Seledie

Package leaflet: Information for the patient

SELEDIE 11,400 IU antiXa/0.6 ml solution for injection, 15,200 IU antiXa/0.8 ml solution for injection, 19,000 IU antiXa/1 ml solution for injection

Nadroparin calcium
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.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What SELEDIE is and what it is used for

SELEDIE contains the active substance nadroparin calcium, an antithrombotic agent derived from heparin, used to
prevent the formation of blood clots.
SELEDIE is used in the treatment of deep venous thrombosis.

2. What you should know before using SELEDIE

Do not use SELEDIE

• if you are allergic to the active substance, nadroparin, to heparin or to a similar product (such as enoxaparin, bemiparin, dalteparin), or to any of the other ingredients of this medicine (listed in section 6).
• if you have a history of thrombocytopenia (low platelet count, the cells responsible for blood clotting) (see also "Warnings and precautions").
• if you are at increased risk of bleeding due to coagulation disorders, except for heparin-induced disseminated intravascular coagulation (a serious syndrome causing blood clotting in many blood vessels).
• if you have lesions at risk of bleeding (active peptic ulcer – an ulcer in the stomach wall).
• if you currently suffer from (or have previously suffered from) retinopathies (diseases of the retina, the membrane lining the inside of the eye).
• if you currently suffer from (or have previously suffered from) hemorrhagic disorders.
• if you currently suffer from (or have previously suffered from) cerebral hemorrhages (bleeding in the brain).
• if you currently suffer from (or have previously suffered from) an infection affecting the inner lining of the heart (acute infective endocarditis).
• if you have severe renal impairment and are being treated for deep vein thrombosis.
• if you have severe kidney or pancreatic diseases.
• if you have high blood pressure (severe arterial hypertension).
• if you have recently undergone surgery for head trauma (surgically treated cranial trauma).
• during loco-regional anesthesia for surgical procedures.

Warnings and precautions
Talk to your doctor or pharmacist before using SELEDIE.
You may develop heparin-induced thrombocytopenia; therefore, your platelet count must be monitored throughout treatment with nadroparin.
Rare cases of thrombocytopenia, occasionally severe, have been reported, which may be associated with arterial or venous thrombosis. This diagnosis should be considered in the following situations:

• thrombocytopenia
• any significant decrease in platelet levels
• worsening of the initial thrombosis during therapy
• new onset thrombosis during treatment
• disseminated intravascular coagulation.

In such cases, treatment with nadroparin must be discontinued.
If thrombocytopenia occurs as a result of treatment with heparin (either standard or low molecular weight), your doctor may consider:

• if necessary, continuing treatment with nadroparin.
• switching to an antithrombotic agent from a different class.
• if switching is not possible, but heparin administration remains necessary, replacing with another low molecular weight heparin.
  In such cases, your doctor must monitor your platelet count at least daily, and if thrombocytopenia occurs, treatment must be immediately stopped (see "Do not use SELEDIE").

Nadroparin must be used with caution in the following conditions, which may be associated with an increased risk of bleeding:

• impaired liver function (hepatic insufficiency)
• high blood pressure (arterial hypertension)
• clinical history of stomach ulcer (peptic ulcer) or other organic lesions at risk of bleeding
• vascular diseases of the choroid and retina (a part of the eye rich in blood vessels)
• during the post-operative period following brain, spinal or eye surgery, and in cases of cranial trauma.

Exercise particular caution:

• if you have impaired renal function: you are at higher risk of bleeding and must be treated with caution.

• if you are elderly: your doctor should check your renal function before starting treatment (see "Do not use SELEDIE").

• if you have high potassium levels in the blood or are at risk of increased potassium levels, for example if you have diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis (disturbances in blood gas and electrolyte concentrations), or if you are taking medications that may increase blood potassium levels (e.g. ACE inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs)). Heparin may suppress aldosterone production (a hormone regulating blood electrolyte concentration), leading to increased blood potassium levels. This risk appears to increase with longer duration of therapy, but is usually reversible.

• if you are undergoing spinal or epidural anesthesia, the use of low molecular weight heparin may be associated with spinal or epidural hematomas, which may lead to prolonged or permanent paralysis of the lower limbs. You should therefore be frequently monitored for signs and symptoms of neurological impairment, such as back pain, sensory and motor deficits (numbness and weakness in the lower limbs), and intestinal and/or bladder dysfunction. You must immediately inform a doctor or healthcare professional if any of these symptoms occur. The risk of spinal/epidural hematomas is increased by the use of catheters placed in the spinal canal (epidural catheters) or by concomitant use of other drugs affecting coagulation, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, or other anticoagulants. The risk is also increased by trauma or repeated lumbar punctures.

• if you notice signs such as dark red discoloration (cutaneous purpura) or infiltrated, painful erythematous plaques, with or without general symptoms, as these may indicate skin necrosis (i.e. death of skin tissue). In such cases, your doctor will immediately discontinue treatment.

Latex allergy
The protective cap of the needle on the pre-filled syringe may contain latex rubber. It may cause severe allergic reactions.

