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    Vaccine Combinations with a Tetanus Component

    DEA CLASS

    Rx

    DESCRIPTION

    Vaccine that contains various pertussis antigens, diphtheria toxoid, and tetanus toxoid
    Used to help protect individuals from pertussis, diphtheria, and tetanus
    Encephalopathy, coma, decreased level of consciousness, or prolonged seizures within 7 days of a dose that is not attributable to another cause is a contraindication to administration

    COMMON BRAND NAMES

    Adacel, Boostrix, Daptacel, Infanrix

    HOW SUPPLIED

    Adacel/Boostrix/Clostridium Tetani Toxoid antigen (Formaldehyde inactivated), Corynebacterium Diphtheriae Toxoid antigen (Formaldehyde inactivated), Bordetella Pertussis Toxoid antigen (Formaldehyde, Glutaraldehyde inactivated), Bordetella Pertussis Filamentous Hemagglutinin antigen (Formaldehyde inactivated), Bordetella Pertussis Pertactin antigen (Formaldehyde inactivated)/Daptacel/Infanrix Intramuscular Inj Susp

    DOSAGE & INDICATIONS

    For diphtheria prophylaxis, tetanus prophylaxis, and pertussis prophylaxis.
    For prophylaxis against diphtheria and tetanus for wound management in patients who also need the pertussis component.
    Intramuscular dosage (Adacel, Boostrix, Tdap)
    Adults

    0.5 mL IM.[31250] [31290] A single dose of Tdap is preferred to Td if patients have 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. If a tetanus toxoid-containing vaccine is indicated for a pregnant woman, use Tdap. [64478] 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.[31250] [31290] [53042]

    Children and Adolescents 10 to 17 years

    0.5 mL IM.[31250] A single dose of Tdap is preferred to Td if patients have 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 if a serious Arthus-type hypersensitivity reaction occurred after previous tetanus toxoid receipt.[31250] [53042]

    Children 7 to 9 years†

    0.5 mL IM. A single dose of Tdap is preferred to Td if patients have 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.

    Intramuscular dosage (Daptacel, Infanrix, DTaP)
    Children 1 to 6 years†


    0.5 mL IM. If 3 doses or more of a tetanus toxoid-containing vaccine have been given, give vaccine for all wounds except clean, minor wounds if 5 years or more have elapsed since the last tetanus toxoid-containing vaccine.

    Intramuscular dosage (Daptacel, Infanrix, DTaP)
    Infants and Children 6 weeks to 6 years

    0.5 mL IM for 3 doses at intervals of 4 to 8 weeks (preferably 8 weeks) for Infanrix or intervals of 6 to 8 weeks for Daptacel, ideally given at 2, 4, and 6 months of age. Although the first dose is usually at 2 months of age, it may be given as early as 6 weeks; the vaccine may be used up to the seventh birthday. A fourth dose is recommended at 15 to 20 months with an interval between the third and fourth dose of at least 6 months. If a fourth dose is inadvertently administered early, but is administered at least 4 months, but less than 6 months, after the third dose, it need not be replaced. A fifth dose is recommended at 4 to 6 years of age, prior to the child entering school. A fifth dose is not necessary if the fourth dose was given at age 4 years or older.

    Intramuscular dosage (Boostrix, Tdap)
    Adults

    0.5 mL IM.[31250] Use Td or Tdap for subsequent booster immunizations. A dose of Tdap is recommended instead of Td to replace 1 of the 10-year Td boosters if Tdap has not been previously received or if vaccine status is unknown. Tdap may be administered as an additional dose 9 years or more after the initial Tdap dose. Administration of Tdap as soon as feasible is advised for all pregnant women (preferably during the early part of gestational weeks 27 through 36), for all postpartum women not vaccinated during pregnancy, close contacts of infants younger than 12 months of age, and health care personnel with direct patient contact. Tdap can be administered regardless of the interval since the most recent tetanus or diphtheria-containing vaccine.[31250] [53026] 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.[31250]

