Trifas 200

Package leaflet: Information for the user

Trifas 200; 10 mg/ml, solution for infusion
Torasemidum
Please read carefully this leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What Trifas 200 is and what it is used for
2. Important information before using Trifas 200
3. How to use Trifas 200
4. Possible side effects
5. How to store Trifas 200
6. Contents of the pack and other information

1. What Trifas 200 is and what it is used for
Trifas 200 contains the active substance torasemid and belongs to a group of medicines called loop diuretics.
Torasemid has diuretic effects and also lowers blood pressure.
Trifas 200 is indicated for use, for a maximum period of 1 week, exclusively for the treatment of patients with severe renal function disorders (creatinine clearance less than 20 ml/min and/or serum creatinine concentration greater than 6 mg/dl). Your doctor can determine the degree of renal impairment by blood tests.
In patients with severe renal insufficiency, Trifas 200 enables sufficient excretion of an adequate amount of urine. The medicine is also effective in dialysed patients. However, in such cases, the patient should still excrete at least 200 ml/24h of urine (residual volume).
Trifas 200 is used in adults for the treatment of:

• fluid retention in tissues (oedema) and (or)
• fluid accumulation in body cavities (effusions),
• high blood pressure

Note:
Trifas 200 should only be used in cases of severe renal function disorders and is not suitable when kidney function is normal!

2. Important information before using Trifas 200

When not to use TRIFAS 200

• if you are allergic to:
  • the active substance torasemid;
  • substances with a similar chemical structure (sulfonylurea derivatives);
  • any of the other components of this medicine (listed in section 6);
• if you have renal failure with anuria;
• if you have liver dysfunction with impaired consciousness (hepatic coma or pre-coma state);
• if you have low blood pressure (hypotension);
• if you have reduced circulating blood volume (hypovolemia);
• if you have low levels of sodium and potassium in the blood (hyponatremia, hypokalemia);
• if you have significant impairment of bladder emptying (e.g., due to benign prostatic hyperplasia);
• if you are breastfeeding;
• in patients with normal or only moderately impaired renal function (creatinine clearance of 30 ml/min and/or serum creatinine concentration below 3.5 mg/100 ml) due to the risk of excessive loss of water and electrolytes. Your doctor should evaluate blood test results in this regard.

Warnings and precautions
Before starting treatment with Trifas 200, discuss this with your doctor or pharmacist.
Due to insufficiently documented research results, Trifas 200 should not be used in the following cases:

• gout;
• severe cardiac arrhythmias, when heartbeats are slowed, myocardial stimulation, and conduction disturbances, e.g.: sinoatrial block, second- or third-degree atrioventricular block;
• acid-base balance disorders;
• patients concurrently using lithium salts (medicines used in mood disorders and depression);
• patients using certain antibiotics for infection treatment, such as: aminoglycosides, cephalosporins;
• patients with blood morphology disorders, e.g.: thrombocytopenia or anemia in patients without renal dysfunction;
• patients with renal dysfunction caused by nephrotoxic agents;
• in patients with creatinine clearance between 20 and 30 ml/min and/or serum creatinine concentration between 3.5 and 6 mg/100 dl.

Children and adolescents
Trifas 200 should not be used in children and adolescents under 18 years of age due to insufficient data on the use of Trifas 200 in this age group.
Effect on doping tests
The use of medicinal product Trifas 200 may result in positive doping test results. The effects of using Trifas 200 as a doping agent cannot be predicted; health risks cannot be excluded.
Trifas 200 and other medicines
Inform your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to use.