Other medicines and SELEDIE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Nadroparin should be administered with caution if you are taking:

• oral anticoagulants, as concomitant administration may increase the anticoagulant effect
• systemic (gluco-)corticosteroids (cortisone and similar), as concomitant administration may increase the risk of bleeding
• dextrans (substances used to increase blood volume), as concomitant administration may increase the risk of bleeding
• ascorbic acid, antihistamines, digitalis, intravenous penicillins, tetracyclines, or phenothiazines, as these may reduce the medicinal activity.

SELEDIE is not recommended if you are taking the following medicines, as the risk of bleeding increases:

• acetylsalicylic acid and other salicylates, non-steroidal anti-inflammatory drugs – NSAIDs (systemic administration). Use other substances for analgesic or antipyretic effects.
• ticlopidine (an oral anticoagulant)
• other platelet aggregation inhibitors (clopidogrel, dipyridamole, sulfinpyrazone, etc.)

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
The use of nadroparin during pregnancy is not recommended unless the therapeutic benefits outweigh the possible risks.
Breastfeeding
Information on the excretion of nadroparin in breast milk is limited. As a precaution, breastfeeding mothers receiving nadroparin should be advised not to breastfeed.
Fertility
No studies on the effect of nadroparin on fertility are available.

Driving and using machines
No studies on the ability to drive vehicles or use machinery have been conducted.

3. How to use SELEDIE

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Do not mix nadroparin calcium with other preparations.
Pay particular attention to dosing instructions, which vary between different brands of low molecular weight heparins, as each low molecular weight heparin uses different measurement systems to express doses (Units or mg).
Therefore, nadroparin must not be used interchangeably with other low molecular weight heparins during treatment.
Nadroparin must not be administered by intramuscular injection.
Administration of nadroparin around the time of spinal/epidural anaesthesia or lumbar puncture must follow specific recommendations (see "Warnings and precautions").

Subcutaneous injection technique
When nadroparin is administered subcutaneously, the injection should be given into the anterolateral or posterolateral abdominal wall, alternating between the right and left sides. The thigh may be used as an alternative site.
To avoid loss of solution when using pre-filled syringes, do not expel the air bubble from the syringe before injecting.
The needle must be inserted fully, perpendicularly (at a 90-degree angle to the abdomen), not tangentially, into a skin fold created between the operator’s thumb and index finger.
The skin fold must be maintained throughout the entire injection. After the injection, do not rub the skin, but apply gentle pressure to the injection site.
If dosing is adjusted according to your body weight, adjust the volume to be administered by moving the plunger to the desired mark while holding the syringe vertically.
Syringes are for single use only, and any unused content of each syringe must be discarded. Solutions must not be mixed with other preparations or re-administered.
For syringes with a needle safety protection system:

Treatment of deep vein thrombosis
Subcutaneous administration
The recommended dose is one injection per day for 10 days at a dose of 171 anti-Xa IU/kg.
If there are no contraindications, initiate oral anticoagulant therapy as soon as possible.
You must monitor platelet count throughout the entire course of treatment with nadroparin (see "Warnings and precautions").

Use in children and adolescents
Nadroparin is not recommended in children and adolescents, as there are insufficient safety and efficacy data to establish a dose in patients under 18 years of age.

Elderly patients
No dose adjustment is required solely due to age, unless renal function is impaired.
Your doctor will assess your renal function before starting treatment (see below "Renal impairment").

Renal impairment
If you have mild renal impairment and are receiving nadroparin for treatment of this condition, no dose reduction is necessary.
If you have moderate or severe renal impairment, you are at increased risk of thromboembolism and bleeding.
Where your doctor considers dose reduction appropriate, taking into account individual thromboembolic and bleeding risk factors, dose reduction should be implemented in cases of moderate renal impairment (see "Warnings and precautions").
SELEDIE is contraindicated if you have severe renal impairment.

Hepatic impairment
No studies have been conducted in patients with hepatic impairment.

If you use more SELEDIE than you should
In case of accidental overdose of SELEDIE, contact your doctor immediately or go to the nearest hospital.
The most evident sign of overdose, whether by subcutaneous or intravenous route, is bleeding. In such cases, your doctor should perform a platelet count and measure other coagulation parameters.
Minor bleeding episodes rarely require specific treatment and usually resolve with dose reduction or delay of subsequent nadroparin doses.

If you stop treatment with SELEDIE
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The side effects are listed below in order of frequency:

Very common (may affect more than 1 in 10 people)

• Bleeding manifestations at various sites (including cases of spinal haematoma), more frequent in patients with other risk factors (see "Do not use SELEDIE" and "Warnings and precautions").
• Bruising at the injection site: in some cases, firm nodules may appear. These nodules usually disappear after a few days.

Common (may affect up to 1 in 10 people)

• Increased transaminases (enzymes produced by the liver), usually transient.
• Reaction at the injection site.

Rare (may affect up to 1 in 1,000 people)

• Thrombocytopenia, i.e. reduced number of platelets in the blood (including heparin-induced thrombocytopenia) (see "Warnings and precautions"), thrombocytosis (increased number of platelets in the blood).
• Skin rashes, urticaria, erythema, pruritus.
• Calcinosis (calcium salt deposits) at the injection site. Calcinosis is more frequent in patients with abnormal calcium phosphate production, as well as in some cases of chronic renal failure.

