NORMOPARIN 25.000 IU/ 5 ML Injectable solution

Зміст інструкції

1. NORMOPARIN 25.000 UI/5 ml injectable solution for intravenous use
   1. What is NORMOPARIN and what is it used for
   2. What you need to know before using NORMOPARIN
   3. How to use NORMOPARIN
2. NORMOPARIN will be administered to you intravenously only by doctors or healthcare professionals.
   1. Possible side effects
   2. How to store NORMOPARIN
   3. Contents of the pack and other information

NORMOPARIN 25.000 UI/5 ml injectable solution for intravenous use

Sodium heparin

Read this leaflet carefully before you start to use this medicine as 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, see your doctor or pharmacist. 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 is NORMOPARIN and what is it used for

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

• To dissolvethrombi that have formed in the veins or arteries (treatment of thromboembolic disease);
• During extracorporeal circulation(a technique used especially in cardiac surgery that allows temporary replacement of cardiopulmonary functions) and hemodialysis(therapy that replaces 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 any of the other ingredients of this medicine (listed in section 6);
• if you have a severe decrease in platelets (severe thrombocytopenia) or disorders accompanied by a predisposition to the development of bleeding (haemorrhagic diathesis);
• if you suffer from severe liver, kidney or pancreas diseases;
• if you cannot undergo analyses useful for monitoring blood coagulation activity at appropriate intervals (coagulation tests);
• if you manifest 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 a rupture of a blood vessel in the brain (haemorrhagic cerebrovascular accidents);
• if you suffer from ulcers in the stomach and/or intestines, cerebral haemorrhage, aneurysm (a dilation of a cerebral artery), brain tumour;
• if you have a trauma or have undergone surgery to the central nervous system, eyes or ears;
• if you have a retinal disease (retinopathy) or vitreous haemorrhage;
• if you have inflammation of the inner lining of the heart caused by germs (infective endocarditis);
• if you have severe bleeding or know you are at risk for this condition. In such cases, the doctor will assess your specific condition and decide whether or not to use NORMOPARIN.

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

Warnings and precautions
Consult your doctor, pharmacist or nurse before using NORMOPARIN.
Before starting treatment and during therapy with NORMOPARIN, the doctor will perform check-up tests to verify blood coagulation (e.g. platelet count) and/or the presence of any bleeding. This is particularly important if you are predisposed to bleeding.
Tell your doctor if:

• you manifest suspected neoplasms with a tendency to bleed;
• you suffer from chronic alcoholism;
• you are an elderly patient, because a dose reduction may be necessary, especially if you are a woman, as women are at greater risk of haemorrhage;
• you have had hypersensitivity reactions to low molecular weight heparin;
• you are at risk of bleeding; this risk is increased if:
• you suffer from blood coagulation disorders (deficiency of coagulation factors, haemophilia);
• you have a decrease or alteration of platelets (thrombocytopenia or thrombopathies);
• you have an alteration of blood vessels that causes red spots on the skin due to bleeding; (haemorrhagic purpura, such as Rendu-Osler disease);
• you suffer from high blood pressure that cannot be controlled with medication;
• you have inflammation of the lining of the heart and heart valves (endocarditis);
• you have liver problems, oesophageal varices or portal hypertension gastropathy;
• you have problems with the stomach or intestines, for example you have a stomach or duodenal ulcer, inflammation of the oesophagus or stomach, inflammatory bowel disease or continuous drainage from the stomach or intestines;
• you have undergone or will undergo a lumbar puncture or a spinal anaesthesia;
• you have undergone or will undergo surgery on the spine, head or eyes;
• you have threats of abortion;
• you are menstruating;
• you are in the postpartum period;
• you are concomitantly treated with certain categories of medicines: fibrinolytics or oral anticoagulants, platelet aggregation inhibitors, non-steroidal anti-inflammatory drugs and/or glycoprotein IIb/IIIa receptor antagonists; Heparin can cause a high concentration of potassium in the blood (hyperkalaemia), especially if you suffer from diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, high levels of potassium before treatment, if you take

therapy at the same time with drugs that increase plasma potassium levels or if you use heparin for a long time. Tell your doctor if any of these conditions apply to you. The doctor will check your plasma potassium levels before starting heparin therapy and at regular intervals during treatment, especially if the therapy is administered for more than 7 days.
In any case of bleeding, the doctor will interrupt treatment with heparin.
Heparin should not be administered to you intramuscularly due to the risk of haematomas.
Furthermore, it should not be administered concurrently with other medicines via intramuscular route due to the increased risk of bleeding.

