Data Sheet

THROMBOSTAT^®

Thrombin
(Topical)

Description

Thrombostat (thrombin) is a protein substance produced through a conversion reaction in which prothrombin of bovine origin is activated by tissue thromboplastin in the presence of calcium chloride. It is supplied as a sterile powder that has been freeze-dried in the final container. Also contained in this preparation are calcium chloride, sodium chloride, and glycine. Glycine is included to make the dried product friable and more readily soluble.

This product is prepared under rigid assay control against standard thrombin.

A unit is defined as the amount required to clot 1 mL of standardised fibrinogen solution in 15 seconds. Approximately 2 units are required to clot 1 mL of oxalated human plasma in the same period of time.

Pharmacology

Thrombostat requires no intermediate physiological agent for its action. It clots the fibrinogen of the blood directly. Failure to clot blood occurs in the rare case where the primary clotting defect is the absence of fibrinogen itself. The speed with which thrombin clots blood is dependent upon its concentration. For example, the contents of a 5000 unit vial of thrombin dissolved in 5 mL of saline diluent is capable of clotting an equal volume of blood in less than a second, or 1000 mL in less than a minute.

Indications

Aid in haemostasis wherever oozing blood from capillaries and small venules is accessible.

In various types of surgery, solutions of thrombostat may be used in conjunction with absorbable gelatin sponge, for haemostasis.

Contraindications

Hypersensitivity to any of its components and/or to material of bovine origin.

Precautions

The use of topical bovine thrombin preparations has occasionally been associated with abnormalities in haemostasis ranging from asymptomatic alterations in laboratory determinations such as prothrombin time (PI), and partial thromboplastin time (PTT), to mild to severe bleeding or thrombosis which rarely have been fatal. These haemostatic effects appear to be related to the formation of antibodies against bovine thrombin and/or factor V which in some cases may cross react with human factor V, potentially resulting in factor V deficiency.

Repeated clinical applications of topical bovine thrombin increase the likelihood that antibodies against thrombin and/or factor V may be formed. Consultation with an expert in coagulation disorders is recommended if a patient exhibits abnormal coagulation laboratory values, abnormal bleeding, or abnormal thrombosis following the use of topical thrombin. Any interventions should consider the immunologic basis of this condition. Patients with antibodies to bovine thrombin preparations should not be re-exposed to these products.

Because of its action in the clotting mechanism, thrombostat must not be injected or otherwise allowed to enter large blood vessels. Extensive intravascular clotting and even death may result. Thrombin is an antigenic substance and has caused sensitivity and allergic reactions including anaphylaxis.

Consult the absorbable gelatin sponge product labelling for complete information for use prior to utilising the thrombin-saturated sponge procedure.

Use in Pregnancy (Category B2)

Animal reproduction studies have not been conducted with thrombin. It is also not known whether thrombin can cause fetal harm when used in pregnant women or if it can affect reproduction capacity.

There are no adequate and well controlled studies in pregnant women therefore, thrombostat should not be given to these patients unless clearly indicated.

Use in Lactation

There are no adequate and well controlled studies in nursing mothers therefore, thrombostat should not be given to these patients unless clearly indicated.

Use in Children

Safety and effectiveness in children have not been established.

Adverse Reactions

An allergic type reaction following the use of thrombin for treatment of epistaxis has been reported. Febrile reactions have also been observed following the use of thrombin in certain surgical procedures, but no cause-effect relationship has been established.

Drug Interactions

None known.

Dosage and Administration

Thrombostat must not be injected. Apply on the surface of bleeding tissue as a solution or powder.

Solutions of thrombin may be prepared in sterile distilled water or isotonic saline. The intended use determines the strength of the solution to prepare. In most cases, regardless of the origin of bleeding, 1000 to 2000 units per mL should be used. Intermediate strengths to suit the needs of the case may be prepared by selecting the proper strength package and dissolving the contents in an appropriate volume of diluent.

It may be advantageous to use thrombostat in dry form on oozing surfaces.

Note: Single use of the solution or powder is recommended. Use once only and discard any residue.

The following techniques are suggested for the topical application of thrombin:

1. the recipient surface should be sponged (not wiped) free of blood before thrombin is applied
2. a spray may be used or the surface may be flooded using a sterile syringe and small gauge needle. The most effective haemostasis results when the thrombin mixes freely with the blood as soon as it reaches the surface
3. in instances where thrombostat in dry form is needed, the vial is opened by removing the metal ring by flipping up the plastic cap and tearing counterclockwise. The rubber-diaphragm cap may be easily removed and the dried thrombin is then broken up into a powder by means of a sterile glass rod or other suitable sterile instrument
4. sponging of treated surfaces should be avoided in order that the clot remain securely in place.

Thrombostat may be used in conjunction with absorbable gelatin sponge as follows:

1. prepare thrombostat solution of the desired strength
2. immerse sponge strips of the desired size in the thrombostat solution. Knead the sponge strips vigorously with moistened gloved fingers to remove trapped air, thereby facilitating saturation of the sponge.
3. apply saturated sponge to bleeding area. Hold in place for 10 to 15 seconds with a pledget of cotton or a small gauze sponge.

Pharmaceutical Precautions

Stability

Solutions should be used the day they are prepared. The solution may be used for up to 6 hours when stored at room temperature, up to 24 hours when stored under refrigeration and, if necessary, up to 48 hours when stored frozen.

Thrombostat should be stored at less than 25°C.

Presentation

Thrombostat is supplied as a sterile powder, 5000 unit vial: 1's

Medicine Classification

Prescription Medicine

Package Quantities

Thrombostat is supplied as sterile powder, 5,000 unit vial : 1's

Name and Address

Pfizer Laboratories Limited
P O Box 3998
Auckland
NEW ZEALAND

Toll Free Number: 0800 736 363

Date of Preparation

9 January 2002