With the exception of tetanus, no differences were found in immunogenicity when Quadracel was used to reconstitute Act-HIB or the 2 vaccines were given at separate sites. Anti-PRP responses were comparable. All children were protected against polio. Pertussis responses were not affected by method of administration. Tetanus antitoxin levels were lower in the combined vaccine groups, but all children had protective levels ( ≥ 0.01 EU*/mL). Following the 18-month dose, all children had tetanus antitoxin levels ≥ 0.10 EU*/mL.
Quadracel was significantly less reactogenic than DPT Polio Adsorbed.
*EU=Elisa Units.
Indications: For the primary immunization of infants, at or above the age of 2 months and as a booster in children up to their 7th birthday against diphtheria, tetanus, whooping cough and poliomyelitis.
When both vaccines are indicated, Quadracel may be used to reconstitute Act-HIB (Haemophilus b Conjugate Vaccine Tetanus Protein-Conjugate) for simultaneous administration of all 5 antigens in a single injection. Quadracel must not be mixed in the same syringe with any other vaccines.
Because simultaneous administration of common childhood vaccines is not known to affect the efficacy or safety of any of the routine recommended childhood vaccines, if return of a vaccine recipient for further immunization is doubtful, simultaneous administration of all vaccines appropriate for age and previous vaccination status (including MMR, other H. influenzae type b conjugate vaccines, hepatitis B vaccine) at separate sites with separate syringes is indicated. Infants born prematurely whose clinical condition is satisfactory should be vaccinated according to their chronological age from birth.
Contraindications: General: Immunization with Quadracel should be deferred in the presence of any acute illness, including febrile illness. A minor afebrile illness such as mild upper respiratory infection is not usually reason to defer immunization.
Quadracel should not be administered to children after their 7th birthday or to adults because of the quantity of diphtheria toxoid and because pertussis is less severe in these age groups than in infants and young children. Absolute Contraindications: Allergy to any component of Quadracel (see Supplied), or an allergic or anaphylactic reaction to a previous dose of DPT Polio Adsorbed are contraindications to vaccination.
Relative Contraindications (based on experience with whole cell pertussis vaccine): 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 Polio Adsorbed in children who have experienced a hypotonic-hyporesponsive episode following a previous dose of pertussis-containing vaccine. Children can continue immunization with Quadracel if the incidence of disease is high in their area.
Deferral: Deferral of the pertussis component of Quadracel 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 Quadracel 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 and poliomyelitis vaccine, when necessary, may be continued using DT Polio Adsorbed.
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 against diphtheria, pertussis, tetanus and poliomyelitis according to standard schedules.
Warnings: I.M. injections should be given with care in patients suffering from coagulation disorders because of the risk of hemorrhage.
If Quadracel is used in persons with malignancies, receiving immunosuppressive therapies, including irradiation, anti-metabolites, alkylating agents, cytotoxic drugs, or who are otherwise immunocompromised (including HIV infected individuals), 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., ≥ 2 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 Quadracel may not protect 100% of susceptible individuals.
Precautions: General: Care is to be taken by the health care provider for the safe and effective use of Quadracel. The possibility of allergic reactions in individuals sensitive to components of the vaccine should be evaluated. Epinephrine HCI solution (1:1000) 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 nonhospital settings.
Before an injection of any vaccine, all 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, current health status, and a current knowledge of the literature concerning the use of the vaccine under consideration.
Antipyretic Prophylaxis: Administration of acetaminophen (15mg/kg/dose) or other appropriate antipyretic at the time of immunization and at 4 and 8 hours after immunization decreases the incidence of febrile and local reactions. Since convulsions after whole cell pertussis vaccine are almost always associated with fever, antipyretic prophylaxis may benefit children at increased risk of seizures. For such children, administration of an antipyretic every 4 to 6 hours for as long as 24 hours after vaccination should be considered. Caregivers should be aware that antipyretic therapy could also obscure fever caused by concomitant, unrelated infection.
Special care should be taken to ensure that the product is not injected into a blood vessel.
A separate, sterile needle and syringe 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. Needles should not be recapped and should be disposed of properly.
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-containing 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 administration of any vaccine causing a febrile reaction. Acetaminophen prophylaxis is particularly recommended for children with a personal or family history of convulsions.
Frequent booster doses of tetanus or diphtheria toxoids in the presence of adequate or excessive serum levels of tetanus or diphtheria antitoxins have been associated with increased incidence and severity of reactions and should be avoided. Before administration of Quadracel, health care personnel should inform the parent or guardian of the patient of the benefits and risks of immunization, and also inquire about the recent health status of the patient to be injected.
Adverse Effects: In clinical trials done in Canada, Quadracel had consistently lower rates of local and .systemic reactions than DPT Polio Adsorbed, whether combined with Act-HIB or given at separate sites. See Tables II and III. Local Reactions: As with whole cell DPT and DPT Polio, there is a trend for increasing local reaction rates at the fourth and fifth doses, but with Quadracel these are still lower than those observed following whole cell DPT and DPT Polio.
In a clinical trial comparing 3 acellular pertussis and 1 whole cell DPT Vaccine in Sweden 20 745 infants received Tripacel, Component Pertussis Vaccine Combined with Diphtheria and Tetanus Toxoids Adsorbed at 2, 4 and 6 months of age. The following serious adverse events were reported: fever > 40°C (within 3 days of immunization) 7; hypotonic-hyporesponsive episode 29; convulsions (within 3 days of immunization) 4; acute severe neurologic event lasting more than 30 minutes 1; infantile spasms 2; invasive bacterial infections 9; deaths 4*.
* Not attributed to the vaccine.
Rates of events were less than or comparable to the rates in the other acellular pertussis vaccine and whole cell DPT groups in this study. Rarely, an anaphylactic reaction (i.e., hives, swelling of the mouth, difficulty breathing, hypotension, or shock) has been reported after receiving preparations containing diphtheria, tetanus, and/or pertussis antigens. Arthus-type hypersensitivity reactions, characterized by severe local reactions (generally starting 2 to 8 hours after an injection), may follow receipt of tetanus and diphtheria toxoids. A few cases of peripheral neuropathy have been reported following tetanus toxoid administration, although a causal relationship has not been established.
Persistent nodules at the site of injection have occurred following the use of adsorbed vaccine, but this complication is unusual. Sterile abscess at the site of injection have been reported following use of adsorbed vaccines (6 to 10 per million doses).
Persistent, inconsolable crying lasting 3 or more hours (1%) and high-pitched, unusual screaming (0.1%) have also been reported after whole cell DPT vaccination. The incidence of both of these events is significantly lower with Quadracel. Convulsions and a hypotonic-hyporesponsive state have each been reported to occur at a frequency of about 1:1750 injections of whole cell 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 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 whole cell 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 whole cell 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 whole cell 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. |
