DIPHTHERIA-TETANUS TOXOIDS-PED

General Administration Information
For storage information, see the specific product information within the How Supplied section.

-Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization. These actions are required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer and lot number of the vaccine; date of administration; and the name, address, and title of the person who administered the vaccine in the recipient's permanent medical record. These actions are required by the National Childhood Vaccine Injury Act of 1986.


Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intramuscular Administration
-Use vaccine as supplied; reconstitution is not necessary.
-Shake vial vigorously just prior to administration to ensure a uniform, white, cloudy suspension. If the vaccine cannot be resuspended, discard it.
-Do not mix with any other vaccine.
-Attach a sterile needle.-For the majority of infants < 1 year, a 1-inch, 22- to 25-gauge needle is sufficient to penetrate thigh muscle.
-For children 1-2 years, a needle at least 1 inch long is preferred for administration into the thigh; a 5/8 inch needle is sufficient for administration into the deltoid if the skin is stretched flat and the needle is inserted at a 90 degree angle.
-For children >= 3 years, the needle size required for deltoid injection ranges from 5/8- to 1-inch.

-Inject into the anterolateral aspect of the mid-thigh (for infants < 1 year) or the deltoid muscle of the upper arm (usually suitable for older children). Do NOT inject into the gluteal area or other areas where there may be a major nerve trunk.
-When concomitant administration of other vaccines or immunoglobulin is required, they should be given with different syringes and at different injection sites.

Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as to the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine is generally well tolerated. The most common adverse reactions are local reactions (i.e., injection site reaction) consisting of erythema and induration with or without tenderness. Among infant DT recipients, 0-3.6% had hardness >= 2.5 cm, 0-3.6% had erythema >= 2.5 cm, 2.2-11% had slight pain, and 0-1.4% had moderate pain at the injection site. Among children aged 4-6 years who received DT, 9% had erythema >= 50 mm, 51% had swelling > 50 mm, 17% had moderate or severe tenderness, and 9% experienced impairment of arm mobility (arm was too sore to move). Children >= 11 years of age and adolescents who received Td during a booster immunization study experienced erythema (25.6%), swelling (15%), and pain (80.1%). Severe pain, defined as incapacitating pain, or pain that limited activities or required medical care, occurred in 0.2% of Td recipients. Other local reactions reported during post-marketing use include mass, warmth, itching, and cellulitis. A nodule may be palpable at the injection site for several weeks after the injection as these have been reported following the use of adsorbed products. Local reactions are usually self-limiting and do not require therapy. Warming the Td vaccine in hands or by using a warmer has not been associated with a reduction in pain or adverse reactions following injection.

Among recipients of diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine during clinical studies, fever of at least 99.5 degrees F occurred in 4.3% of children >= 11 years of age and adolescents who received Td during a booster immunization study. Among infants who received DT during a primary immunization study, fever of 100.4-102.2 degrees F occurred in 6.6% of infants when the vaccine was administered alone without concomitant vaccines. Crying was reported in 13% of infants who received DT during primary immunization. Instruct patients to report any signs and symptoms of a fever to their health care provider.

Arthus reaction is occasionally reported following administration of diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Arthus-type hypersensitivity reactions may be associated with high levels of circulating antitoxin in persons who have had overly frequent injections of tetanus toxoid. Do not administer the DT or Td vaccine more frequently than recommended. The local, type III, immune complex mediated hypersensitivity reaction is usually self-limiting, and patients may experience redness and erythema at the injection site, which usually appears within 2-8 hours of vaccine administration. Persons who experienced Arthus-type hypersensitivity reactions or a temperature of > 103 degrees F (> 39.4 degrees C) following a prior dose of tetanus toxoid usually have high serum tetanus antitoxin levels and should not be given even emergency doses of Td vaccine more frequently than every 10 years, even if they have a wound that is neither clean nor minor.

Anaphylactoid reactions, bronchospasm, angioedema, urticaria, maculopapular rash, pruritus, urticaria, and rash (unspecified) have been observed during post-marketing surveillance with the diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Hypersensitivity reactions at the injection site have occurred. Patients should be advised to report any signs and symptoms of a systemic reaction to their health care provider. Also, have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis.

Headache was reported by 23% of children >= 11 years of age and adolescents within 3 days after Td administration during a booster immunization study; headache has also been noted after DT immunization. Guillain-Barre syndrome has been reported during post-marketing observation with Td vaccine. A causal relationship between tetanus toxoid receipt and both brachial neuritis and Guillain-Barre syndrome appears to exist. If Guillain-Barre syndrome occurs within 6 weeks of receipt of a prior vaccine that contained tetanus toxoid, base the decision to give any vaccine containing tetanus toxoid such as diphtheria toxoid; tetanus toxoid adsorbed, DT, Td on careful consideration of the potential benefits and possible risks, as the risk for Guillain-Barre syndrome may be increased. When a decision is made to withhold tetanus toxoid, administer other available vaccines, as indicated. Other neurological reactions reported during post-marketing experience with DT or Td vaccine include convulsions or seizures, paresthesias, dizziness, and syncope. Procedures should be in place to manage syncopal episodes and prevent falling injury.

