Label: Information for the User

FRAGMIN 2.500 UI/0.2 ml injectable solution in preloaded syringes

dalteparin sodium

Read this label carefully before starting to use the medicine because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nursing staff.
• This medicine has been prescribed only for you and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nursing staff, even if they are not listed in this label. See section 4.

Fragmin belongs to a group of medications called low molecular weight heparins.

Fragmin 2.500 UI/0.2 ml is used in adults aged 18 years and older for:

- Prophylaxis of thromboembolic disease in surgery (to prevent venous thrombosis when you undergo an operation) and

- Prophylaxis of thromboembolic disease in non-surgical patients who are immobilized and whose situation can be defined as moderate or high risk (to prevent venous thrombosis when you are not undergoing an operation, but are immobilized and have a significant risk of developing thrombosis).

No use Fragmin si:

• Is allergic (hypersensitive) to dalteparin sodium, to any of the other components of this medication (including in section 6), to any type of heparin (blood clotting medications) other than dalteparin sodium or to products derived from pork
• Has acute peptic ulcer, cerebral hemorrhage, or other significant bleeding
• Has severe coagulation disorders
• Has acute or subacute bacterial endocarditis (inflammation of one of the heart membranes due to an infection)
• Has undergone surgery in the central nervous system, eyes, or ears, or presents trauma to these organs or system
• Has a decrease in the number of platelets (cells present in the blood that intervene in blood clotting) and when a platelet aggregation test is performed in the presence of dalteparin sodium, the result is positive.

If you are being treated with Fragmin, you will not be able to receive epidural or spinal anesthesia.

Warnings and precautions:

Consult your doctor, pharmacist, or nurse before starting to use Fragmin if:

• You are to receive intramuscular injections of other medications due to the risk of hematomas.
• You have a decrease in the number of platelets or defects in them. Your doctor may request specific tests to determine the cause of this problem.
• You have severe renal insufficiency (decrease in kidney function) or severe hepatic insufficiency (decrease in liver function).
• You have uncontrolled high blood pressure.
• You have retinal disorders (part of the eye) due to diabetes or high blood pressure.
• You have recently undergone surgery or have a high risk of bleeding.
• You have had an acute myocardial infarction and are being treated with this medication.
• You are at risk of developing hyperkalemia (elevated potassium levels in the blood) due to a disease or taking certain medications. Your doctor may perform tests to measure potassium levels.
• You are undergoing epidural or spinal anesthesia, or lumbar puncture, and are being administered heparin for prevention; rarely, hematomas may occur in these areas. If you experience back pain, numbness, weakness in the lower extremities, or any disorder in the functioning of the intestines or bladder, immediately inform your doctor.
• You have a cardiac valve prosthesis, the preventive doses of Fragmin may not be sufficient to prevent valve thrombosis.
• You are receiving prolonged treatment for unstable coronary disease, such as before revascularization, your doctor may reduce your Fragmin dose.
• You are allergic or suspect you have a possible allergy to latex (natural rubber) or if the cap of the preloaded syringe of Fragmin is to be handled by someone with a known or possible latex allergy. The cap of the preloaded syringe of Fragmin is made of latex (natural rubber) and may cause severe allergic reactions in people with latex allergy.

Considering your condition and/or age, your doctor may perform tests to control anticoagulant activity and prevent the risk of bleeding or recurrence of thrombosis.

Do not interchange Fragmin with other non-fractionated heparins, low molecular weight heparins, or synthetic polysaccharides, as its effect may not be the same.

Children and adolescents:

Fragmin is not used in newborns under 1 month of age.

Use of Fragmin with other medications:

Inform your doctor, pharmacist, or nurse if you are using, or have recently used, other medications, even those purchased without a prescription.

Certain medications may interact with Fragmin 2.500 UI/0.2 ml; in these cases, it may be convenient to change the dose or discontinue treatment with one of the medications.

It is especially important to inform your doctor if you take any of the following medications:

• Those that affect the blood and blood clotting, such as aspirin, vitamin K antagonists (which prevent the action of vitamin K, whose function is to facilitate blood clotting, such as Sintrom -acenocoumarol-), and dextran. However, if you suffer from unstable angina or myocardial infarction without Q wave (a type of myocardial infarction), you should receive low-dose aspirin orally, unless contraindicated.
• A type of medications called nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, for the treatment of inflammation and pain, especially in patients with renal insufficiency (decrease in kidney function).

Pregnancy and breastfeeding:

Consult your doctor or pharmacist before taking or using a medication, including Fragmin.

If you are pregnant, you should only use this medication when clearly necessary, although Fragmin does not cross the placenta.

Do not use this medication with epidural anesthesia. Inform your doctor if you have an artificial heart valve.

If you are breastfeeding, inform your doctor; he will evaluate if treatment with this medication is appropriate, as Fragmin passes in small amounts into breast milk.

