SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCTS
Torahexal, 2.5 mg tablets
Torahexal, 5 mg tablets
Torahexal, 10 mg tablets
Torahexal, 20 mg tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Torahexal, 2.5 mg tablets
Each tablet contains 2.5 mg torasemide.
Torahexal, 5 mg tablets
Each tablet contains 5 mg torasemide.
Torahexal, 10 mg tablets
Each tablet contains 10 mg torasemide.
Torahexal, 20 mg tablets
Each tablet contains 20 mg torasemide.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Tablet
Torahexal, 2.5 mg tablets
white to off-white, round tablet
Torahexal, 5 mg tablets
white to off-white, round tablet with break notch
The tablet can be divided into equal halves.
Torahexal, 10 mg tablets
white to off-white, round tablet with cross break notch
The tablet can be divided into equal halves.
Torahexal, 20 mg tablets
white to off-white, round tablet with cross break notch
The tablet can be divided into equal quarters.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Torahexal, 2.5 mg/ - 5 mg tablets
Essential hypertension
Torahexal, 5 mg/- 10 mg/- 20 mg tablets
Oedema in patients with heart failure
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4.2 Posology and method of administration
Torahexal, 2.5 mg/ - 5 mg tablets – treatment of essential hypertension
Adults
The usual dose is 2.5 mg daily, preferably at breakfast time. Dose increase should
not take place until 2 months after the initiation of the treatment and maximum dose
is 5 mg, taken once daily.
Torahexal, 5 mg/- 10 mg/- 20 mg tablets – treatment of oedema in patients with
heart failure
Adults
The usual dose is 5 mg orally once daily. Usually this is the maintenance dose. If
necessary, the dose can be increased stepwise up to 20 mg once daily.
Elderly
There are no deviating dosage recommendations for elderly. However there are
insufficient comparative studies between older and younger patients.
Children (< 12 years)
There is no experience with torasemide in children (see 4.4 Special warnings and
special precautions for use).
Hepatic and Renal Insufficiency
There is limited information on dosage adjustments in patients with hepatic and renal
insufficiency. Patients with hepatic insufficiency should be treated with some caution
since plasma concentrations might be increased (see 5.2 Pharmakokinetic
properties).
Route of administration
Oral use.
The tablets should be taken in the morning, without chewing, with a small quantity of
liquid.
Torasemide is usually given for long-term treatment or until disappearance of
oedema.
4.3 Contraindications
Hypersensitivity to torasemide, to sulphonylureas or to any of the excipients;
Renal failure with anuria;
hepatic coma and pre-coma;
hypotension;
lactation
4.4 Special warnings and special precautions for use
Hypokalaemia, hyponatraemia and hypovolaemia must be corrected before
treatment.
Disorders of micturition (e.g. Benign Prostatic Hypertension).
Cardiac arrhythmias (e.g. sino-atrial-block, atrioventricular-block second or third
degree).
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On long-term treatment with torasemide, regular monitoring of the electrolyte balance
(in particular in patients with concomitant therapy with digitalis glycosides,
glucocorticoids, mineralacorticoids or laxatives), glucose, uric acid, creatinine and
lipids in the blood and the blood cells (red and white blood cells and platelets), 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.
Due to insufficient experience with torasemide treatment, care should be exerted in
the following conditions:
- Pathological changes of the acid-base balance,
- Concomitant treatment with lithium, aminoglycosides or cephalosporins
- Renal insufficiency due to nephrotoxic agents
- Children below 12 years
- Pathological changes of the blood cells (e.g. thrombocytopenia or anaemia in
patients without renal insufficiency)
The use of Torahexal, may produce positive results in doping controls.
Torasemide tablets contain lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.
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 medicinal products.
The kaliuretic effect of mineralo-and glucocorticoids and laxatives may be increased.
The effect of antihypertensive medicinal products, in particular ACE inhibitors, given
concomitantly may be potentiated.
