Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed.
Each single dose (0.5 mL) contains: Active Ingredients: Tetanus Toxoid 5 Lf, Diphtheria Toxoid 2 Lf, Acellular Pertussis: Pertussis Toxoid (PT) 2.5 μg, Filamentous Haemagglutinin (FHA) 5 μg, Pertactin (PRN) 3 μg, Fimbriae Types 2 and 3 (FIM) 5 μg.
ADACEL, [Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed], is a sterile, uniform, cloudy, white suspension of tetanus and diphtheria toxoids adsorbed separately on aluminum phosphate, combined with acellular pertussis vaccine and suspended in water for injection. The acellular pertussis vaccine is composed of 5 purified pertussis antigens (PT, FHA, PRN and FIM).
Excipients/Inactive Ingredients: Aluminum Phosphate (adjuvant) 1.5 mg, 2-phenoxyethanol 0.6% v/v.
Manufacturing Process Residuals: Formaldehyde and glutaraldehyde are present in trace amounts.
Pharmacology: Tetanus and Diphtheria: Tetanus is an acute and often fatal disease caused by an extremely potent neurotoxin produced by C. tetani. The toxin causes neuromuscular dysfunction, with rigidity and spasms of skeletal muscles. Protection against disease attributable to C. tetani is due to the development of neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assay, is considered the minimum protective level. A tetanus antitoxin level of at least 0.1 IU/mL as measured by the ELISA used in clinical studies of ADACEL is considered as protective for tetanus. Levels of 1.0 IU/mL have been associated with long-term protection.
Strains of C. diphtheriae that produce diphtheria toxin can cause severe or fatal illness characterized by membranous inflammation of the upper respiratory tract and toxin-induced damage to the myocardium and nervous system. Protection against disease attributable to C. diphtheriae 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. Antitoxin levels of at least 0.1 IU/mL are generally regarded as protective. Levels of 1.0 IU/mL have been associated with long-term protection.
Pertussis: Pertussis (whooping cough) is a respiratory disease caused by B. pertussis. This Gram-negative coccobacillus produces a variety of biologically active components, though their role in either the pathogenesis of, or immunity to, pertussis has not been clearly defined. The mechanism of protection from B. pertussis disease is not well understood. However, in a clinical trial in Sweden (Sweden I Efficacy Trial), the same pertussis components as in ADACEL (i.e., PT, FHA, PRN and FIM) have been shown to prevent pertussis in infants with a protective efficacy of 85.2% using the World Health Organization (WHO) case definition (≥ 21 consecutive days of paroxysmal cough with culture or serologic confirmation or epidemiological link to a confirmed case). In the same study, the protective efficacy against mild disease was 77.9 %. A household contact study that was nested in this efficacy trial demonstrated that there were statistically significant correlations between clinical protection and the presence of antibodies against PT, PRN and FIM in pre-exposure sera.
Minimum serum antibody levels to specific pertussis vaccine components that confer protection against the development of clinical pertussis have not been identified. Nevertheless, a number of studies have demonstrated a correlation between the presence of serum antibody responses to pertussis vaccine components and protection against clinical disease. In ADACEL clinical trials, in children, adolescents and adults <65 years of age, post vaccination Geometric Mean Concentrations (GMCs) for all pertussis antibodies were consistently above those of TRIPACEL in the SWEDEN I Efficacy Trial. Older adults (≥65 years of age) vaccinated with a single dose of ADACEL achieved lower GMCs for some of the pertussis antibodies than did infants who had received 3 or 4 doses of TRIPACEL. Nevertheless, their post-immunization anti-pertussis antibody levels were 4.4- to 15.1-fold higher than pre-immunization levels, suggested an improved degree of protection against pertussis.
