Normoparin

Package leaflet: Information for the user

NORMOPARIN 25,000 IU/5 ml solution for injection for intravenous use

Sodium heparin
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What NORMOPARIN is and what it is used for
2. What you need to know before you use NORMOPARIN
3. How to use NORMOPARIN
4. Possible side effects
5. How to store NORMOPARIN
6. Contents of the pack and other information

1. What NORMOPARIN is and what it is used for

NORMOPARIN is a medicine containing the active substance sodium heparin. Heparin
belongs to a group of medicines called anticoagulants, which help make the blood
more fluid.
When blood is not sufficiently fluid, there is a risk that blood clots ( thrombi ) may form, which
can obstruct or block normal blood circulation. Some thrombi may be carried by the blood flow to another area of the body ( embolism ) and cause occlusion
of a blood vessel.
NORMOPARIN is used:

• To dissolve thrombi that have formed in the veins or arteries (treatment of thromboembolic disease);
• During extracorporeal circulation (a technique used primarily in cardiac surgery that temporarily replaces heart and lung functions) and hemodialysis (a therapy that substitutes the main functions of the kidneys).

2. What you need to know before using NORMOPARIN

Do not use NORMOPARIN:

• if you are allergic to sodium heparin or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe thrombocytopenia (severe decrease in platelets) or disorders associated with a predisposition to bleeding (hemorrhagic diathesis);
• if you suffer from severe liver, kidney, or pancreatic diseases;
• if you cannot undergo tests necessary to monitor blood coagulation activity at appropriate intervals (coagulation tests);
• if you have disseminated intravascular coagulation (DIC), a condition in which blood clots form throughout the body, blocking small blood vessels, attributable to heparin-induced thrombocytopenia;
• if you have experienced a rupture of a blood vessel in the brain (hemorrhagic cerebrovascular accidents);
• if you suffer from stomach and/or intestinal ulcers, cerebral hemorrhage, aneurysm (a dilation of a cerebral artery), or brain tumor;
• if you have experienced trauma or undergone surgery involving the central nervous system, eyes, or ears;
• if you have a retinal disease (retinopathy) or vitreous hemorrhage;
• if you have endocarditis (infection-induced inflammation of the inner lining of the heart);
• if you have severe bleeding or know you are at risk for this condition. In such cases, your doctor will evaluate your specific condition and decide whether NORMOPARIN should be used.

If you are being treated with NORMOPARIN to dissolve blood clots, loco-regional anesthesia (a type of anesthesia affecting only a specific part of the body, such as lumbar puncture or spinal or epidural anesthesia) must be avoided.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using NORMOPARIN.

Before starting treatment and during therapy with NORMOPARIN, your doctor will perform monitoring tests to check blood coagulation (e.g., platelet count) and/or the presence of possible bleeding. This is particularly important if you are predisposed to bleeding.

Inform your doctor if:

• you have suspected tumors with a tendency to bleed;
• you suffer from chronic alcoholism;
• you are an elderly patient, as a dose reduction may be necessary, especially if you are a woman, since women are at higher risk of bleeding;
• you have had hypersensitivity reactions to low molecular weight heparins;
• you are at risk of bleeding; this risk is increased if:
  • you suffer from coagulation disorders (coagulation factor deficiencies, hemophilia);
  • you have decreased or abnormal platelets (thrombocytopenia or thrombocytopathies);
  • you have blood vessel abnormalities causing red spots on the skin due to bleeding (hemorrhagic purpura, such as in Rendu-Osler disease);
  • you have uncontrolled high blood pressure despite medication;
  • you have inflammation of the heart lining and heart valves (endocarditis);
  • you have liver problems, esophageal varices, or portal hypertensive gastropathy;
  • you have stomach or intestinal problems, such as a stomach or duodenal ulcer, esophagitis or gastritis, inflammatory bowel disease, or continuous drainage of stomach or intestinal contents;
  • you have undergone or will undergo lumbar puncture (spinal tap) or spinal anesthesia;
  • you have undergone or will undergo surgery on the spine, head, or eyes;
  • you have threatened miscarriage;
  • you are menstruating;
  • you are in the postpartum period;
• you are receiving concomitant treatment with certain types of medicines: fibrinolytics or oral anticoagulants, platelet aggregation inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and/or glycoprotein IIb/IIIa receptor antagonists.