    Children and Adolescents 11 to 17 years

    0.5 mL IM.[31250] Give 1 dose of Tdap to patients at 11 to 12 years of age; Td or Tdap booster needed every 10 years thereafter. Tdap may be administered as an additional dose 9 years or more after the initial Tdap dose.[31250] [64951] Give 1 dose of Tdap to patients 13 to 17 years of age who have not received a dose and to pregnant adolescents during each pregnancy (preferably during the early part of gestational weeks 27 through 36). Tdap can be administered regardless of the interval since the most recent tetanus or diphtheria-containing vaccine.[53026] [64951] 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.[31250]

    Children 10 years

    0.5 mL IM.[31250] A single dose of Tdap is recommended for children 7 to 10 years old who do not have a contraindication for pertussis vaccine and who are not fully vaccinated against pertussis, which is defined as 5 doses of DTaP, 4 doses if the fourth dose was administered on or after the fourth birthday, or an unknown immunization history. Further, a dose of Tdap is recommended as the first of a 3-dose vaccine regimen containing tetanus and diphtheria toxoids for children 7 to 10 years who were never vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccination status.[53026]

    Children 7 to 9 years†

    Safety and efficacy have not been established.[31250] A single dose of Tdap is recommended for children 7 to 10 years old who do not have a contraindication for pertussis vaccine and who are not fully vaccinated against pertussis, which is defined as 5 doses of DTaP, 4 doses if the fourth dose was administered on or after the fourth birthday, or an unknown immunization history. Further, a dose of Tdap is recommended as the first of a 3-dose vaccine regimen containing tetanus and diphtheria toxoids for children 7 to 10 years who were never vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccination status.[53026]

    Intramuscular dosage (Adacel, Tdap)
    Adults

    0.5 mL IM.[31290] Use Td or Tdap for subsequent booster immunizations.[64951] A dose of Tdap is recommended instead of Td to replace 1 of the 10-year Td boosters if Tdap has not been previously received or if vaccine status is unknown. Administration of Tdap as soon as feasible is advised for all pregnant women (preferably during the early part of gestational weeks 27 through 36), for all postpartum women not vaccinated during pregnancy, close contacts of infants 12 months and younger, and health care personnel with direct patient contact. Tdap can be administered regardless of the interval since the most recent tetanus or diphtheria-containing vaccine.[46272] [53026] [64951] 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.[31290]

    Children and Adolescents 11 to 17 years

    0.5 mL IM.[31290] Give 1 dose of Tdap to patients 11 to 12 years of age; Td or Tdap booster doses are then needed every 10 years thereafter. Patients 13 to 17 years of age who have not received Tdap should receive a dose. Give 1 dose of Tdap to pregnant adolescents during each pregnancy (preferably during the early part of gestational weeks 27 through 36). Tdap can be administered regardless of the interval since the most recent tetanus or diphtheria-containing vaccine.[53026] [64951] If a serious Arthus-type hypersensitivity reaction occurred after tetanus toxoid receipt, at least 10 years should elapse before Tdap administration.[31290]

    Children 10 years

    0.5 mL IM.[31290] A single dose of Tdap is recommended for children 7 to 10 years old who do not have a contraindication for pertussis vaccine and who are not fully vaccinated against pertussis, which is defined as 5 doses of DTaP, 4 doses if the fourth dose was administered on or after the fourth birthday, or an unknown immunization history. Further, a dose of Tdap is recommended as the first of a 3-dose vaccine regimen containing tetanus and diphtheria toxoids for children 7 to 10 years who were never vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccination status.[53026]

    Children 7 to 9 years†

    Safety and efficacy have not been established.[31290] A single dose of Tdap is recommended for children 7 to 10 years old who do not have a contraindication for pertussis vaccine and who are not fully vaccinated against pertussis, which is defined as 5 doses of DTaP, 4 doses if the fourth dose was administered on or after the fourth birthday, or an unknown immunization history. Further, a dose of Tdap is recommended as the first of a 3-dose vaccine regimen containing tetanus and diphtheria toxoids for children 7 to 10 years who were never vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccination status.[53026]

    Intramuscular dosage (whole-cell pertussis DTP, DTwP, Tri-Immunol)
    Infants and Children 2 months to 6 years

    NOTE: This product is not commercially available in the U.S. 0.5 mL IM at intervals of 4 to 8 weeks for 3 doses beginning at 2 months of age. A fourth dose is recommended 6 to 12 months after the third dose, and a fifth dose is recommended at 4 to 6 years of age prior to the child entering school. A fifth dose is not necessary if the fourth dose was given at age 4 years or older. The vaccine may be used up to the seventh birthday.

