HEPARIN WZF

Package leaflet: Information for the patient

Warning! Keep the leaflet. Information on the immediate packaging in a foreign language.
Heparinum WZF
5 000 IU/ml, solution for injection
Heparinum natricum
Please read the entire leaflet carefully 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, pharmacist, or nurse.
• This medicine has been prescribed strictly 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 adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What Heparinum WZF is and what it is used for

Heparinum WZF contains unfractionated heparin, an anticoagulant substance. It reduces the blood's ability to clot, thereby preventing the formation of blood clots in blood vessels. Heparinum WZF may also be used to flush intravenous catheters and cannulae to maintain their patency prior to intravenous injection.
Heparinum WZF is used:

• in the treatment of thrombotic disorders: deep vein thrombophlebitis, pulmonary embolism, unstable angina pectoris, acute peripheral arterial embolism;
• during procedures involving extracorporeal circulation and hemodialysis procedures (used to remove toxic substances from the blood in cases of severe kidney dysfunction);
• in the diagnosis and treatment of acute and chronic coagulation disorders such as disseminated intravascular coagulation;
• for flushing intravenous catheters and cannulae to maintain their patency prior to intravenous injection.

2. Important information before using Heparinum WZF

When not to use Heparinum WZF:

• if the patient is allergic to heparin or benzyl alcohol, or to any of the other ingredients of this medicine (listed in section 6).

For intravenous administration:

• if the patient has uncontrolled bleeding from sites such as, for example: gastrointestinal ulcer, areas affected by tumour processes, haemorrhoids;

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• if the patient has had intracranial haemorrhage, cerebral vascular thrombosis, threatened miscarriage, bacterial endocarditis (inflammation of the innermost layer of the heart), retinal changes (retinopathy);
• if the patient has haemophilia, haemorrhagic diathesis (except disseminated intravascular coagulation);
• if the patient has or has previously had reduced platelet count;
• if the patient has severe liver disease;
• if the patient has purpura (skin lesions appearing as single or confluent petechiae);
• if the patient has active tuberculosis;
• if the patient has severe arterial hypertension;
• if the patient has increased capillary permeability, manifested by skin petechiae and oedema;
• if the patient has sustained extensive trauma;
• before ophthalmic and neurosurgical procedures (brain surgery).

Warnings and precautions
Before starting treatment with Heparinum WZF, discuss this with the doctor.
The doctor will exercise particular caution when using Heparinum WZF and will take appropriate measures:

• if the patient has demonstrated hypersensitivity to low molecular weight heparins;
• if the patient has diabetes;
• if the patient has experienced metabolic acidosis (appearance in blood of acidic metabolic products, e.g. from carbohydrates);
• if the patient has conditions causing increased blood potassium concentration or if the patient is taking potassium-sparing drugs, because heparin may increase blood potassium levels;
• if the patient develops reduced platelet count (when heparin is used long-term);
• if the patient has severe renal and/or hepatic dysfunction;
• if the patient is over 60 years of age and is using heparin long-term, due to the risk of haemorrhagic complications;
• if the patient is elderly.

Immediately inform the doctor if, after a procedure with spinal or epidural anaesthesia,
the patient develops symptoms such as: back pain, sensory disturbances, motor disturbances,
or disturbances of bowel or bladder function (e.g. urinary incontinence).
During prolonged use of Heparinum WZF, the doctor may recommend monitoring platelet count. If a decrease in platelet count is detected, the doctor will recommend discontinuing heparin.
Precautions regarding use for flushing intravenous catheters and cannulae to maintain patency: Use of the medicine is recommended with caution in patients with hypersensitivity to low molecular weight heparins.
Strict aseptic technique must be observed during use.
The doctor may recommend blood tests if Heparinum WZF has been used for flushing a catheter or cannula for more than five days. Repeated flushing with heparin may result in anticoagulant effects.

Heparinum WZF and other medicines
Inform the doctor about all medicines currently used or recently used, as well as any medicines the patient plans to use.
Heparinum WZF and other concomitantly used medicines may interact and affect each other's actions, particularly the following:

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• The anticoagulant effect of heparin is increased by:
• acetylsalicylic acid, phenylbutazone, indomethacin (anti-inflammatory drugs);
• dipyridamole, antithrombin III (anticoagulant drugs);
• cefamandole, cefoperazone (antibiotics – drugs used in bacterial infections);
• dextran (used as a blood volume expander).
• The anticoagulant effect of heparin is decreased by:
• nitroglycerin, especially when administered intravenously (a drug that dilates blood vessels, mainly veins);
• digitalis glycosides (used in heart diseases);
• tetracyclines (antibiotics – drugs used in bacterial infections);
• nicotine (contained in tobacco);
• quinine (an antimalarial drug);
• antihistamines.
• Concomitant use of heparin and antihypertensive drugs belonging to the angiotensin-converting enzyme (ACE) inhibitors group (e.g. enalapril, captopril) may lead to increased blood potassium levels.
• When heparin and so-called thrombolytic drugs (which dissolve clots, e.g. streptokinase) are used together, the risk of haemorrhagic complications increases.
• Simultaneous administration of heparin and aprotinin (a drug reducing bleeding) may prolong whole blood clotting time.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.
The doctor may recommend using Heparinum WZF during pregnancy only in strictly justified cases, after careful consideration of risks and benefits for the woman. The medicine should be administered with particular caution during the third trimester of pregnancy and the peripartum period due to the risk of bleeding.
If the patient is pregnant and intends to receive epidural anaesthesia during childbirth, she should not use heparin. Discuss this with the doctor.
The safety of using Heparinum WZF for flushing intravenous catheters and cannulae in pregnant women has not been established, but the heparin doses used for this purpose are not expected to pose a risk.
Heparin does not pass into breast milk.
See also below – "Heparinum WZF contains benzyl alcohol and sodium".