Heparin may cause high potassium levels in the blood (hyperkalemia), especially if you have diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, high potassium levels before treatment, if you are taking concomitant medications that increase plasma potassium levels, or if you are using heparin long-term. Inform your doctor if any of these conditions apply to you. Your doctor will monitor your plasma potassium levels before starting heparin therapy and at regular intervals during treatment, especially if treatment lasts longer than 7 days.

In case of any bleeding, your doctor will discontinue heparin treatment.

Heparin must not be administered intramuscularly due to the risk of hematoma formation.

Additionally, intramuscular administration of other medications should be avoided during heparin treatment due to the increased risk of bleeding.

Undesirable effects on the blood and risk of thrombosis

During treatment with NORMOPARIN, between 4 and 10 days after starting therapy, a decrease in platelets (heparin-induced thrombocytopenia) may occur, potentially leading to complications affecting the heart, lungs, brain, and limbs (thrombotic and/or embolic events).

Inform your doctor immediately if, during treatment with NORMOPARIN, you experience any of the following conditions, even several days after administration:

• worsening of your condition;
• blood clots in the limbs (peripheral vessels), especially in the legs. This condition manifests as pain, swelling, redness, loss of sensation, and increased temperature in the affected area. In severe cases, gangrene may occur;
• blood clots in the heart leading to heart attack. This condition manifests as pressure, tightness, pain, or heaviness in the center of the chest spreading to shoulders, neck, arms, or back, cold sweating, dizziness, shortness of breath, and nausea;
• blood clots in the lungs. This condition manifests as difficulty breathing, chest pain, and cough;
• blood clots in the brain leading to stroke. This condition manifests as severe headache or vomiting, dizziness, fainting, vision or speech disturbances, weakness, or numbness in one arm or leg.

IN ALL THESE CASES, YOUR DOCTOR WILL EVALUATE WHETHER TO DISCONTINUE TREATMENT WITH NORMOPARIN OR PRESCRIBE AN ALTERNATIVE TREATMENT.

Use of NORMOPARIN to prevent thrombus formation and loco-regional anesthesia

In patients undergoing loco-regional anesthesia (e.g., lumbar puncture or spinal or epidural anesthesia), the doctor will carefully evaluate whether to use NORMOPARIN to prevent venous thrombus formation.

If your doctor decides to use NORMOPARIN, after administering the anesthetic, the doctor or nurse will monitor for bleeding or bruising (hematoma) at the injection site, as hematoma formation in the area where anesthesia was administered may lead to paralysis, even permanent. The risk of this event is increased if:

• indwelling epidural catheters are used for continuous infusion;
• you have coagulation disorders or are taking medications affecting coagulation, such as anti-inflammatory drugs (NSAIDs) or blood-thinning drugs (see "Other medicines and NORMOPARIN");
• you are elderly;
• you have experienced trauma or repeated spinal punctures.

Inform your doctor or nurse immediately if, after receiving anesthesia, you notice symptoms of paralysis such as tingling, weakness, or numbness in the legs, back pain, or difficulty urinating or defecating.

Other information

The effectiveness of NORMOPARIN may be reduced if:

• you have antithrombin III deficiency (a blood component involved in coagulation);
• you have fever or infections;
• you have inflammation, for example in a vein (thrombophlebitis);
• you have cancer;
• you are experiencing a heart attack;
• you have recently undergone surgery.

Other medicines and NORMOPARIN

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is particularly important if you are taking:

• medicines that may affect blood coagulation and/or increase the risk of bleeding, such as:
  • oral anticoagulants, used to prevent blood clot formation by interfering with the coagulation process;
  • platelet aggregation inhibitors, which reduce the risk of blood clot formation by preventing platelet aggregation:
    • acetylsalicylic acid (aspirin) and dipyridamole;
  • non-steroidal anti-inflammatory drugs (NSAIDs) used to reduce pain (such as ibuprofen, phenylbutazone, indomethacin, ketorolac, diclofenac);
  • medicines with antiplatelet effects (ticlopidine, clopidogrel, sulfinpyrazone);
  • cephalosporins (cefaclor, cefixime, ceftriaxone, cefamandole, cefoperazone), a class of antibiotics;
  • dextran, a medicine used to increase blood volume;
  • hydroxychloroquine, a medicine used in rheumatic diseases;
  • fibrinolytic agents, used to dissolve blood clots:
    • streptokinase, urokinase, alteplase;
  • other medicines that increase the risk of bleeding:
    • coumarin derivatives;
    • glycoprotein IIb/IIIa receptor antagonists (eptifibatide, abciximab);
    • epoprostenol or other drugs interfering with platelet aggregation, as they may cause bleeding: these must be used with extreme caution if you are being treated with sodium heparin;
  • intravenous nitroglycerin, used to manage cardiovascular conditions;
  • medicines that increase potassium levels in the blood (ACE inhibitors, sartans, potassium-sparing diuretics, potassium salts, beta-blockers);
  • digitalis, a medicine used in heart diseases;
  • penicillins or tetracyclines, antibiotic medicines;
  • medicines containing nicotine;
  • phenothiazines, medicines used, for example, for anxiety;
  • corticosteroids, antihistamines, medicines used for allergies.