    MAXIMUM DOSAGE

    Adults

    0.5 mL/dose IM for Tdap (Boostrix or Adacel). Do not use DTaP (Daptacel or Infanrix); safety and efficacy have not been established in this age group.

    Geriatric

    0.5 mL/dose IM for Boostrix; safety and efficacy have not been established for Adacel. Do not use DTaP (Daptacel or Infanrix); safety and efficacy have not been established in this age group.

    Adolescents

    0.5 mL/dose IM for Tdap (Boostrix or Adacel). Do not use DTaP (Daptacel or Infanrix); safety and efficacy have not been established in this age group.

    Children

    10 to 12 years: 0.5 mL/dose IM for Tdap (Boostrix or Adacel). Do not use DTaP (Daptacel or Infanrix); safety and efficacy have not been established in this age group.
    7 to 9 years: 0.5 mL/dose IM for Tdap (Boostrix or Adacel) may be used; however, Tdap and DTaP vaccines are not FDA-approved in this age group.
    1 to 6 years: 0.5 mL/dose IM for DTaP (Infanrix or Daptacel). Do not use Tdap (Boostrix or Adacel); safety and efficacy have not been established in this age group.

    Infants

    6 weeks and older: 0.5 mL/dose IM for DTaP (Daptacel or Infanrix). Do not use Tdap (Boostrix or Adacel); safety and efficacy have not been established in this age group.
    younger than 6 weeks: Use not recommended.

    Neonates

    Use not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

     
    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. The action is 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.
    If a prior DTP dose has been given, question the parent, guardian, or patient about any symptoms or signs of an adverse reaction after the previous dose. Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1-800-822-7967. Also, report an adverse event to the manufacturer of the specific agent administered. Depending on the adverse reaction, a subsequent dose may be contraindicated.
    The health care professional should have immediate availability of epinephrine 1 mg/mL injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction.

    Injectable Administration

    DTaP and Tdap are administered intramuscularly; do not give intravenously or subcutaneously.
    Do not administer fractional doses (i.e., doses < 0.5 mL).
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    Preparation:
    Shake vial vigorously just before withdrawing dose (use aseptic technique) to ensure a uniform, cloudy suspension. If the vaccine cannot be resuspended, discard it.
    Do not mix Daptacel, Tri-Immunol, Boostrix, Adacel, or Infanrix with any other vaccine.[30295] [31250] [31290] [44533]
    When Daptacel and Menactra are to be given together for children 4 through 6 years, the two vaccines should be administered concomitantly or Menactra should be administered before Daptacel. Clinical trials found a reduced meningococcal antibody response when Menactra was administered one month after Daptacel.[30295]
    Storage of unopened vials:
    Manufacturer recommendations: Store refrigerated at 2 to 8 degrees C (36 to 46 degrees F); do not freeze.[30295] [31250] [31290] [44533]
    Off-label storage information (Infanrix only): According to a 2007 published article, storage of Infanrix (GlaxoSmithKline) at room temperature for up to 72 hours is acceptable.[58514] NOTE: Because changes in vaccine formulation may affect stability and effectiveness, confirmation of acceptable duration of storage at room temperature directly from the manufacturer for the specific vaccine being administered is recommended.
     
    Intramuscular injection:
    Use a separate syringe and needle for each person receiving DTaP or Tdap.
    Clean skin over the injection site with a suitable cleansing agent before administration.
    The preferred injection sites are the anterolateral aspect of the thigh (particularly for infants) and 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.

    STORAGE

    Adacel:
    - Do not freeze
    - Store between 35 to 46 degrees F
    Boostrix:
    - Discard if product has been frozen
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    Daptacel:
    - Protect from freezing
    - Store between 36 to 46 degrees F
    Infanrix:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    Tripedia:
    - Protect from freezing
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Children, infants, neonates, premature neonates

    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 the diphtheria/tetanus toxoids; pertussis vaccines (DTP) to infants born prematurely. The DTaP vaccines (Infanrix and Daptacel) are not recommended in adults or children >= 7 years of age, and safety and efficacy in neonates or infants < 6 weeks of age have not been established. Safety and efficacy of the Tdap vaccines (Boostrix and Adacel) have not been established in pediatric patients < 10 years of age; however, the ACIP and AAP recommend a single dose of Tdap for children 7—10 years old who do not have a contraindication to pertussis vaccine and who are not fully vaccinated against pertussis (defined as 5 doses of DTaP, 4 doses if the fourth dose was administered on or after the fourth birthday) or have an unknown immunization history. Further, a dose of Tdap is recommended as the first of a 3-dose vaccine regimen containing tetanus and diphtheria toxoids for children 7 through 10 years who were never vaccinated against tetanus, diphtheria, or pertussis or who have unknown vaccination status.