Adverse effects on the blood and risk of thrombosis
During therapy with NORMOPARIN, after 4 - 10 days from the start of treatment, a decrease in platelets (heparin-induced thrombocytopenia) may occur, with possible complications affecting the heart, lungs, brain and limbs (thrombotic and/or embolic events).

Immediately inform your doctorif you experience any of the following conditions during treatment with NORMOPARIN, even days after taking the dose:

• worsening of your condition;
• blood clots in the limbs (peripheral vessels), especially in the legs. This condition manifests with pain, swelling, redness, loss of sensitivity and increased temperature of the affected part. In more severe cases, gangrene may occur;
• blood clots in the heart with consequent infarction. This condition manifests with a feeling of oppression, compression, pain or weight in the centre of the chest that may radiate to the shoulders, neck, arms or back, cold sweat, dizziness, shortness of breath and nausea;
• blood clots in the lungs. This condition manifests with difficulty breathing, chest pain and cough;
• blood clots in the brain with consequent stroke. This condition manifests with severe headache or vomiting, dizziness, fainting or alterations of vision or speech, weakness or numbness of an arm or leg. IN ALL THESE CASES THE DOCTOR WILL ASSESS WHETHER TO STOP TREATMENT WITH NORMOPARIN OR TO PRESCRIBE ALTERNATIVE TREATMENT.

Use of NORMOPARIN to prevent the formation of thrombi and loco-regional anaesthesia
In patients who are to undergo loco-regional anaesthesia (e.g. lumbar puncture or spinal or epidural anaesthesia), the doctor will carefully assess whether to use NORMOPARIN to prevent the formation of clots (thrombi) in the veins.
If the doctor decides to use NORMOPARIN, after administering the anaesthetic, the doctor or nurse will check for bleeding or bruising (haematoma) at the site where the injection was made, as the formation of a haematoma in the area where the anaesthetic was administered may cause permanent paralysis. The risk of this event occurring is increased if:

• peridural catheters are used for continuous infusion;
• you have coagulation problems or are taking medications that affect coagulation, such as anti-inflammatory drugs (NSAIDs), blood-thinning medications (see "Other medicines and NORMOPARIN");
• you are elderly;
• you have had trauma or repeated spinal punctures. Immediately warn your doctor or nurseif you notice symptoms of paralysis after receiving the anaesthetic, such as: tingling, weakness or numbness in the legs, back pain, problems evacuating or urinating.

Other information
The effectiveness of NORMOPARIN may be lower if:

• you suffer from antithrombin III deficiency (a blood component that acts on coagulation);
• you have a fever, or infections;
• you have inflammation, for example in a vein (thrombophlebitis);
• you have cancer;
• you have an ongoing heart attack;
• you have recently undergone surgery.

Other medicines and NORMOPARIN
Tell your doctor or pharmacist if you are taking, have recently taken or may take any other medicines. This is particularly important if you are taking:

• medicines that can affect blood coagulation and/or increase the risk of bleeding, such as:
• oral anticoagulant medicines, used to prevent the formation of thrombi in the blood by interfering with the coagulation process;
• antiplatelet agents, which reduce the risk of thrombus formation in the blood by hindering platelet aggregation:
• acetylsalicylic acid (commonly known as aspirin) and dipyridamole;
• non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve pain (such as ibuprofen, phenylbutazone, indometacin, ketorolac, diclofenac);
• medicines with antiplatelet effect (ticlopidine, clopidogrel, sulfinpyrazone);
• cephalosporins (cefaclor, cefixime, ceftriaxone, cefamandole, cefoperazone), which are a class of antibiotics;
• dextran, a medicine used to increase blood volume;
• hydroxychloroquine, a medicine used in rheumatic diseases;
• fibrinolytic medicines, used to dissolve thrombi that have formed in the blood:
• streptokinase, urokinase, alteplase;
• other medicines that increase the risk of bleeding:
• coumarin derivatives;
• glycoprotein IIb/IIIa receptor antagonists (eptifibatide, abciximab);
• epoprostenol or other medicines that interfere with platelet aggregation because they may induce bleeding: they must be used with great caution if you are being treated with sodium heparin;
• intravenous nitroglycerin, used to manage cardiovascular diseases;
• 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 are to undergo thyroid function tests, you should consider that, if you are being treated with heparin, these may be altered.
If you are being treated with NORMOPARIN to dissolve blood clots, the administration of medicines via the intramuscular route should be avoided.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor for advice before taking this medicine.

