EPSODILAVE 250 UI/5 ML Injectable solution

Зміст інструкції

1. EPSODILAVE 250 U.I./5 ml solution for catheter patency, 300 U.I./3 ml solution for catheter patency, 500 U.I./2 ml solution for catheter patency
   1. What EPSODILAVE is and what it is used for
   2. What you need to know before using EPSODILAVE
   3. How to use EPSODILAVE
   4. Possible side effects
   5. How to store EPSODILAVE
   6. Contents of the pack and other information

EPSODILAVE 250 U.I./5 ml solution for catheter patency, 300 U.I./3 ml solution for catheter patency, 500 U.I./2 ml solution for catheter patency

Sodium heparin

Read this leaflet carefully before using 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 nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What EPSODILAVE is and what it is used for

EPSODILAVE contains the active ingredient sodium heparin belonging to the group of medicines called
anticoagulants which work by preventing the formation of blood clots (thrombi).
This medicine is used to keep medical devices inserted into a vein (catheters
placed in a vein and cannulas) clean and free, used for the administration of medicines intravenously, both intermittently, continuously (for infusion) or in case of repeated blood draws.
This medicine can be used at rest, after each administration or after each blood draw in
order to avoid the formation of blood clots inside the devices themselves, which may interfere
with the passage of medicines to be administered. The dose of EPSODILAVE used is sufficient to
obtain an anticoagulant effect without causing effects in the patient.

2. What you need to know before using EPSODILAVE

Do not use EPSODILAVE

• if you are allergic to sodium heparin or to other substances closely related chemically or to any of the other ingredients of this medicine (listed in section 6);
• if you have low levels of platelets in your blood (severe thrombocytopenia);
• if you suffer from severe liver, kidney or pancreatic diseases
• if coagulation tests cannot be carried out at appropriate intervals (exclusively for therapeutic dosages).
• If you suffer from disseminated intravascular coagulation (DIC) (a serious syndrome leading to blood clotting in many blood vessels) attributable to heparin-induced thrombocytopenia
• If you suffer (or have suffered) from cerebral haemorrhages;
• If you suffer from lesions at risk of bleeding, such as gastric and/or intestinal ulcers, aneurysm, brain neoplasm.
• If you have a trauma or have undergone surgery to the central nervous system, eyes or ears
• If you suffer from retinopathy or vitreous haemorrhage
• If you suffer from infective endocarditis (an infection of the inner lining of the heart).
• If you are to undergo loco-regional anaesthesia for elective surgical procedures.

Furthermore, if you suffer from organ lesions at high risk of bleeding, your doctor will need to assess
the use of heparin considering the risk-benefit ratio in your case.

Warnings and precautions
Consult your doctor or nurse before using EPSODILAVE.
This medicine must not be injected, nor used for anticoagulant therapy.
Before you are administered this medicine, inform your doctor if:

• You suffer from suspected neoplasm with a tendency to haemorrhage;
• you suffer from chronic alcoholism;
• you are elderly; a dose reduction may be necessary, particularly in women who are at higher risk of haemorrhage
• you are at risk of haemorrhage, in particular:
• if you suffer from uncontrolled high blood pressure (uncontrolled hypertension);
• if you suffer from inflammation of the membrane lining the cavities of the heart (subacute bacterial endocarditis)
• if you suffer from blood disorders with an increased tendency to bleed (haemophilic syndromes or coagulation factor deficiency);
• if you have a reduction in the number of platelets in your blood (thrombocytopenia) or impaired platelet function (thrombocytopathy)
• if you suffer from certain haemorrhagic vascular purpura (such as Rendu-Osler disease).
• you suffer from stomach and/or intestinal ulcer
• if you suffer from erosive oesophagitis or gastritis
• if you suffer from active inflammatory bowel disease;
• if you have a continuous drainage tube in your stomach or small intestine
• if you have recently undergone lumbar puncture or spinal anaesthesia
• if you have recently undergone surgery to the brain, spinal cord, eye.
• if you suffer from liver diseases with alterations in coagulation parameters and/or problems with the veins of the oesophagus (oesophageal varices)
• if you suffer from stomach diseases caused by increased blood pressure in the circulation of the liver (portal hypertension gastropathy),
• in case of threatened abortion;
• during the menstrual cycle
• in the postpartum period
• In case of concomitant treatment with fibrinolytics or oral anticoagulants, with drugs that inhibit platelet aggregation, with non-steroidal anti-inflammatory drugs and/or glycoprotein IIb/IIIa receptor antagonists.