    Intraarterial administration, intravenous administration, subcutaneous administration

    Do not give DTP or Tdap vaccines via intravenous administration or subcutaneous administration. The vaccines are for intramuscular (IM) use only. Take care to avoid injecting into a blood vessel (avoid intraarterial administration). Prior to administration, health care personnel should inform the patient, parent, guardian, or responsible adult of the vaccine's benefits and risks. This should include the provision of the vaccine information statement from the manufacturer. The responsible adult should report any adverse reaction following vaccine administration to the health care provider. The U.S. Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. This includes, but is not limited to, the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 800—822—7967.

    Guillain-Barre syndrome

    Careful consideration of the potential risks and benefits of diphtheria/tetanus toxoids; pertussis vaccine, DTP 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 both brachial neuritis and Guillain-Barre syndrome.[30295] [31250] [31290]

    Latex hypersensitivity

    Diphtheria/tetanus toxoids; pertussis vaccine, DTP 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. DTP vaccines should also be used with caution in patients with latex hypersensitivity; some products contain latex. Dry natural latex rubber is contained in the tip caps on the prefilled syringes of Infanrix and Boostrix. With any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. Epinephrine 1 mg/mL 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 after the last dose of a tetanus toxoid containing vaccine.

    Coma, encephalopathy, neurological disease, seizure disorder, seizures

    Diphtheria/tetanus toxoids; pertussis vaccine, DTP is contraindicated in patients who have experienced encephalopathy (coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous dose of a pertussis-containing vaccine that is not attributable to another cause. The DTaP vaccine is also contraindicated in patients with a progressive neurological disease including infantile spasms, an uncontrolled seizure disorder, or progressive encephalopathy; do not administer the pertussis vaccine to patients with these conditions until a treatment regimen has been established and the condition has stabilized. Tdap vaccines should be used with caution in patients progressive or unstable neurologic conditions, which may also include uncontrolled seizure disorders and acute encephalopathic conditions, as well as cerebrovascular events (i.e., stroke); vaccination may be deferred until the condition stabilizes. The Advisory Committee on Immunization Practices (ACIP) recognizes that immunization with a vaccine containing DTaP in infants or children with stable neurological disease, including well-controlled seizures, may not be contraindicated. For children at higher risk of seizures than the general population, the ACIP recommends that acetaminophen or ibuprofen be administered at the time of vaccination and for 24 hours after to reduce the possibility of postvaccination pyrexia.

    Fever, shock

    Certain events were previously regarded as contraindications to continuation of DTP immunization but are now considered precautions to subsequent DTP doses according to 1996 recommendations of the ACIP. This is due to the recognition that there may be circumstances when pertussis vaccination benefits outweigh possible risks, and these events have not been proven to cause permanent sequelae. If any of the following events occur in temporal relation to DTP, the decision to give subsequent doses of vaccine containing the pertussis component should be carefully considered: hypotonia (shock like state with hyporesponsiveness) within 48 hours, seizure within 3 days, inconsolable crying for >= 3 hours occurring within 48 hours, or fever of >= 40.5 degrees C (105 degrees F) not attributable to other causes and occurring within 48 hours of immunization. If a decision is made to withhold the pertussis vaccine, booster immunization of patients 10—18 years of age should be made with the Td vaccine instead of Tdap.

    Anticoagulant therapy, bleeding, coagulopathy, hemophilia, thrombocytopenia, vitamin K deficiency

    Any condition that contraindicates the use of intramuscular (IM) injections contraindicates the use of DTP or Tdap. These conditions include thrombocytopenia, coagulopathy, or other bleeding disorders. The manufacturer states that DTP or Tdap may be used in such individuals if the potential benefits clearly outweigh the risks of administration. Patients with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia) or receiving anticoagulant therapy should be monitored closely when given DTP or Tdap because bleeding can occur at the IM injection site. All steps to avoid hematoma formation are recommended.