Driving and operating machinery:

This medication does not alter the ability to drive vehicles or use machinery.

Fragmin contains sodium

This medication contains less than 23 mg (1 mmol) of sodium per preloaded syringe; it is essentially "sodium-free".

Follow exactly the administration instructions for Fragmin 2.500 UI/0.2 ml as indicated by your doctor. Consult your doctor, pharmacist, or nursing staff if you have any doubts.

Remember to take or use your medication.

Your doctor will inform you of the dose, method of use, and duration of your treatment with Fragmin.

Fragmin is administered subcutaneously (injection under the skin).

If you are to be administered Fragmin 2.500 UI/0.2 ml to prevent venous thrombosis when undergoing surgery, the dose will depend on the type of surgery you are undergoing.

If you are to undergo general surgery with a moderate risk of thrombosis, you will be administered 2.500 UI (anti-Xa), one injection of Fragmin 2.500 UI/0.2 ml, applied subcutaneously, 2-4 hours before the surgery. After the surgery, you will be administered an injection (2.500 UI) once a day, during the risk period or until you can move again.

If you are to undergo oncological or orthopedic surgery with a high risk of thrombosis, you will be administered 2.500 UI (anti-Xa), one injection of Fragmin 2.500 UI/0.2 ml, applied subcutaneously, 2-4 hours before the surgery. Twelve hours after the surgery, you will be administered again 2.500 UI (anti-Xa), and subsequently 5.000 UI (anti-Xa) per day while the risk period lasts or until you can move again.

If you are to be administered Fragmin 2.500 UI/0.2 ml to prevent venous thrombosis when not undergoing surgery, but are immobilized, the dose will depend on the risk you present. If the risk of thrombosis is moderate, you will be administered 2.500 UI - one injection of Fragmin 2.500 UI/0.2 ml - once a day. If it is high, the dose will be 5.000 UI per day. In both cases, you will be administered this medication while the risk period lasts or until you can move again.

The Fragmin injections will normally be administered by a healthcare professional, and will be applied subcutaneously, in the anterior or posterior abdominal region, and alternately on the right and left sides.

Use in children and adolescents

Treatment of blood clots in veins (symptomatic deep vein thrombosis [DVT])

The recommended doses depend on the child's body weight and age group. The doctor will perform the calculation. The doctor will advise you on the individualized dose of Fragmin according to these criteria. Do not change the dose or treatment schedule without consulting your doctor first.

This medication is not suitable for use in the pediatric population becausethe pre-filled syringes do not allow for dose adjustmentbased on the child's body weight. It is recommended to use the 2.500 UI/ml injectable solution in 4 mL vials.

The effect of Fragmin will be controlled after the initial dose and subsequent dose adjustment through a blood test.

How to inject Fragmin

Fragmin is administered by subcutaneous injection. This section of the leaflet explains how to administer Fragmin. You should only follow these instructions after being trained by your doctor. If you are unsure of what to do, speak with your doctor immediately. You should inject (or administer) the Fragmin dose at the recommended times by your doctor.

If dilution is necessary before administering Fragmin, it should be done by a healthcare professional. You should follow your doctor's instructions on how and when to inject the diluted medication provided.

Please follow the steps explained below

Step1: The way to prepare the syringe for injection will depend on the specific Fragmin presentation to be used.

The Needle-Trap safety system is especially designed to help prevent needlestick injuries after the correct use of Fragmin. It consists of a plastic safety device attached to the syringe label. It is used to prevent accidental needlesticks after the correct injection of Fragmin. The needle trap consists of a plastic latch (pinch) aligned parallel to the needle, firmly attached to the syringe cylinder label.

The following actions are required to activate the safety system: Lift the syringe, hold the plastic needle block, and fold it away from the protector (see Figure1).

Figure1

Remove the gray rubber cap by pulling it outwards (see Figure2).

Figure2

You will notice a bubble of air in the syringe. This is expected and can be ignored. It is essential not to push the plunger yet, as some of the medication may be lost. The air bubble in disposable syringes should not be expelled before injection, as this may cause the loss of medication and, therefore, a reduction in dose.

You are now ready to administer the injection. Continue with Step2.

Step2: Choosing and preparing the subcutaneous injection site

Choose one of the recommended injection sites below (see the shaded areas in Figure3):

• A "U"-shaped area around the navel.
• Central thigh area.

Figure3

•Use a different injection site each time a dose is administered.

•Do not administer the injection in areas where the skin is painful, bruised, red, or hard. Avoid areas with scars.

•If you or the child have psoriasis, do not administer the injection directly on any raised, thick, red, or scaly skin patches ("psoriasis skin lesions").

•Wash and dry your hands.

•Clean the injection site with a new alcohol-soaked swab, moving in circular motions. Allow the skin to dry completely. Do not touch this area again before administering the injection.

