Tetanus and Diphtheria Toxoids Adsorbed

TETANUS AND DIPHTHERIA TOXOIDS ADSORBED (Td Adsorbed) Connaught Active Immunizing Agent

Action and Clinical

Tetanus is an acute and often fatal disease caused by an extremely potent neurotoxin produced by C. tetani. The organism is ubiquitous and its occurrence in nature cannot be controlled. Immunization is highly effective, produces long-lasting protection and is recommended for the whole population. Only 2 to 3 cases of tetanus are now reported annually in Canada. Two deaths have been recorded in the past 5 years.

Diphtheria is a serious communicable disease caused by toxigenic strains of C. diphtheriae. The case-fatality rate remains 5 to 10%, with highest death rates in the very young and the elderly. The organism may be harbored in the nasopharynx, skin and other sites of asymptomatic carriers, making eradication of the disease difficult.

Routine immunization against diphtheria in infancy and childhood has been widely practised in Canada since 1930. This has resulted in a remarkable decline in the morbidity and mortality of this disease. In 1924, there were 9 000 cases reported, but less than 5 annually in recent years and no deaths since 1983. However, toxigenic strains of diphtheria bacilli are still detected each year in diphtheria carriers (pharyngeal, skin and ear) in Northern and Western Canada. Asymptomatic carriage of C. diphtheriae is far more common than clinical diphtheria. The disease occurs most frequently in unimmunized or partially immunized individuals. Although occasional cases of mild clinical diphtheria do occur in apparently fully immunized persons, antitoxin stimulated by immunization persists at protective levels for 10 years or more.

In a clinical trial involving 347 individuals ranging in age from 17 to 29 years, previously immunized against diphtheria and tetanus, a single 0.5 mL dose of any of the three clinical trial lots of Tetanus and Diphtheria Toxoids Adsorbed stimulated a prompt antibody response to both antigens.

Four weeks following a single 0.5 mL injection, of 245 individuals tested, 100% had tetanus antitoxin titers ³ 0.02 IU/mL with a geometric mean titer of 3.91 IU/mL; 98% of 244 individuals treated had diphtheria antitoxin titers ³ 0.02 IU/mL with a geometric mean titer of 1.12 IU/mL.

The immunogenicity of Tetanus and Diphtheria Toxoids Adsorbed administered as a series of 3 (0.5 mL) injections for primary immunization has been demonstrated in a small number (17) of individuals whose ages ranged from 6 to 56 years. These individuals were all confirmed unimmunized to both tetanus and diphtheria. Four weeks following the second injection of vaccine, given 2 months after the first, all had responded with serum tetanus antitoxin levels ranging from 0.11 to 14.0 IU/mL and with diphtheria antitoxin levels ranging from 0.01 to 1.28 IU/mL. Following the third injection of vaccine 6 to 8 months after second, the 8 individuals tested developed antitoxin titers to tetanus of 0.56 to 14.0 IU/mL and to diphtheria of 0.16 to 5.12 IU/mL.

During clinical trials, reactions associated with the injection of Td Adsorbed occurred at a low level of frequency, were usually transient in duration and consisted largely of discomfort, pain, swelling and redness at the injection site.

Indications And Clinical Uses:

For secondary immunization in children aged 7 years and older and adults who have been previously immunized against tetanus and diphtheria.

Tetanus and Diphtheria Toxoids Adsorbed may also be used for primary immunization of older children (7 years of age and older) and of adults who have not been previously immunized against tetanus and diphtheria.

Contra-Indications:

General: Immunization with Tetanus and Diphtheria Toxoids Adsorbed should be deferred in the presence of any acute illness, including febrile illness (to avoid superimposing adverse effects from the vaccine on the underlying illness or mistakenly identifying a manifestation of the underlying illness as a complication of vaccine use). A minor afebrile illness such as mild upper respiratory infection is not usually reason to defer immunization.

