

 

  1. How furosemide injection is given to you
  • Furosemide Injection will always be given to you by a doctor or nurse. This is because it can only be given by injection. It may be given by injecting the solution into a muscle (intramuscular) or by injecting it slowly into a vein (intravenous).
  • Your doctor will decide on the most suitable dose for you, and how the medicine will be given. The dosage and frequency of repeated doses may change depending on how you respond to treatment.
  • The recommended dose is;
  • Adults: The initial dose may vary from 20 mg to 250 mg depending on how you respond.
  • Elderly: Furosemide is generally cleared from the body more slowly in the If you are elderly, your doctor may decide to start with a low dose and increase the dose gradually according to your response.
  • Children: The doctor will decide on the dosage, depending on how severely the kidneys are affected and on the response to initial doses.
  • Whilst you are receiving treatment with this medicine, your doctor may want to take blood for testing which will show if you have the right balance of fluid and chemicals in the
  • If you have any further questions on the use of this product, ask your doctor or nurse.
  • If you think you have been given more Furosemide Injection than you should have As the injection will be administered by a doctor, it is unlikely that you will be given more than is However, if you think that you have been given too much, tell your doctor immediately.

–      If you have missed an administration of Furosemide Injection

  • If you think you may have missed a dose, tell the doctor or nurse.
  • If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

  • If any of the below mentioned side effects are observed please inform your doctor immediately
  • allergic reactions such as itching, skin rash with severe itching and nettle rash, fever, allergic to light, severe allergic reaction with (high) fever, red patches on the skin, joint pain and/or inflammation of the eyes,“acute generalised exanthematous pustulosis (AGEP)”, DRESS, (acute febrile drug eruption) characterized by severe acute (allergic) reaction accompanied by fever and blisters on the skin/peeling skin and tiny spots from bleeding in the skin
  • sudden inflammation of the pancreas accompanied by severe pain in the upper abdomen, shifting towards the back
  • abnormal blood counts, severe changes in blood count- and signs e.g. sore throat, mouth ulcers, fever, unexplained bruising or bleeding
  • signs of kidney inflammation e.g. blood in the urine, pain in the lower back
  • signs of metabolic acidosis: chest pain, irregular heartbeat, nausea, vomiting, weakness.
  • The other possible side effects are listed under headings of frequency, using the following categories:
  • Uncommon (may affect up to 1 in 100 people)
  • blurred vision
  • lowering of blood pressure, resulting in impaired concentration and reactions, light-headedness, a feeling of pressure in the head, headache, dizziness, drowsiness, a feeling of weakness, visual disturbances, dry mouth and an inability to stand upright
  • sensitivity to light (photosensitivity)
  • feeling of tiredness
  • dry mouth, thirst, disturbances of bowel like diarrhoea, constipation or vomiting.
  • raised blood levels of creatinine and urea
  • deafness (sometimes irreversible).
  • Rare (may affect up to 1 in 1,000 people)
  • abnormal blood count (white blood cell deficiency) accompanied by an increased susceptibility to infection
  • increase in certain substances (eosinophilic cells) in the blood
  • a crawling sensation on the skin, itching or tingling without any reason
  • a life-threatening form of unconsciousness
  • acute kidney failure
  • hearing disorders & ringing in the ears. These disorders are usually temporary in nature
  • inflammation of a blood vessel
  • shock (severe drop in blood pressure, extreme paleness, restlessness, weak fast pulse, clammy skin, impaired consciousness) as a result of a sudden severe dilatation of the blood vessels due to allergy to certain substances
  • fever
  • muscle aches
  • inability to control urination
  • if you have a urinary tract obstruction, increased urine production may occur or worsen
  • if you have a bladder disorder, enlarged prostate or narrowing of the ureters, urine production can stop suddenly
  • minor mental disturbances.
  • Very rare (may affect up to 1 in 10,000 people)
  • anaemia (a condition characterised by shortage of red blood cells)
  • very severe blood abnormality (white blood cell deficiency) accompanied by a sudden high fever, severe throat pain and ulcers in the mouth.
  • Not known (frequency cannot be estimated from the available data)
  • certain liver function disorders or increase in certain liver enzymes
  • furosemide can cause an excessive depletion of bodily fluids (e.g. passing urine more often than normal) and minerals (sodium, potassium, magnesium, calcium). Symptoms that can occur are thirst, headache, confusion, muscle cramps, increased irritability of the muscles, muscular weakness, heart rhythm disturbances and gastrointestinal problems such as sensation of unease and discomfort in stomach with an urge to vomit or diarrhoea
  • reduced concentration, light-headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, confusion
  • if you have a shortage of sodium (sodium deficiency):
  • cramp in the calf muscles
  • loss of appetite
  • listlessness
  • feeling of weakness
  • dizziness
  • drowsiness
  • confusion
  • if you have a shortage of potassium (potassium deficiency):
  • muscular weakness and the inability to contract one or more muscles (paralysis)
  • increased excretion of urine
  • heart problems
  • in the case of severe potassium deficiency: interference with the function of the intestine or confusion which can result in coma
  • if you have a shortage of magnesium and calcium (magnesium and calcium deficiency):
  • increased irritability of the muscles
  • heart rhythm disturbances
  • deposits of calcium salts in the kidneys or heart defects like patent ductus arteriosus have been reported in premature babies following treatment with furosemide
  • during treatment with furosemide, the blood levels of some fats (cholesterol and triglyceride) may rise, but usually return to normal within 6 months
  • in the elderly, this can lead to a low blood volume, fluid depletion and thickening of the blood. This can cause clots to form in the blood
  • dizziness, fainting and loss of consciousness (caused by symptomatic hypotension)
  • bullous pemphigoid (an acute or chronic autoimmune skin disease, involving the formation of blisters, more appropriately known as bullae, at the space between the skin layers).
  • Reporting of side effects
  • If you get any side effects, talk to your doctor or nurse.

5.How to store furosemide injection

  • Keep this medicine out of the sight and reach of children.
  • Do not use this medicine after the expiry date which is stated on the ampoule or carton. The expiry date refers to the last day of that month.
  • Do not store above 25°C. Do not refrigerate or freeze.
  • Keep the container in the outer carton in order to protect from light. If only part used, discard the remaining solution.

6. CONTENTS OF THE PACK AND OTHER INFORMATION  

  • What Furosemide Injection contains
  • The active substance is furosemide.
  • The other ingredients are sodium chloride and sodium hydroxide in water for injections.
  • What Furosemide Injection looks like and contents of pack
  • Furosemide Injection is a clear, colourless, or almost colourless, sterile solution. Each 1ml of solution contains 10mg of furosemide.
  • The solution is presented in amber glass ampoules (small bottles) and then packed in to cardboard cartons as follows:
  • Furosemide 20mg/2ml Solution for Injection – packs of 10 x 2 ml ampoules. Furosemide 50mg/5ml Solution for Injection – packs of 10 x 5 ml ampoules. Furosemide 250mg/25ml Solution for Injection – packs of 10 x 25 ml ampoules.
  • Not all pack sizes may be marketed.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.