Loss of appetite or anorexia was noted in 2.9% of infants age 6 months who received DT during a primary immunization study. Nausea and vomiting have been reported during post-marketing experience with diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Instruct patients to report any signs or symptoms of a systemic reaction to their health care provider.

A feeling of malaise occurred within 3 days after immunization in 14.5% (n = 492) of children >= 11 years of age and adolescents who received a Td as a booster immunization during a multicenter study. Lymphadenopathy has been observed during post-marketing surveillance of diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Pallor has been reported following use of the DT vaccine. Instruct patients to report any signs or symptoms of a systemic reaction to their health care provider.

Drowsiness (or somnolence) and fatigue have been observed post-marketing after immunization with diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Since these reactions are reported voluntarily from a population of unknown size, incidence and causality cannot be established. Instruct patients to report any signs or symptoms of a systemic reaction to their health care provider.

During a booster immunization study with Td, muscle weakness occurred in 32.3% of children >= 11 years of age and adolescents within 3 days following immunization with diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Moderate muscle weakness (interfered with daily activities) occurred in 7.3% of Td recipients, and severe muscle weakness (incapacitating weakness prohibiting usual daily activities, or requiring medical care or absenteeism) was noted in 0.6%. Arthralgia was reported in 15.7% of Td recipients. Myalgia and extremity pain have been noted during post-marketing observation.

Peripheral edema been reported during post-marketing experience with diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Since the reaction is reported voluntarily from a population of unknown size, incidence and causality cannot be established. Instruct patients to report any signs or symptoms of a systemic reaction to their health care provider.

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine is contraindicated in patients who have had an immediate anaphylactic reaction, temporally associated with a previous dose of this vaccine or any of its components. Dry natural latex rubber is contained in the tip caps of Tenivac prefilled syringes; therefore, use caution in individuals with latex hypersensitivity as allergic reactions may occur with use. With any biologic product, the prescriber or health care provider should take precautions to prevent allergic reactions. Epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis should be immediately available in the event of a serious allergic reaction to the vaccine. If immunizations are to be considered in a patient with a history of a severe allergic reaction to the vaccine or a component of the vaccine, referral of the potential vaccine recipient to an allergist may be appropriate. Patients who have experienced an Arthus-type hypersensitivity reaction after a tetanus toxoid dose should not be given Tdap as an emergency or routine booster vaccination until 10 years following the last dose of a tetanus toxoid-containing vaccine.

In some premature neonates, apnea after intramuscular vaccination has been observed. Consider the infant's medical status and the vaccine's potential benefits and possible risks when deciding when to administer an intramuscular vaccine such as diphtheria toxoid; tetanus toxoid adsorbed (DT) to infants born prematurely.

The diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine is indicated for intramuscular administration. Therefore, the vaccine should be given cautiously to persons receiving anticoagulant therapy. Also, patients with thrombocytopenia, coagulopathy (e.g., hemophilia), other bleeding disorders, or vitamin K deficiency should be monitored closely for bleeding at IM injection sites. Steps to avoid hematoma are recommended.

The decision to administer or to delay vaccination with diphtheria toxoid; tetanus toxoid adsorbed, DT, Td because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute febrile illness and administered after the acute phase of illness has resolved. All vaccines can be given to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness.

Patients with significant immunosuppression may not have an adequate antibody response to diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine. Immunosuppressed persons may include patients with human immunodeficiency virus (HIV) infection; severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to generalized neoplastic disease; or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (< 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive.

Careful consideration of the potential risks and benefits of diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine is needed if a patient had Guillain-Barre syndrome within 6 weeks of receipt of a prior vaccine that contained tetanus toxoid. The Institute of Medicine (IOM) has found evidence suggesting a causal relationship between tetanus toxoid receipt and brachial neuritis and Guillain-Barre syndrome.

Diphtheria toxoid; tetanus toxoid adsorbed, DT, Td vaccine is only indicated for intramuscular administration; do not give via intravenous administration, subcutaneous administration, or intradermal administration. Incorrect administration may result in inadequate immunity.

Safety and efficacy of the diphtheria and tetanus toxoids adsorbed vaccine (DT) have not been established in neonates and infants < 6 weeks of age. Safety and efficacy of the tetanus and diphtheria toxoids adsorbed vaccine (Td) have not been established in children < 7 years of age.