    Infection

    DTP immunization should be postponed in patients with moderate or severe febrile illness, a severe respiratory infection, or acute infection. DTP immunization should also be deferred in areas experiencing an outbreak of poliomyelitis because of the risk of provoking paralysis. Minor illness, such as a mild upper respiratory infection with or without low grade fever, does not preclude DTP administration.

    Human immunodeficiency virus (HIV) infection, immunosuppression

    Patients suffering significant immunosuppression may not have an adequate antibody response to vaccination with DTP toxoids and vaccines. The vaccine should be administered before or 1 month after completing immunosuppressive therapy, if possible. According to the guidelines for prevention and treatment of opportunistic infections, patients with human immunodeficiency virus (HIV) infection should receive the Tdap immunization.

    Pregnancy

    Safety of administering Tdap to pregnant women was not evaluated in pre-licensure trials; however, data from manufacturer pregnancy registries and small studies have found no increase in unusual adverse reactions when Tdap is administered to pregnant women. An assessment of U.S. pregnancy registry data from 2005 to 2018 included 1,388 reports of Tdap administration within 28 days prior to conception or during pregnancy. After exclusions, there were 45 pregnancies with exposure within 28 days prior to conceptions through the second trimester with known outcomes. These outcomes included 3 cases of miscarriage with first trimester exposure and no major birth defects. An assessment of spontaneous and postmarketing data through August 2018 included 595 reports of exposure to non-U.S. formulations of Tdap or Tdap-IPV within 28 days prior to conception or during pregnancy. Of the 83 known pregnancy outcomes with exposure during the 28 days prior to conception through the second trimester, there was 1 infant was born with a major birth defect, 1 stillbirth, and 4 miscarriages (all in women exposed in the first trimester).[31250] Available data suggest infants of mothers who receive a Tdap vaccination may receive early protection against pertussis from Tdap-induced transplacental maternal antibodies. The half-life of transferred maternal pertussis antibodies is approximately 6 weeks; however, the effectiveness of maternal anti-pertussis antibodies in preventing infant pertussis is unknown. Based on this data, the Center for Disease Control's Advisory Committee on Immunization Practices (ACIP) recommends administering Tdap during pregnancy, preferably between 27 and 36 weeks gestation, to all pregnant woman regardless of the patient's prior Tdap vaccination history. If vaccination during pregnancy is not achieved, health care providers are advised to administer Tdap immediately postpartum. Patients may receive Tdap regardless of the interval since the most recent tetanus and reduced diphtheria toxoids (Td) vaccine. Pregnant women who have never been vaccinated against tetanus should receive a 3-dose Td vaccination series at 0, 4 weeks, and 6 to 12 months; Tdap should replace 1 of the 3 Td doses, preferably between 27 and 36 weeks gestation. Additionally, the ACIP recommends administering Tdap to pregnant women requiring a tetanus booster as part of standard wound care. The ACIP also recommends a 1-time Tdap vaccination for close contacts of infants younger than 12 months of age (e.g., parents, siblings, grandparents, childcare providers, and health care providers). The risk of vaccination to a human fetus or to reproductive capacity is not fully known. Health care providers should weigh the theoretical risks and benefits before choosing to administer Tdap vaccine to a pregnant woman. If a woman who is pregnant receives Boostrix or Adacel, registration of the patient in the manufacturer's pregnancy registry is recommended. Health care providers are encouraged to call 1-888-452-9622 for Boostrix and 1-800-822-2463 for Adacel.[31250] [31290] [33545] [33936] [33545] [45958] [46272] [52189] [53242]

    Breast-feeding

    There is no information on the excretion of DTP antigens or antibodies in breast milk or the effects on the breastfed infant or milk production.[31290] According to the Advisory Committee on Immunization Practices, inactivated, recombinant, subunit, polysaccharide, conjugate vaccines and toxoids, such as DTaP and Tdap, pose no risk for nursing mothers or their infants. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens.[43236] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[31290]

