Antithrombin III NF: Uses, Side Effects and Dosage

What is ANTITHROMBIN III NF used for?

• ANTITHROMBIN III NF is used for treatment and/or prevention of thrombotic and thromboembolic disorders in people with hereditary Antithrombin III deficiency.

• ANTITHROMBIN III NF may be used in surgical procedures or pregnancy and delivery in people with congenital antithrombin III deficiency.

How does ANTITHROMBIN III NF work?

ANTITHROMBIN III NF treats and/or prevents thrombotic or thromboembolic events by temporarily raising the level of ATIII in plasma and reducing blood coagulation.

What are the ingredients in ANTITHROMBIN III NF?

Medicinal ingredients: Human Antithrombin III protein.

Non-medicinal ingredients: Glucose, Protein, Sodium Chloride, Sodium Citrate Dihydrate, Sterile water for injection.

ANTITHROMBIN III NF contains no preservative.

ANTITHROMBIN III NF comes in the following dosage form:

ANTITHROMBIN III NF is available as a freeze-dried powder that is to be reconstituted with sterile water prior to intravenous injection/infusion. ANTITHROMBIN III NF is available in glass vials that contain:

• 450 - 550 International Units (IU) per vial at release with 10 mL Sterile Water for Injection
• 900 - 1100 IU per vial at release with 20 mL Sterile Water for Injection

The exact amount of antithrombin III (in IU) is stated on the label of each vial.

Do not use ANTITHROMBIN III NF:

• unless your doctor confirms that you have thrombotic or thromboembolic disorders.
• if you are hypersensitive to the product or if you have a known history of heparin-induced thrombocytopenia.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take ANTITHROMBIN III NF. Talk about any health conditions or problems you may have:

ANTITHROMBIN III NF is prepared from human plasma which may contain causative agents of hepatitis and other viral diseases.

This also applies to unknown or emerging viruses and other pathogens.

BEFORE you use ANTITHROMBIN III NF talk to your doctor or pharmacist if:

• You are undergoing or planning to undergo heparin treatment.
• You are pregnant or may be pregnant.
• You are a nursing mother.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with ANTITHROMBIN III NF:

Drugs that may interact with ANTITHROMBIN III NF include:

Heparin – The effects of ANTITHROMBIN III NF may be accelerated in the presence of heparin. Please consult your doctor before using antithrombin III in combination with heparin treatment.

ANTITHROMBIN III NF must not be mixed with other medicines.

How to take ANTITHROMBIN III NF:

Reconstitution

ANTITHROMBIN III NF is to be reconstituted immediately before its use. Entered vials must not be reused. The product does not contain a preservative and must be handled with aseptic technique to prevent contamination.

Before proceeding, ensure that the expiration date on the ANTITHROMBIN III NF concentrate vial or package is still valid.

For reconstitution, proceed as follows:

1. 1. Remove the unopened bottle containing Sterile Water for Injection (diluent) from the refrigerator and allow it warm up to room temperature (not above 37°C, 98°F).
2. 2. Remove the caps of both the concentrate and the diluent bottles to expose the central portions of the rubber stoppers (fig. A).
3. 3. Cleanse exposed surface of the rubber stoppers with germicidal solution and allow to dry.
4. 4. Using aseptic technique, remove protective covering from one end of the double-ended needle and insert the exposed end through the diluent bottle stopper (fig. B and C).
5. 5. Remove protective covering from the other end of the double-ended needle, taking care not to touch the exposed end. Invert diluent bottle over the concentrate bottle, then rapidly insert the free end of the needle through the concentrate bottle stopper (fig. D). Diluent will be drawn into the concentrate bottle by vacuum.
6. 6. Disconnect the two bottles by removing the needle from the concentrate bottle stopper (fig. E). Gently agitate or rotate the concentrate bottle until all material is dissolved.
7. 7. Visually inspect the reconstituted product for particulate matter and discolouration prior to administration. Discard if particulate matter or discolouration exists.