Description: Diphtheria and tetanus toxoids (Td) is an intramuscular vaccine indicated for the prevention of diphtheria and tetanus. Diphtheria toxoid is isolated from Corynebacterium diphtheriae whereas tetanus toxoid is isolated from Clostridium tetani. Although Td is only FDA-approved in people 7 years and older, it may be administered off-label to people 6 weeks to 6 years in whom concomitant immunization against pertussis is contraindicated (i.e., encephalopathy). Encephalopathy, within 7 days of vaccination, is a contraindication when it's not attributable to another identifiable cause. A causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barre syndrome has been established. If individuals experience Guillain-Barre syndrome within 6 weeks of receipt of prior vaccine containing tetanus toxoid, base the decision to administer a vaccine containing tetanus toxoid on the potential risks and benefits. Td is FDA-approved for primary and booster immunization in people 7 years and older; it is used off-label in infants and children 6 weeks to 6 years.

General Dosing Information
-NOTE: It is anticipated that the supply of tetanus and diphtheria (Td) vaccine will be constrained due to the discontinued production of TdVax. Preserve the limited supply of Td for those with a contraindication to receiving pertussis-containing vaccines. The CDC recommends vaccination providers transition to use of diphtheria, tetanus, and acellular pertussis (Tdap) vaccine in lieu of Td vaccine whenever possible while Td vaccine supplies are constrained. Tdap vaccine is an acceptable alternative to Td vaccine, including when a tetanus booster is indicated for wound management. Tdap vaccine is not an acceptable alternative only when a person has a specific contraindication to pertussis-containing vaccines, which is very rare.
-DTaP vaccine is for use in infants and children 6 weeks up to 7 years of age for primary immunization; Td is recommended off-label for infants and children 6 weeks to 7 years who have a contraindication to pertussis-containing vaccines.
-Td vaccine is for use in people 7 years of age or older for booster and catch-up immunization; Td may be used to complete the primary immunization series for tetanus and diphtheria after 1 or more doses of DTaP.
-Interruption of the recommended schedule with a delay between doses should not interfere with the final immunity achieved with Td vaccine. There is no need to start the primary series over again, regardless of the time between doses.

For diphtheria prophylaxis and tetanus prophylaxis:
-for primary immunization against diphtheria and tetanus:
Intramuscular dosage:
Infants and Children 6 weeks to 6 years*: 0.5 mL IM at 2, 4, 6, 15 to 18 months, and 4 to 6 years. Use in place of DTaP for primary immunization in people with a contraindication to a pertussis containing vaccine.
Children and Adolescents 7 to 17 years: 0.5 mL IM for 3 doses. For Tenivac dosing, the first 2 doses are administered 2 months apart, and the third dose is administered 6 to 8 months after the second dose. For TDVAX dosing, the first 2 doses are administered 1 to 2 months apart, and the third dose is administered 6 to 12 months after the second dose. For patients never immunized against diphtheria, tetanus, or pertussis, or with unknown immunization, a 3-dose series is recommended, with an interval of 4 to 8 weeks between doses 1 and 2, and an interval of 6 to 8 months between doses 2 and 3. Tdap is recommended for the first dose, followed by doses of Td or Tdap as necessary to complete the catch-up series. For catch-up immunization in patients who are not fully vaccinated, a single dose of Tdap is recommended if the patient has not received Tdap before, followed by doses of Td or Tdap as necessary to complete the catch-up series. If the first dose of diphtheria or tetanus toxoid-containing vaccine was administered before 12 months of age, the minimum interval between doses 2 and 3 may be lowered to 4 weeks, and a fourth dose of Td or Tdap is recommended at least 6 months after the third dose. Wait at least 10 years before giving a tetanus toxoid-containing vaccine if a serious Arthus-type hypersensitivity reaction occurred after previous tetanus toxoid receipt.
-for booster immunization against diphtheria and tetanus:
Intramuscular dosage:
Children 11 to 12 years: 0.5 mL IM when at least 5 years have passed since the last dose of toxoid-containing vaccine. Tdap is recommended if there are no contraindications, followed by Td or Tdap booster every 10 years; Td may be substituted for Tdap if immunization against pertussis is not indicated.
Adolescents: 0.5 mL IM. A single dose of Tdap is recommended, followed by Td or Tdap booster every 10 years; Td may be substituted for Tdap if immunization against pertussis is not indicated. Wait at least 10 years before giving a tetanus toxoid-containing vaccine if a serious Arthus-type hypersensitivity reaction occurred after previous tetanus toxoid receipt.
-for prophylaxis against diphtheria and tetanus for patients with large, contaminated wounds:
Intramuscular dosage:
Children and Adolescents 7 to 17 years: 0.5 mL IM. A single dose of Tdap is preferred to Td if the patient has not previously received Tdap. If immunization history is unknown or less than 3 doses of a tetanus toxoid vaccine have previously been given, give vaccine for clean, minor wounds or other severe or contaminated wounds. If 3 doses or more of a tetanus toxoid-containing vaccine have been given, give vaccine for clean, minor wounds if 10 years or more have elapsed since the last tetanus toxoid-containing vaccine, or for other severe or contaminated wounds if 5 years or more have elapsed since the last tetanus toxoid-containing vaccine. Wait at least 10 years before giving a tetanus toxoid-containing vaccine for emergency prophylaxis if a serious Arthus-type hypersensitivity reaction occurred after previous tetanus toxoid receipt.
-for prophylaxis against diphtheria for case contacts:
Intramuscular dosage:
Children and Adolescents 7 to 17 years: 0.5 mL IM. For patients never immunized against diphtheria, tetanus, or pertussis, or with unknown immunization, a 3-dose series is recommended, with an interval of 4 to 8 weeks between doses 1 and 2, and an interval of 6 to 8 months between doses 2 and 3. Tdap is recommended for the first dose, followed by doses of Td or Tdap as necessary to complete the catch-up series. For catch-up immunization in patients who are not fully vaccinated, a single dose of Tdap is recommended if the patient has not received Tdap before, followed by doses of Td or Tdap as necessary to complete the catch-up series. If the first dose of diphtheria or tetanus toxoid-containing vaccine was administered before 12 months of age, the minimum interval between doses 2 and 3 may be lowered to 4 weeks, and a fourth dose of Td or Tdap is recommended at least 6 months after the third dose. Close contacts who have completed a primary series of 3 or more doses of a diphtheria toxoid-containing vaccine and who have not been vaccinated with diphtheria toxoid in the previous 5 years should receive a booster dose of a diphtheria toxoid-containing vaccine. Tdap is recommended in patients 11 years and older who have not previously received the vaccine. Wait at least 10 years before giving a tetanus toxoid-containing vaccine if a serious Arthus-type hypersensitivity reaction occurred after previous tetanus toxoid receipt.

