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.
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
Children who have had tetanus or diphtheria should still be immunized since these clinical infections do not always confer immunity. Children who have had natural pertussis can continue to receive pertussis-containing vaccines.
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 to avoid superimposing adverse events from the vaccine on the underlying illness or mistakenly attributing to the vaccine a manifestation of the underlying illness. A minor afebrile illness such as mild upper respiratory infection is not usually reason to defer immunization.
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.
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.
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.
Elective immunization of individuals over 6 months of age should be deferred during an outbreak of poliomyelitis.
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.
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.
Precautions: General: 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, including proper airway management. Before administration 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. (See dosage).
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 and comply with any local requirements with respect to information to be provided before immunization.
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. There was a trend towards increasing local reaction rates at the fourth and fifth doses, but these were still significantly lower than with whole-cell pertussis combination vaccines. 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 conducted in Sweden comparing 3 acellular pertussis vaccines and 1 whole-cell DPT vaccine, 20,745 infants received Tripacel at 2, 4 and 6 or 2, 5 and 12 months of age. Rates of adverse events were less than or comparable to the rates in the other acellular pertussis vaccine and whole-cell DPT groups in this study. The rates of reports of fever > 40.5°C and seizures or suspected seizures were significantly higher following whole-cell DPT than following acellular pertussis vaccines. Rates of hypotonic-hyporesponsive episodes were comparable, with 29 reports following administration of Tripacel. No deaths or cases of encephalitis/acute encephalopathy, invasive bacterial infection, infantile spasms or anaphylactic reactions were reported within 48 hours of vaccination.
Rare cases of allergic or anaphylactic reaction (i.e., hives, swelling of the mouth, difficulty breathing, hypotension, or shock) have been reported after receiving some preparations containing diphtheria, tetanus and/or pertussis antigens. Death following vaccine-caused anaphylaxis has been reported.
Localized reactions consisting of discomfort, pain, swelling and redness at the injection site may be associated with tetanus and diphtheria toxoids. These are usually of low frequency and transient in duration. Following booster doses, local erythema and swelling are not uncommon and Arthus-type sensitivity may occur. Severe local reactions are often associated with high levels of circulating antitoxin, usually resulting from over-immunization due to toxoid being given too frequently.
Systemic reactions, such as generalized urticaria, are uncommon. Influenza-like symptoms have been reported and usually occur within 12 hours of vaccination with diphtheria and tetanus toxoids.
Neurological complications such as peripheral neuropathies and demyelinating diseases of the CNS following some tetanus toxoids or diphtheria toxoids have been documented but are rare. The U.S. Institute of Medicine has concluded that the evidence is inadequate to accept or reject a causal relation between tetanus toxoid, DT or Td and demyelinating diseases of the CNS (acute demyelinating encephalomyelitis, transverse myelitis, optic neuritis) or peripheral mononeuropathy (other than those caused by direct intraneural injection).
The following neurologic illnesses have been reported as temporally associated with some vaccines containing tetanus toxoid: neurological complications including cochlear lesion, brachial plexus neuropathies, paralysis of the radial nerve, paralysis of the recurrent nerve, accommodation paresis, and EEC disturbances with encephalopathy (with or without permanent intellectual and/or motor function impairment). In the differential diagnosis of polyradiculoneuropathies following administration of a vaccine containing tetanus toxoid, tetanus toxoid should be considered as a possible etiology. The Institute of Medicine concluded that the evidence favors acceptance of a causal relation between tetanus toxoid and brachial neuritis.
On the basis of a case report and evidence that a vaccine-induced immunologic response can cause Guillain-Barre Syndrome(GBS), the Institute of Medicine concluded that tetanus toxoid-containing vaccines can trigger GBS in adults. No increased risk for GBS has been observed with the use of DPT in children. Persistent nodules at the site of injection have occurred following the use of an adsorbed product, but this complication is unusual, and may be related to s.c. administration. Sterile abscess at the site of injection has been reported following use of adsorbed vaccines (6 to 10 per million doses).
Quadracel does not contain a whole-cell pertussis vaccine however, persistent, inconsolable crying lasting 3 or more hours (1%) and high-pitched, unusual screaming (0.1%) have 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 doses 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, without 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 [with or without permanent intellectual and/or motor function impairment]) occurring within 72 hours of the administration of whole-cell pertussis containing vaccines to previously healthy infants, the risk of association is so small compared to the background rate for the types of events that the question of causation probably can be answered.
Reanalysis of the National Childhood Encephalopathy Study (NCES) 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 (including permanent intellectual and/or motor function impairment).
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. As with any vaccine, there is the possibility that broad use of the vaccine could reveal rare adverse reactions not observed in clinical trials.
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 Ave West, Toronto, Ontario, Canada, M2R 3T4. |