    Syncope

    Syncope has been associated with the administration of diphtheria/tetanus toxoids; pertussis vaccine, DTP. These events may be accompanied by transient visual disturbance, paresthesia, and tonic-clonic limb movements. Prior to administration of the vaccine, ensure procedures are in place to prevent falls and restore cerebral perfusion.[30295] [31250] [31290]

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    seizures / Delayed / Incidence not known
    Guillain-Barre syndrome / Delayed / Incidence not known
    myelitis / Delayed / Incidence not known
    apnea / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    cyanosis / Early / Incidence not known
    myocarditis / Delayed / Incidence not known

    Moderate

    erythema / Early / 6.0-50.0
    myasthenia / Delayed / 22.0-30.0
    lymphadenopathy / Delayed / 7.0-7.0
    hypotension / Rapid / Incidence not known
    dyspnea / Early / Incidence not known
    edema / Delayed / Incidence not known
    hypotonia / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    neuritis / Delayed / Incidence not known
    hypoxia / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    Arthus reaction / Early / Incidence not known
    meningitis / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 4.0-88.0
    irritability / Delayed / 23.0-76.0
    myalgia / Early / 58.0-61.0
    drowsiness / Early / 18.0-54.0
    headache / Early / 12.0-53.0
    lethargy / Early / 13.0-51.0
    malaise / Early / 33.0-38.0
    fatigue / Early / 12.0-37.0
    fever / Early / 1.0-30.0
    anorexia / Delayed / 8.0-28.0
    arthralgia / Delayed / 9.0-18.0
    chills / Rapid / 8.0-15.0
    inconsolable crying / Delayed / 2.0-14.0
    nausea / Early / 9.0-13.0
    diarrhea / Early / 10.0-10.0
    vomiting / Early / 3.0-7.0
    rash / Early / 2.0-3.0
    infection / Delayed / 0-2.0
    maculopapular rash / Early / Incidence not known
    purpura / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    cough / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    syncope / Early / Incidence not known
    back pain / Delayed / Incidence not known
    weakness / Early / Incidence not known
    otalgia / Early / Incidence not known

    DRUG INTERACTIONS

    Ocrelizumab: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Ofatumumab: (Major) Administer all needed non-live vaccines according to immunization guidelines at least 2 weeks before initiation of ofatumumab. Ofatumumab may interfere with the effectiveness of inactivated vaccines due to its actions, which cause B-cell depletion.
    Satralizumab: (Major) Administer all non-live vaccines according to immunization guidelines at least 2 weeks before initiation of satralizumab.
    Siponimod: (Moderate) Administer all non-live vaccines at least 4 weeks before siponimod initiation, whenever possible. Vaccines may be less effective if given during siponimod treatment and for 1 month after discontinuation of siponimod treatment.

    PREGNANCY AND LACTATION

    Pregnancy

    Safety of administering Tdap to pregnant women was not evaluated in pre-licensure trials; however, data from manufacturer pregnancy registries and small studies have found no increase in unusual adverse reactions when Tdap is administered to pregnant women. An assessment of U.S. pregnancy registry data from 2005 to 2018 included 1,388 reports of Tdap administration within 28 days prior to conception or during pregnancy. After exclusions, there were 45 pregnancies with exposure within 28 days prior to conceptions through the second trimester with known outcomes. These outcomes included 3 cases of miscarriage with first trimester exposure and no major birth defects. An assessment of spontaneous and postmarketing data through August 2018 included 595 reports of exposure to non-U.S. formulations of Tdap or Tdap-IPV within 28 days prior to conception or during pregnancy. Of the 83 known pregnancy outcomes with exposure during the 28 days prior to conception through the second trimester, there was 1 infant was born with a major birth defect, 1 stillbirth, and 4 miscarriages (all in women exposed in the first trimester).[31250] Available data suggest infants of mothers who receive a Tdap vaccination may receive early protection against pertussis from Tdap-induced transplacental maternal antibodies. The half-life of transferred maternal pertussis antibodies is approximately 6 weeks; however, the effectiveness of maternal anti-pertussis antibodies in preventing infant pertussis is unknown. Based on this data, the Center for Disease Control's Advisory Committee on Immunization Practices (ACIP) recommends administering Tdap during pregnancy, preferably between 27 and 36 weeks gestation, to all pregnant woman regardless of the patient's prior Tdap vaccination history. If vaccination during pregnancy is not achieved, health care providers are advised to administer Tdap immediately postpartum. Patients may receive Tdap regardless of the interval since the most recent tetanus and reduced diphtheria toxoids (Td) vaccine. Pregnant women who have never been vaccinated against tetanus should receive a 3-dose Td vaccination series at 0, 4 weeks, and 6 to 12 months; Tdap should replace 1 of the 3 Td doses, preferably between 27 and 36 weeks gestation. Additionally, the ACIP recommends administering Tdap to pregnant women requiring a tetanus booster as part of standard wound care. The ACIP also recommends a 1-time Tdap vaccination for close contacts of infants younger than 12 months of age (e.g., parents, siblings, grandparents, childcare providers, and health care providers). The risk of vaccination to a human fetus or to reproductive capacity is not fully known. Health care providers should weigh the theoretical risks and benefits before choosing to administer Tdap vaccine to a pregnant woman. If a woman who is pregnant receives Boostrix or Adacel, registration of the patient in the manufacturer's pregnancy registry is recommended. Health care providers are encouraged to call 1-888-452-9622 for Boostrix and 1-800-822-2463 for Adacel.[31250] [31290] [33545] [33936] [33545] [45958] [46272] [52189] [53242]

