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TETANUS ANTITOXIN

Category Passive immunizing agent.

          Tetanus Antitoxin for human use is a sterile, nonpyrogenic solution containing the specific antitoxic globulins obtained from the serum or plasma of horses, or other mammals, that have been immunized against tetanus toxin or toxoid. It has the power of neutralizing the toxin formed by Clostridium tetani.

          The antitoxin complies with the requirements stated under Antisera, with the following modification.

Description Transparent or slightly opalescent, faint brownish or yellowish or greenish liquid; odour, practically odourless or of the antimicrobial agent.

Strengths available 1500 IU and 20,000 IU per container.

Dose Prophylaxis: Intramuscular or subcutaneous, 1500 to 5000 IU.

          Therapeutic: Intravenous or intramuscular, 50,000 to 100,000 IU; part of this dose is administered by intravenous injection with the remainder being given intramuscularly.

          The dosage may be administered as prescribed by the physician.

Warning

          1. Reactions to Tetanus Antitoxin are rather common and often severe. In sensitized persons the administration of a heterologous serum may trigger an anaphylactic reaction. Therefore, it is recommended to take a precise anamnesis and to perform an intradermal test in every case (eventually to begin with a high serum dilution). Before the application of a heterologous serum all the preparations for the treatment of cardiovascular and respiratory complications which may accompany such anaphylactic reactions have to be made. A few days after the injection of a heterologous serum, serum sickness may also occur.

          2. Difficulty in breathing and swallowing; feeling of discomfort; fever; hives; itching; muscle aches; rash; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; swelling of joints; swollen lymph glands; unusual tiredness or weakness, sudden and severe, may occur.

Expiration date The expiration date for Tetanus Antitoxin containing a 20 per cent excess of potency is not later than 5 years from the date of the last satisfactory test for potency.

Packaging and storage Tetanus Antitoxin shall be stored at a temperature of 2º to 8º; avoid freezing.

Labelling See under Diphtheria Antitoxin, p. 228.

Identification It specifically neutralizes the toxin formed by Clostridium tetani, rendering it harmless to susceptible animals. The potency test may serve as an identification test.

Assay Not less than 400 IU of antitoxin per ml. The potency of tetanus antitoxin is determined by comparing the dose necessary to protect guinea-pigs or mice against the paralytic effects of a fixed dose of tetanus toxin with the quantity of the standard preparation of tetanus antitoxin necessary to give the same protection. If the lethal method is used, the number of animals and the procedure are identical with those described for the paralysis method but the end-point is the death of the animal rather than the onset of paralysis and the L+/10 dose is used instead of the Lp/10 dose. For this comparison a reference preparation of tetanus antitoxin, calibrated in International Units, and a suitable preparation of tetanus toxin, for use as a test toxin, are required. The potency of the test toxin is determined in relation to the reference preparation; the potency of the tetanus antitoxin being examined is determined in relation to the potency of the test toxin by the same method.

          The International Unit of antitoxin is the specific neutralizing activity for tetanus toxin contained in a stated amount of the International Standard, which consists of a quantity of dried immune horse serum.

          Selection of animals If mice are used, the body masses should be such that the difference between the lightest and the heaviest does not exceed 5 g.

          Preparation of test toxin Prepare the test toxin from a sterile filtrate of an approximately 9-day culture in liquid medium of Clostridium tetani. To the filtrate add 1 to 2 volumes of glycerol and store slightly below 0º. Alternatively, treat the filtrate with ammonium sulfate, collect the precipitate, which contains the toxin, dry in vacuum over phosphorus pentoxide desiccant and store dry, either in sealed ampoules or in vacuum over phosphorus pentoxide desiccant.

          Determination of test dose of toxin (Lp/10 dose) Prepare a solution of the reference preparation in a suitable liquid such that it contains 0.5 IU of antitoxin per ml.

          If the test toxin is stored dry, reconstitute it using a suitable liquid.

          Prepare mixtures of the solution of the reference preparation and the test toxin such that each contains 2.0 ml of the solution of the reference preparation, one of a graded series of volumes of the test toxin and sufficient of a suitable liquid to bring the volume to 5.0 ml. Allow the mixtures to stand at room temperature, protected from light, for 60 minutes. Using six mice for each mixture, inject a dose of 0.5 ml subcutaneously into each mouse. Observe the mice for 96 hours. Mice that become paralyzed may be killed.

          The test dose of toxin is the quantity in 0.5 ml of the mixture made with the smallest amount of toxin capable of causing, despite partial neutralization by the reference preparation, paralysis in all six mice injected with the mixture within the observation period.

Determination of potency of the antitoxin Prepare a solution of the reference preparation in a suitable liquid such that it contains 0.5 IU of antitoxin per ml.

          Prepare a solution of the test toxin in a suitable liquid such that it contains five test doses per ml.

          Prepare mixtures of the solution of the test toxin and the antitoxin being examined such that each contains 2.0 ml of the solution of the test toxin, one of a graded series of volumes of the antitoxin being examined and sufficient of a suitable liquid to bring the total volume to 5.0 ml. Also prepare mixtures of the solution of the test toxin and the solution of the reference preparation such that each contains 2.0 ml of the solution of the test toxin, one of a graded series of volumes of the solution of the reference preparation centred on that volume (2.0 ml) that contains 1 IU and sufficient of a suitable liquid to bring the total volume to 5.0 ml. Allow the mixtures to stand at room temperature, protected from light, for 60 minutes. Using six mice for each mixture, inject into each mouse subcutaneously a dose of 0.5 ml. Observe the mice for 96 hours. Mice that become paralyzed may be killed.

          The mixture that contains the largest volume of antitoxin that fails to protect the mice from paralysis contains 1 IU. This quantity is used to calculate the potency of the antitoxin in International Units per ml.

          The test is not valid unless all the mice injected with mixtures containing 2.0 ml or less of the solution of the reference preparation show paralysis and all those injected with mixtures containing more do not.

MONOGRAPHS • TETANUS ANTITOXIN
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หมายเหตุ / Note : TP II 2011 PAGE 229-230