3. How to use NORMOPARIN

NORMOPARIN will be administered to you intravenously only by doctors or healthcare professionals.

The doctor will determine the most appropriate dose for you based on the reason why you are using
NORMOPARIN and your blood tests (coagulation tests).

If you use more NORMOPARIN than you should
NORMOPARIN will be administered to you exclusively by doctors or healthcare professionals; an
overdose is unlikely. However, if high doses of this
medicine are administered, the risk of bleeding, even serious bleeding, is increased. If you notice any signs of
bleeding, contact your doctor or nurse immediatelywho will administer
appropriate therapy (protamine administration).

Further “Information intended exclusively for doctors or healthcare professionals” is
If you have any doubts about the use of this medicine, ask your doctor or nurse.

If you forget to use NORMOPARIN
This medicine will be administered by the doctor or a nurse, so it is unlikely that a dose will be forgotten. A double dose should not be administered to
make up for a missed dose.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist or
nurse.

If you stop taking NORMOPARIN
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop usingNORMOPARIN immediately and contact your doctor if any of the following conditions occur:

• allergic reactions (hypersensitivity), even severe ones, manifesting with chills, fever, hives, difficulty breathing (asthma), nasal inflammation (rhinitis), increased tearing, nausea, vomiting, itching and burning of the feet, low blood pressure, vasospasm, altered heart rate, swelling of the face, eyes, lips, tongue and throat (anaphylactic shock);
• severe skin lesions with inflammation (skin necrosis), hematomas, more or less large purple or reddish spots (purpura or petechiae);
• severe bleeding (hemorrhage), even difficult to identify in any part of the body (paragraph“The following information is intended exclusively for”

intracranial extradural, non-traumatic spinal subdural hematoma, ventricular hemorrhage;

• decreased platelets (thrombocytopenia), (paragraph 2- “Side effects on the blood and risk of thrombosis”);
• increased platelet aggregation, or worsening of initial conditions, blood clots in the limbs, heart, lungs, brain (paragraph 2- “Side effects on the blood and risk of thrombosis”);
• disseminated intravascular coagulation (DIC);
• hematomas or ulcers at the injection site;
• difficulty breathing or chest pain (may be symptoms of pulmonary edema or hemopneumothorax);
• liver toxicity (hepatotoxicity);
• melena (presence of blood in the stool);

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

• cerebral hemorrhage, intracranial extradural hematoma, non-traumatic spinal subdural hematoma, ventricular hemorrhage;
• decreased bone mass with consequent weakening and increased risk of fractures (osteoporosis);
• suppression of the production of a hormone called aldosterone;
• transient hair loss (alopecia);
• increased potassium levels in the blood (hyperkalemia);
• metabolic acidosis (particularly in patients with kidney damage and diabetes mellitus);
• persistent and non-stimulation-related erection, often painful (priapism);
• increased fat levels at the end of heparin therapy (rebound hyperlipidemia) of FT3 and FT4 levels or liver enzymes (transaminases) in the blood;
• amnesia;
• bronchospasm (abnormal contraction of the bronchi);
• increased transaminases (enzymes produced by the liver);
• irritation, redness, bruising, pain at the injection site.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects you can help 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 any medicine in wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What NORMOPARIN contains
The active ingredient is: sodium heparin.
1 ml of solution contains 5,000 I.U. of sodium heparin.
The other ingredients are: 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 Authorisation Holder
Laboratorios Farmacéuticos ROVI, S.A.
Julián Camarillo, 35

• 28037 – Madrid Spain

Distributor for sale
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
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The following information is intended exclusively for healthcare professionals:
Dosage and administration
Extracorporeal circulation (cardiopulmonary bypass)
300 IU/Kg intravenously, to be adjusted to maintain the Activated Clotting Time (ACT)
within the range of 400-500 seconds.