Maximum Dosage Limits:
-Neonates
Use not recommended.
-Infants
Younger than 6 weeks: Use not recommended.
6 weeks and older: 0.5 mL/dose IM has been used off-label.
-Children
1 to 6 years: 0.5 mL/dose IM has been used off-label.
7 to 12 years: 0.5 mL/dose IM.
-Adolescents
0.5 mL/dose IM.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, consult current immunization schedules for recommended vaccines for use in young dialysis patients; the ACIP states that all routine vaccinations are likely effective in patients with chronic renal disease.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Diphtheria toxoid; tetanus toxoid, Td confers immunity against the bacteria that cause diphtheria and tetanus.

Diphtheria Toxoid: Corynebacterium diphtheriae infections are mediated by diphtheria exotoxin, an extracellular protein metabolite of toxogenic strains of C. diphtheriae. Diphtheria toxoid induces the production of neutralizing antibodies against the exotoxin. A serum diphtheria antitoxin concentration of at least 0.1 International Units/mL is considered protective.

Tetanus Toxoid: Exotoxin release by C. tetani causes the neuromuscular dysfunction associated with tetanus. The tetanus toxoid contains antigens that induce the production of antibodies against the exotoxin. A serum tetanus antitoxin concentration of at least 0.1 International Units/mL is considered protective.

Pharmacokinetics: Diphtheria toxoid; tetanus toxoid adsorbed, DT, Td is administered intramuscularly. The pharmacokinetics of these vaccines are not well defined.


-Special Populations
Pediatrics
Infants 2-6 months
The immunogenicity of DT vaccines was evaluated in 137 infants who received DT at 2, 4, 6 months of age. At 8 months of age, diphtheria and tetanus antitoxin concentrations >= 0.01 International Units/ml (a minimum protective level) were detected in 99% and 100% of infants, respectively. Geometric mean titers ranged from 0.25-0.35 International Units/ml for diphtheria antibodies, and from 0.75-0.8 International Units/ml for tetanus antibodies.

Children >= 11 years and Adolescents
During a booster immunization study, 470 children >= 11 years of age and adolescents received a booster dose of Td. After immunization, the percent of subjects with tetanus antitoxin concentrations >= 1 International Unit/ml increased from 48.7% to 99.8%; all subjects developed antitoxin concentrations >= 0.1 International Units/ml. The percent of subjects with diptheria antitoxin concentrations >= 1 International Unit/ml increased from 18.5% to 98.9%, with 99.8% of subjects achieving antitoxin concentrations >= 0.1 International Units/ml.