If this medicine is administered to you during spinal or epidural anaesthesia, epidural analgesia or
lumbar puncture, the use of low molecular weight heparin may be rarely associated with haematomas, which
can lead to prolonged or permanent paralysis of the lower limbs. You will therefore need to be
frequently monitored for signs and symptoms of neurological alterations, such as back pain, sensory and motor deficits (numbness and weakness in the lower limbs), bowel and/or
bladder dysfunction. Immediately inform your doctor or nurse if you experience any of the above symptoms. The
risk of spinal/epidural haematomas is increased by the following conditions:

• placement of catheters in the spinal cord (continuous infusion indwelling epidural catheter)
• concomitant use of other drugs that can affect coagulation, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors or other anticoagulants.
• trauma or repeated lumbar punctures.
• haemostasis disorders
• advanced age.

In all cases of bleeding, even minor, stop treatment with EPSODILAVE and contact your
doctor.
EPSODILAVE can cause an increase in potassium levels in the blood (hyperkalaemia). If you suffer from or have ever
suffered from hyperkalaemia, a condition characterized by an increase in potassium in the blood, your
doctor will perform tests to measure potassium in your blood before starting therapy and at
regular intervals during treatment, especially in case of treatment lasting more than 7 days.
if the number of platelets in the blood decreases (thrombocytopenia) treatment must be stopped.
This effect may be associated with the formation of clots (arterial or venous thrombosis), may be of an allergic type or may occur following accidental administration of the medicine into a vein.
The doctor will carefully monitor your platelet count throughout the course of treatment with
sodium heparin.
If you experience fever, thrombosis, thrombophlebitis, infections with a tendency to thrombosis, inflammatory states, sometimes
during myocardial infarction, cancer, congenital or developed deficiency of antithrombin III following
surgery, you may have a decreased sensitivity to heparin; your doctor will assess these
conditions.
During treatment with EPSODILAVE avoid intramuscular administration of other drugs, due to
the risk of haematomas.

• It is not strictly necessary, as with dicoumarol therapy, to monitor heparin therapy with laboratory tests; however, your doctor will monitor the progress of your therapy with appropriate diagnostic tests (prothrombin coagulation time - Lee White).
• The use of heparin can alter your thyroid function tests (e.g. false high levels of T3 and T4).
• Since heparin is an animal-derived substance, if you have had previous allergic reactions, your doctor may administer a reduced dose of heparin to test for any reactions. Children and adolescents
• Sodium heparin is not recommended in children and adolescents under the age of 18 years.

Other medicines and EPSODILAVE
Tell your doctor or nurse if you are taking, have recently taken or might take any other
medicines.
Even if at the recommended doses, accidental administration of this medicine into a vein does not cause effects,
inform your doctor if you are taking:

• oral anticoagulants, as concomitant administration may increase the anticoagulant effect
• antiplatelet agents, fibrinolytics or other medicines associated with interference with platelet aggregation and may induce bleeding, such as acetylsalicylic acid, non-steroidal anti-inflammatory drugs (such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indometacin, ketorolac or diclofenac), drugs with antiplatelet effect (e.g. ticlopidine, clopidogrel or sulfinpyrazone), some antibiotics of the cephalosporin class (e.g. cefaclor, cefixime, ceftriaxone, cefamandole, cefoperazone), dextran, dipyridamole, hydroxychloroquine, fibrinolytics (e.g. streptokinase, urokinase, alteplase), coumarin derivatives, glycoprotein IIb/IIIa receptor antagonists (e.g. eptifibatide, abciximab), epoprostenol.
• Nitroglycerin, administered intravenously, because it can cause a decrease in the effect of heparin
• Drugs that increase potassium levels in the blood, such as ACE inhibitors, sartans, potassium-sparing diuretics, potassium salts or beta-blockers (drugs used in the treatment of cardiovascular diseases)
• Other drugs that can reduce the anticoagulant effect of heparin, such as digitalis, tetracyclines, nicotine, glucocorticoids, penicillins, phenothiazines, antihistamines. In addition, heparin can alter the results of tests for thyroid function, determining a false increase in some thyroid hormones (T3 and T4).

Fertility, pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you are pregnant, or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
The safety of use in pregnancy has not been fully established. In the absence of reliable data, the
decision to use heparin during pregnancy must be made after careful evaluation of the risk-benefit ratio in individual circumstances.
Breastfeeding
Heparin is not excreted in breast milk.
Fertility
There are no data available regarding the effect of heparin on human fertility.

Driving and using machines
This medicine does not impair the ability to drive and operate machinery.

EPSODILAVE contains sodium
This medicine contains less than 1 millimole (23 mg) of sodium per vial and bottle, i.e.
it is essentially “sodium-free”.

