Torem 2.5 Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Torem 2.5mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 2.5mg torasemide.
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Tablets.
White to off-white round tablets with the imprint “T 2.5” on one side and plain on the other side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Essential hypertension.
4.2 Posology and method of administration Adults
Essential hypertension: A dose of 2.5mg torasemide p.o. 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.
Elderly
No special dosage adjustments are necessary.
Children
There is no experience of torasemide in children.
4.3 Contraindications
Renal failure with anuria; hepatic coma and pre-coma; hypotension; pregnancy and lactation; hypersensitivity to torasemide and sulphonylureas; cardiac arrhythmias simultaneous, therapy with aminoglycosides or cephalosporins, or renal dysfunction due to drugs which cause renal damage.
4.4 Special warnings and precautions for use
Hypokalaemia, hyponatraemia, 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.
Patients with rare hereditary problems of glucose intolerance, the Lapp lactase deficiency or 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. Indometacin) and probenecid may reduce the diuretic and hypotensive effect of torasemide.
Concomitant use of torasemide and colestyramine has not been studied in humans, but in an animal study co-administration of colestyramine decreased absorption of oral torasemide.
4.6 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 contra-indicated in pregnancy and lactation.
4.7 Effects on ability to drive and use machines
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.
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 system:
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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Symptoms and signs
No typical picture of intoxication is known. If overdosage occurs, then there may be marked diuresis with the danger of loss of fluid and electrolytes which may lead to somnolence and confusion, hypotension, circulatory collapse. Gastrointestinal disturbances may occur.
Treatment
No specific antidote is known. Symptoms and signs of overdosage require the reduction of the dose or withdrawal of torasemide, and simultaneous replacement of fluid and electrolytes.
5 PHARMACOLOGICAL PROPERTIES
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 40ml/min and renal clearance about 10ml/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 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 effect, 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,
Colloidal silicon dioxide,
Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
5 years.
6.4 Special precautions for storage
No special precautions for storage.
6.5 Nature and contents of container
Blister packs, PVC/aluminium, containing 14 and 28 tablets.
6.6 Special precautions for disposal
Not applicable.
7. MARKETING AUTHORISATION HOLDER
Meda Pharmaceuticals Ltd Skyway House Parsonage Road
Takeley
Bishop’s Stortford CM22 6PU
8 MARKETING AUTHORISATION NUMBER(S)
PL 15142/0115
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
1st March 1997
10 DATE OF REVISION OF THE TEXT
26/02/2014