Torasemide 5mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Torasemide 5mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each [Torasemide] tablet contains 5 mg torasemide.
Excipients with known effect:
Each tablet contains 58.44 mg of lactose (as monohydrate).
For excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
Torasemide 5mg Tablets are white to off-white, round, biconvex tablets with a break line on one side and embossing 915 on the other side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Torasemide 5mg Tablets
Essential hypertension; oedema due to congestive heart failure; hepatic, pulmonary or renal oedema.
4.2 Posology and method of administration
Adults
Essential hypertension: A dose of 2.5mg torasemide orally once daily is recommended. If necessary, the dose may be increased to 5mg once daily. Studies suggest that doses above 5mg daily will not lead to further reduction in blood pressure. The maximum effect is exhibited after approximately twelve weeks of continuous treatment.
Oedema: The usual dose is 5 mg orally once daily. If necessary, the dose can be increased stepwise up to 20 mg once daily. In individual cases, as much as 40mg torasemide/day has been administered.
Elderly
No special dosage adjustments are necessary.
Paediatric population
There is no experience with torasemide in children.
4.3 Contraindications
Hypersensitivity to torasemide or to any of the excipients listed in section 6.1 Renal failure with anuria; hepatic coma and pre-coma; hypotension; pregnancy and lactation;hypersensitivity to sulphonylureas ; cardiac arrhythmias, simultaneous therapy with aminoglycosides or cephalosporins, or renal dysfunction due to drugs which cause renal damage.
4.4 Special warning and precautions for use
Hypokalaemia, hyponatraemia and hypovolaemia and disorders of micturition must be corrected before treatment.
On long-term treatment with torasemide, regular monitoring of the electrolyte balance, glucose, uric acid, creatinine and lipids in the blood, is recommended.
Careful monitoring of patients with a tendency to hyperuricaemia and gout is recommended. Carbohydrate metabolism in latent or manifest diabetes mellitus should be monitored.
As for other drugs which produce changes in blood pressure, patients taking torasemide should be warned not to drive or operate machinery if they experience dizziness or related symptoms.
Torasemide tablets contain lactose. Patients with rare hereditary problems of glucose intolerance, the Lapp lactase deficiency of glucose-galactose malabsorption should not take this medication.
4.5 Interaction with other medicinal products and other forms of interaction
When used simultaneously with cardiac glycosides, a potassium and/or magnesium deficiency may increase sensitivity of the cardiac muscle to such drugs. The kaliuretic effect of mineralo-and glucocorticoids and laxatives may be increased.
As with other diuretics, the effect of antihypertensive drugs given concomitantly may be potentiated.
Torasemide, especially at high doses, may potentiate the toxicity of aminoglycoside antibiotics, cisplatin preparations, the nephrotoxic effects of cephalosporins, and the cardio- and neurotoxic effect of lithium.
The action of curare-containing muscle relaxants and of theophylline can be potentiated. In patients receiving high doses of salicylates, salicylate toxicity may be increased. The action of anti-diabetic drugs may be reduced.
Sequential or combined treatment, or starting a new co-medication with an ACE inhibitor may result in transient hypotension. This may be minimised by lowering the starting dose of the ACE inhibitor and/or reducing or stopping temporarily the dose of torasemide. Torasemide may decrease arterial responsiveness to pressor agents e.g. adrenaline, noradrenaline.
Non-steroidal anti-inflammatory drugs (eg. Indomethacin) and probenecid may reduce the diuretic and hypotensive effect of torasemide.
Concomitant use of torasemide and cholestyramine has not been studied in humans, but in an animal study co-administration of cholestyramine decreased absorption of oral torasemide.
4.6 Fertility, pregnancy and lactation
There are no data from experience in humans of the effect of torasemide on the embryo and foetus.
Whilst studies in the rat have shown no teratogenic effect, malformed foetuses have been observed after high doses in pregnant rabbits. No studies have been conducted on excretion in breast milk.
Consequently, torasemide is contraindicated in pregnancy and lactation.
4.7 Effects on ability to drive and use machines
As for other drugs that produce changes in blood pressure, patients taking torasemide should be warned not to drive or operate machinery if they experience dizziness or related symptoms.
4.8 Undesirable effects Blood chemistry/ volume:
As with other diuretics, depending on the dosage and duration of treatment, there may be disturbances of water and electrolyte balance, especially with markedly limited salt intake.