3. How to use EPSODILAVE

This medicine will be administered by a doctor or another healthcare professional, respecting sterility conditions. If you have any doubts, consult your doctor or nurse.
With each use of the catheter or another device for administering medicines intravenously, the amount of EPSODILAVE to be used corresponds to the intraluminal volume of the circuit.
It is recommended to change the solution every time the catheter or perfusion device is used.
With each new use of the device, it is necessary to aspirate the intraluminal heparin solution before proceeding with the administration of a medicine (infusion treatment) or a blood draw.
The concentration to be used is established by the doctor, taking into account the procedures for using catheters.

If you use more EPSODILAVE than you should
If an excessive dose of EPSODILAVE is administered, bleeding (hemorrhage) may occur.
In case of ingestion/intake of an excessive amount of this medicine, seek immediate medical attention or go to the nearest hospital.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the side effects gets serious, or if you notice any side effect not listed in this leaflet, please inform your doctor.
If you experience any of the following serious reactions, inform your doctor immediately:

• Bleeding (haemorrhage), in any part of the body
• Severe allergic reactions (may include chills, high fever, hives, asthma, rhinitis, increased tearing, nausea and vomiting, itching and burning of the feet, hypotension, vasospasm, anaphylactic shock)
• Severe skin lesions with inflammation (skin necrosis), bruises, spots of varying sizes, purplish or reddish (purpura or petechiae)
• Thrombocytopenia (reduction in the number of platelets in the blood);
• Disseminated intravascular coagulation (DIC)
• Bruises or ulcers at the injection site
• Liver damage (hepatotoxicity)
• Difficulty breathing or chest pain (may be symptoms of pulmonary edema or hemopneumothorax)
• Blood in the stool (melena) Other side effects that you may experience, with frequency not known (the frequency of which cannot be estimated based on available data) are listed below:
• Reactions at the site of administration (local irritation, erythema, mild pain)
• Amnesia
• Cerebral haemorrhage, extradural intracranial haematoma, non-traumatic spinal subdural haematoma, ventricular haemorrhage
• Osteoporosis
• Alopecia (hair loss)
• Hypoaldosteronism (reduced production of aldosterone)
• Hyperkalaemia (increased potassium levels in the blood)
• Metabolic acidosis (particularly in patients with kidney damage and diabetes mellitus)
• Hyperlipidemia (increased lipids in the blood) rebound, upon discontinuation of therapy
• Bronchospasm (difficulty breathing)
• Increased transaminases (enzymes produced by the liver)
• Increased levels of FT3 and FT4 (thyroid hormones)
• Priapism (persistent and painful erection, not associated with sexual stimulation)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly through the Italian Medicines Agency - Website: http://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 EPSODILAVE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after “Scad”.
The expiry date refers to the last day of that month.
Do not dispose of any medicine in the drain or in 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 EPSODILAVE 250 U.I./5 ml solution for catheter patency contains

• The active ingredient is sodium heparin. 1 ml of solution contains 50 U.I. of sodium heparin.
• The other ingredients are sodium chloride, water for injections.

What EPSODILAVE 300 U.I./3 ml solution for catheter patency contains

• The active ingredient is sodium heparin. 1 ml of solution contains 100 U.I. of sodium heparin.
• The other ingredients are sodium chloride, water for injections.

What EPSODILAVE 500 U.I./2 ml solution for catheter patency contains

• The active ingredient is sodium heparin. 1 ml of solution contains 250 U.I. of sodium heparin.
• The other ingredients are sodium chloride, water for injections.

Description of the appearance of EPSODILAVE and contents of the pack
EPSODILAVE 250 U.I./5 ml solution for catheter patency
Pack of 10 vials of 5 ml solution.
EPSODILAVE 300 U.I./3 ml solution for catheter patency
Pack of 10 vials of 3 ml solution.
EPSODILAVE 500 U.I./2 ml solution for catheter patency
Pack of 10 vials of 2 ml solution.

Marketing Authorisation Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Italy

Manufacturer
Biologici Italia Laboratories S.r.l.
Via Filippo Serpero, 2
20060 Masate (MI)
Italy

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The following information is intended exclusively for doctors or healthcare professionals
To determine the appropriateness of use in a given patient, the prescriber must be
aware of the entire content of the Summary of Product Characteristics.
Dosage and method of administration
With each use of the catheter or perfusion device, inject a volume of EPSODILAVE,
corresponding to the intraluminal volume of the circuit. The solution should be changed each time the
catheter or perfusion device is used.
When reusing the circuit, it is recommended to aspirate the intraluminal solution of
heparin before proceeding with the infusion treatment or sampling.
The concentration of use is left to the physician's judgement, taking into account the procedures for use of the
catheters.