Sequential or combined treatment, or starting a new co-medication with an ACE
inhibitor may result in severe hypotension. This may be minimised by lowering the
starting dose of the ACE inhibitor and/ or reducing or stopping temporarily the dose
of torasemide, 2 or 3 days before treatment with the ACE inhibitor.
Torasemide may decrease arterial responsiveness to pressor agents e.g. adrenaline,
noradrenaline.
Torasemide may reduce the effect of anti-diabetics.
Torasemide, especially at high doses, may potentiate the nephrotoxic and ototoxic
effects of aminoglycoside antibiotics, toxicity of cisplatin preparations and the
nephrotoxic effects of cephalosporins.
The action of curare-containing muscle relaxants and of theophylline can be
potentiated.
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Non-steroidal anti-inflammatory drugs (eg. Indomethacin) may reduce the diuretic
and hypotensive effect of torasemide possibly through an inhibition of prostaglandin
synthesis.
Probenecid may reduce efficacy of torasemide by inhibition of tubular secretion.
Lithium serum-concentrations and cardio- and neurotoxic effects of lithium may be
increased.
Torasemide inhibits the renal excretion of salicylates, increasing the risk for salicylate
toxicity in patients receiving high doses of salicylates.
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 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, foetal and maternal
toxicity have been observed after high doses in pregnant rabbits and rats.
Torasemide passes into the foetus and causes electrolyte disturbances. There is
also a risk of neonatal thrombocytopenia.
There is no information on the excretion of torasemide in human or animal breast
milk.
The use of torasemide is therefore not recommended during breastfeeding.
Until further experience is available, torasemide should only be given during
pregnancy after careful consideration of whether the benefits clearly outweigh the
risks. The lowest possible dose should be used.
4.7 Effects on ability to drive and use machines
As for other medicinal products 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. This applies in particular at the beginning
of the therapy, when increasing the dosage, changing the preparation or when
concomitantly ingesting alcohol.
4.8 Undesirable effects
The following undesirable effects can occur during therapy with Torahexal,:
The following categories are the basis for the information on frequencies:
Very common:  10%
Common:
 1% - < 10%
Uncommon:
 0.1% - < 1%
Rare:
 0.01% - < 0.1%
Very rare:
< 0.01%
Not known:
cannot be estimated from the available data
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Metabolism and nutrition disorders
Common:
Enhancement of metabolic alkalosis. Myospasm (particularly at the
beginning of therapy). Increases in the concentration of uric acid and
glucose in the blood and in blood fats (triglycerides, cholesterol).
Hypokalaemia in concomitant low-potassium diet, in cases of
vomiting, diarrhoea, after excessive use of laxatives as well as in
patients with chronic hepatic dysfunction.
Depending on the dosage and duration of treatment, disorders in the
water and electrolyte balance can occur, particularly e.g.
hypovolaemia, hypokalaemia and/or hyponatraemia.
Cardiovascular disorders
Very rare:
On account of haemoconcentration, thromboembolic complications,
confusion, hypotension as well as cardiac and central circulation
disorders (including ischaemia of heart and brain) can occur. These
can lead to e.g. arrhythmias, angina pectoris, acute myocardial
infarction or syncopes.
Gastrointestinal disorders
Common:
Gastrointestinal disorders (e.g. inappetence, gastric pain, nausea,
vomiting, diarrhoea, constipation), particularly at the beginning of
treatment.
Very rare:
Pancreatitis.
Renal and urinary disorders
Uncommon:
Increase in the concentrations of creatinine and urea in the blood.
In patients with impaired micturition (e.g. due to prostatic
hyperplasia), increased urinary production can lead to urinary
retention and overexpansion of the bladder.
Hepatobiliary disorders
Common:
Increase in certain liver enzyme concentrations (gamma-GT) in the
blood.
Skin and subcutaneous tissue disorders
Very rare:
Allergic reactions (e.g. pruritus, exanthema, photosensitivity), severe
skin reactions.
Blood and lymphatic system disorders
Very rare:
Reduction in thrombocytes, erythrocytes and/or leukocytes.
