TORIFAS [Torasemide] 10 mg Film-coated tablets
instructions for the medical use of the medicinal
product
TORIFAS
Tradename
Torifas, Торифас
International non-proprietary name or generic name
Torasemide, Торасемид
Composition
Each film-coated tablet contains:
active ingredient: torasemide 10 mg;
excipients: starch, sucrose,
hydroxypropyl cellulose, talc, hypromellose, sodium starch glycolate, magnesium
stearate, propylene glycol, ethanol, hydrochloric acid, purified water.
Dosage form
Tablets.
Pharmacotherapeutic group
Diuretic agent.
Code АТХ: С03С А04
Pharmacological properties
Pharmacodynamics
The primary mechanism of diuretic action is due to
reversible binding to the Na+/2Cl-/K+ cotransporter in the apical limb of the
loop of Henle. This results in decreased or completely inhibited renal
reabsorption of sodium and chloride ions in the ascending limb of the loop of
Henle, decreased osmotic pressure of intracellular fluid, and decreased water
reabsorption. In the dose range of 5-100 mg, the increase in diuresis is proportional
to the logarithm of the dose. Increased diuresis also occurs in cases where
other diuretics (e.g., thiazides) are no longer effective, for example, with
limited renal function. It eliminates edema and has an antihypertensive effect
due to a decrease in peripheral vascular resistance due to a decrease in free
calcium content in the cells of the arterial muscular layer and the
normalization of electrolyte imbalance. As a result, contractility and vascular
response to the body's own pressor substances, particularly catecholamines, are
reduced. It improves cardiac performance by reducing pre- and afterload. After
oral administration, the maximum diuretic effect lasts for 1-3 hours, and the
diuretic effect persists for almost 12 hours. The hypotensive effect of
torasemide develops gradually over the first week and reaches its maximum no
later than 12 weeks.
Pharmacokinetics
After oral administration, torasemide is rapidly and almost completely
absorbed from the gastrointestinal tract. Peak plasma concentrations are
observed after 1-2 hours. Plasma protein binding of torasemide is over 99%,
while that of metabolites M1, M3, and M5 is 86%, 95%, and 97%, respectively.
Bioavailability is approximately 80%, with minor individual variations, and is
unaffected by food intake. It is metabolized in the liver by the cytochrome
P450 system to form metabolites (M1, M3, and M5). The main metabolite, M5, has
no diuretic effect; the active metabolites M1 and M3 together account for
approximately 10% of the pharmacodynamic effect. The half-life of torasemide
and its metabolites in healthy volunteers is 3-4 hours. Approximately 83% of
the administered dose is excreted via the renal tubules: unchanged (24%) and as
metabolites (M1 – 12%, M3 – 3%, M5 – 41%). Total clearance is 40 ml/min, renal
clearance is approximately 10 ml/min. In renal insufficiency, the total
clearance and half-life of torasemide remain unchanged, while the half-life of
M3 and M5 is prolonged. However, the pharmacodynamic characteristics remain
unchanged, and the severity of renal insufficiency does not affect the duration
of action. In patients with impaired liver function or heart failure, the
half-lives of torasemide and metabolite M5 are slightly prolonged, and
accumulation of torasemide and its metabolites is not observed.
Indications for use
Edema caused by heart failure, kidney, liver and lung diseases.
Contraindications
• Hypersensitivity
to torasemide, sulfonylureas, or any of the excipients;
• Renal
failure with anuria;
•
Hepatic coma or precoma;
•
Arterial hypotension;
•
Sinoatrial and atrioventricular block grades II and III;
•
Hypovolemia;
•
Hyponatremia and hypokalemia;
• Severe
urination disorders (e.g., due to prostatic hyperplasia);
•
Pregnancy;
•
Lactation;
•
Children and adolescents under 18 years of age.
Use with
caution in patients with a predisposition to hyperuricemia, gout, and severe
diabetes mellitus.
Method of administration and dosage
For oral
administration. Take the tablets once daily in the morning after meals, whole,
with a small amount of liquid. The dose and duration of treatment are
determined individually based on the indication, efficacy, and tolerability of
the therapy.
Depending
on the indication, the dose is 5-20 mg once daily.
Special instructions and precautions
Before using this
medication, consult a doctor.
During long-term
therapy with Torisemide, regular monitoring of electrolyte balance (in particular,
serum potassium), glucose, uric acid, creatinine, and serum lipids, as well as
blood count (erythrocytes, leukocytes, and platelets) is necessary.