    There is no information on the excretion of DTP antigens or antibodies in breast milk or the effects on the breastfed infant or milk production.[31290] According to the Advisory Committee on Immunization Practices, inactivated, recombinant, subunit, polysaccharide, conjugate vaccines and toxoids, such as DTaP and Tdap, pose no risk for nursing mothers or their infants. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens.[43236] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[31290]

    MECHANISM OF ACTION

    The pathologic sequelae of Corynebacterium diphtheriae infections are mediated by diphtheria exotoxin, an extracellular protein metabolite of toxogenic strains of C. diphtheriae. Diphtheria toxoid induces the production of antibodies against the exotoxin, which inactivate it, presumably by standard antibody-antigen interactions. Infection with C. diphtheriae does not necessarily confer immunity, and previously infected individuals should still receive toxoid.
     
    Tetanus, the neuromuscular dysfunction associated with C. tetani infections, is caused by exotoxin elaboration. The tetanus toxoid contains antigens that induce the production of antibodies against the exotoxin, thereby inactivating it. Natural immunity to C. tetani does not occur in the U.S., and even patients previously infected with C. tetani should receive the tetanus toxoid.
     
    Bordetella pertussis has a variety of cellular components that contribute to the pathogenesis of whooping cough by mechanisms that are poorly understood. The various acellular vaccines contains different pertussis antigens (e.g., agglutinogen, filamentous hemaggutinin, pertactin, and pertussis toxin) derived from B. pertussis, which confer immunity by inducing the production of antibodies against these cellular components. Clinical studies suggest it has an efficacy of 79—93% in protecting against clinical pertussis after household exposure. In addition, pertussis occurring in vaccinees is typically less severe than pertussis in unimmunized patients.

    PHARMACOKINETICS

    DTP vaccines are administered intramuscularly. After 3 doses of DTP, 70% to 90% of recipients develop protective antibodies against B. pertussis. In patients receiving 4 doses of DTP, immunity has been shown to persist for 10 years or more. In those receiving 4 doses of DTP, immunity starts to decline 4 to 6 years after immunization, and fewer than 50% of recipients have protective antibodies against B. pertussis 10 years after immunization. Lifelong immunity occurs, however, most likely from subsequent B. pertussis infections.
     
    The immunogenicity of Boostrix was compared with Adacel when administered as a single-dose booster to 2,284 adults, ages 19 to 64 years, who had not received a tetanus-diphtheria booster within 5 years. One month after a single dose, the anti-tetanus seroprotective rate (0.1 International Units/mL or more) of Boostrix was non-inferior to the seroprotective rate of Adacel (99.6% vs.100% respectively). Similarly, the anti-diphtheria seroprotective rate of Boostrix was also non-inferior to that of Adacel (98.2% vs. 98.6%). In addition, the pertussis antigen response was evaluated for Boostrix. The anti-pertussis exotoxin, anti-filamentous hemagglutinin antigen, and anti-pertactin antibody concentrations in adults 1 month after a single dose of Boostrix were non-inferior to those of infants after a primary vaccination series with Infanrix.[31250]