Tri-Immunol (DPT Adsorbed) New Product 1993 - First year listed in CPS 1994, 1995, 1996, last year listed - 1997 - Lederle
Active Immunizing Agent
Pharmacology: Simultaneous immunization against diphtheria, tetanus, and pertussis during infancy and childhood is a routine practice in Canada. It has played a major role in markedly reducing the incidence of cases and deaths from each of these diseases.
Diphtheria is primarily a localized and generalized intoxication caused by diphtheria toxin, an extracellular protein metabolite of toxigenic strains of C. diphtheriae. While the incidence of diphtheria in Canada has decreased from 9000 cases reported in 1924, before the general use of diphtheria toxoid, to only 3 cases reported in 1989, the case fatality rate has remained constant at about 5 to 10%. The highest case fatality rates are in the very young and in the elderly. Following adequate immunization with diphtheria toxoid, it is thought that protection lasts for at least 10 years. Antitoxin levels of at least 0.01 antitoxin units/ml are generally regarded as protective. This significantly reduced both the risk of developing diphtheria and the severity of clinical illness. It does not, however, eliminate carriage of C. diphtheriae in the pharynx or on the skin.
Tetanus is an intoxication manifested primarily by neuro-muscular dysfunction caused by a potent exotoxin elaborated by C. tetani. The incidence of tetanus in Canada has dropped dramatically with the routine use of tetanus toxoid. Currently about 17 persons are hospitalized with tetanus each year in Canada. In 1989 there was only 1 reported case of tetanus. Spores of C. tetani are ubiquitous, and there is essentially no natural immunity to tetanus toxin. Thus, universal. primary immunization with tetanus toxoid with subsequent maintenance of adequate antitoxin levels, by means of timed boosters, is necessary to protect all age groups. Tetanus toxoid is a highly effective antigen and completed primary series generally induces serum antitoxin levels of at least 0.01 antitoxin units/ml, a level which has been reported to be protective. It is thought that protection persists for at least 10 years.
It is believed that the toxoids of tetanus and diphtheria induce neutralizing antibodies to the toxins produced by the infecting organism. In clinical studies with Lederle-produced diphtheria and tetanus toxoids, administered in combination with pertussis vaccine, serum antitoxin levels have been shown to be greater than 0.01 antitoxin units/ml in 97 to 100% of 372 infants following 3 doses. These levels are generally regarded to be protective.
Pertussis (whooping cough) is a disease of the respiratory tract caused by B. pertussis. This gram-negative coccobacillus produces a variety of active components including endotoxin and a number of other substances that have been defined primarily on the basis of their biological activity in animals. These active components have been associated with a number of effects, such as lymphocytosis, leukocytosis, sensitivity to histamine, changes in glucose and/or insulin levels, possible neurological effects and adjuvant activity. The role of each of the different components in either the pathogenesis of, or immunity to, pertussis is not well understood. However, the potency of the pertussis component is measured and shown to be acceptable in the mouse potency test. In addition, serum agglutinin titers have been correlated with protection in clinical trials. The pertussis component induces immunity against the pertussis disease in humans.
Pertussis (whooping cough) is a highly communicable disease of the respiratory tract that has an attack rate in the unimmunized household contacts of over 90%. During the last 30 years, immunization has been widely practised. The incidence and mortality from pertussis in Canada have declined remarkably. However, outbreaks of pertussis continue to occur in Canada. Over the past 5 years, there have been from just over 1 000 to more than 8 000 cases reported annually. These figures likely under-represent the true incidence of pertussis because of under-reporting. In 1989, of the 2440 reported cases, approximately half, 1179, involved children between the ages of 0 (infants) to 48 months. Precise data do not exist since bacteriological confirmation of pertussis can be obtained in less than half of the suspected cases. Most reported illness from B. pertussis occurs in infants and young children; two thirds of reported deaths occur in children less than 1 year old. Older children and adults, in whom classic signs are often absent, may go undiagnosed and serve as reservoirs of disease. Although rare, deaths and brain damage still occur from pertussis particularly in young infants who have not been immunized.
Indications: For active immunization of infants and children from 2 months through 6 years of age against diphtheria, tetanus and pertussis. Typically this is at 2, 4, 6 and 15 to 18 months of age, with a booster dose at 4 to 6 years of age. Children who have recovered from culture-confirmed pertussis need not receive further doses of a vaccine containing pertussis. However, these children should receive additional doses of Diphtheria and Tetanus Toxoids Adsorbed as appropriate to complete the series.
