Attetrium

PACKAGE LEAFLET: INFORMATION FOR THE USER

Attertium “500 UI/10 ml Powder and solvent for solution for infusion”, “1000 UI/20 ml Powder and solvent for solution for infusion”

Human Antithrombin III
Please read all of this leaflet carefully before you start 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, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. WHAT ATTERTIUM IS AND WHAT IT IS USED FOR

Attertium is an anticoagulant agent belonging to the group of medicines known as injectable anticoagulants.
Attertium is used in congenital or acquired antithrombin deficiency for the prevention of increased risk of blood clot formation in the leg vessels (deep vein thrombosis), or in other parts of the body (thromboembolism) during surgery or in the peri-partum period, and in combination with heparin when indicated.

2. WHAT YOU SHOULD KNOW BEFORE USING ATTERTIUM

Do not use Attertium

• if you are allergic to human antithrombin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Attertium.

• As with all intravenous protein-based products, allergic-type reactions may occur. You must be closely monitored and carefully observed for any symptoms that may occur during infusion. If you notice any signs of hypersensitivity reaction such as hives, generalized erythema, tightness in the chest, wheezing (difficulty breathing), contact your doctor immediately.
• When medicines are prepared from human blood or plasma, certain procedures are implemented to prevent transmission of infections to patients:
• careful selection of blood and plasma donors to ensure that individuals at risk of carrying infections are excluded,
• screening of individual donations and pooled plasma to detect signs of viruses/infections,
• inclusion of manufacturing steps that can inactivate or remove viruses. Despite these measures, when medicines derived from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be completely ruled out. This also applies to unknown or emerging viruses and other pathogens.

The procedures adopted are considered effective against lipid-enveloped viruses such as the Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV), as well as against the non-enveloped Hepatitis A virus (HAV). However, the measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19 (B19V). Parvovirus B19 infection can be severe in pregnant women (fetal infection) and in individuals with depressed immune systems or certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).

• Your doctor may recommend considering appropriate vaccination against hepatitis A and B if you regularly or repeatedly receive antithrombin concentrates derived from plasma.
• It is strongly recommended that each time you receive a dose of Attertium, both the name and batch number of the product are recorded, in order to ensure traceability between the patient and the batch used.

Children
There are insufficient data to recommend the use of Attertium in children under 6 years of age.
Other medicines and Attertium
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

• Simultaneous administration of antithrombin and heparin at therapeutic doses increases the risk of bleeding. The effect of antithrombin is strongly enhanced by heparin. Concurrent administration of heparin and antithrombin in patients with an increased risk of bleeding must be monitored both clinically and biologically.

Pregnancy and breastfeeding
Attertium should be used during pregnancy and breastfeeding in women with antithrombin deficiency only if clearly indicated, taking into account that pregnancy increases the risk of thromboembolic events in these patients.
Ask your doctor or pharmacist for advice before using this medicine.
Driving and using machines
Attertium does not affect, or affects only negligibly, the ability to drive vehicles or operate machinery.
Attertium contains sodium
This medicine contains 33.35 mg of sodium (a main component of table salt) per 500 IU/10 ml vial and 66.7 mg per 1000 IU/20 ml vial. This corresponds to 1.67% and 3.3% of the maximum recommended daily dietary intake for an adult, respectively.
This should be taken into consideration in individuals with impaired renal function or those following a low-sodium diet.

3. HOW TO USE ATTERTIUM

Your doctor will prepare the Attertium solution for administration by intravenous infusion.
Your doctor will determine the dose, frequency, and duration of treatment.
For instructions on correct use and dosage, refer to the section “The following information is intended exclusively for physicians or healthcare professionals”.
Use in children
There are insufficient data to recommend the use of Attertium in children under 6 years of age.
If you use more Attertium than you should
No consequences of overdose have been reported.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine may cause side effects, although not everybody will experience them.
Hypersensitivity or allergic reactions (which may include angioedema, burning and pain at the injection site, chills, flushing, generalized urticaria, headache, wheals, hypotension, lethargy, nausea, restlessness, tachycardia, chest tightness, tingling, vomiting, wheezing) have been observed not frequently and, in some cases, may progress to severe anaphylaxis (including shock).
Fever has been observed rarely.
If any of these symptoms occur after administration, inform your doctor immediately.
For information on viral safety, see section 2.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You may also report side effects directly via the website: https://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 ATTERTIUM

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after "Exp".
The expiry date refers to the product stored unopened and under the recommended conditions.
Store below 30 °C. Do not freeze.
Protect from light. Store in the outer packaging.

