[AVN] FW: TETANUS FROM PDR

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Tetanus Toxoid

Tetanus Toxoid Adsorbed

Chemistry and Stability

CHEMISTRY

Tetanus toxoid is a sterile suspension of the formaldehyde-treated products

of growth of Clostridiumm tetani. Tetanus toxoid adsorbed is tetanus toxoid

which has been adsorbed onto aluminum hydroxide, aluminum phosphate. or

aluminum potassium su!fate. Each 0.5 mL of tetanus toxoid adsorbed contains

not more than 0.85 mg of aluminum when determined analytically. or not more

than 1.14 mg when calculated on the basis of the amount of aluminum compound

added. Both preparations meet standards established by the Office of

Biologics of the US Food and Drug Administration. The antigen content of the

toxoids is expressed in flocculating units (Lf). Depending on the

manufacturer, each 0.5 mL of commercially available tetanus toxoid contains

4 or 5 Lf units of tetanus toxoid and each 0.5 mL of commercially available

tetanus toxoid adsorbed contains 5 or 10 Lf units of tetanus toxoid.

Commercially available tetanus toxoid is a clear, colorless to brownish

yellow, or slightly turbid liquid which may have a faint characteristic

odor. Commercially available tetanus toxoid adsorbed is a turbid, white,

slightly gray, or slightly pink suspension. The toxoids contain thimerosal

as a preservative and are made isotonic with sodium chloride.

STABILITY

Tetanus toxoid and tetanus toxoid adsorbed should be stored at 2-80C and

should not be frozen. The expiration date for tetanus toxoid or tetanus

toxoid adsorbed is not later than 2 years after the date of issue from the

manufacturer's cold storage (e.g.. 1 year when the manufacturer's cold

storage was 50C). The toxoids should be free from clumps after vigorous

shaking and should not be used if resuspension cannot be achieved.

Pharmacology

Tetanus toxoid and tetanus toxoid adsorbed promote active immunity to

tetanus by inducing production of specific antitoxin. A single IM dose of

either toxoid does not provide protection against the disease. However.

primary immunization with either 3 doses of tetanus toxoid adsorbed or 4

doses of tetanus

toxoid (see Dosage and Administration: Dosage) in susceptible individuals

induces production of antitoxin levels which result in immunity to tetanus

in more than 90% of vaccinees. Immunity to tetanus has been reported to

persist at least 10 years in most individuals following primary immunization

with 3 doses of tetanus toxoid adsorbed. Although the rate of seroconversion

is essentially the same with either form of the toxoid, tetanus toxoid

adsorbed induces more persistent antit6xin titers than tetanus toxoid.

Uses

Tetanus toxoid and tetanus toxoid adsotbed are used to provide active

immunity to tetanus in adults and children older than 6 weeks of age. The US

Public lHealth Service Immunization Practices Advisory Committee (ACIP) and

the Committee on Infectious Diseases of the American Academy of Pediatrics

(AAP) currently recommend that all individuals receive immunization against

both diphtheria and tetanus, and that children younger than 7 years of age

also receive immunization against pertussis. Therefore, diphtheria and

tetanus toxoids and pertussis vaccine adsorbed (DTP) is the preparation of

choice for

primary and booster immunization against tetanus in children 6 weeks through

6 years of age (see Diphtheria and Tetanus Toxoids and Pertussis Vaccine

Adsorbed 80:08), and tetanus and diphtheria toxoids adsorbed for adult use

is the preparation of choice for primary and booster immunization against

tetanus in individuals 7 years of age or older (See Diphtheria and Tetanus

Toxoids Adsorbed/Tetanus and Diphtheria Toxoids Adsorbed for Adult Use

80:08.) The ACIP states that because adults are generally less likely to

have adequate circulating levels of diphtheria antitoxin than adequate

circulating levels of tetanus antitoxin, tetanus and diphtheria toxoids

adsorbed for adult use should be used routinely in all medical settings

(e.g., private practice, clinics, emergency rooms) for individuals 7 years

of age or older requiring primary immunization or booster doses of tetanus

toxoid adsorbed. Tetanus toxoid or tetanus toxoid adsorbed should be used

for primary or booster immunization against tetanus only when preparations

containing combined antigens are contraindicated. Because tetanus toxoid

adsorbed induces more persistent antitoxin titers than tetanus toxoid, it is

the preferred preparation when the individual tetanus antigen is indicated.

