Diphtheria and Tetanus Toxoids Adsorbed and Pertussis Vaccine and Inactivated Poliomyelitis Vaccine

Diphtheria and Tetanus Toxoids Adsorbed and Pertussis Vaccine and Inactivated Poliomyelitis Vaccine (DPT Polio Adsorbed)



Action And Clinical Pharmacology: Immunization against diphtheria, tetanus, pertussis and poliomyelitis has been associated with a striking decrease in the incidence of morbidity and mortality from these diseases. Simultaneous vaccination with a combination vaccine containing diphtheria and tetanus toxoids and pertussis and poliomyelitis vaccines have been used in Canada since 1958.

Injection of bacterial proteins such as diphtheria and tetanus toxoids results in the production of protective antibodies. The peak antibody levels achieved with the first dose are usually low, and a primary series is required to prime the immune system and produce a high antibody level. After completion of a primary series, circulating antibodies to tetanus and diphtheria toxoids gradually decline but are thought to persist at protective levels for up to 10 years. Tetanus antitoxin levels of >0.01 IU/mL are generally accepted as good evidence of immunity from tetanus. Diphtheria antitoxin levels of ³0.01 IU/mL are thought to be the minimal level required for protection. Levels >0.05 IU/mL are considered optimal for protection.

Diphtheria is a serious communicable disease caused by toxigenic strains of C. diphtheriae. The organism may be harboured in the nasopharynx, skin or other sites of asymptomatic carriers, making eradication of the disease difficult. Routine immunization against diphtheria in infancy and childhood has been widely practised in Canada since 1930, resulting in a decline in morbidity and mortality. Fewer than 5 cases are now reported annually in Canada. The case-fatality rate remains 5 to 10%, with the highest death rates in the very young and elderly. The disease occurs most frequently in unimmunized or partially immunized individuals. Diphtheria toxoid is a cell-free preparation of diphtheria toxin detoxified with formaldehyde. The immunity conferred is antitoxic, not antibacterial, and thus protects against the potentially lethal systemic effects of diphtheria toxin but not directly against local infection.

Tetanus is an acute and often fatal disease caused by an extremely potent neurotoxin produced by C. tetani. The organism is ubiquitous and its occurrence in nature cannot be controlled. Immunization is highly effective, provides long-lasting protection, and is recommended for the whole population. Only 2 to 3 cases of tetanus are now reported annually in Canada. Tetanus toxoid is prepared by detoxification of tetanus toxin with formaldehyde.

Pertussis (whooping cough) is a highly communicable bacterial disease caused by B. pertussis. Severity and mortality are greatest in infancy, and even infants born to apparently immune mothers are highly susceptible to infection, particularly if maternal immunity was vaccine-induced. During the last 30 years, vaccination has been widely practised in Canada and the incidence and mortality from pertussis have declined remarkably. However, outbreaks of pertussis continue to occur across Canada, with an annual reported rate of 1 000 to 8 000 cases over the past 5 years. Deaths and brain damage from pertussis infections still occur, particularly in young infants who have not been vaccinated. Pertussis vaccine is a suspension of killed B. pertussis organisms. A primary series of 4 doses of vaccine is begun in infancy. Protection from infection is estimated to be 60 to 80%; protection against severe disease is 85% or higher. Protection from disease afforded by the vaccine decreases as the time interval since vaccination increases.

Poliomyelitis is caused by infection with one of the 3 antigenic types of poliovirus. Following introduction of poliovirus vaccine in Canada in 1955, the indigenous disease has been virtually eliminated. The last significant outbreak of poliomyelitis occurred in 1978-79, when there were 11 cases of paralytic disease among unimmunized contacts of imported cases. The last case of poliomyelitis attributed to imported, wild virus occurred in 1988. However, circulation of wild viruses does occur in rare circumstances, and it remains crucial that the highest possible level of vaccine-induced immunity be maintained in the population. Inactivated Poliomyelitis Vaccine (Diploid Cell Origin) – IPV, (sometimes referred to as e-IPV), is an enhanced formalin-inactivated product which has a higher potency than the original IPV.