• Trifas 200 may affect the action of the following medicines:
  • Blood pressure-lowering medicines, especially ACE inhibitors: concomitant administration or immediate sequential use of angiotensin-converting enzyme inhibitors with torasemid may cause a rapid drop in blood pressure.
  • Theophylline (a medicine used in asthma treatment): Trifas 200 may enhance the effect of theophylline.
  • Neuromuscular blocking agents: increased muscle-relaxing effect.
  • Antidiabetic medicines: Trifas 200 may weaken the effect of antidiabetic medicines.
  • Painkillers and rheumatic medicines – when high doses of salicylates are used, torasemid may intensify their toxic effects on the central nervous system.
  • Medicines used in circulatory disorders (epinephrine and norepinephrine): Trifas 200 may weaken the effect of these medicines.
• The following medicines may affect the action of Trifas 200:
  • Probenecid (a medicine used in gout treatment): probenecid may inhibit the diuretic and antihypertensive effects of Trifas 200.
  • Certain anti-inflammatory medicines (e.g., indomethacin, acetylsalicylic acid): these medicines may inhibit the diuretic and antihypertensive effects of Trifas 200.
• During high-dose treatment (see section 3), Trifas 200 may intensify the following adverse effects:
  • Hearing and kidney damage caused by aminoglycoside antibiotics (e.g., kanamycin, gentamicin, tobramycin) used in infection treatment.
  • Hearing and kidney damage caused by cisplatin (used in cancer treatment).
  • Kidney damage caused by cephalosporins (a group of antibiotics) used in infection treatment.
• Other interactions of Trifas 200 with other medicines:
  • Hypokalemia (low potassium levels) caused by Trifas 200 may intensify adverse effects of concurrently administered digitalis glycosides (used in heart failure treatment).
  • Laxatives may increase potassium loss caused by Trifas 200.
  • Adrenal cortex hormones (mineralo- and glucocorticoids, e.g., cortisone), when used concomitantly with Trifas 200, may increase potassium loss induced by the medicine.
  • Concurrent treatment with Trifas 200 and lithium salts (used in treatment of acute mood disorders and various types of depression) may increase serum lithium concentration, thereby intensifying the cardiotoxic and nephrotoxic effects of lithium salts.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.
Pregnancy
Trifas 200 may be used during pregnancy only if absolutely necessary. The lowest possible dose should be used.
There is insufficient clinical knowledge regarding the effects of Trifas 200 on the unborn child.
Breastfeeding
It is unknown whether the active substance of Trifas 200 passes into human milk. Therefore, Trifas 200 must not be used during breastfeeding. If use of the medicine during breastfeeding is necessary, breastfeeding must be discontinued.
Driving and operating machinery
Trifas 200 may alter reaction time. Trifas 200 may impair the ability to actively participate in road traffic, operate machinery, or work without safe foot support.
This especially applies during:

• the initial treatment period,
• the period after dose increase,
• the period after switching from another medicine,
• the period when starting concomitant treatment with another product.

Alcohol may intensify this effect. Do not consume alcohol during treatment with Trifas 200.

3. How to use Trifas 200

This medicine should always be used exactly as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.

Dosage
The dosage should be individually adjusted for each patient depending on the degree of renal impairment.
The recommended initial dose is a single daily dose of 5 ml of Trifas 200 (equivalent to 50 mg of torasemide). If diuresis is insufficient, the dose may be increased to 10–20 ml of Trifas 200 per day (equivalent to 100–200 mg of torasemide per day).

• Patients with hepatic impairment Treatment should be administered with particular caution due to the possibility of increased blood concentration of torasemide.
• Elderly patients Dose adjustment is not required in elderly patients.

Method of administration
The Trifas® 200 injection solution should be administered intravenously as a slow infusion, usually by an infusion pump. The infusion rate must not exceed 0.4 ml of Trifas 200 solution per minute (equivalent to 4 mg of torasemide).
If necessary, Trifas 200 may be diluted with the following compatible solutions:
Depending on requirements, the contents of one Trifas 200 ampoule may be diluted with 30 ml, 125 ml, 250 ml, or 500 ml of 0.9% isotonic sodium chloride solution or 5% glucose solution.
The diluted solution must be used immediately!
Trifas 200 must not be administered in combination with other medicines in the same infusion.
Only a clear solution should be administered!
Intra-arterial administration is not permitted!
Any unused solution must be discarded.

Administration
Handling OPC-type ampoules (one-point-cut). Warning! Do not file the ampoule!

Hold the ampoule with the Hold the ampoule with the
coloured mark facing upwards coloured mark facing upwards
By gently shaking or tapping the ampoule, ensure that the solution flows from the tip of the ampoule to its base. Break off the tip of the ampoule.

Duration of treatment
The duration of treatment with Trifas 200 is determined by the attending physician.
Trifas 200 should not be administered intravenously for longer than 1 week.
During treatment with Trifas 200, the patient must be closely monitored by the physician.
If treatment needs to be continued, switching from intravenous to oral formulation should be done as soon as possible.

Overdose of Trifas 200
Administration of a dose higher than recommended may cause:

• pronounced, potentially dangerous diuresis with loss of fluids and electrolytes,
• disturbances in consciousness,
• confusion,
• hypotension,
• circulatory collapse,
• gastrointestinal disturbances.