Spores of C. tetani are umbiquitus and there is essentially no natural

immunity against tetanus toxin. Universal, primary immunization and

maintenance of adequate antitoxin levels with appropriately timed booster

doses is necessary for all ages. The need for immunization, active (with

tetanus toxoid

or, preferably, tetanus toxoid adsorbed) and/or passive (with tetanus immune

globulin), against tetanus depends on the individuals history of

immunizations and the likelihood of contamination with tetanus bacilli

(e.g., condition of the wound, source of contamination). The ACIP currently

describes wounds as

being tetanus prone (e.g., a severe puncture) or as clean, minor wounds.

Alternatively, some clinicians describe wounds as being very tetanus prone,

moderately tetanus prone, or. not tetanus prone. A wound is considered very

tetanus prone if it has been exposed to a high level of bacterial

contamination

(e.g., from sources such as barnyards, sewers, waste rnaterial at meat

packing plants, bullet wounds of the colon), is more than 24 hours old at

the time of treatment, or contains devitalized tissue that cannot be

completely debrided. A wound is considered moderately tetanus prone if it

has been exposed to a

moderate level of bacterial contamination(e.g., from sources such as wood,

pavement, most industrial areas, nonabdominal.bullet wounds), is a crush

injury or puncture wound, or extends into muscle. Although wounds from human

bites are usually highly contarninated, they are generally considered

moderately tetanus prone, since tetanus is:not part.of.the normal oral

flora. A wound is considered not tetanus prone if it is 24 or less hours

old, has a low level of bacterial contamination (e.g., from sources such as

household objects), contains no devitalized tissue, is not a crush injury or

puncture wound, and

does not extend into muscle. Neonatal tetanus occurs in infants born under

conditions where infection is likely to women who are not adequately

immunized; immune pregnant women confer protection to their infants through

transplacental maternal antibody. The ACIP states that in l0-20% of recent

tetanus

cases, no wound could be implicated, and that in 5-10% of cases, only minor

wounds or chronic skin lesions (e.g., decubitus ulcers) were reported. In

recent years, about two-thirds of reported cases of tetanus have occurred in

individuals 50 years of age or older. The disease has occurred almost

exclusively in individuals who are inadequately or not irnmunized or whose

immunization history is

unknown.

To maintain adequate immunity against tetanus following prirnary

immunization with tetanus toxoid or tetanus toxoid adsorbed., it is

necessary to administer routine booster doses of the toxoid every 10 years.

In the event of injury and possible exposure to tetanus infection,

additional emergency booster

doses are unnecessary if the wound is clean and minor (not tetanus prone)

and the patient has received primary or booster immunization against tetanus

within the.last 10 years. However, an emergency booster dose of tetanus

toxoid or, preferably, tetanus toxoid adsorbed is necessary in individuals

with a clean, minor wound if less than 3 doses of tetanus toxoid adsorbed or

4 doses of tetanus toxoid were administered.in the past (incompletely

immunized), or if more than 10 years have elapsed since.primary immunization

or the last booster dose. If the wound is extensive (moderately or very

tetanus prone), an emergency booster dose of tetanus toxoid or, preferably,

tetanus toxoid adsorbed should be given if less than 3 doses of tetanus

toxoid adsorbed or 4 doses of tetanus toxoid were administered in the past

(incompletely immunized), or if more than 5 years have elapsed since primary

immunization or the last booster dose. Antibodies develop rapidly

following administration of a booster dose in individuals who have

previously received at least 2 doses of toxoid. Tetanus immune globulin

(TIG) should be administered concomitantly with the toxoid at a separate

site if the wound is extensive (moderately or very tetanus prone) and the

patient has previously received less than 3 doses of tetanus toxoid or

tetanus toxoid adsorbed or the patients tetanus.immunization history is

uncertain. TIG is also indicated if the wound has been left untended for

more than 24 hours in a patient who has previously received less than 3

doses of tetanus toxoid adsorbed or 4 doses of tetanus toxoid. (See Tetanus

Immune Globulin

80:04.) -

Adverse reactions to tetanus toxoid and tetanus toxoid adsorbed, especially

Arthus-type hypersensitivity reactions, occur most frequently in individuals

older than 25 years of age who have received a large number of booster doses

of either toxoid.

