Label: TDVAX- tetanus and diphtheria toxoids adsorbed injection, solution

TETANUS

Tetanus (also known as lockjaw) is a serious, often fatal disease caused by an extremely potent neurotoxin produced by C. tetani.

Protection against disease is due to the development of neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level of 0.01 IU/mL measured via a neutralization assay is considered the minimum protective level. 3, 4The efficacy against tetanus of MassBiologics' TDVAX is supported by the following:

1. Response to primary series. Of 20 adults with less than 0.0025 units/mL of tetanus antitoxin in preimmunization serum, 14 (70%) had antitoxin concentrations of 0.01 or greater after 2 doses of TDVAX (2 Lf tetanus toxoid dose). After 3 doses of TDVAX, 16 of 16 adults achieved 0.01 antitoxin units/mL.
2. Response to booster doses. Booster doses of TDVAX at doses of 1 Lf and 5 Lf of tetanus toxoid induced tetanus antitoxin levels greater than 0.01 units/mL when administered to all 36 adults who had received prior tetanus immunizations. 5

DIPHTHERIA

Diphtheria is an acute toxin-mediated disease caused by toxigenic strains of C. diphtheriae. Protection against disease is due to the development of neutralizing antibodies to diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level giving some degree of protection. 3, 6The efficacy against diphtheria of MassBiologics' TDVAX is supported by the following:

1. Response to primary series. Of 10 adults with less than 0.001 units/mL of diphtheria antitoxin in preimmunization serum, 50% had antitoxin concentrations of 0.01 or greater after 2 doses of TDVAX (2 Lf diphtheria toxoid dose). After 3 doses of TDVAX, 6 of 6 adults achieved 0.01 antitoxin units/mL.
2. Response to booster doses. In clinical trials, booster doses of TDVAX formulated to contain 1 Lf and 5 Lfof diphtheria toxoid, both induced antitoxin levels greater than 0.01 units/mL when administered to adults with prior diphtheria immunity. 5, 7, 8In 140 adolescent males given a single booster dose of the 1 Lf formulation, all achieved an antitoxin titer of 0.01 units/mL or higher. 8

FREQUENCY OF ADMINISTRATION

More frequent administration of MassBiologics' TDVAX than described in DOSAGE AND ADMINISTRATIONmay be associated with an increased incidence and severity of adverse reactions.

ARTHUS REACTIONS

Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of a tetanus toxoid-containing vaccine usually have high serum tetanus antitoxin levels and should not receive MassBiologics' TDVAX more frequently than every 10 years, even for tetanus prophylaxis as part of wound management. (See DOSAGE AND ADMINISTRATION).

GUILLAIN-BARRÉ SYNDROME

A review by the Institute of Medicine found evidence for a causal relation between tetanus toxoid and Guillain-Barré Syndrome. 9If Guillain-Barré Syndrome occurred within 6 weeks after receipt of a previous dose of tetanus toxoid-containing vaccine, the decision to give subsequent doses of MassBiologics' TDVAX or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks. 10

Vaccination with MassBiologics' TDVAX may not protect all individuals.

GENERAL

Epinephrine injection (1:1000) and other appropriate agents and equipment must be immediately available should an acute anaphylactic reaction occur.

Prior to the administration of MassBiologics' TDVAX, the vaccine recipient's current health status and health history should be reviewed. This includes a review of the immunization history of the patient, the presence of any contraindications to immunization, and any adverse events after previous immunizations to allow an assessment of the benefits and risks of vaccination. (See CONTRAINDICATIONSand WARNINGS).

If MassBiologics' TDVAX is administered to immunocompromised persons (whether from disease or treatment) the expected immune response may not be obtained.

INFORMATION FOR PATIENTS

Prior to administration of MassBiologics' TDVAX, patients, parents or guardians should be informed by the health care provider of the benefits and risks of immunization with TDVAX and of the importance of completing the primary immunization series or receiving recommended booster doses.

The health care provider should inform the patient, parent, or guardian of the potential for adverse reactions that have been temporally associated with MassBiologics' TDVAX or other vaccines containing similar ingredients. Patients, parents or guardians should be instructed to report any suspected adverse reactions to their health care provider.

According to the National Childhood Vaccine Injury Act of 1986, Vaccine Information Statements must be provided by the health care provider with each vaccine dose administered. 10

DRUG INTERACTIONS

Patients who are on immunosuppressive therapy, including alkylating agents, antimetabolites, cytotoxic drugs, irradiation, or corticosteroids (used in greater than physiologic doses), may have a reduced immune response to vaccines.

No safety and immunogenicity data are available on the concomitant administration of MassBiologics' TDVAX vaccine with other U.S. licensed vaccines.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

No studies have been performed with MassBiologics' TDVAX to evaluate carcinogenicity, mutagenic potential, or impairment of fertility.

