FRAGMIN 5,000 IU/0.2 ml PRE-FILLED SYRINGE SOLUTION FOR INJECTION

2. What you need to know before you use Fragmin

Do not use Fragmin if:

• you are allergic (hypersensitive) to dalteparin sodium, to any of the other ingredients of this medicine (listed in section 6), to any other type of heparin (medicines that prevent blood clotting) different from dalteparin sodium, or to products derived from pork
• you have acute gastroduodenal ulcer, cerebral hemorrhage, or other significant bleeding
• you have severe coagulation disorders
• you have a disease called acute or subacute septic endocarditis (inflammation of one of the heart membranes due to an infection)
• you have had an operation on the central nervous system, eyes, or ears, or if you have trauma to these organs or system
• you have a decrease in the number of platelets (cells present in the blood that are involved in blood clotting) and when a test of aggregation in the presence of dalteparin sodium is performed, 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 treatment with Fragmin if:

• You are going to receive intramuscular injections of other medicines 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 impairment (reduced kidney function) or severe hepatic impairment (reduced liver function).
• You have uncontrolled high blood pressure.
• You have retinal disorders (a 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 medicine.
• You are at risk of elevated potassium levels in the blood due to some disease or taking certain medications. Your doctor may perform tests to measure potassium levels.
• You are undergoing epidural (in one of the membranes surrounding the brain and spinal cord) or spinal anesthesia (in the spinal cord) or a lumbar puncture, and you are being administered heparin for preventive purposes; very rare hematomas may occur in these areas. If you feel back pain, numbness, weakness in the lower limbs, or some disorder in the functioning of the intestine or bladder, inform your doctor immediately.
• You have a prosthetic heart valve, the preventive doses of Fragmin may not be sufficient to prevent valve thrombosis.
• You are receiving prolonged treatment for unstable coronary disease, such as prior to revascularization, your doctor may reduce the dose of Fragmin.
• You are allergic or suspect you have a possible allergy to latex (natural rubber) or if the needle cap of the Fragmin pre-filled syringes is going to be handled by someone with a known or possible allergy to latex (natural rubber). The needle cap of the Fragmin pre-filled syringes is made of latex (natural rubber) that can cause severe allergic reactions in people with a latex allergy (natural rubber).

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

Fragmin should not be exchanged with other unfractionated heparins, low molecular weight heparins, or synthetic polysaccharides since their effect may not be the same.

Children and adolescents:

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

Using Fragmin with other medicines:

Tell your doctor, pharmacist, or nurse if you are using, or have recently used, other medicines, including those obtained without a prescription.

Certain medicines may interact with Fragmin 5,000 IU/0.2 ml; in these cases, it may be convenient to change the dose or interrupt treatment with one of the medicines.

Thrombolytic treatment (which dissolves the clot) or some medicines that affect blood clotting may increase the risk of bleeding when combined with Fragmin:

• Aspirin (acetylsalicylic acid).
• Platelet inhibitors (used to decrease platelet aggregation and reduce the risk of blood clots).
• Thrombolytics (used to dissolve blood clots).
• Non-steroidal anti-inflammatory drugs (NSAIDs) (medicines used to treat inflammation).
• Vitamin K antagonists and other types of anticoagulants.
• Dextran (used in some artificial tears).

Pregnancy and breastfeeding:

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

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

It is not recommended to use it with epidural anesthesia. Inform your doctor if you have an artificial heart valve.

If you are breastfeeding, inform your doctor; he will assess whether treatment with this medicine is suitable, as Fragmin passes into breast milk in small amounts.

Driving and using machines:

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

Fragmin contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe; this is, essentially “sodium-free”.

3. How to use Fragmin

Follow the instructions for administration of Fragmin 5,000 IU/0.2 ml exactly as indicated by your doctor. Consult your doctor, pharmacist, or nurse if you have doubts.

Remember to take or use your medicine.

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

Fragmin is administered subcutaneously (under the skin) to treat blood clots.

If you are undergoing hemodialysis or hemofiltration (procedures used to purify the blood), Fragmin will be administered in a vein or in the tube of the dialysis machine.

If you are going to be administered Fragmin to prevent venous thrombosis when you are going to have an operation, the dose will depend on the type of operation you are going to have.

If you are going to have a general surgery operation that involves a moderate risk of thrombosis, you will be administered 2,500 IU (anti-Xa) by injection under the skin, 2-4 hours before the operation. After the operation, you will be administered 2,500 IU once a day, during the risk period or until you can move.

If you are going to have an oncological or orthopedic surgery operation that involves a high risk of thrombosis, you will be administered 2,500 IU (anti-Xa) by injection under the skin, 2-4 hours before the operation. Twelve hours after the operation, you will be administered 2,500 IU (anti-Xa) again, and then 5,000 IU (anti-Xa) per day, one injection of Fragmin 5,000 IU/0.2 ml or two injections of Fragmin 2,500 IU/0.2 ml, while the risk period lasts or until you can move.

If you are going to be administered Fragmin 5,000 IU/0.2 ml to prevent venous thrombosis when you are not going to have an operation, but you are immobilized, the dose will depend on the risk you present. If the risk of thrombosis is moderate, you will be administered 2,500 IU once a day. If it is high, the dose will be 5,000 IU, one injection of Fragmin 5,000 IU/0.2 ml, per day. In both cases, you will be administered this medicine while the risk period lasts or until you can move.

If you are going to be administered Fragmin 5,000 IU/0.2 ml to treat blood clots already present in the deep veins or to prevent clot formation in the dialyzer during dialysis or blood filtration performed because kidney function is reduced, your doctor will indicate how often this medicine is going to be administered, as well as the dose to be used and the duration of treatment.