The 3 poliovirus types are propagated in human diploid cells. A primary series induces protective antibody levels in more than 99% of recipients.

In a clinical trial done in Canada in 1987-88, 120 infants 2 months of age received three 0.5 mL i.m. doses of DPT-P at 2-month intervals. One month following the third dose, 98% had diphtheria antitoxin levels of ³0.01 IU/mL, 99% had tetanus antitoxin levels of ³0.01 IU/mL, 99% had pertussis agglutinin levels of ³1:8. Poliovirus antibody levels of ³1:4 developed to type 1 in 99%, to type 2 in 100% and to type 3 in 100%.

Indications And Clinical Uses: For the primary immunization of infants and of children at or above the age of 2 months up to their 7th birthday against diphtheria, tetanus, whooping cough and poliomyelitis.

When both vaccines are indicated, DPT Polio Adsorbed may be used to reconstitute Act-HIB for simultaneous administration of all 5 antigens in a single injection. DPT Polio Adsorbed must not be mixed in the same syringe with any other vaccines.

DPT Polio Adsorbed may be administered simultaneously with other Hib conjugate vaccines and with MMR each at separate sites with separate syringes.

Contra-Indications: General: Immunization with this product should be deferred in the presence of any acute illness, including febrile illness.

DPT Polio Adsorbed should not be administered to children after their 7th birthday or to adults because of reactions to diphtheria toxoid or to pertussis vaccine and because pertussis is less severe in these age groups than in infants and young children.

Absolute Contraindications: Allergy to any component of DPT Polio Adsorbed, or an allergic or anaphylactic reaction to a previous dose of DPT Polio Adsorbed are contraindications to vaccination.

Relative Contraindications: Hypotonic-hyporesponsive episodes: No long-term sequelae have been associated with hypotonic-hyporesponsive episodes; however, it may be prudent in areas of low pertussis incidence to withhold the pertussis component and continue immunization with DT and IPV in children who have experienced a hypotonic-hyporesponsive episode following a previous dose of pertussis-containing vaccine. Immunization of children with DPT Polio can continue if the incidence of disease is high in their area.

Deferral: Deferral of the pertussis component of DPT Polio Adsorbed should be considered in children with a progressive, evolving, or unstable neurologic condition (including seizures) because administration of the pertussis component may coincide with the onset of overt manifestations of such disorders and result in confusion about causation. It is prudent to delay initiation of immunization with pertussis vaccine until further observation and study have clarified the child’s neurologic status. In addition, the effect of treatment, if any, can be assessed. Immunization with DPT Polio Adsorbed should be reinstituted when the condition has resolved, been corrected or controlled.

When immunization with pertussis vaccine is contraindicated or deferred, immunization with diphtheria and tetanus toxoids, when necessary, may be continued using DT Adsorbed and Inactivated Poliomyelitis Vaccine (DCO). The use of fractional doses in an attempt to reduce the severity of adverse reactions cannot be recommended because there is insufficient evidence on the safety or efficacy of such smaller doses.

Elective immunization of individuals over 6 months of age should be deferred during an outbreak of poliomyelitis.

Human Immunodeficiency Virus (HIV) Infected Persons: HIV-infected individuals, both asymptomatic and symptomatic, should be immunized with DPT Polio vaccine according to standard schedules.

Manufacturers’ Warnings In Clinical States: If this product is used in persons with malignancies, receiving immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, or who are otherwise immunocompromised, the expected immune response may not be obtained.

Corticosteroid therapy can result in immunosuppression although the exact dose and duration of therapy required to suppress the immune system is not well defined. Persons treated with high doses of systemic steroids, e.g., ³2 mg/kg/day of prednisone orally for more than 2 weeks, should be considered to have a compromised immune system.