Duration of Effect: Long-term follow up of serum antibody levels in adolescents and adults who received a single dose of ADACEL show that protective levels for tetanus antitoxin (≥0.01 EU/mL) and diphtheria antitoxin (≥0.01 IU/mL) persist in 99.2 % and 92.6 % of participants, respectively, 10 years post-vaccination. While protective levels against pertussis have not yet been clearly defined, pertussis antibody levels remain 2 to 9 fold higher than pre-immunization levels after 5 years. However at 10 years post-vaccination pertussis antibody levels were observed to decline towards pre-vaccination levels.
Tetanus and diphtheria toxoid boosters are recommended every 10 years. The serology follow-up and redosing data for ADACEL suggests that it can be used instead of tetanus and diphtheria toxoid vaccine for boosting at 10-years intervals in adults.
ADACEL is indicated for active booster immunization for the prevention of tetanus, diphtheria and pertussis (whooping cough) in persons 4 years of age and older.
In accordance with local recommendations, ADACEL may be considered as an alternative for the fifth dose of tetanus, diphtheria and acellular pertussis vaccine (DTaP) in children 4 through 6 years of age, concomitantly administered with Inactivated Poliomyelitis Vaccine (IPV) at separate sites to complete the vaccination series for this age, when indicated.
Persons who have had tetanus, diphtheria or pertussis should still be immunized since these clinical infections do not always confer immunity. Human Immunodeficiency Virus (HIV)-infected persons, both asymptomatic and symptomatic, should be immunized against tetanus, diphtheria and pertussis according to standard schedules.
ADACEL is not to be used for the treatment of disease caused by Bordetella pertussis, Corynebacterium diphtheriae or Clostridium tetani infections.
Pediatrics: ADACEL is not indicated for immunization of children below the age of 4 years.
Tetanus Prophylaxis in Wound Management: The need for active immunization with a tetanus toxoid-containing preparation such as Td Adsorbed vaccine or ADACEL, with or without passive immunization with Tetanus Immune Globulin, depends on both the condition of the wound and the patient's vaccination history. (See Dosage & Administration.)
The immunization schedule with ADACEL should follow local recommendations. ADACEL (0.5 ml) should be administered as a booster dose by the intramuscular route.
Re-dosing with ADACEL can be used to boost immunity to diphtheria, tetanus and pertussis at 5- to 10-year intervals in adolescents and adults.
The preferred site is into the deltoid muscle.
Fractional doses (doses <0.5 mL) should not be given. The effect of fractional doses on the safety and efficacy has not been determined.
The use of ADACEL in management of tetanus-prone wounds should follow local recommendations. (See Table 1.)
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Inspect for extraneous particulate matter and/or discolouration before use. (See Description.) If these conditions exist, the product should not be administered.
Shake the vial well until a uniform, cloudy, suspension results. Cleanse the vial stopper with a suitable germicide prior to withdrawing the dose. Do not remove either the stopper or the metal seal holding it in place. Aseptic technique must be used. Use a separate sterile needle and syringe, or a sterile disposable unit for each individual recipient, to prevent disease transmission. Needles should not be recapped but should be disposed of according to biohazard waste guidelines. (See Precautions.)
Before injection, the skin over the site to be injected should be cleansed with a suitable germicide. Administer the total volume of 0.5 mL intramuscularly (IM). The preferred site of injection is the deltoid muscle.
Hypersensitivity: Known systemic hypersensitivity reaction to any component of ADACEL or a life-threatening reaction after previous administration of the vaccine or a vaccine containing one or more of the same components are contraindications to vaccination. (See Description.) Because of uncertainty as to which component of the vaccine may be responsible, none of the components should be administered. Alternatively, such persons may be referred to an allergist for evaluation if further immunizations are considered.
Acute Neurological Disorders: Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine not attributable to another identifiable cause is a contraindication to vaccination with any pertussis-containing vaccine, including ADACEL.
General: Before administration of ADACEL, health-care providers should inform the recipient or the parent or guardian of the recipient of the benefits and risks of immunization, inquire about the recent health status of the recipient, review the recipient's history concerning possible hypersensitivity to the vaccine or similar vaccine, previous immunization history, the presence of any contraindications to immunization and comply with any local requirements regarding information to be provided to the recipient/guardian before immunization.