If you need to undergo thyroid function tests, you should be aware that these may yield altered results if you are receiving heparin treatment.

If you are being treated with NORMOPARIN to dissolve blood clots, intramuscular administration of other medicines should be avoided.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.

3. How to use NORMOPARIN

NORMOPARIN will be administered to you intravenously only by doctors or healthcare professionals.
Your doctor will determine the most appropriate dose for you based on the reason for which you are using
NORMOPARIN and on your blood tests (coagulation tests).
If you use more NORMOPARIN than you should
NORMOPARIN will be administered exclusively by doctors or healthcare professionals; therefore, overdose is unlikely. However, if high doses of this medicine are administered, the risk of bleeding, even severe bleeding, is increased. If you notice any signs of bleeding, contact your doctor or nurse immediately, who will provide appropriate treatment (administration of protamine).
Additional “Information intended exclusively for doctors or healthcare professionals” is available at the end of this leaflet.
If you have any doubts about the use of this medicine, consult your doctor or nurse.
If you forget to use NORMOPARIN
This medicine will be administered to you by a doctor or nurse, so it is unlikely that a dose will be missed. Do not administer a double dose to make up for a missed dose.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.
If you stop treatment with NORMOPARIN
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Stop using NORMOPARIN immediately and contact your doctor if you experience any of the following:

• allergic reactions (hypersensitivity), even severe, manifesting as chills, fever, urticaria, breathing difficulties (asthma), nasal inflammation (rhinitis), increased lacrimation, nausea, vomiting, itching and burning in the feet, drop in blood pressure, vasospasm, irregular heartbeat, swelling of the face, eyes, lips, tongue, and throat (anaphylactic shock);
• severe skin lesions with inflammation (skin necrosis), bruising, purple or reddish spots of varying size (purpura or petechiae);
• severe bleeding (haemorrhage), even difficult to detect, occurring anywhere in the body (see section “The following information is intended exclusively for healthcare professionals:” at the end of this leaflet ) (cerebral haemorrhage, extradural intracranial haematoma, non-traumatic spinal subdural haematoma, ventricular haemorrhage);
• reduction in platelet count (thrombocytopenia), (section 2 - “Adverse effects on blood and risk of blood clots” ) ;
• increased platelet aggregation, or worsening of initial conditions, blood clots in limbs, heart, lungs, brain (section 2 - “Adverse effects on blood and risk of blood clots” ) ;
• disseminated intravascular coagulation (DIC);
• haematomas or ulcers at the injection site;
• breathing difficulties or chest pain (may be symptoms of pulmonary oedema or haemopneumothorax);
• liver toxicity (hepatotoxicity);
• melena (presence of blood in faeces);

Other adverse effects
Inform your doctor if, during treatment with NORMOPARIN, you notice or are diagnosed with:

• cerebral haemorrhage, extradural intracranial haematoma, non-traumatic spinal subdural haematoma, ventricular haemorrhage;
• reduction in bone mass leading to weakening and increased risk of fractures (osteoporosis);
• suppression of production of a hormone called aldosterone;
• temporary hair loss (alopecia);
• increased potassium levels in the blood (hyperkalaemia);
• metabolic acidosis (particularly in patients with renal impairment and diabetes mellitus);
• persistent and unprovoked erection, often painful (priapism);
• rebound increase in lipid levels after heparin therapy (rebound hyperlipidaemia), or increased levels of FT3 and FT4 or transaminases (liver enzymes) in the blood;
• amnesia;
• bronchospasm (abnormal contraction of the bronchi);
• increased transaminase levels (enzymes produced by the liver);
• irritation, redness, bruising, pain at the injection site.

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report adverse effects directly via
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store NORMOPARIN

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date, which is stated on the packaging after "Exp". The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What NORMOPARIN contains
The active substance is: sodium heparin.
1 ml of solution contains 5,000 IU sodium heparin.
The other component is: water for injections.

Description of the appearance of NORMOPARIN and contents of the pack
This medicine is available in packs containing 10 vials of 25,000 IU/5 ml.