Absolute Contraindications: Allergy to any component of Td Adsorbed (see Supplied), an anaphylactic or other allergic reaction to a previous dose of Td Adsorbed are contraindications to vaccination.

Elective immunization of persons over 6 months of age should be deferred during an outbreak of poliomyelitis because of the risk of provocation paralysis.

Warnings in Clinical States:

I.M. injections should be given with care in persons suffering from coagulation disorders or on anticoagulant therapy because of the risk of hemorrhage.

If Tetanus and Diphtheria Toxoids Adsorbed is used in persons with malignancies, persons receiving immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, or persons who are otherwise immunocompromised (including HIV-infected individuals, transplant recipients, persons suffering from autoimmune disorders), the expected immune response may not be obtained.

Corticosteroid therapy can result in immunosuppression although the exact dose and duration of therapy required to suppress the immune system is not well defined. Persons treated with high doses of systemic steroids, e.g., ³ 2 mg/kg/day of prednisone orally for more than 2 weeks, should be considered to have a compromised immune system.

As with any vaccine, immunization with Td Adsorbed may not protect 100% of susceptible individuals.

Precautions:

General: The possibility of allergic reactions in individuals sensitive to components of the vaccine should be evaluated. Epinephrine HCl solution (1:1 000) and other appropriate agents should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs. Health care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management.

Before administration of any vaccine, all appropriate precautions should be taken to prevent adverse reactions. This includes a review of the patient’s history with respect to possible hypersensitivity to the vaccine or similar vaccine, determination of previous immunization history, and the presence of any contraindications to immunization, current health status, and a current knowledge of the literature concerning the use of the vaccine under consideration.

Frequent booster doses of tetanus toxoid in the presence of adequate or excessive serum levels of tetanus antitoxin have been associated with increased incidence and severity of reactions and should be avoided. If hypersensitivity to the diphtheria component is suspected, tetanus toxoid should be used for reinforcing doses.

Special care should be taken to ensure that the product is not injected into a blood vessel.

Caution: A separate sterile needle and syringe, or a sterile disposable unit, must be used for each individual patient to prevent the transmission of infectious agents.

There have been case reports of transmission of HIV and hepatitis by failure to scrupulously observe sterile technique. In particular, the same needle and/or syringe must never be used to re-enter a multidose vial to withdraw vaccine even when it is to be used for inoculation of the same patient. This may lead to contamination of the vial contents and infection of patients who subsequently receive vaccine from the vial.

Needles should not be recapped and should be disposed of properly.

Before administration of Tetanus and Diphtheria Toxoids Adsorbed health care personnel should inform the parent or guardian or the patient to be immunized of the benefits and risks of immunization, inquire about the recent health status of the patient and comply with any local requirements with respect to information to be provided to the patient before immunization.

Adverse Reactions:

Localized reactions consisting of discomfort, pain, swelling and redness at the injection site may be associated with the toxoids. These are usually of low frequency and transient in duration. Following booster doses, local erythema and swelling are not uncommon and Arthus-type sensitivity may occur. Persistent nodules at the site of injection have occurred following the use of adsorbed vaccine, but this complication is unusual.

Generalized reactions may develop following immunization and may take the form of allergic reactions including urticaria and, less commonly, angioneurotic edema. Influenza-like symptoms have been reported and usually occur within 12 hours of vaccination. Neurological complications such as peripheral neuropathies following tetanus toxoid or diphtheria toxoid have been documented but are rare.

It has been shown that the incidence of reactions to toxoids (especially to tetanus toxoid) rises according to the number of previously administered doses. This incidence in adults is unlikely to exceed 1% and occurs mainly in the overimmunized.

Nervous System: The following neurologic illnesses have been reported as temporally associated with vaccine containing tetanus toxoid: neurological complications including cochlear lesion, brachial plexus neuropathies, paralysis of the radial nerve, paralysis of the recurrent nerve, accommodation paresis, and EEG disturbances with encephalopathy. In the differential diagnosis of polyradiculoneuropathies following administration of a vaccine containing tetanus toxoid, tetanus toxoid should be considered as a possible etiology.