Hemodialysis
Initial dose of 1000-5000 IU intravenously followed by 1000-2000 IU/h, to be adjusted based on needs.

Monitoring:
Routine monitoring is not required.

Treatment of arterial and venous thromboembolism
The initial dose is 80 IU/kg i.v. as a bolus or 5,000 IU as an intravenous bolus injection
(10,000 IU in case of severe pulmonary embolism).
The dose of ma
Alternative treatment regimens
Intermittent intravenous injection: 10,000 IU i.v. as a bolus followed by 5000-10,000 IU i.v. every
4-6 hours.

Monitoring:
When sodium heparin is administered at an anticoagulant dose, the dosage must be determined
based on coagulation tests. The most commonly used test is the activated partial thromboplastin time (aPTT). The aPTT of patients undergoing treatment must be maintained at a value
1.5-2.5 times the normal values. Regular monitoring of aPTT values is recommended, possibly on a daily basis.
If coagulation tests are above the therapeutic range or if bleeding occurs, the
dose must be reduced or, if appropriate, heparin must be discontinued (see section 4.4).

Special populations
Paediatric population
Treatment of arterial and venous thromboembolism
The initial dose is 50 IU/kg as an intravenous bolus injection.
The maintenance dose is 15-25 IU/kg/hour in continuous intravenous infusion, or 100
IU/kg i.v. every 4 hours as an intermittent injection.

Monitoring:
When sodium heparin is administered at an anticoagulant dose, the dosage must be adjusted
based on aPTT values.
Smaller children may require higher doses and infusion rates to achieve
levels of anticoagulation and aPTT prolongations similar to those of older children.

Elderly
Lower doses may be necessary due to an increased risk of bleeding.

Monitoring:
When sodium heparin is administered at an anticoagulant dose, doses must be adjusted in
accordance with aPTT values.

Route of administration
Intravenously by continuous infusion or intermittent injection.
Since the effects of sodium heparin are short-term, administration by
intravenous infusion is preferred over intermittent intravenous injection.
Do not administer NORMOPARIN by intramuscular or subcutaneous injection.
Bleeding
Bleeding is the main complication that can occur during treatment with sodium heparin
particularly at anticoagulant doses.
Coagulation times above the therapeutic range or minor bleeding during
therapy can generally be resolved by reducing the dosage or, if appropriate, temporarily suspending
the drug. Gastrointestinal or urinary bleeding during anticoagulant therapy
may indicate the presence of an underlying occult lesion. Bleeding can occur in any district of the body but certain specific
hemorrhagic complications may be difficult to identify:

• (a) Adrenal hemorrhage, with consequent acute adrenal insufficiency has been described 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 developed in women of childbearing age undergoing short- or long-term anticoagulant therapy.
• (c) Retroperitoneal hemorrhages.

Overdose
Symptoms of overdose
Bleeding, mainly from the skin and mucous membranes, from wounds, from the gastrointestinal or
genitourinary tract (epistaxis, hematuria, melena, hematomas, petechiae). A decrease in blood pressure
or a reduction in hematocrit may be signs of occult bleeding.

Treatment of overdose

Minor bleeding
Discontinuation of heparin therapy.

Severe bleeding
Protamine serves for the rapid neutralization of heparin activity, in case of
significant bleeding.
The amount required depends on the blood heparin level administered and the time elapsed
since the injection. Protamine administration should be done as a slow intravenous infusion; 50 mg of protamine neutralize 5,000 IU of heparin. The dose of protamine to be
administered to neutralize a heparin bolus decreases in proportion to the time elapsed since
the administration of the bolus (immediately after the bolus 100% of the dose, after 1 hour 50%, after 2
hours 25%).
The dose of protamine to be administered in case of continuous heparin infusion is that useful
to neutralize the IU of heparin infused in the last 4 hours.