Special warnings
Heparin may rarely cause thrombocytopenia, possibly associated with arterial or venous thrombosis.
These effects, probably of an immune nature, may also occur following accidental
systemic passage of EPSODILAVE and require discontinuation of the medicine. The immune-allergic effects of heparin usually manifest between the 5th and 21st day of
treatment. Therefore, platelet counts should be monitored in patients using
EPSODILAVE: perform a platelet count before use and twice a week after starting
use; if prolonged use is necessary, this monitoring schedule should be
respected at least during the first month; subsequently, monitoring may be reduced.
Sodium heparin suppresses aldosterone secretion from the adrenal gland with possible consequent
hyperkalaemia, particularly in patients with diabetes mellitus, chronic renal insufficiency, a history
of metabolic acidosis, increased plasma potassium levels or patients treated
with potassium-sparing drugs. The risk of hyperkalaemia appears to increase with the duration of
treatment but is normally reversible. Serum electrolytes should be measured in at-risk patients
before starting heparin therapy and subsequently monitored regularly, in
particular when treatment is prolonged for more than 7 days.
Cases of skin necrosis, sometimes preceded by purpura or painful erythematous lesions,
have been reported when heparin is administered subcutaneously. In these cases, treatment should be stopped immediately.
In patients undergoing epidural or spinal anesthesia or lumbar puncture, prophylactic use
of heparin has been very rarely associated with epidural or spinal hematomas with resulting prolonged or
permanent paralysis. The risk increases when using epidural or spinal catheters for anesthesia, using
concomitantly drugs that affect coagulation such as non-steroidal anti-inflammatory drugs (NSAIDs),
drugs that inhibit platelet aggregation or anticoagulants, and in case of traumatic or
repeated punctures.
When deciding the interval between the administration of heparin at prophylactic doses and the placement or
removal of the spinal or epidural catheter, both the characteristics of the medicine and the patient's clinical profile must be evaluated.
In the case of unfractionated heparin, it is recommended to administer the pre-operative dose of heparin no earlier than 1 hour after placement of the catheter for anesthesia, to remove the
catheter no earlier than 4 hours after the last dose of heparin and to administer the first dose of heparin post-
operative no earlier than 1 hour after removal of the catheter.
If anticoagulant treatment is to be administered during spinal or epidural anesthesia, it must
be carefully monitored to identify early signs or symptoms of neurological impairment such as lower back pain, sensory and motor deficits (numbness and weakness of the lower limbs),
bowel or bladder dysfunction. Staff must be prepared to identify these signs and
symptoms. In addition, patients should be advised to immediately inform the doctor or nurse if
they experience the symptoms highlighted above.
When signs or symptoms indicative of suspected spinal or epidural hematoma occur, urgent diagnostic tests must be performed and, if indicated, spinal decompression (laminectomy) must be performed promptly (within 6-12 hours).

Overdosage
The main clinical symptom of overdose is bleeding. When bleeding occurs, treatment
with sodium heparin should be immediately stopped. Mild bleeding rarely requires
specific treatments. For severe bleeding, slow intravenous infusion of protamine sulfate may be necessary. The dose of protamine sulfate varies depending on the time elapsed between the injection
of heparin and the time when its effects need to be neutralized (100% of the
dose immediately after the bolus, 50% after 30 minutes) and depending on the dose injected. Each mg of protamine neutralizes
approximately the activity of 100 IU of heparin.
Vitamin K does not reverse the activity of heparin.

Incompatibilities
Protamine sulfate (heparin antidote).
In general, it is not recommended to mix EPSODILAVE with other drugs.
In aqueous solution, there is incompatibility between heparin and the following drugs: haloperidol lactate, amikacin
sulfate, amiodarone hydrochloride, aprotinin, chlorpromazine hydrochloride, ciprofloxacin lactate, cefaloridine,
cisatracurium besilate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam, doxorubicin hydrochloride,
droperidol, erythromycin, gentamicin sulfate, hyaluronidase, hydroxyzine hydrochloride, hydrocortisone sodium
succinate, kanamycin sulfate, labetalol hydrochloride, levofloxacin, methotrimeprazine, narcotic analgesics,
netilmicin sulfate, nicardipine hydrochloride, novobiocin sodium, pethidine hydrochloride, polymyxin B sulfate,
prochlorperazine, promazine hydrochloride, prometazine hydrochloride, streptomycin sulfate, tobramycin sulfate,
trifluperazine hydrochloride, vinblastine sulfate, vinorelbine tartrate, viomycin sulfate and, depending on the
diluent, cephalothin sodium and vancomycin hydrochloride. Conflicting results have been reported with
ampicillin
sodium, benzylpenicillin, dimenhydrinate, methicillin sodium, oxytetracycline hydrochloride, sulfafurazole
diethanolamine and tetracycline hydrochloride.
Dobutamine hydrochloride and heparin must not be mixed or infused through the same intravenous
route, due to the risk of precipitation.
Heparin and reteplase are incompatible when combined in solution.