On the basis of a case report and evidence that a vaccine-induced immunologic response can cause Guillain Barre Syndrome (GBS), the Institute of Medicine concluded that tetanus toxoid-containing vaccines can trigger GBS in adults. No increased risk for GBS has been observed with the use of DTP in children.

Physicians, nurses, and pharmacists should report any adverse occurrences temporally related to the administration of the product in accordance with local requirements and to the Medical Director, Connaught Laboratories Limited, 1755 Steeles Avenue West, Toronto, Ontario, Canada M2R 3T4.

Dosage And Administration:

For persons who have previously been immunized against tetanus and diphtheria, a dose of 0.5 mL should be administered as a reinforcing dose at approximately 10 year intervals.

For primary immunization of individuals 7 years or older a series of 3 (0.5 mL) injections is required with the first 2 injections being administered 2 months apart followed by the third injection 6 to 12 months later. Thereafter reinforcing doses are recommended at approximately 10 year intervals.

Tetanus Prophylaxis in Wound Management: If not clearly documented, a history of immunization should be regarded as “uncertain”. If a tetanus booster is required it is preferred to choose a combined preparation such as this product containing 5 Lf of tetanus toxoid and 2 Lf of diphtheria toxoid per 0.5 mL dose. Appropriate cleansing and debridement of the wound is imperative. Booster doses given more frequently than recommended above may lead to adverse local and systemic reactions.

Note: Diphtheria and Tetanus Toxoid Adsorbed, containing 25 Lf of diphtheria toxoid and 5 Lf of tetanus toxoid per 0.5 mL dose, should not be administered as a tetanus booster to children over 7 years of age or adults due to the risk of reaction to the high diphtheria toxoid component in this vaccine.

Note: Tetanus toxoid, or a combined vaccine containing tetanus toxoid, and tetanus immune globulin should be administered in separate syringes at different sites.

Parenteral biological products should be inspected visually for extraneous particulate matter and/or discoloration before administration. If these conditions exist, the product should not be administered.

Shake the vial or ampul well to distribute uniformly the suspension before withdrawing each dose. Before withdrawing a dose from an ampul, tap the container first to ensure that any vaccine in the ampul neck falls to the lower portion of the ampul. Once the ampul has been opened, any of its contents not used immediately should be discarded. When administering a dose from a rubber-stoppered vial, do not remove either the rubber stopper or the metal seal holding it in place. Aseptic technique must be used for withdrawal of each dose (see Precautions)

Before injection, the skin over the site to be injected should be cleansed with a suitable germicide.

Administer the vaccine i.m. The preferred site is into the deltoid muscle.

After insertion of the needle, aspirate to ensure that the needle has not entered a blood vessel.

Do not inject i.v.

Each person who is immunized should be given a permanent personal immunization record. In addition, it is essential that the physician or nurse record the immunization history in the permanent medical record of each patient. This permanent office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.

Availability And Storage:

Tetanus and Diphtheria Toxoids Adsorbed is a sterile, cloudy, uniform suspenison of diphtheria and tetanus toxoids adsorbed on aluminum phosphate and suspended in isotonic sodium chloride solution. Each dose (0.5 mL) contains: tetanus toxoid (5 Lf), diphtheria toxoid (2 Lf) and aluminum phosphate 1.5 mg. Thimerosal 0.01% is added as a preservative. Ready for use rubber stoppered multiple-dose vials of 5 mL, and glass ampuls of 0.5 mL (1 dose). Store at 2 to 8°C. Do not freeze. Product exposed to freezing should not be used. Do not use vaccine after expiry date.

TETANUS AND DIPHTHERIA TOXOIDS ADSORBED (Td Adsorbed) Connaught Active Immunizing Agent

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Diphtheria

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