The Manufacturer Inserts - Summarized

Chapter 5: Article 6


Below, I provide a summary of the safety data for the approved Canadian childhood vaccines (Link Here), focusing only on the clinical trial data where infants, children and adolescents participated. I summarize BOTH the Canadian inserts and American inserts (if available).

Please note, I've listed and summarized the vaccines below in an order which follows the Canadian and American childhood vaccine schedules. (The schedules are slightly different, so I prioritize by the schedule which administers a vaccine first). Beneath each illness heading I explain the number of doses recommended, and the ages when this vaccine is given if you were to follow the recommended vaccination schedule. My summaries below provide and emphasize the information as follows:

  • the manufacturer (noted in brackets)

  • the number of clinical trial participants, (underlined)

  • the length of time that participants were monitored for (bolded)

  • the control substance that was used in the trial, (bolding for saline placebo only) 

  • any interesting information or warnings quoted directly from the manufacturer (italics)

Below is a consolidated list of the various side effects that researchers specifically looked for in the trial participants, usually during the two week or less monitoring time period. The side effects listed below are called "solicited events" within the package insert:

  • Fever / Chills

  • Sweating

  • Flushing

  • Malaise (feeling unwell)

  • Sore Throat

  • Rhinorrhea (excess mucous secretion from nose)

  • Ear Ache or Ear Infection

  • Upper Respiratory Infection

  • Cough

  • Irritability

  • Prolonged and Unusual Crying and/or High pitched Screaming (in young infants this can be indication of brain injury and swelling)

  • Fatigue / Drowsiness

  • Impaired Sleeping / Insomnia

  • Loss of Appetite

  • Abdominal Pain / Cramps

  • Nausea / Vomiting

  • Diarrhea

  • Hypersensitivity

  • Apnea (suspension of breathing)

  • Hypotonic-Hyporesponsive Episode (Collapse or shock-like state within 3 days of vaccination, which can involve cardiovascular or respiratory arrest)

  • Allergic Reaction / Anaphylaxis

  • Angioedema (swelling of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, eyes, lips, tongue, larynx, abdomen, or arms and legs.)

  • Urticaria (Hives)

  • Rash

  • Dermatitis (eczema, itchy, red rash)

  • Lymphadenopathy (disease in lymph nodes producing swollen or enlarged lymph nodes)

  • Nodule formation (elevated areas of tissue or fluid inside or under the skin that feels hard and has a diameter greater than 0.5 cm)

  • Swelling (of limb, joint(s) or localized at injection site) 

  • Erythema (redness of the skin)

  • Ecchymosis (bleeding under the skin, causing bruising larger than 1cm)

  • Pruritus (undesirable feeling on skin, which provokes desire to scratch)

  • Paresthesia (sensation on the skin, tingling, prickling, burning, numbness)

  • Pain (at injection site, muscle pain, body ache, joint aches or headache)

  • Muscle Weakness or Stiffness

  • Hypotension (low blood pressure)

  • Vertigo, Dizziness, Lightheadedness, Fainting

  • Dysuria (painful urination)

Vaccine names are abbreviated below as follows:

  • Hep B - Hepatitis B

  • DTaP - Diphtheria, Tetanus, Acellular Pertussis (Whooping Cough)

  • DwPT / DPT - Diphtheria, Whole Cell Pertussis (Whooping Cough), Tetanus

  • TD - Tetanus and Diphtheria

  • IPV - Inactivated Polio Virus

  • OPV - Oral Polio Virus

  • HIB - Haemophilus Influenzae Type B

  • MMR - Measles, Mumps, Rubella

  • MMRV - Measles, Mumps Rubella, Varicella (Chicken Pox)

  • V - Varicella (Chicken Pox)


HEPATITIS B VACCINES:

  • 3 total doses given to American infants: on day 1 of life, at 2 and 6 months of age

  • 3 total doses given to Canadian infants: at 2, 4 and 6 months of age (New change to Alberta vaccination schedule effective May 1, 2018) OR 3 total doses given to Canadian children: in grade 5 (this childhood series will end in 2028, when infants born in 2018 reach grade 5 as babies born in 2018 received this series in infancy)

  • At risk Canadian infants may also be given a dose on their day of birth.

Brands available in Canada, for Hepatitis B vaccine include:

  • Recombivax HB (Merck) - On the Canadian insert there is no safety data provided for children. The insert states that the vaccine was tested on 1252 adults, who were monitored for 5 days post vaccination. Link Here On the American insert, it says the vaccine was tested for safety on 147 children (infant to less than 10 years of age - distribution of ages was not provided). The participants were monitored for some of the reactions listed above, during the 5 days following vaccination. The comparator vaccine information  (used as control) was not provided. The package insert states, "RECOMBIVAX HB has not been evaluated for its carcinogenic or mutagenic potential, or its potential to impair fertility."  FDA link Here The Canadian insert is silent on this.