The injections of Fragmin are usually administered by a healthcare professional; they will be applied under the skin, in the anterior or posterior area of the abdomen, and alternately on the right and left sides.

Use in children and adolescents

Treatment of symptomatic venous thromboembolism (TEV)

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

This medicine is not suitable for use in the pediatric population because the pre-filled syringes do not allow the dose to be adjusted based on the child's body weight. It is recommended to use the 2,500 IU/ml solution for injection in 4 mL vials.

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

How to inject Fragmin

Fragmin is administered by subcutaneous injection (under the skin). This section of the leaflet explains how to administer Fragmin. You should follow these instructions only after being trained by your doctor. If you are not sure what to do, talk to your doctor immediately. You must inject (or administer) the dose of Fragmin at the recommended times by your doctor.

If it is necessary to dilute Fragmin before administration, this must be done by a healthcare professional. You should follow your doctor's instructions on how and when to inject the diluted medicine that is provided to you.

Please follow the steps explained below

Step 1: Preparing the syringe for injection will depend on the specific presentation of Fragmin being used.

The Needle-Trapsafety system is specially designed to help prevent accidents with needles after correct use of Fragmin. It consists of a plastic safety device attached to the label of the syringe. It is used to prevent accidental pricks after the correct injection of Fragmin. The needle protection device (Needle-Trap) consists of a plastic tab (clip) that is aligned in parallel with the needle, firmly attached to the label of the syringe cylinder.

The following actions are required to activate the safety system: Lift the syringe, hold the tip of the plastic needle blocker, and bend it away from the protector (see Figure 1).

Figure 1

Remove the gray rubber cap by pulling it outward (see Figure 2).

Figure 2

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

Now you are ready to administer the injection. Continue with step 2.

Step 2: Choosing and preparing the subcutaneous injection site

Choose one of the recommended injection sites below (see shaded areas in Figure 3):

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

Figure 3

• Use a different injection site each time you administer a dose.
• Do not administer the injection in areas where the skin is painful, bruised, red, or hard. Avoid areas with scars.
• If you or your child have psoriasis, do not administer the injection directly into any raised, thick, red, or scaly skin plaque ("psoriatic skin lesions").
• Wash and dry your hands.
• Clean the injection site with a new alcohol swab, using circular motions. Let the skin dry completely. Do not touch this area again before administering the injection.

Step 3: Adopting the correct posture

You or your child should be sitting or lying down for the administration of the subcutaneous injection. If you are going to self-inject the medicine, sit in a comfortable position where you can see your abdomen (see Figure 4).

Figure 4

Step 4:

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

Step 5:

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 completely inside (see Figure 5).

Figure 5

If you are going to inject Fragmin into a child,insert the needle into the skin until the end with a small, quick motion, at an angle of 45° to 90° (see Figure 6).

Figure 6

Step 6:

Push the plunger all the way down at a slow and constant speed to administer the correct dose. Continue to pinch 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 swab for 10 seconds. A slight bleeding may occur. Do not rub the injection site. You can put a bandage over the injection site.

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

Place the plastic blocker against a hard, stable surface and, with one hand, turn the syringe cylinder upward against the needle, forcing the needle into the blocker until it clicks (see Figure 7).

Continue bending the needle until the syringe exceeds an angle of 45 degrees with the flat surface to permanently disable it (see Figure 8).

(see Figure 7) (see Figure 8)

Step 8:

Discard the syringe and needle in a sharps container. Keep your sharps container out of the reach of others. When the sharps container is almost full, discard it according to the instructions or talk to 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, phone 91 562 04 20.

If you forget to use Fragmin

Consult your doctor or pharmacist immediately.

Do not administer a double dose to make up for forgotten doses.

4. Possible Adverse Effects

Like all medicines, Fragmin can cause adverse effects, although not all people suffer from them.

Frequently observed adverse effects (may affect up to one in 10 patients):

• Pain and bruising 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 inside the skull, inside the abdomen, or in other locations, sometimes fatal
• Rash
• Accumulation of blood inside the skull or spinal column (epidural or spinal hematoma)
• Elevation of blood potassium levels
• Osteoporosis (porous bones)

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

Reporting of Adverse Effects:

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

5. Storage of Fragmin

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 indicated month.

Do not use Fragmin if it contains particles or appears discolored.

Medicines should not be thrown away in drains or trash. Deposit the packaging and unused medicines in the SIGRE Point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Fragmin 5,000 IU/0.2 ml:

The active ingredient of Fragmin 5,000 IU/0.2 ml is sodium dalteparin. Each milliliter of solution contains 25,000 IU (anti-Xa) of sodium dalteparin. The total content per package is 5,000 IU (anti-Xa).

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

Appearance of Fragmin 5,000 IU/0.2 ml and Package Contents:

Pre-filled syringes with needle protection device: injectable solution for subcutaneous administration in pre-filled syringes with 5,000 IU (anti-Xa)/0.2 ml in packages of 10 and 25 pre-filled syringes.

Marketing Authorization Holder:

Pfizer, S.L.

Avda. de Europa 20-B. Parque Empresarial La Moraleja.

28108 Alcobendas (Madrid) Spain

Manufacturer:

Catalent France Limoges S.A.S.

Z.I. Nord

53, Rue de Dion Bouton

87280 Limoges (France)

or

Pfizer Manufacturing Belgium NV

Rijksweg 12

2870 Puurs-Sint-Amands

Belgium

Additional Information for Healthcare Professionals/Users:

Fragmin 5,000 IU/0.2 ml is compatible with isotonic sodium chloride solutions (9 mg/ml) or glucose (50 mg/ml), both in glass vials and plastic containers.

The compatibility of this medicine with other products has not been investigated.

This prospectus was approved in June 2025

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