Step3: Adopting the correct posture

You or your child should be seated or lying down for the subcutaneous injection. If you are self-administering the medication, sit comfortably in a position where you can see your abdomen (see Figure4).

Figure4

Step4:

With your thumb and index finger, lift a fold of skin with one hand. With the other hand, hold the syringe as if it were a pencil. This will be the injection site.

Step5:

If you are injecting Fragmin into an adult or yourself,hold the syringe over the skin fold, keeping it at a right angle (i.e., vertically, as in the diagram, and not at an angle). Insert the needle into the skin until it is fully inside (see Figure5).

Figure5

If you are injecting Fragmin into a child,insert the needle into the skin until it reaches the bottom with a small, quick movement, at an angle of between 45° and 90° (see Figure6).

Figure6

Step 6:

Push the plunger all the way down at a slow and constant speed to administer the correct dose. Continue pinching the skin fold while administering the injection and then release the skin fold and remove the needle.

If there is any bleeding at the injection site, apply gentle pressure. Do not rub the injection site, as this may cause hematomas.

Press the injection site with a cotton ball for 10seconds. Some minor bleeding may occur. Do not rub the injection site. You may place a bandage over the injection site.

Step 7: If your syringe has a Needle-Trap safety device, activate it

Place the plastic needle block against a hard, stable surface and, with one hand, turn the syringe cylinder upwards against the needle, forcing the needle into the block until it fits(see Figure7).

Continue folding the needle until the syringe exceeds a 45degree angle with the flat surface to permanently inactivate it(see Figure8).

(see Figure7)(see Figure8)

Step 8:

Dispose of the syringe and needle in a sharp object container. Keep your sharp object container out of reach of others. When the sharp object container is almost full, dispose of it according to the instructions or speak with your doctor or nurse.

If you use more Fragmin than you should

If you have used more Fragmin than you should, consult your doctor or pharmacist immediately, go to the nearest hospital, or contact the Toxicology Information Service, Tel. 91 562 04 20.

If you forgot to use Fragmin

Consult your doctor or pharmacist immediately.

Do not administer a double dose to compensate for the missed dose.

Like all medications, Fragmin may produce adverse effects, although not all people will experience them.

Adverse effects observed frequently (may affect up to one in 10 patients):

• Pain and appearance of petechiae at the injection site
• Reversible decrease in blood platelet count not mediated by immune mechanisms (type 1)
• Bleeding at any site, which has sometimes been fatal
• Temporary increase in liver enzymes

Rare adverse effects (may affect up to one in 1,000 patients):

• Hair loss, skin cell death

Adverse effects of unknown frequency (cannot be estimated from available data):

• Decrease in blood platelet count mediated by immune mechanisms induced by heparin (type 2)
• Severe allergic reactions
• Localized bleeding in the interior of the skull, abdomen, or other areas, sometimes fatal
• Rash
• Accumulation of blood in the interior of the skull or spinal column (epidural or spinal hematoma)
• Elevation of potassium levels in the blood
• Osteoporosis (bone porosity)

It is expected that adverse effects in children will be the same as those in adults. However, there is limited information available on possible adverse effects with prolonged use in children.

Reporting Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not store at a temperature above 30°C.

Do not use Fragmin after the expiration date (CAD) shown on the packaging and outer carton. The expiration date is the last day of the month indicated.

Do not use Fragmin if it presents particles or discoloration appears.

Medicines should not be disposed of in the drains or trash. Dispose of the containers and medicines you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need.This will help protect the environment.

Composition of Fragmin 2.500 UI/0.2 ml:

The active principle of Fragmin 2.500 UI/0.2 ml is dalteparin sodium. Each milliliter of solution contains 12,500 UI (anti-Xa) of dalteparin sodium. The total content per package is 2,500 UI (anti-Xa).

The other components are: sodium chloride, sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Appearance of Fragmin 2.500 UI/0.2 ml and contents of the package:

Preloaded syringes with needle protection device: subcutaneous injectable solution in preloaded syringes with 2,500 UI (anti-Xa)/0.2 ml in packages with 10 preloaded syringes.

Holder of the Marketing Authorization:

Pfizer, S.L.

Avda. de Europa 20-B.

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid) Spain

Responsible for manufacturing:

Catalent France Limoges S.A.S

Z.I. Nord

53, Rue de Dion Bouton

87280 Limoges (France)

or

Pfizer Manufacturing Belgium NV

Rijksweg 12

2870Puurs-Sint-Amands

Belgium

Additional information for the healthcare professional/user:

Fragmin 2.500 UI/0.2 ml is compatible with isotonic sodium chloride solutions (9 mg/ml) or glucose solutions (50 mg/ml), both in glass bottles and plastic containers.

No compatibility investigation has been conducted with this medication and other products.

This prospectus was approved in September 2023

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es