Reconstituted product
After reconstitution, the product has been shown to be chemically and physically stable for 12 hours at 25 °C.
From a microbiological standpoint, the product should be used immediately. If not used immediately,
the duration and conditions of storage prior to use are under the user's responsibility and, normally,
should not exceed 24 hours at 2 - 8 °C, unless the reconstitution has been carried out under controlled
and validated aseptic conditions.

The solution should be clear or slightly opalescent. Do not use this medicine if you notice cloudiness or deposits.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What Attertium contains

• The active substance is human antithrombin III. Each vial of lyophilized powder contains 500 IU or 1000 IU of human antithrombin III. Once reconstituted, the antithrombin III concentration is 50 IU/ml (500 IU/10 ml or 1000 IU/20 ml).
• The other components are D-mannitol, sodium chloride and sodium citrate.
• Each pre-filled syringe containing solvent holds 10 ml or 20 ml of water for injections.

Description of the appearance of Attertium and packaging contents
Vial containing a white, hygroscopic powder or friable solid, and a pre-filled syringe with water for injections.
Each Attertium 500 IU pack contains one vial with 500 IU of human antithrombin III (powder for infusion) and one pre-filled syringe containing 10 ml of water for injectable preparations (solvent).
Each Attertium 1000 IU pack contains one vial with 1000 IU of human antithrombin III (powder for infusion) and one pre-filled syringe containing 20 ml of water for injectable preparations (solvent).
The accessories supplied with Attertium for reconstitution of the product are: vial adapter and filter.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Grifols Italia S.p.A.
Viale Enrico Forlanini, 23
20134 Milano - ITALY

Manufacturer:
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN

The following information is intended exclusively for physicians or healthcare professionals:
In congenital deficiency, dosing must be individualized for each patient, taking into account family history of thromboembolic events, current risk factors, and laboratory data.
In acquired deficiency, the dosage and duration of replacement therapy depend on plasma antithrombin levels, the presence of signs indicating increased turnover, the underlying disease, and the severity of the clinical condition. The amount and frequency of administration should always be based on the clinical efficacy of treatment and individual laboratory assessments.
The number of antithrombin units administered is expressed in International Units (IU), in accordance with the current WHO standard for antithrombin. Antithrombin activity in plasma is expressed as a percentage (relative to normal human plasma) or in International Units (relative to the International Standard for antithrombin in plasma).
One International Unit (IU) of antithrombin activity corresponds to the amount of antithrombin present in one milliliter of normal human plasma. The calculation of the required antithrombin III dose is based on the experimental observation that 1 International Unit of antithrombin III per kilogram of body weight increases plasma antithrombin activity by approximately 1%.
The initial dose to be administered can be calculated using the following formula:
Units required = body weight (kg) × (100 – measured antithrombin activity at the time, expressed as a percentage) × 0.8
The target initial antithrombin activity depends on the clinical situation. When antithrombin replacement is indicated, the dosage should be sufficient to achieve and maintain the desired activity level. The dose must be determined and monitored based on laboratory-measured antithrombin activity, which should be assessed at least twice daily until the patient is stabilized, and thereafter once daily, preferably just before the next infusion. Dose adjustments should take into account both signs of increased antithrombin turnover, as indicated by laboratory monitoring, and the clinical course. Antithrombin activity should be maintained above 80% throughout treatment, unless clinical conditions suggest a different target level.
In congenital deficiency, the usual initial dose is 30–50 IU/kg.
Subsequently, dosage, frequency, and duration of treatment should be adjusted according to biological values and clinical status.

Paediatric population
There are insufficient data to recommend the use of Attertium in children under 6 years of age.
The product must be administered by slow intravenous infusion. The infusion rate must not exceed 0.08 ml/kg/min.

To prepare the solution:

1. Warm the vial and syringe, not exceeding 30°C.
2. Insert the plunger into the syringe containing the solvent.
3. Remove the filter from its packaging. Remove the cap from the syringe connector and attach the syringe to the filter.
4. Remove the vial adapter from its packaging and connect it to the filter on the syringe.
5. Remove the plastic protector from the vial and clean the stopper with a disinfectant swab.
6. Pierce the vial stopper with the needle of the adapter.
7. Transfer all the solvent from the syringe into the vial.
8. Gently rotate the vial without shaking until the entire product is dissolved.
9. Disconnect the syringe with filter from the vial with adapter. Pull back the plunger to introduce air equal in volume to the solution. Reconnect the syringe with filter to the vial with adapter and inject the air.
10. Holding the vial upside down, draw the solution into the syringe.
11. Disconnect the syringe from the vial and administer the solution slowly by intravenous infusion. The infusion rate must not exceed 0.08 ml/kg/min.

Any unused product must never be stored for later use.
Do not reuse the administration set.
If infusion devices are used, their compatibility with the pre-filled syringe must be verified. If necessary, use adapters to ensure proper administration of the product.