Hypokalaemia may occur (especially if a low potassium diet is being taken, or if vomiting, diarrhoea, or excessive use of laxatives takes place, or in cases of hepatic failure).
Symptoms and signs of electrolyte and volume depletion, such as headache, dizziness, hypotension, weakness, drowsiness, confusional states, loss of appetite and cramps, can occur if diuresis is marked, especially at the start of treatment and in elderly patients. Dose adjustment may be necessary.
Raised serum uric acid, glucose and lipids can occur.
There may be aggravation of metabolic alkalosis.
Cardiovascular system:
In isolated cases, thromboembolic complications and circulatory disturbances due to haemoconcentration may occur.
Gastro-intestinal systems:
Patients may experience gastro-intestinal symptoms.
Pancreatitis has been reported in isolated cases.
Renal and urinary system:
In patients with urinary outflow obstruction, retention of urine may be precipitated. Raised serum urea and creatinine may occur.
Liver:
Increases in certain liver enzymes, eg. gamma-GT.
Haematology:
Isolated cases of decreases in red and white blood cells and platelets have been reported.
Skin / allergy:
In isolated cases, there may be allergic reactions, such as pruritis, rash and photosensitivity.
Nervous system:
Isolated reports of visual disturbance.
Tinnitus and hearing loss have occurred in isolated cases.
Rarely, limb paraesthesia has been reported.
Others:
Dry mouth.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via www.mhra.gov.uk/yellowcard
4.9 Overdose
Symptoms and signs
No typical picture of intoxication is known. If overdose occurs, then there may be marked diuresis with the danger of loss of fluid and electrolytes that may lead to somnolence and confusion, hypotension, circulatory collapse. Gastrointestinal disturbances may occur.
Treatment
No specific antidote is known. Symptoms and signs of overdose require the reduction of the dose or withdrawal of torasemide, and simultaneous replacement of fluid and electrolytes.
5.1 Pharmacodynamic properties
Torasemide is a loop diuretic. However, at low doses its pharmacodynamic profile resembles that of the thiazide class regarding the level and duration of diuresis. At higher doses, torasemide induces a brisk diuresis in a dose dependant manner with a high ceiling of effect.
5.2 Pharmacokinetic properties
Absorption: Torasemide is absorbed rapidly and almost completely after oral administration, and peak serum levels are reached after one to two hours.
Serum protein binding: More than 99% of torasemide is bound to plasma proteins.
Distribution: The apparent distribution volume is 16 litres.
Metabolism: Torasemide is metabolised to three metabolites, M1, M3 and M5 by stepwise oxidation, hydroxylation or ring hydroxylation.
Elimination: The terminal half-life of torasemide and its metabolites is three to four hours in healthy subjects. Total clearance of torasemide is 40 ml/min and renal clearance about 10 ml/min. About 80% of the dose administered is excreted as torasemide and metabolites into the renal tubule - torasemide 24%, M1 12%, M3 3%, M5 41%.
In the presence of renal failure, elimination half-life of torasemide is unchanged.
5.3 Preclinical safety data
Acute toxicity
Very low toxicity.
Chronic toxicity
The changes observed in toxicity studies in dogs and rats at high doses are considered attributable to an excess pharmacodynamic action (diuresis). Changes observed were weight reduction, increases in creatinine and urea and renal alterations such as tubular dilatation and interstitial nephritis. All drug induced changes were shown to be reversible.
Teratogenicity
Reproduction toxicology studies in the rat have shown no teratogenic effects, but malformed foetuses have been observed after high doses in pregnant rabbits. No effects on fertility have been seen.
Torasemide showed no mutagenic potential. Carcinogenicity studies in rats and mice showed no tumourigenic potential.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate Maize starch
Sodium starch glycollate Type A Silica colloidal anhydrous Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
24 months
6.4 Special precautions for storage
Do not store above 30°C. Store in the original package
6.5 Nature and contents of container
PVC /PVDC //Al blisters containing 14, 28, 30, 50, 100 or 112 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Pharmathen SA 6 Dervenakion Street 153 51 Pallini Athens Greece
8 MARKETING AUTHORISATION NUMBER
PL 17277/0004
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 07/06/2013
10
DATE OF REVISION OF THE TEXT
03/08/2015