Driving and operating machinery
Heparinum WZF has no effect on the ability to drive or operate machinery.

Heparinum WZF contains benzyl alcohol and sodium
The medicine contains 9 mg of benzyl alcohol in each millilitre, equivalent to 45 mg/5 ml. Benzyl alcohol may cause allergic reactions. Administration of benzyl alcohol to young children is associated with a risk of serious adverse effects, including respiratory disturbances (so-called "gasping syndrome").
Do not administer to neonates (under 4 weeks of age) without medical advice.
Do not administer to young children (under 3 years of age) for longer than one week without medical advice.

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Pregnant or breastfeeding women should contact a doctor before using the medicine, as large amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).
Patients with liver or kidney disease should contact a doctor before using the medicine, as large amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).
The medicine contains 26.65 mg of sodium (the main component of table salt) in 5 ml. This corresponds to 1.33% of the maximum recommended daily dietary sodium intake for adults.
The medicine can be diluted – see below: "Information intended exclusively for healthcare professionals". The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared diluted solution. For precise information on the sodium content of the solution used to dilute the medicine, refer to the leaflet of the diluent used.

3. How to use Heparinum WZF

This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult
your doctor.

• Heparinum WZF is usually administered by medical personnel.
• The medicine is given intravenously – either by direct injection into a vein or by infusion.
• After dilution, the medicine may be used to flush intravenous catheters and cannulae to maintain their patency before administration of intravenous injections.
• The doctor will determine the dosage and duration of treatment individually for each patient.

Use of a higher than recommended dose of Heparinum WZF
The symptom of overdose with Heparinum WZF is bleeding – if this occurs, seek immediate medical advice.
Missed dose of Heparinum WZF
Do not use a double dose to make up for a missed dose. Heparinum WZF should be used exactly as prescribed by the doctor.
Stopping treatment with Heparinum WZF
The decision to discontinue treatment with Heparinum WZF will be made by the doctor.
If you have any further questions regarding the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You must immediately inform the attending physician:

• if bleeding occurs, which may indicate that the patient has received more medication than needed;
• if the patient develops first signs of hypersensitivity (e.g. swelling of the face, lips, tongue, throat, causing difficulty in breathing or swallowing, urticaria, itching, conjunctivitis). Such symptoms are rare after administration of heparin.

The physician will decide on further management.
After intravenous administration the following may occur:
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• Skin and systemic hypersensitivity reactions (particularly reported in individuals who previously experienced allergic reactions to low-molecular-weight heparin). These include: urticaria, conjunctivitis, rhinitis, asthma, cyanosis, dyspnea, sense of impending doom, fever, chills, angioedema, and anaphylactic shock (reported sporadically). See information provided above.
• Burning sensation in the feet, lacrimation. Such symptoms were reported rarely.
• Decrease in platelet count (thrombocytopenia) – most commonly occurs between the 6th and 12th day of treatment and is usually mild and asymptomatic. Platelet count typically returns to baseline within 48–72 hours after discontinuation of heparin. However, it may recur upon re-administration of heparin. Cases with severe course, so-called "white clot syndrome," associated with skin necrosis or limb gangrene, have also been reported.
• Deficiency of the hormone called aldosterone, leading to increased potassium concentration in blood, which may occur between 5 and 27 days after starting heparin therapy. Elevated potassium levels are reversible and resolve after discontinuation of the drug, particularly affecting patients with diabetes or renal insufficiency.
• Increased liver enzyme activity (aminotransferases) and elevated levels of free fatty acids in serum – these are asymptomatic and usually reversible.
• Osteoporosis – observed in women receiving more than 10,000 IU per day for six months.
• Transient alopecia occurred after prolonged use of heparin, usually at high doses.

It is highly unlikely that Heparinum WZF used for flushing intravenous catheters and cannulae would produce systemic effects due to the low concentration of heparin in blood. However, rare cases of immune-mediated thrombocytopenia and thrombosis have been reported in patients receiving heparin for catheter flushing. Hypersensitivity reactions to heparin are rare; symptoms – see above.
Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform a doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions allows the collection of additional information on the safety of the medicine.