It is extremely important that the recipient, parent or guardian be questioned concerning any signs or symptoms of an adverse reaction after a previous dose of vaccine. (See Contraindications and Adverse Reactions.)
The rates and severity of adverse events in recipients of tetanus toxoid are influenced by the number of prior doses and level of pre-existing antitoxins.
As with any vaccine, ADACEL may not protect 100% of vaccinated persons.
Administration Route Related Precautions: Do not administer ADACEL by intravascular injection: ensure that the needle does not penetrate a blood vessel.
Intradermal or subcutaneous routes of administration are not to be utilized.
ADACEL should not be administered into the buttocks.
Febrile and Acute Disease: Vaccination should be postponed in cases of an acute or febrile disease. However, a disease with low-grade fever should not usually be a reason to postpone vaccination.
Hematologic: Because any intramuscular injection can cause an injection site hematoma in persons with any bleeding disorders, such as hemophilia or thrombocytopenia, or in persons on anticoagulant therapy, intramuscular injections with ADACEL should not be administered to such persons unless the potential benefits outweigh the risk of administration. If the decision is made to administer any product by intramuscular injection to such persons, it should be given with caution, with steps taken to avoid the risk of hematoma formation following injection.
Immune: The possibility of allergic reactions in persons sensitive to components of the vaccine should be evaluated. Hypersensitivity reactions may occur following the use of ADACEL even in persons with no prior history of hypersensitivity to the product components.
As with all other products, epinephrine hydrochloride solution (1:1,000) and other appropriate agents should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs. Health-care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management.
Immunocompromised persons (whether from disease or treatment) may not achieve the expected immune response. If possible, consideration should be given to delaying vaccination until after the completion of any immunosuppressive treatment. Nevertheless, vaccination of persons with chronic immunodeficiency such as HIV infection is recommended even if the immune response might be limited.
Neurologic: ADACEL should not be administered to individuals with progressive or unstable neurological disorders, uncontrolled epilepsy or progressive encephalopathy until a treatment regimen has been established, the condition has stabilized and the benefit clearly outweighs the risk.
A review by the US Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barre syndrome (GBS). If GBS occured within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give ADACEL or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.
A few cases of demyelinating diseases of the central nervous system, peripheral mononeuropathies and cranial mononeuropathies have been reported following vaccines containing tetanus and/or diphtheria toxoids, although the IOM concluded that the evidence is inadequate to accept or reject a causal relation between these conditions and vaccination.
Use in Pregnancy: The effect of ADACEL on the development of the embryo and fetus has not been assessed. Vaccination in pregnancy is not recommended unless there is a definite risk of acquiring pertussis. As the vaccine is inactivated, risk to the embryo or the fetus is improbable. The benefits versus the risks of administering ADACEL during pregnancy should be carefully evaluated when there is a high probable risk of exposure to a household contact or during an outbreak in the community.
Use in Lactation: The effect of administration of ADACEL during lactation has not been assessed. As ADACEL is inactivated, any risk to the mother or the infant is improbable. However, the effect on breast-fed infants of the administration of ADACEL to their mothers has not been studied. The risks and benefits of vaccination should be assessed before making the decision to immunize a nursing woman.
Pregnant Women: The effect of ADACEL on the development of the embryo and fetus has not been assessed. Vaccination in pregnancy is not recommended unless there is a definite risk of acquiring pertussis. As the vaccine is inactivated, risk to the embryo or the fetus is improbable. The benefits versus the risks of administering ADACEL during pregnancy should be carefully evaluated when there is a high probable risk of exposure to a household contact or during an outbreak in the community.
Nursing Women: The effect of administration of ADACEL during lactation has not been assessed. As ADACEL is inactivated, any risk to the mother or the infant is improbable. However, the effect on breast-fed infants of the administration of ADACEL to their mothers has not been studied. The risks and benefits of vaccination should be assessed before making the decision to immunize a nursing woman.
Clinical Trial Adverse Reactions:
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. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events.
