Label: Information for the User

FRAGMIN 5,000 UI/0.2 ml injectable solution in preloaded syringes

Dalteparin sodium

Read the label carefully before starting to use the medication 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 medication has been prescribed only to 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.

1. What you need to know before starting to use Fragmin
2. How to use Fragmin
3. Possible adverse effects
4. Storage of Fragmin

6. Contents of the package and additional information

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

Fragmin 5,000 UI/0.2 ml is used in adults aged 18 years and older for:

• Prevention of thromboembolic disease in surgery (to prevent deep vein thrombosis when you undergo an operation).
• Prevention of thromboembolic disease in non-surgical patients who are immobilized and at moderate or high risk (to prevent deep vein thrombosis when you are not undergoing an operation, but are immobilized and at high risk of developing thrombosis).
• Treatment of deep vein thrombosis with or without pulmonary embolism (to treat existing blood clots in deep veins).
• Prevention of extracorporeal coagulation during hemodialysis and hemofiltration in patients with chronic renal insufficiency (to prevent coagulation in the dialyzer during dialysis or blood filtration in patients with decreased kidney function).
• Prevention of thromboembolic disease in patients with cancer.

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 disease, 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 systems
• Has a decreased platelet count (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 decreased platelet count or platelet defects. Your doctor may request specific tests to determine the cause of this problem.
• You have severe renal insufficiency (decreased kidney function) or severe hepatic insufficiency (decreased liver function).
• You have uncontrolled high blood pressure.
• You have retinal disorders (part of the eye) due to diabetes or uncontrolled 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 certain medications. Your doctor may perform tests to measure potassium levels.
• You are undergoing epidural or spinal anesthesia or lumbar puncture, and heparin is being administered for prevention; rare cases of hematomas in these areas may occur. If you experience back pain, numbness, weakness in the lower extremities, or any disturbances in bowel or urinary function, 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 suspected latex allergy. The cap of the preloaded syringe of Fragmin is made of latex (natural rubber) and may cause severe allergic reactions in individuals 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 unfractionated heparins, low molecular weight heparins, or synthetic polysaccharides, as their 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 5,000 UI/0.2 ml; in these cases, it may be advisable to change the dose or discontinue treatment with one of the medications.

It is especially important to inform your doctor if you are taking 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 (decreased kidney function).

Pregnancy and lactation:

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 whether 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 operate machinery.

Fragmin contains sodium

This medication containsless than 1 mmol of sodium (23 mg) per preloaded syringe; it is essentially “sodium-free”.

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

Remember to take or use your medicine.

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

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

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

If you are to be administered Fragmin toprevent deep vein thrombosis when you are to undergo an operation, the dose will depend on the type of operation you are to undergo.

If you are to undergo a general surgery operation that carries a moderate risk of thrombosis, you will be administered 2,500 UI (anti-Xa) via subcutaneous injection, 2-4 hours before the operation. After the operation, you will be administered 2,500 UI once a day, during the risk period or until you can move again.

If you are to undergo an oncological or orthopedic surgery operation that carries a high risk of thrombosis, you will be administered 2,500 UI (anti-Xa) via subcutaneous injection, 2-4 hours before the operation. Twelve hours after the operation, you will be administered another 2,500 UI (anti-Xa), and then 5,000 UI (anti-Xa) per day, one injection of Fragmin 5,000 UI/0.2 ml or two injections of Fragmin 2,500 UI/0.2 ml, until the risk period or until you can move again.

If you are to be administered Fragmin 5,000 UI/0.2 ml toprevent deep vein thrombosis when you are not undergoing an operation, but are immobile, the dose will depend on your risk level. If the risk of thrombosis is moderate, you will be administered 2,500 UI once a day. If it is high, the dose will be 5,000 UI, one injection of Fragmin 5,000 UI/0.2 ml per day. In both cases, you will be administered this medication until the risk period or until you can move again.

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

Fragmin injections will usually be administered by a healthcare professional; they 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. Your doctor will perform the calculation. Your 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 monitored after the initial dose and subsequent dose adjustment through a blood test.

How to inject Fragmin

Fragmin is administered via subcutaneous injection. This section of the prospectus explains how to administer Fragmin. You should follow these instructions only 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 device consists of a plastic clip (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 blocker, 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 medication loss and 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-injecting 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 in (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:

Pull the plunger all the way down slowly and steadily 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 bleeding may occur. Do not rub the injection site. You can place a bandage over the injection site.

Step7: If your syringe has a Needle-Trap device, activate it

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

Continue folding the needle until the syringe exceeds a 45degree angle with the flat surface to permanently render it unusable(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, phone 91 562 04 20.

If you forget to use Fragmin

Consult your doctor or pharmacist immediately.

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

Like all medications, Fragmin may produce adverse effects, although not all people may 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 the number of blood platelets not mediated by immune mechanisms (type 1)
• Bleeding at any point, which has sometimes been fatal
• Temporary increase in liver enzymes

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

• Hair loss, death of skin cells

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

• Decrease in the number of blood platelets 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 spine (epidural or spinal hematoma)
• Elevation of potassium levels in the blood
• Osteoporosis (porosity in 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 not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines 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 86°F (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 contains particles or appears discolored.

Medicines should not be disposed of in the drains or trash. Dispose of the containers and unused medicines at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and unused medicines.This will help protect the environment.

Composition of Fragmin 5.000 UI/0.2 ml:

The active principle of Fragmin 5.000 UI/0.2 ml is dalteparin sodium. Each milliliter of solution contains 25,000 UI (anti-Xa) of dalteparin sodium. The total content per package is 5,000 UI (anti-Xa).

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

Appearance of Fragmin 5.000 UI/0.2 ml and contents of the package:

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

2870 Puurs-Sint-Amands

Belgium

Additional information for healthcare professional/user:

Fragmin 5.000 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