As with any vaccine, immunization with DPT Polio Adsorbed may not protect 100% of susceptible individuals.

Precautions: General: The possibility of allergic reactions in individuals sensitive to components of the vaccine should be evaluated. Epinephrine HCl solution (1:1 000) and other appropriate agents should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.

Before an injection of any vaccine, appropriate precautions should be taken to prevent adverse reactions. This includes a review of the patient’s history with respect to possible hypersensitivity to the vaccine or similar vaccine, determination of previous immunization history, and the presence of any contraindications to immunization.

Special care should be taken to ensure that the product is not injected into a blood vessel.

A separate, sterile syringe and needle, or a sterile disposable unit, must be used for each individual patient to prevent the transmission of infectious agents. There have been case reports of transmission of HIV and hepatitis by failure to scrupulously observe sterile technique. In particular, the same needle and/or syringe must never be used to re-enter a multi-dose vial to withdraw vaccine even when it is to be used for inoculation of the same patient. This may lead to contamination of the vial contents and infection of patients who subsequently receive vaccine from the vial.

Do not recap needles.

A family history of convulsions in parents and siblings is not a contraindication to pertussis vaccination and children with such family histories should receive Pertussis Vaccine according to the recommended schedule. Parents of infants and children with family histories of convulsions should be informed of their children’s increased risk of seizures following DPT vaccination.

Acetaminophen prophylaxis is particularly recommended for children with a personal or family history of convulsions.

Frequent booster doses of tetanus toxoid in the presence of adequate or excessive serum levels of tetanus antitoxin have been associated with increased incidence and severity of reaction and should be avoided.

Adverse Reactions: Mild local reactions consisting of erythema, pain and tenderness, swelling and induration at the injection site are common, usually self-limited and subside without treatment.

Up to 70% of children receiving a booster dose at 4 to 6 years of age have been reported to develop local redness and/or swelling ³5 cm in diameter. This is generally self-limiting and subsides without treatment.

Persistent nodules at the site of injection have occurred following the use of an adsorbed vaccine, but this complication is unusual. Sterile abscess at the site of injection has been reported (6 to 10 per million doses).

Mild to moderate systemic reactions occur frequently following injections of this vaccine. These usually consist of one or more of the following symptoms and signs; temperature elevation ³38°C, drowsiness, fretfulness, listlessness, anorexia, vomiting, irritability, persistent or unusual crying. These symptoms are most frequent during the first 24 hours following vaccine injection and may persist for 1 to 2 days. The incidence and severity of fever and irritability can be reduced by administration of acetaminophen (15 mg/kg/dose) at the time of inoculation and again 4 and 8 hours after vaccination.

Persistent, inconsolable crying lasting 3 or more hours (1%) and high-pitched, unusual screaming (0.1%) have also been reported after DPT vaccination. Convulsions and a hypotonic-hyporesponsive state have each been reported to occur at a frequency of about 1:1 750 injections of DPT. Most convulsions are brief, generalized and self-limited, and are usually associated with fever. Neither febrile nor afebrile convulsions have been shown to be associated with subsequent seizure disorder. Complete recovery, with no persistent sequelae, has been observed on follow-up of children with hypotonic-hyporesponsive episodes or convulsions. (See also Contraindications and Precautions.)

Although there has been a concern about the possible association of severe neurologic illness (including encephalopathy) occurring within 72 hours of the administration of pertussis-containing vaccines to previously healthy infants, the risk of an association is so small compared to the background rate for these types of events that the question of causation probably cannot be answered.

Reanalysis of the National Childhood Encephalopathy study (NECS) in the United Kingdom has failed to confirm that there was an increased risk of permanent brain damage following acute neurological illness occurring within 7 days of pertussis vaccination. Additional studies have also failed to demonstrate an association between pertussis vaccine and permanent neurologic sequelae.