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

• Eosinophilia, i.e. increased number of a type of white blood cells in the blood, reversible upon discontinuation of treatment.
• Hypersensitivity reactions (including angioedema and skin reactions), anaphylactoid reaction.
• Reversible increase in blood potassium concentration, particularly in patients at risk (see "Warnings and precautions").
• Priapism (abnormal, prolonged and painful erections).
• Skin necrosis (death of skin tissue), usually at the injection site (see "Warnings and precautions").

Not known (frequency cannot be estimated from the available data)
Headache, migraine

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at 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 SELEDIE

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 Exp.
The expiry date refers to the last day of that month. The stated expiry date applies to the product in its original, unopened packaging, correctly stored.
Do not use this medicine if you notice the presence of particulate matter (i.e. solid material in a liquid solution) or any change in the colour of the nadroparin solution for injection. If you observe any visible changes, the solution must be discarded.
This medicine does not require any special storage conditions.
Do not freeze. Do not store in the refrigerator, as injections that are too cold may be painful.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What SELEDIE contains

• The active substance is nadroparin calcium (antiXa I.U.). One pre-filled syringe contains:
  o 0.6 ml of SELEDIE 11,400 antiXa I.U.;
  o 0.8 ml of SELEDIE 15,200 antiXa I.U.;
  o 1 ml of SELEDIE 19,000 antiXa I.U.
• The other components are: calcium hydroxide solution or diluted hydrochloric acid – water for injectable preparations.

Description of the appearance of SELEDIE and contents of the pack
Injectable solution for subcutaneous use.

• Carton box containing 2 or 10 pre-filled glass syringes (Type I colourless glass) of 0.6 ml Seledie 11,400 antiXa I.U./0.6 ml injectable solution, with or without safety device, in blister
• Carton box containing 2 or 10 pre-filled glass syringes (Type I colourless glass) of 0.8 ml Seledie 15,200 antiXa I.U./0.8 ml injectable solution, with or without safety device, in blister
• Carton box containing 2 or 10 pre-filled glass syringes (Type I colourless glass) of 1 ml Seledie 19,000 antiXa I.U./1 ml injectable solution, with or without safety device, in blister
  It is possible that not all pack sizes are marketed.

Marketing Authorization Holder
Viatris Italia S.r.l. Via Vittor Pisani, 20, 20124 Milano, Italy
Manufacturer
Italfarmaco S.p.A. Viale Fulvio Testi, 330 Milano - Italy
Aspen Notre Dame de Bondeville - 1, Rue de l’Abbaye – 76960 Notre Dame de Bondeville - (France)

The following information is intended for healthcare professionals only

Do not mix nadroparin calcium with other preparations.
Exercise particular caution regarding dosage instructions, which are specific for different brands of low molecular weight heparin, as different measurement systems (Units or mg) are used to express doses for each low molecular weight heparin.
Therefore, nadroparin must not be used interchangeably with other low molecular weight heparins during the course of treatment.
Nadroparin must not be administered by intramuscular route.
Administration of nadroparin close in time to spinal/epidural anesthesia or lumbar puncture must follow specific recommendations (see "Warnings and Precautions").
Treatment of deep vein thrombosis
Subcutaneous administration
One injection per day for 10 days at a dose of 171 anti-Xa IU/kg.
For example, and depending on the patient's body weight, the dosages to be administered are as follows.
Platelet count must be monitored throughout the duration of treatment with nadroparin (see "Warnings and Precautions").

If there are no contraindications, initiate oral anticoagulant therapy as soon as possible.
Treatment with nadroparin should not be discontinued before the required INR (International Normalised Ratio) is achieved.
Platelet count must be monitored throughout the duration of treatment with nadroparin (see "Warnings and Precautions").
In patients undergoing lumbar puncture, spinal anaesthesia, or epidural anaesthesia, a minimum interval of 12 hours must elapse between the administration of prophylactic doses of nadroparin and the insertion or removal of the spinal/epidural catheter or needle, and at least 24 hours for therapeutic doses of nadroparin, taking into account the product characteristics and the patient's profile.
For patients with renal impairment, longer intervals should be considered.
The next dose must not be administered until at least 4 hours have elapsed. Re-administration of nadroparin should be delayed until after completion of the surgical procedure.
If signs or symptoms suggestive of spinal haematoma occur, urgent diagnosis and intervention, including spinal cord decompression, must be performed.
If significant or obvious bleeding occurred during catheter placement, a careful benefit-risk assessment must be carried out before initiating/restarting heparin therapy.

Overdose
Treatment
Only in severe cases should protamine sulfate be considered, which largely neutralizes the anticoagulant effect of nadroparin, although some anti-Xa activity may remain.
0.6 ml of protamine sulfate neutralizes approximately 950 IU anti-Xa of nadroparin. The amount of protamine to be administered should take into account the time elapsed since heparin administration, and the dose of protamine may need to be reduced accordingly.