The safety of ADACEL was evaluated in a total of 5,818 participants who received a single dose of ADACEL in 6 clinical trials (298 children ≥4 years of age, 1,508 adolescents, 2,842 adults <65 years of age and 1,170 adults ≥65 years of age).
Pain at the injection site was the most common solicited injection site reaction. Most injection site reactions occurred within 3 days following vaccination and their mean duration was less than 3 days. The most frequent systemic reaction was tiredness in children and headache in adolescents and adults (18-64 years). Myalgia was the most frequently reported systemic reaction among older adults ≥ 65 years of age. Fever was reported in less than 10% of vacinees. These reactions were usually transient and of mild to moderate intensity. In addition, in adolescents and adults the incidence of injection site and systemic reactions following ADACEL was comparable to those observed with a Td vaccine booster. In children the observed frequencies of injection site and fever following ADACEL were significantly lower than those observed with QUADRACEL (DTaP-IPV) when administered as a booster at 4 to 6 years of age. Except for fever, the observed rates for the systemic reactions were comparable between the two vaccines. The frequency of the solicited injection site and systemic reactions reported in two clinical trials are shown in Table 2.
Two serious adverse events were reported during Study Td506 which were considered related to the vaccination: a case of severe migraine with unilateral facial paralysis, and a diagnosis of nerve compression in the neck and left arm. Both of these conditions resolved spontaneously or with treatment. (See Table 2.)
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(See Table 3.)
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Data from Post-marketing Experience:
The following additional adverse events have been spontaneously reported during the post-marketing use of ADACEL. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Decisions to include these events in labelling were based on one or more of the following factors: 1) severity of the event, 2) frequency of reporting, or 3) strength of causal connection to ADACEL.
Immune System Disorders:
Hypersensitivity (anaphylactic) reaction (angioedema, edema, rash, hypotension).
Nervous System Disorders:
Paraesthesia, hypoesthesia, Guillain-Barre syndrome, brachial neuritis, facial palsy, convulsion, syncope, myelitis.
Skin and Subcutaneous Tissue Disorders:
Musculoskeletal and Connective Tissue Disorders:
Myositis, muscle spasm.
General Disorders and Administration Site Conditions:
Large injection site reactions (>50 mm) and extensive limb swelling from the injection site beyond one or both joints have been reported after administration of ADACEL in adolescents and adults. These reactions usually start within 24 - 72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3 - 5 days. The risk appears to be dependent on the number of prior doses of acellular pertussis containing vaccine.
Injection site bruising, sterile abscess.
Vaccine-Drug Interactions: Immunosuppressive treatments may interfere with the development of the expected immune response. (See Precautions.)
Concomitant Vaccine Administration: ADACEL may be administered concurrently with a dose of trivalent inactivated influenza vaccine and with a dose of hepatitis B vaccine in 11 to 12 year-olds.
The concomitant use of ADACEL and trivalent inactivated influenza vaccine was evaluated in a clinical trial involving 696 adults 19 to 64 years of age. The safety and immunogenicity profiles in adults that received the vaccines concomitantly were comparable to those observed when the vaccines were given on separate occasions one month apart.
The concomitant use of ADACEL and hepatitis B vaccine was evaluated in a clinical trial involving 269 adolescents 11 to 12 years of age. The safety and immunogenicity profiles in adolescents that received the vaccines concomitantly were comparable to those observed when the vaccines were given on separate occasions one month apart. No interference was observed in the immune responses to any of the vaccine antigens when ADACEL and hepatitis B vaccines were given concurrently or separately.
Vaccines administered simultaneously should be given using separate syringes at separate injection sites and preferably in separate limbs. ADACEL should not be mixed in the same syringe with other parenterals.
Store at 2° to 8°C. Do not freeze. Discard product if exposed to freezing.
J07AJ52 - pertussis, purified antigen, combinations with toxoids ; Belongs to the class of pertussis bacterial vaccines.
Vaccine (sterile, uniform, cloudy, white suspension in vial) 0.5 mL x 1's.