You should contact your doctor immediately, who will advise on appropriate management.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.

Common (may affect up to 1 in 10 patients)

• Acid-base imbalance (metabolic alkalosis)
• Muscle cramps (especially at the beginning of treatment)
• Increased levels of uric acid, glucose and lipids (triglycerides, cholesterol) in blood
• Potassium deficiency (hypokalaemia) when combined with a low-potassium diet, vomiting, diarrhoea, laxative abuse, or in patients with chronic liver dysfunction
• Depending on the dose used and duration of treatment, disturbances in water and electrolyte balance may occur, particularly reduction in circulating blood volume (hypovolaemia), loss of potassium and sodium (hypokalaemia and/or hyponatraemia)
• Gastrointestinal disturbances (e.g. loss of appetite, abdominal pain, nausea, vomiting, diarrhoea, constipation), especially at the beginning of treatment
• Increased activity of certain liver enzymes (gamma-GT) in blood
• Headache and dizziness, feeling of fatigue, weakness (especially at the beginning of treatment)

Uncommon (may affect up to 1 in 100 patients)

• Increased levels of urea and creatinine (a muscle protein) and urea in blood. In patients with impaired urine excretion (e.g. due to benign prostatic hyperplasia), urine retention may occur. In such cases, urination is impaired or impossible
• Dryness of the mouth
• Sensation of numbness and coldness in the extremities (paraesthesiae)

Very rare (may affect up to 1 in 10,000 patients)

• Decreased number of red and white blood cells (erythrocytes and lymphocytes) and reduced platelet count (thrombocytes)
• Allergic reactions, such as itching, rash, photosensitivity, severe allergic skin reactions. When administered intravenously, acute, even potentially fatal hypersensitivity reactions (anaphylactic shock) cannot be excluded
• Formation of blood clots in blood vessels (thromboembolic complications)
• Confusion
• Low blood pressure (hypotension)
• Circulatory disturbances in coronary or central circulation (including myocardial and cerebral ischaemia). These conditions may lead to cardiac rhythm disturbances (arrhythmia), sensation of chest tightness (angina pectoris), acute myocardial infarction, or, for example, sudden loss of consciousness (syncope)
• Pancreatitis
• Visual disturbances
• Tinnitus
• Hearing loss

If any of the adverse effects listed above occur, inform your doctor immediately. The doctor will assess the severity of symptoms and decide which tests are necessary.
In case of sudden onset of adverse effects with severe course, immediate medical consultation is required. This is very important, as some side effects may potentially be life-threatening. The doctor will decide which analyses should be performed and whether treatment should be continued.
If any hypersensitivity reactions occur (e.g. severe allergic skin reaction), Trifas 200 must not be re-administered.

Management in case of hypersensitivity reaction
Serious, potentially life-threatening hypersensitivity reactions (anaphylactic shock) may occur, requiring immediate intervention. The patient should be placed flat on their back with legs elevated, airways should be cleared, oxygen therapy initiated, intravenous access established, and intravenous epinephrine (adrenaline), glucocorticosteroids, and fluid replacement administered as appropriate.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw,
tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Trifas 200

Keep the medicine in a place inaccessible and out of sight of children.
Store below 30ºC.
Only clear solutions should be administered.
The infusion solution must be used immediately after opening. Any unused portion should be discarded.
Do not use this medicine after the expiry date (EXP) stated on the carton box and
on the vials. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask a
pharmacist what to do with medicines no longer required. This will help protect
the environment.

6. Contents of the pack and other information

What Trifas 200 contains
The active substance is torasemide.
Each 20 ml vial of infusion solution contains 212.62 mg of torasemide sodium salt, corresponding to
200 mg of torasemide.
Other ingredients are: sodium hydroxide, trometamol, macrogol 400, water for injections.
The pH of Trifas 200 is between 8.7 and 9.7.
What Trifas 200 looks like and contents of the pack
The vials contain a clear, colourless solution.
Trifas 200 is available in packs containing 5 vials of 20 ml each.
Marketing Authorisation Holder
Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare,
L-1611 Luxembourg, Luxembourg
Manufacturer
A. Menarini Manufacturing Logistics and Services S.r.I.
Via Sette Santi 3,
50131 Florence,
Italy
For further information, please contact the representative of the Marketing Authorisation Holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel: (22) 566 2100
Fax: (22) 566 2101