Tri-Immunol is intended for active immunization against diphtheria, tetanus and pertussis, and is not to be used for treatment of actual infection.
As with any vaccine, Tri-Immunol may not protect 100% of individuals receiving the vaccine.
Contraindications: Hypersensitivity to any component of the vaccine, including thimerosal, a mercury derivative, is a contraindication. Immunization should be deferred during the course of any febrile illness or acute infection. A minor afebrile illness such as a mild upper respiratory infection is not usually reason to defer immunization.
Immunization with Tri-Immunol is contraindicated if the child has experienced any event following previous immunization with a pertussis-containing vaccine which is considered by the Canadian Immunization Guide (3rd Edition), the Canadian National Advisory Committee on Immunization (NACI), as well as the American Academy of Pediatrics (AAP) or the U.S. Immunization Practices Advisory Committee (ACIP), to be a contraindication to further doses of pertussis vaccine. The ACIP states that if any of the following events occur in temporal reaction to receipt of DPT, the decision to give subsequent doses of vaccine containing the pertussis component should be carefully considered.
Contraindications and Precautions to Further DPT Vaccination: Contraindications: An immediate anaphylactic reaction. Encephalopathy occurring within 7 days following DPT vaccination. This is defined as an acute severe CNS disorder generally consisting of major alterations in consciousness, unresponsiveness, generalized or focal seizures that persist more than a few hours, with failure to recover within 24 hours.
Precautions Temperature of > 40.5°C within 48 hours not due to another identifiable cause. Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours. Persistent, inconsolable crying lasting > 3 hours, occurring within 48 hours. Convulsions with or without fever occurring within 3 days.
Although these events have been considered absolute contraindications, there may be circumstances, such as a high incidence of pertussis, in which the potential benefits outweigh the possible risks, particularly because these events are not associated with permanent sequelae.
The occurrence of any type of neurological symptoms or signs, including one or more convulsions (seizures) following administration of Tri-Immunol is generally a contraindication to further use. Any decision to administer subsequent doses of a vaccine containing diphtheria, tetanus, or pertussis antigens should be delayed until the patient's neurological status is better defined.
The presence of any evolving or changing disorder affecting the CNS is a contraindication to administration of a pertussis-containing vaccine such as Tri-Immunol regardless of whether the suspected neurological disorder is associated with occurrence of seizure activity of any type.
Studies have indicated that a personal or family history of seizures is associated with increased frequency of seizures following pertussis immunization.
The AAP a nd ACIP recognize certain circumstances in which children with stable CNS disorders, including well-controlled seizures or satisfactorily explained single seizures, may receive pertussis vaccine.
The NACI, ACIP and AAP do not consider a family history of seizures to be a contraindication to pertussis vaccine despite the increased risk of seizures in these individuals. The decision to administer a pertussis-containing vaccine to such children must be made by the physician on an individual basis, with consideration of all relevant factors, and assessment of potential risks and benefits for that individual. The physician should review the full text of Canadian Immunization Guide (3rd Edition) or ACIP and AAP guidelines prior to considering vaccination for such children. The parent or guardian should be advised of the increased risk involved.
There are no data on whether the prophylactic use of antipyretics can decrease the risk of febrile convulsions. However, data suggest that acetaminophen will reduce the incidence of postvaccination fever. The NACI, ACIP and AAP suggest administering acetaminophen at age-appropriate doses at the time of vaccination and every 4 to 6 hours to children at higher risk for seizures than the general population.
The clinical judgment of attending physician should prevail at all times.
Warnings: Tri-Immunol is not recommended for immunizing persons on or after their seventh birthday. If a contraindication to any of the components of this combination vaccine exists (see Contraindications) then Tri-Immunol should not be used. For example, if there is a contraindication against the use of a pertussis vaccine component, then Diphtheria and Tetanus Toxoids, Adsorbed, for Pediatric Use (DT) should be substituted for each of the remaining doses. DPT should be given with caution to infants or children with thrombocytopenia or any coagulation disorder that would contraindicate i.m. injection (see Drug Interactions).
Children with impaired immune responsiveness, whether due to the use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents), a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have a reduced antibody response to active immunization procedures. Deferral of administration of vaccine may be considered in individuals receiving immunosuppressive therapy. Other groups should receive this vaccine according to the usual recommended schedule.
Special care should be taken to prevent injection into a blood vessel.
Routine immunization should be deferred during an outbreak of poliomyelitis providing the patient has not sustained an injury that increases the risk of tetanus and providing an outbreak of diphtheria or pertussis does not occur simultaneously.