LOCAL EFFECTS

The most frequent adverse effects of tetanus toxoid and tetanus toxoid

adsorbed are mild to moderate local reactions at the injection site

including tenderness, erythema, induration, warmth, and edema. A nodule may

be palpable at the injection site for a few weeks following administration

of tetanus toxoid adsorbed. Sterile abscesses have also been reported rarely

with tetanus toxoid adsorbed. Rarely, extensive local reactions manifested

by erythema and boggy edema (Arthus-type hypersensitivity reactions) occur

after injection of tetanus toxoid or tetanus toxoid adsorbed (generally

beginning 2-8 hours after administration but may begin 12 or more hours

after administration). There may be itching of the edematous area, and it

may resemble a giant hive. The edema may occasionally extend from shoulder

to elbow or shoulder to wrist if the injection was given into the deltoid.

The ACIP states that local reactions alone to a tetanus containing toxoid do

not preclude future use of the toxoid.

SYSTEMIC EFFECTS

Rarely, systemic reactions including transient fever, malaise, generalized

aches and pains, flushing, rash, generalized urticaria or pruritus,

lymphadenopathy, tachycardia, and hypotension have been reported following

administration of tetanus toxoid or tetanus toxoid adsorbed. Neurologic

disorders including cochlear lesions, brachial plexus neuropathies,

paralysis of radial or recurrent nerves, accommodation paresis, EEG

disturbances, and dysphagia have been reported rarely following injection of

tetanus toxoid or tetanus toxoid adsorbed. In the differential diagnosis of

a polyradiculoneuropathy which occurs following administration of tetanus

toxoid or tetanus toxoid adsorbed, the toxoid should be considered as a

possible cause.

PRECAUTIONS AND CONTRAINDICATIONS

The manufacturers state that prior to injection of tetanus toxoid or tetanus

toxoid adsorbed, the physician should review the patient's history regarding

possible sensitivity and take all precautions known for prevention of

allergic or any other adverse effects. Epinephrine and other appropriate

agents should be

available for immediate use in case an anaphylactic-reaction occurs. One

manufacturer states that tetanus toxoid adsorbed should be used with caution

in infants or children with cerebral damage, neurologic disorders, or a

history of febrile seizures. Tetanus toxoid and tetanus toxoid adsorbed

are contraindicated in individuals who have had a prior systemic

hypersensitivity reaction to either toxoid.

Although skin testing has been suggested for determining whether

immunization with a tetanus toxoid containing preparation can be continued

in individuals who develop a systemic reaction to the toxoid, the utility of

skin testing has been questioned since mild, nonspecific skin test

reactivity to tetanus toxoid appears to occur commonly. The ACIP states that

tetanus toxoid and tetanus toxoid adsorbed are also contraindicated in

individuals who experienced a neurologic reaction after a previous dose of a

tetanus toxoid.containing preparation. One manufacturer also states that the

toxoids are contraindicated

during an outbreak of poliomyelitis. The ACIP states that individuals who

experience Arthus-type hypersensitivity reactions or fever greater than

39.40C after administration of tetanus toxoid or tetanus toxoid adsorbed

usually have very high serum tetanus antitoxin levels and often are adults

who have

received frequent (e.g., annual) doses of a tetanus toxoid.containing

preparation; individuals experiencing these severe reactions should

generally not be given additional routine or emergency booster doses of a

tetanus toxoid containing preparation more frequently than every 10 years,

even if they have a wound that is extensive (moderately or very tetanus

prone). The manufacturers state that routine immunization doses of tetanus

toxoid and tetanus toxoid adsorbed are contraindicated in individuals with

acute or active infections. However, the ACIP states that minor illness such

as upper respiratory infection does not preclude immunization. If a

contraindication to using a tetanus toxoid containing preparation exists in

an individual who has previously received less than 3 doses of tetanus

toxoid or tetanus toxoid adsorbed, only passive immunization with tetanus

immune globulin should be considered when injury other than a clean minor

wound (not tetanus prone) is sustained.

PREGNANCY

Although tetanus toxoid and tetanus toxoid adsorbed have been administered

to pregnant women to prevent tetanus in neonates considered to be at high

risk for the disease, safe use of the toxoids during pregnancy has not been

definitely established. (See Cautions: Pregnancy, in Diphtheria and Tetanus

Toxoids Adsorbed/Tetanus and Diphtheria Toxoids Adsorbed for Adult Use

80:08.)