It is important
to note that elevated blood glucose levels may be associated with latent or
overt diabetes mellitus, so these patients should have their blood sugar levels
closely monitored. Particularly at the beginning of treatment in elderly
patients, special attention should be paid to the appearance of symptoms of
electrolyte loss and blood thickening.
In the absence of
sufficient clinical experience, torasemide should not be prescribed for the
following diseases and conditions: gout; arrhythmia (sinoatrial block, atrioventricular
block II and III degrees); pathological changes in acid-base metabolism;
Concomitant therapy with lithium, aminoglycosides, or cephalosporins; abnormal
blood counts (thrombocytopenia or anemia in patients without renal
insufficiency); renal impairment caused by nephrotoxic substances.
Influence on the
ability to drive vehicles and mechanisms
During treatment,
patients should avoid potentially hazardous activities that require increased
alertness and rapid psychomotor reactions.
Interaction with other medicinal products
Torasemide
enhances the effects of other antihypertensive medications, particularly ACE
inhibitors. The use of ACE inhibitors as an adjunctive or sequential therapy
may result in a significant decrease in blood pressure.
Hypokalemia
resulting from torasemide may increase the severity and frequency of adverse
effects of concomitant digitalis preparations.
Torasemide
may reduce the effectiveness of antidiabetic medications.
Probenecid
and nonsteroidal anti-inflammatory drugs (e.g., indomethacin, acetylsalicylic
acid) may reduce the diuretic and hypotensive effects of torasemide. When used
with high doses of salicylates, torasemide may enhance their neurotoxic
effects. Torasemide, especially at high doses, may potentiate the following
adverse effects: the ototoxic and nephrotoxic effects of aminoglycoside
antibiotics (e.g., kanamycin, gentamicin, tobramycin), the cytotoxicity of
platinum derivatives, and the nephrotoxic effect of cephalosporins.
Torasemide
may enhance the effects of curare-containing muscle relaxants and theophylline.
The
potassium-uretic effect of mineralocorticoids, glucocorticoids, and laxatives
may be enhanced.
When
torasemide is coadministered with lithium, serum concentrations and,
consequently, the action and side effects of the latter may be increased.
Torasemide
may reduce the pressor effect of catecholamines (e.g., epinephrine,
norepinephrine).
Concomitant
use of cholestyramine may reduce the absorption and, therefore, the
effectiveness of orally administered torasemide.
Side effect
Cardiovascular: fluid and electrolyte
imbalance (hypovolemia, hypokalemia, hyponatremia); increased metabolic
alkalosis. Significant fluid and electrolyte losses due to excessive urination
may cause arterial hypotension, confusion, thrombosis, cardiac and cerebral
ischemia, possibly leading to cardiac arrhythmia, angina, acute myocardial
infarction, and syncope.
Central nervous system: headache, dizziness,
increased fatigue, drowsiness, confusion, muscle cramps.
Digestive: anorexia, nausea, vomiting, stomach pain,
constipation, diarrhea, elevated liver enzymes, pancreatitis.
Urinary system: in patients with urination
disorders (e.g., prostatic hypertrophy), urinary retention and excessive
bladder distension; increased blood creatinine and urea.
Metabolic: increased blood levels of uric acid,
glucose, and lipids (triglycerides, cholesterol).
Hematologic: decreased platelet, red blood cell, and/or
white blood cell count.
Immune system: allergic reactions, including rash,
itching, exanthema, photosensitivity, severe skin reactions.
Other: general weakness, dry mouth, paresthesia,
visual disturbances, tinnitus, hearing loss, hearing loss.
If any of the side effects listed in the
instructions worsen, or you notice any other side effects not listed in the
instructions, please inform your doctor.
Overdose
Symptoms: Forced urination may occur, accompanied by
hypovolemia, electrolyte imbalance, followed by a drop in blood pressure,
drowsiness, confusion, and collapse. Gastrointestinal disturbances may also
occur.
Treatment: Dose reduction or discontinuation of the
drug, along with fluid and electrolyte replacement. There is no specific
antidote.
Storage conditions
Store at
temperatures not exceeding 30°C.
Keep out of reach
of children.
Shelf life
3 years. Do not
use after the expiration date printed on the package.
Vacation conditions
Without a prescription.
Release form
10 tablets in a PVC-aluminum blister. 2 blisters with instructions for use in a cardboard box.