Precautions: General: This product should not be used in individuals on or after their seventh birthday. Prior to administration of any dose of DPT, the parent or guardian should be asked about the personal history, family history and the recent health status of the infant or child to be immunized. The health care provider should ascertain previous immunization history, current health status and occurrence of any symptoms and/or signs of an adverse event after previous immunizations in the child to be immunized in order to determine the existence of any contraindication to immunization with DPT and to allow an accurate assessment of benefits and risks.
Before the injection of any biological, the health care provider should take all precautions known for the prevention of allergic or any other side reactions. This should include: a review of the patient's history regarding possible sensitivity; the ready availability of epinephrine 1:1000 and other appropriate agents used for control of immediate allergic reactions; and a knowledge of the recent literature pertaining to use of the biological concerned, including the nature of side effects and adverse reactions that may follow its use.
Children with impaired immune responsiveness, whether due to the use of immunosuppressive therapy (including irradi- ation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents), a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have reduced antibody response to active immunization procedures. Deferral of administration of vaccine may be considered in individuals receiving immunosuppressive therapy. Other groups should receive this vaccine according to the usual recommended schedule (see Drug Interactions).
This product is not contraindicated for use in individuals with HIV.
Since this product is a suspension containing an adjuvant, shake vigorously to obtain a uniform suspension prior to withdrawing each dose from the multiple dose vial. A separate sterile syringe and needle or a sterile disposable unit should be used for each individual patient to prevent transmission of hepatitis or other infectious agents from one person to another. Needles should be disposed of properly.
Special care should be taken to prevent injection into a blood vessel.
Drug Interactions: Children receiving immunosuppressive therapy may have a reduced response to active immunization procedures.
As with other i.m. injections, Tri-lmmunol should be given with caution to children on anticoagulant therapy. Tetanus Immune Globulin or Diphtheria Antitoxin, if used, should be given in a separate site with a separate needle and syringe.
The AAP recommends that influenza virus vaccine should not be administered within 3 days of immunization with a pertussis-containing vaccine since both vaccines may cause febrile reactions in young children.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Tri-Inmunol has not been evaluated for its carcinogenic, mutagenic potential or for impairment of fertility.
Pregnancy: Animal reproductive studies have not been conducted with Tri-lmmunol.
Children: The safety and effectiveness of Tri-lmmunol in children below the age of 6 weeks have not been established.
Information for the Patient: Prior to administration of this vaccine, health care personnel should inform the parent, guardian, or other responsible adult of the recommended immunization schedule for protection against diphtheria, tetanus and pertussis and the benefits and risks to the child receiving the vaccine. Guidance should be provided on measures to be taken should adverse events occur, e.g. antipyretic measures for elevated temperatures. Parents or guardians should be instructed to report any serious adverse reactions to their health care provider.
Adverse Effects: Local reactions are common after administration of DPT, occurring in 35 to 50% of recipients and are manifested by varying degrees of erythema, induration and tenderness which may occasionally be severe. Such local reactions are usually self-limited and require no therapy. A nodule may be palpable at the injection site for a few weeks. Sterile abscess formation, or s.c. atrophy at the site of injection has been reported. Cervical lymphadenopathy has been reported following DPT injections into the arm.
Temperature elevations, fretfulness, drowsiness, vomiting, and anorexia frequently follow DPT administration. Approximately 50% of DPT recipients will develop temperature elevations >38°C after 1 or more doses of the series; approximately 6% >39°C; and approximately 0.3% > 40.5°C. Some data suggest that febrile reactions are more likely to occur in those who have experienced such responses after prior doses.
Significant reactions attributed to the pertussis vaccine component have been: high fever of 40.5°C, a transient shock-like episode, excessive screaming (persistent crying or screaming for 3 or more hours duration), an unusual high-pitched cry and convulsions. The ACIP states: "Although DPT may rarely produce symptoms that some have classified as acute encephalopathy, a causal relation between DPT vaccine and permanent brain damage has not been demonstrated. If the vaccine ever causes brain damage, the occurrence of such an event must be exceedingly rare. A similar conclusion has been reached by the Committee on Infectious Diseases of the American Academy of Pediatrics, the Child Neurology Society, the Canadian National Advisory Committee on Immunization, the British Pediatric Association, and the Institute of Medicine."
The incidence of convulsion or transient shock-like (hypotonic hyporesponsive) episode occurring within 48 hours of vaccination has been estimated to be 1 per 1750 doses.