IMMUNOSUPPRESSIVE AGENTS

Individuals receiving immunosuppressive agents (e.g., corticotropin,

corticosteroids, alkylating agents, antimetabolites, irradiation) may have a

diminished immunologic response to tetanus toxoid or tetanus toxoid

adsorbed, and immunization with the toxoids should generally be deferred

until the immunosuppressive agent is discontinued. If primary immunization

is started in individuals receiving an immunosuppressive agent, an

additional dose of the toxoid should be given at least 1 month after the

immunosuppressive agent is discontinued. If possible the immunosuppressive

agent should be temporarily discontinued if an emergency booster dose of

tetanus toxoid or tetanus toxoid adsorbed is

required.

VACCINES

Tetanus toxoid or tetanus toxoid adsorbed may be administered simultaneously

with diphtheria and/or pertussis antigens, an inactivated vaccine,

poliovirus vaccine live oral, measles virus vaccine live, mumps virus

vaccine live, and/or rubella virus vaccine live.

Dosage and Administration

ADMINISTRATION

Tetanus toxoid is administered by IM or subcutaneous injection and tetanus

toxoid adsorbed is administered only by deep IM injection, preferably into

the midlateral muscles of the thigh or deltoid. The same muscle site should

not be used more than once during the course of primary immunization. To

ensure a uniform suspension of antigen, containers of tetanus toxoid or

tetanus toxoid adsorbed should be shaken vigorously prior to withdrawing a

dose.

DOSAGE

Tetanus toxoid and tetanus toxoid adsorbed are administered in 0.5-mL doses.

Depending on the manufacturer, each 0.5.mL dose of tetanus toxoid contains 4

or 5 Lf units of tetanus toxoid and each 0.5 mL of tetanus toxoid adsorbed

contains 5 or 10 Lf units of tetanus toxoid. For primary immunization in

adults or children 6 weeks of age or older, tetanus toxoid adsorbed is given

in a series of 3 doses and tetanus toxoid is given in a series of 4 doses.

The second dose of tetanus toxoid adsorbed is given 4-8 weeks after the

first dose and the third dose is given 6 months to 1 year after the second

dose. If tetanus toxoid is used for primary immunization, 3 doses are given

3-8 weeks apart and a fourth dose

is given 6 months to 1 year after the third dose. The ACIP states that

interruption of the recommended immunization schedules, regardless of the

length of time between doses, does not interfere with the final immunity

achieved, nor does it necessitate additional doses or starting the series

over. All individuals who received primary immunization with tetanus

toxoid or tetanus toxoid adsorbed should receive routine booster doses every

10 years to maintain adequate immunity against tetanus. In the event of

injury and

possible exposure to tetanus infection. an emergency booster dose of tetanus

toxoid or, preferably. tetanus toxoid adsorbed should be given as soon as

possible if the individual has received less than 3 doses of tetanus toxoid

adsorbed or 4 doses of tetanus toxoid in the past. If the injury is a clean,

minor

wound (not tetanus prone), an emergency booster dose should be given if more

than 10 years have elapsed since primary immunization or the last booster

dose:

If the wound is extensive (moderately or very tetanus prone), an emergency

booster dose should be given if more than 5 years have elapsed since primary

immunization or the last booster dose. (See Uses.)

Preparations

TETANUS TOXOID

Parenteral

Injection

4 Lf units/0.5 mL

Tetanus Toxoid (with thimernsal 100 ug/mL). Antigen Supply House,

Squibb/Connaught

5 Lt units/0.5 mL

Tetanus Toxoid Purogenated (with thimerosal 100 tigimLI, Lederle; Tetanus

Toxoid Ultrafined (with thimerosal 100 iug/mL). Wyeth

TETANUS TOXOID ADSORBED

Parenteral

Injection

5 Lf units/0.5 mL

Tetanus Toxoid Adsorbed Purogenate~ (with thimernsal 100 uSImL and aluminum

phosphate). Lederle; Tetanus Toxoid Adsorbed Ultrafined (with thimerosal 100

ug/mL and aluminum phosphate), Wyeth; Tetanus Toxoid Adsorbed (with

thimerosal 100 ug/mL and aluminum potassium sulfate), Squibb/Connaught

10 LI units/0.5 mL

Tetanus Toxoid Adsorbed (with thimerosal 100 ug/mL and aluminum hydroxide),

Sclavo