PREGNANCY

Animal reproduction studies have not been conducted with MassBiologics' TDVAX. It is also not known whether MassBiologics' TDVAX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. MassBiologics' TDVAX should be given to a pregnant woman only if clearly needed.

NURSING MOTHERS

It is not known whether MassBiologics' TDVAX is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when MassBiologics' TDVAX is administered to a nursing woman.

PEDIATRIC USE

MassBiologics' TDVAX is not approved for use in infants and children younger than 7 years of age. The safety and effectiveness of MassBiologics' TDVAX in this age group have not been established.

GERIATRIC USE

No studies have been performed with MassBiologics' TDVAX in adults aged 65 years and older in order to determine whether they respond differently than younger subjects.

DATA FROM CLINICAL TRIALS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. However, the adverse reaction information from clinical trials provides a basis for identifying adverse events that appear to be related to vaccine use and for approximating rates. Data on adverse reactions following fluid and adsorbed preparations of MassBiologics' TDVAX with various doses of the diphtheria and tetanus components have been reported in a series of studies. 5, 7, 8, 11, 12

POSTMARKETING REPORTS

The following adverse events have been identified during post-approval use of MassBiologics' TDVAX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequencies or to establish a causal relationship to vaccination. The following adverse events were included because of seriousness or frequency of reporting:

General Disorders and Administration Site Conditions:Injection site reactions, including pain, tenderness, erythema, induration, pruritis, swelling and warmth; peripheral oedema, pyrexia, malaise

Nervous System Disorders:Dizziness, headache, convulsions

Musculoskeletal and Connective Tissue Disorders:Myalgia, musculoskeletal stiffness or pain, arthralgia

Skin and Subcutaneous Tissue Disorders:Rash

Gastrointestinal Disorders:Nausea

Infections and Infestations:Cellulitis

REPORTING OF SUSPECTED ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact MassBiologics at 1-800-457-4626 or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.

PRIMARY IMMUNIZATION

MassBiologics' TDVAX may be used in persons 7 years of age and older who have not been previously immunized against tetanus and diphtheria, as a primary immunization series consisting of three 0.5 mL doses. The first two doses are administered 4-8 weeks apart and the third dose is administered 6-12 months after the second dose.

MassBiologics' TDVAX may be used to complete the primary immunization series for tetanus and diphtheria, following one or two doses of Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (wholecell DTP), Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) and/or Diphtheria and Tetanus Toxoids Adsorbed (DT) vaccine. However, the safety and efficacy of MassBiologics' TDVAX in such regimens have not been evaluated.

ROUTINE BOOSTER IMMUNIZATION

MassBiologics' TDVAX may be used for routine booster immunization against tetanus and diphtheria in persons 7 years of age and older who have completed primary immunization against tetanus and diphtheria. Routine booster immunization against tetanus and diphtheria is recommended in children 11-12 years of age and every 10 years thereafter. 10

The Advisory Committee on Immunization Practices (ACIP) has specific recommendations on booster immunization against tetanus and diphtheria for adolescents and adults. 10, 13, 14

TETANUS PROPHYLAXIS IN WOUND MANAGEMENT

For active tetanus immunization in wound management of patients 7 years of age and older, a preparation containing tetanus and diphtheria toxoids is preferred instead of single-antigen tetanus toxoid to enhance diphtheria protection. 15MassBiologics' TDVAX is approved for wound management of patients 7 years of age and older.

The need for active immunization with a tetanus toxoid-containing preparation, with or without Tetanus Immune Globulin (TIG) (Human) depends on both the condition of the wound and the patient's vaccination history ( Table 1).

When indicated, TIG (Human) should be administered using a separate needle and syringe at a different anatomic site, according to the manufacturer's package insert. If a contraindication to using a tetanus toxoid-containing vaccine exists in a person who has not completed tetanus primary immunization and other than a clean, minor wound is sustained, only passive immunization with TIG (Human) should be given. 15

DIPHTHERIA PROPHYLAXIS FOR CASE CONTACTS

MassBiologics' TDVAX may be used for post-exposure diphtheria prophylaxis in persons 7 years of age and older who have not completed primary vaccination, whose vaccination status is unknown, or who have not been vaccinated with diphtheria toxoid within the previous 5 years. Consult ACIP recommendations for additional interventions for post-exposure diphtheria prophylaxis. 15

ADMINISTRATION

Shake the vial well to resuspend the vaccine before withdrawing the dose. After shaking, MassBiologics' TDVAX is a homogenous milky white suspension. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If these conditions exist, MassBiologics' TDVAX should not be administered.

Inject 0.5 mL of MassBiologics' TDVAX intramuscularly. The preferred site is the deltoid muscle. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.

Do not administer this vaccine intravenously, subcutaneously, or intradermally.

MassBiologics' TDVAX should not be combined through reconstitution or mixed with any other vaccine.