Bulging fontanel has been reported after DPT immunization, although no cause and effect relationship has been estab- lished.
Cardiac effects and respiratory difficulties, including apnea have been reported rarely.
Neurological complications, such as convulsions, encephalopathy and various mono - and polyneuropathies including Guillain-Barre syndrome have been reported following administration of preparations containing diphtheria, tetanus and/or pertussis antigens.
Urticaria, erythema multiforme or other rash, arthralgias and more rarely, a severe anaphylactic reaction (e.g., urticaria with swelling of the mouth, difficulty breathing, hypotension or shock) have been reported following administration of preparations containing diphtheria, tetanus, and pertussis antigens.
The occurrence of sudden-infant-death syndrome (SIDS) has been reported following administration of DPT. However, a large case-control study in the U.S.A. revealed no causal relationship between receipt of DPT vaccine and SIDS. Onset of infantile spasms has occurred in infants who have recently received DPT or DT. Analysis of data from the National Childhood Encephalopathy Study in the U.S.A. on children with infantile spasms showed that receipt of DPT or DT was not causally related to infantile spasms. The incidence of onset of infantile spasms increases at 3 to 9 months of age, the time period in which the second and third doses of DPT are generally given. Therefore, some case of infantile spasms can be expected to be related by chance alone to recent receipt of DPT.
Dosage: For I.M. Use Only: The primary immunizing course for infants and children from 2 months of age through 6 years of age consists of 3 doses of 0.5 mL each at 4 to preferably 8 week intervals, followed by a fourth dose of 0.5 mL 6 to 12 months after the third dose.
A booster dose of 0.5 mL is indicated at age 4 to 6 years, preferably prior to entrance into kindergarten or elementary school. (Substitute DT when contraindication to pertussis-containing vaccine exists.) (See Contraindications and Warnings). However, if the fourth dose of the basic immunizing series was administered after the fourth birthday, a booster prior to school entry in not considered necessary. The customary age for the first dose is 2 months of age but may be given as young as 6 weeks of age and through 6 years of age.
For either primary or booster immunization against tetanus and diphtheria of individuals 7 years of age and older, the use of Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (Td) is recommended.
Preterm infants should be vaccinated with DPT according to their chronological age from birth.
The simultaneous administration of DPT, Haemophilus b Conjugate Vaccine, Oral Poliovirus Vaccine (OPV), and/or Measles-Mumps-Rubella Vaccine (MMR) has resulted in sero-conversion rates and rates of side effects similar to those observed when the vaccines are administered separately. Therefore, if there is any doubt that a vaccine recipient will return for further vaccine doses, Tri-lmmunol may be given simultaneously with other routine childhood vaccines such as Haemophilus b Conjugate Vaccine, OPV, IPV and/or MMR at separate sites.
Interruption of the recommended schedule with a delay between doses does not interfere with the final immunity achieved: nor does it necessitate starting the series over again, regardless of the length of time elapsed between doses. If a contraindication to the pertussis component occurs, Diphtheria and Tetanus Toxoids, Adsorbed for Pediatric Use (DT) should be substituted for the remaining doses.
Shake vigorously to obtain a uniform suspension prior to withdrawing each dose from the multiple dose vial. The vaccine should not be used if it cannot be resuspended. After shaking, the vaccine is a homogeneous white suspension.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
The vaccine should be injected i.m. Preferred sites are the anterolateral aspect of the thigh or the deltoid muscle of the upper arm. Care should be taken to avoid major peripheral nerve trunks. Before injection, the skin at the injection site should be cleansed and prepared with a suitable germicide. After insertion of the needle, aspirate to help avoid inadvertent injection into a blood vessel.
Influenza Virus Vaccine should not be administered within 3 days of immunization with a pertussis-containing vaccine.
Supplied: Each 0.5 mL dose contains: diphtheria toxoid 12.5 Lf and tetanus toxoid 5 Lf. The total human immunizing dose (the first three 0.5 mL doses given) contains an estimate of 12 units of pertussis vaccine. Each component of the vaccine—diphtheria, tetanus and pertussis—meets the required potency standards. The final concentration of thimerosal (mercury derivative) in the combined vaccine is 1:10,000. The aluminum content (from aluminum phosphate adjuvant) of the final product as determined by assay does not exceed 0.85 mg/0.5 mL dose. Vials of 7.5 mL. Do not freeze. Store refrigerated, away from freezer compartment at 2 to 8°C.
New Product 1993
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