5. How to store Heparinum WZF

Store below 25°C.
Keep the medicine out of sight and reach of children.
Warning: after the first dose has been withdrawn, store the vials in a refrigerator (2°C – 8°C)
for no longer than 3 days.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

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What Heparinum WZF contains

• The active substance is sodium heparin. Each ml of solution contains 5,000 IU of sodium heparin.
• The other ingredients are: sodium chloride, benzyl alcohol, sodium hydroxide 10% (for pH adjustment), water for injections.

What Heparinum WZF looks like and contents of the pack
Heparinum WZF is a colourless, pale yellow or pale green transparent liquid.
The pack contains 10 vials with a capacity of 5 ml each.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Bulgaria, country of export:
Warszawskie Zakłady Farmaceutyczne Polfa S.A., ul. Karolkowa 22/24, 01-207 Warsaw
Manufacturer:
Warszawskie Zakłady Farmaceutyczne Polfa S.A., ul. Karolkowa 22/24, 01-207 Warsaw
Parallel importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Marketing authorisation number in Bulgaria, country of export: 20011026
Parallel import authorisation number: 14/22

Information intended exclusively for medical personnel:

Heparinum WZF
5,000 IU/mL, solution for injection
Heparinum natricum

Administration instructions for Heparinum WZF

• Heparinum WZF is intended for intravenous administration via repeated injections or, after prior dilution with 5% glucose solution or 0.9% NaCl solution, by continuous infusion. It is also indicated for flushing intravenous catheters and cannulae.

• Heparinum WZF used for flushing intravenous catheters and cannulae should be diluted with 0.9% NaCl solution.

• Heparinum WZF may be diluted:

  • with 0.9% NaCl solution to concentrations ranging from 1 IU/mL to 1,000 IU/mL,
  • with 5% glucose solution to concentrations ranging from 100 IU/mL to 1,000 IU/mL. Chemical and physical stability has been demonstrated for 24 hours at 25°C. From a microbiological standpoint, the diluted product should be used immediately. If not used immediately, the user is responsible for the conditions and duration of storage. If necessary, the prepared solution may be stored for up to 24 hours at a temperature below 25°C, provided that dilution is performed under controlled and validated aseptic conditions. Any solution not used within 24 hours must be discarded.

• All dilution procedures must be carried out under controlled and validated aseptic conditions. Aseptic techniques must be maintained for both the Heparinum WZF medicinal product and the equipment used during administration.

• After the first dose has been withdrawn, vials should be stored in the refrigerator (2°C–8°C) for no longer than 3 days.

• Dosage and infusion rate should be individually adjusted based on coagulation function test results. It is recommended to achieve an activated partial thromboplastin time (aPTT) prolonged 1.5 to 2.5 times compared to the normal mean or pre-treatment values. Treatment is usually administered for 7 to 10 days.

• Penicillin, tetracycline, erythromycin, gentamicin, kanamycin, colistin, novobiocin, vancomycin, chlordiazepoxide, hydroxyzine, prochlorperazine, hydrocortisone sodium succinate, dobutamine hydrochloride, morphine, and its derivatives form insoluble complexes with heparin. Heparin and reteplase must not be mixed in the same solution.

• When a cannula is permanently placed and used for repeated blood sampling for laboratory analysis, the presence of heparin or physiological saline may potentially interfere with or alter blood test results. Prior to blood sampling, the heparin solution in situ should be removed from the cannula by aspiration and discarded.

Dosage

Treatment of thrombophlebitis, pulmonary embolism, unstable angina, acute peripheral arterial embolism

Adults:
Initial dose: 5,000 IU intravenously (1 mL of solution); in severe pulmonary embolism, the dose may be increased to 10,000 IU (2 mL of solution).
Maintenance doses: 1,000 to 2,000 IU/hour by continuous intravenous infusion, or 5,000 to 10,000 IU by intravenous injections repeated every 4 hours.

Elderly patients:
Dosage reduction may be required in elderly patients.

Children and adults with low body weight:
Initial dose: 50 IU/kg body weight intravenously.
Maintenance doses: 15 to 25 IU/kg body weight/hour by continuous intravenous infusion, or 100 IU/kg body weight by intravenous injections repeated every 4 hours.

Patients undergoing extracorporeal circulation and hemodialysis

Adults:
Extracorporeal circulation:
Initial dose: 300 IU/kg body weight, followed by continued administration aiming to maintain activated clotting time (ACT) between 400 and 500 seconds.

Hemodialysis:
Initial dose: 1,000 to 5,000 IU.
Maintenance doses: 1,000 to 2,000 IU/hour, to maintain clotting time above 40 minutes.

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For flushing intravenous catheters and cannulae to ensure patency prior to intravenous injection.

The product must be diluted before use – see above section: "Administration instructions for Heparinum WZF".
Typically, flush with a dose of 200 IU heparin (e.g., 2 mL of a solution containing 100 IU/mL), once every 4 hours or as clinically required.

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