Marketing Authorization Holder
Laboratorios Farmacéuticos ROVI, S.A.
Julián Camarillo, 35
28037 – Madrid
Spain

Seller
Rovi Biotech, S.R.L.
Viale Achille Papa, 30
20149 - Milan
Italy

Manufacturer
B.Braun Medical, S.A.
Ronda de Los Olivares, parcela 11, Polígono Industrial Los Olivares
23009-Jaén
Spain

The following information is intended exclusively for healthcare professionals:

Dosage and administration
Extracorporeal circulation (cardiopulmonary bypass)
300 IU/kg intravenously, adjusted to maintain the Activated Clotting Time (ACT)
within the range of 400–500 seconds.
Hemodialysis
Initial dose of 1,000–5,000 IU intravenously, followed by 1,000–2,000 IU/hour, adjusted
according to clinical requirements.
Monitoring:
Routine monitoring is not required.
Treatment of arterial and venous thromboembolism
Initial dose is 80 IU/kg IV as a bolus or 5,000 IU as an intravenous bolus injection (10,000 IU in case of severe pulmonary embolism).
The maintenance dose is
Alternative treatment regimens
Intermittent intravenous injection: 10,000 IU IV bolus followed by 5,000–10,000 IU IV every
4–6 hours.
Monitoring:
When administering sodium heparin at anticoagulant doses, dosage must be determined
based on coagulation tests. The most commonly used test is activated partial thromboplastin time (aPTT). The aPTT of patients under treatment should be maintained at 1.5 to 2.5 times the normal control values. Regular monitoring of aPTT values is recommended, preferably on a daily basis.
If coagulation tests exceed the therapeutic range or if bleeding occurs, the dose should be reduced or, if necessary, heparin should be discontinued (see section 4.4).

Special populations
Paediatric population
Treatment of arterial and venous thromboembolism
Initial dose: 50 IU/kg as an intravenous bolus injection.
Maintenance dose: 15–25 IU/kg/hour by continuous intravenous infusion, or 100 IU/kg IV every 4 hours as intermittent injection.
Monitoring:
When administering sodium heparin at anticoagulant doses, dosage should be adjusted based on aPTT values.
Younger children may require higher doses and infusion rates to achieve anticoagulation levels and aPTT prolongation comparable to older children.

Elderly
Lower doses may be required due to an increased risk of bleeding.
Monitoring:
When administering sodium heparin at anticoagulant doses, doses should be adjusted according to aPTT values.

Method of administration
Intravenous administration via continuous infusion or intermittent injection.
Because the effects of sodium heparin are short-acting, intravenous infusion is preferred over intermittent intravenous injection.
Do not administer NORMOPARIN by intramuscular or subcutaneous injection.

Bleeding
Bleeding is the main complication that may occur during treatment with sodium heparin, particularly at anticoagulant doses.
Coagulation times above the therapeutic range or minor bleeding during therapy can generally be managed by reducing the dose or, if necessary, temporarily discontinuing the drug. Gastrointestinal or urinary bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding may occur in any part of the body, but certain specific hemorrhagic complications may be difficult to detect:
(a) Adrenal hemorrhage, leading to acute adrenal insufficiency, has been reported during anticoagulant therapy. Therefore, treatment should be discontinued if the patient develops signs and symptoms of acute adrenal insufficiency.
(b) Ovarian hemorrhage (corpus luteum) has occurred in women of reproductive age receiving short- or long-term anticoagulant therapy.
(c) Retroperitoneal hemorrhages.

Overdose
Symptoms of overdose
Bleeding, primarily from the skin and mucous membranes, wounds, gastrointestinal or genitourinary tract (epistaxis, hematuria, melena, ecchymoses, petechiae). A drop in blood pressure or a reduction in hematocrit may indicate occult bleeding.
Antidote for overdose
Minor bleeding
Discontinuation of heparin therapy.
Severe bleeding
Protamine sulfate is used for the rapid neutralization of heparin activity in cases of significant bleeding.
The amount required depends on the blood level of administered heparin and the time elapsed since administration. Protamine should be administered by slow intravenous infusion; 50 mg of protamine neutralizes 5,000 IU of heparin. The dose of protamine required to neutralize a heparin bolus decreases proportionally with time since bolus administration (100% of the dose immediately after bolus, 50% after 1 hour, 25% after 2 hours).
The dose of protamine required to reverse ongoing continuous heparin infusion is that needed to neutralize the amount of heparin infused over the preceding 4 hours.