General disorders
Common:
Headache, vertigo, fatigue, asthenia (particularly at the beginning of
therapy).
Uncommon:
Xerostomia, paraesthesia.
Very rare:
Dysopia, tinnitus, hearing loss.
Note
Longer-term therapy with torasemide requires regular monitoring of the electrolyte
balance, particularly serum potassium.
Glucose, uric acid, creatinine and lipids in the blood are to be monitored as well at
regular intervals.
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Since an increase in blood glucose can occur, careful monitoring of the carbohydrate
balance is recommended in patients with latent or manifest diabetes mellitus.
The blood count (erythrocytes, leukocytes, thrombocytes) are also to be monitored at
regular intervals.
Be aware of signs of electrolyte loss and haemoconcentration, particularly at the
beginning of treatment and in elderly patients.
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. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Sulfonamides, plain
ATC Code: C03 CA 04
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. Torasemide has maximal diuretic activity 2-3 hours after oral
administration. In healthy subjects given doses between 5 and 100mg it has a logproportional increase in diuretic activity.
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. Systemic bioavailability after
oral administration is 80-90%.
Serum protein binding
More than 99% of torasemide is bound to plasma proteins, while metabolites M1, M3
and M5 are bound 86%, 95% and 97%, respectively.
Distribution
The apparent distribution volume is 16 l (Vz: 16 l).
Metabolism
Torasemide is metabolised to three metabolites, M1, M3 and M5 by stepwise
oxidation, hydroxylation or ring hydroxylation. The hydroxyl-metabolites have diuretic
activity. Metabolites M1 and M3 add to about 10% of the pharmacodynamic action,
whereas M5 is inactive.
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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, the elimination half-life of torasemide is unchanged
but the half-lives of metabolites M3 and M5 are increased. Torasemide and its
metabolites are not significantly removed by hemodialysis or hemofiltration.
In patients with hepatic impairment, increases in plasma concentrations of
torasemide have been observed, likely due to decreased hepatic metabolism. In
patients with cardiac or hepatic failure the half-lives of torasemide and metabolite M5
are slightly increased but accumulation is unlikely. (See 4.2 Posology and method of
administration).
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on single dose toxicity,
genotoxicity and carcinogenicity studies.
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 medicinal product
induced changes were shown to be reversible.
Reproduction toxicology: Studies in the rat have shown no teratogenic effects, but
foetal and maternal toxicity have been observed after high doses in pregnant rabbits
and rats. No effects on fertility have been seen. Torasemide passes into the foetus
and causes electrolyte disturbances.
In mice torasemide showed no evidence of tumorigenic potential. In rats a
statistically significant increase in renal adenomas and carcinomas was observed in
the high-dose female group. This seems to have no relevance for therapeutic doses
in humans.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose
Lactose monohydrate
Magnesium stearate
Maize starch
Colloidal anhydrous silica
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
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Do not store above 25 °C.
6.5 Nature and contents of container
The tablets are packed in PVC/PVdC/Al blister or Al/Al blister and inserted into a
carton.
Pack sizes: 10, 14, 20, 28, 30, 50, 56, 100, 400 (20 x 20) tablets
Not all pack sizes may be marketed.
6.6 Special Precautions for Disposal
No special requirements
7. MARKETING AUTHORISATION HOLDER
<[for Sweden only]>
Hexal AG
Industriestrasse 25
83607 Holzkirchen
Germany
Tel: +49 8024 908 0
Fax: +49 8024 908 1277
Sandoz A/S
C.F. Tietgens Boulevard 40
5220 Odense SØ
Denmark
8. MARKETING AUTHORISATION NUMBERS
<[for Sweden only]>
Torahexal 2,5 mg tablets: 18236
Torahexal 5 mg tablets: 18237
Torahexal 10 mg tablets: 18238
Torahexal 20 mg tablets: 18239
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
18/07/2003
10. DATE OF REVISION OF THE TEXT
30/11/2011.
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