Sudden infant death syndrome (SIDS) has been reported in temporal relationship to the administration of vaccines containing diphtheria and tetanus toxoids and pertussis vaccine (DPT). Review of the evidence does not indicate a causal relationship between DPT vaccine and SIDS. Studies showing a temporal relation between these events are consistent with the expected occurrence of SIDS over the age range in which DPT immunization usually occurs.

Physicians, nurses, and pharmacists should report any adverse occurrences temporally related to the administration of the product in accordance with local requirements and report to the Medical Director at Connaught Laboratories Limited, 1755 Steeles Avenue West, Toronto, Ontario, Canada, M2R 3T4.

Dosage And Administration: For primary immunization of infants the following routine immunization schedule is recommended: one 0.5 mL dose administered at 2, 4, 6 and 18 months of age.

If for any reason this schedule is delayed, it is recommended that 3 doses of 0.5 mL be administered with an interval 4 to 8 weeks between doses, followed by a fourth dose of 0.5 mL administered approximately 1 year after the third dose.

A booster dose of 0.5 mL should be administered between 4 and 6 years of age (i.e., at the time of school entry). This booster dose is unnecessary if the fourth primary immunizing dose has been administered after the fourth birthday.

Administration: Parenteral biological products should be inspected visually for extraneous particulate matter and/or discoloration before administration. If these conditions exist, the product should not be administered.

Shake the vial or ampul well to distribute uniformly the suspension before withdrawing each dose. Before withdrawing a dose from an ampul, tap the container first to ensure that any vaccine in the ampul neck falls to the lower portion of the ampul. Once the ampul has been opened, any of its contents not used immediately should be discarded.

When administering a dose from a rubber-stoppered vial, do not remove either the rubber stopper or the metal seal holding it in place. Aseptic technique must be used for withdrawal of each dose.

Before injection, the skin over the site to be injected should be cleansed with a suitable germicide.

Administer the vaccine i.m. The preferred site is into the anterolateral aspect of the mid-thigh (vastus lateralis muscle) or into the deltoid muscle.

The former is the site of choice for infants 1 year of age, the deltoid is the preferred site since use of the anterolateral thigh results in frequent complaints of limping due to muscle pain.

After insertion of the needle, aspirate to ensure that the needle has not entered a blood vessel.

Do not inject i.v.

Each person who is immunized should be given a permanent personal immunization record. In addition, it is essential that the physician or nurse record the immunization history in the permanent medical record of each patient. This permanent office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.

Storage: Store between 2 and 8°C. Do not freeze. Product which has been exposed to freezing should not be used.

Availability And Storage: Each single dose (0.5 mL) contains: diphtheria toxoid (25 Lf), tetanus toxoid (5 Lf), pertussis vaccine (4 to 12 Protective Units [P.U.]), aluminum phosphate (1.5 mg), purified inactivated poliomyelitis vaccine (Type 1 Mahoney, Type 2 M.E.F.1, Type 3 Saukett), 2-phenoxyethanol 0.5% and formaldehyde (27 ppm) added as preservatives. By calculation, the vaccine contains 10 ppm Tween 80, 0.05% albumin (Human) and less than 1 ppm of bovine serum. Trace amounts polymyxin B and neomycin may be present from the cell growth medium. Multiple-dose rubber-stoppered vials of 5 mL and single-dose glass ampuls of 0.5 mL.

DPT Polio Adsorbed is also available in a package containing 5 single dose vials of Act-HIB for reconstitution with 5 single dose ampuls of DPT Polio Adsorbed. This product provides an efficient means of administering routine immunization against diphtheria, tetanus, pertussis, poliomyelitis and H. influenzae type b disease in a single injection at a single visit.

Diphtheria and Tetanus Toxoids Adsorbed and Pertussis Vaccine and Inactivated Poliomyelitis Vaccine (DPT Polio Adsorbed) Connaught Vaccine

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