Do not refrigerate after reconstitution.

Administration

The reconstituted solution must be given by intravenous injection or infusion immediately after preparation. The injection or infusion rate must not exceed 5 mL/minute.

For intravenous injection:

1. 1. After reconstituting the concentrate as described above (see Reconstitution), attach the enclosed filter needle to a sterile disposable syringe and insert the needle through the bottle stopper (fig. F).
2. 2. Inject air and withdraw solution into syringe.
3. 3. Remove and discard filter needle. Attach a suitable intravenous needle or infusion set with winged adapter to the syringe and inject solution intravenously.

For intravenous infusion:

Prepare a solution of ANTITHROMBIN III NF as described above (see Reconstitution). If not filtered during dissolution, a disposable infusion set with a filter (range between 149 micrometer and 5 micrometer) is to be used.

Usual dose:

The dosage of ANTITHROMBIN III NF, Antithrombin III (human) depends on the cause and the severity of antithrombin III deficiency. Thus, the antithrombin III activity must be determined for accurate dosage calculation.

For Disseminated Intravascular Coagulation (DIC):

Dosage of ANTITHROMBIN III NF should be based on a determination of your antithrombin III activity prior to therapy and thereafter at intervals of approximately 4-6 hours. The initial dose should be large enough to raise the plasma level to normal (80-120%). Additional doses are required whenever the antithrombin III activity has dropped to less than 70%.

For Other Antithrombin III Defects:

As a guideline, an initial dose of 1500 IU and a maintenance dose of one half the initial dose given at 8 to 24 hour intervals is suggested for an average sized adult. However, the dosage should be adjusted to individual needs, which can only be estimated by determination of your antithrombin III activity at regular intervals.

Overdose:

No symptoms of overdosage with ANTITHROMBIN III NF are known.

Missed Dose:

The duration of treatment varies from case to case. In general, the administration of ANTITHROMBIN III NF may be discontinued after normalization of laboratory parameters and/or remission of clinical symptoms. Further monitoring of the antithrombin III plasma level at regular intervals may, however, be necessary for a prolonged period of time.

What are possible side effects from using ANTITHROMBIN III NF?

• Although rare, as with any other product that is prepared from the liquid part of the blood (plasma), severe allergic reactions may occur.
• If you develop fever, skin rashes, nausea, retching, shortness of breath, you should discontinue use of ANTITHROMBIN III NF.
• In the case of shock, medical attention should be initiated as appropriate.
• Mild allergic reactions may be managed with antihistamine.

The following side effects have been reported:

• Tremor (Involuntary Shaking)
• Hot flush

These are not all the possible side effects you may feel when taking ANTITHROMBIN III NF. If you experience any side effects not listed here, contact your healthcare professional.

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, talk to your healthcare professional.

Reporting Side Effects

Storage:

• Do not freeze ANTITHROMBIN III NF.

  ANTITHROMBIN III NF should be refrigerated (stored between 2ºC and 8ºC).

• ANTITHROMBIN III NF must not be used beyond the expiration date indicated on the label.
• ANTITHROMBIN III NF should be used immediately after preparation.
• Do not place back into refrigerator after reconstitution.
• Any unused portion of reconstituted solution should be discarded.
• Do not use solutions that are cloudy or have deposits.
• If devices other than those supplied with ANTITHROMBIN III NF are used, ensure use of an adequate filter. A disposable infusion set with a filter (range between 149 micrometer and 5 micrometer) is to be used.

Keep out of reach and sight of children.

If you want more information about ANTITHROMBIN III NF:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website; (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website (https://www.takeda.com/en-ca/antithrombin-iiipm) or by calling 1-800-268-2772.

Takeda Canada Inc.

22 Adelaide Street West, Suite 3800

Toronto Ontario M5H 4E3

Last Revised: APR-28-2021

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