  • Engerix-B (GSK) - the Canadian insert states the vaccine was tested on 5300 people. It didn't provide a description of ages, or how long the participants were monitored for. Link Here On the American insert it says the vaccine was tested on 5071 healthy adults, children and newborn infants (didn't provide the distribution through age groups). The participants were monitored for many of the above listed reactions during the 4 daysfollowing vaccination. The comparator vaccine information (used as control) was not provided. The insert states, "ENGERIX-B has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." FDA link Here. The Canadian insert is silent on this.

  • Twinrix Jr. (GSK) (Canadian insert) - the vaccine is approved for use in the childhood population, age 1-18 years old. The insert provided very few details regarding the safety studies that have been conducted. It stated that in the pediatric population, Twinwrix was tested on 800 participants and 778 participants (ages not specified). Those two groups received 3 total doses each, based on two different vaccine schedules. The participants were monitored for some of the above listed reactions. It does not say how long participants were monitored for. Link Here

  • Infanrix - Hexa - see description in the DTaP section below


DTaP VACCINES

(Combination of three vaccines in one vial, for illnesses Diptheria, Tetanus, Pertussis):

  • 6 total doses given to each Canadian and American infants and children, administered at: ages 2, 4, 6 and 18 months of age, at 4-6 years of age, and in grade 9

Available brands in Canada, for DTaP vaccines include:

  • Pediacel (Sanofi Pasteur) Canadian Insert) - is a combination of 5 vaccines in one vial, DTaP, IPV, HIB. It was tested on 339 Infants (at 2, 4, & 6 months of age) and 301 of these infants were later immunized as toddlers (18 months). The participants were monitored for some of the above listed reactions during the 24 hours after vaccination. Control information was not provided. The package insert states, "The potential risk of apnea and the need for respiratory monitoring for 48 – 72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." The package insert also states, "Sudden infant death syndrome (SIDS) has occurred in infants following administration of DTaP vaccines. By chance alone, some cases of SIDS can be expected to follow receipt of PEDIACEL®." You will often hear health officials state that vaccines do not cause SIDS deaths. SIDS is the cessation of breathing, usually during sleep, which results in death, and an admitted vaccine side effect is apnea - the suspension of breathing. If vaccination can cause the suspension of breathing, why can't it also cause the cessation of breathing. It needs to also be noted that recently there was a vaccine court ruling that determined a child's SIDS death was in fact likely caused by the infant's recent vaccination. The insert also states, "the following events are contraindications to administration of a pertussis containing vaccine. "Encephalopathy(e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause." Encephalopathy means brain injury, and so the package insert is warning that vaccination may cause brain injury, which may not be reversible. The package also insert states, "A review by the IOM found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome." Link Here.

  • Infanrix (GSK) (American Insert) - has been tested in several clinical trials on a total of 29,243 infants receiving the primary series (3 doses in infancy), of which 6081 of those infants then went on to receive  a 4th dose in childhood, and 1,764 received a 5th dose. A US study observed 335 infants (at 2, 4 and 6 months of age), who received the test Infanrix vaccine with Engerix-B, IPV, HIB and Pneumococcal vaccines administered at the same time. The participants were monitored for some of the above listed reactions during the 4 days following vaccination. Control information was not provided. It was also tested as a booster dose in 810 children (age 15-18 months). MMR, pneumococcal, and HIB vaccines were administered simultaneously with the test Infanrix vaccine. The children were monitored for some of the above listed reactions in the 4 days following vaccination. No control information was provided. It was tested as a booster on 1053 children (age 4-6). IPV and MMR vaccines were administered simultaneously with the test Infanrix vaccine. The children were monitored for some of the above listed reactions in the 4 days following vaccination. No control information was provided. In an Italian Trial, 4,696 infants (at 2, 4, and 6 months of age) received Infanrix, and 4,678 infants received a whole cell DTwP vaccine as control. (The whole cell DTwP vaccine is no longer used in North America as it is no longer deemed to be safe enough for our infants as side effects are more severe). All infants were monitored for 48 hours, and the insert states that infants who received Infanrix vaccine experienced significantly fewer severe reactions as compared to infants who received the DTwP vaccine. Serious adverse events reported in the Infanrix group were, 5 fevers greater than 104°, 6 episodes of persistent crying for 3 hours or longer, and 1 seizure. In a German study which involved 22,505 infants (at 3, 4 and 5 months of age), a diary card was sent home to record reactions during the 28 days following vaccination. A subset of 2,457 of those infants were given a diary card to monitor their reactions over 3 months, (from day 1 with the 1st dose to 30 days following the 3rd dose). Those studies that list an extended monitoring period (28 days and 3 months) were likely gathering unsolicited event information, where the onus falls onto the parents (not researchers) to record possible side effects. The package insert states, "Apnea following intramuscular vaccination has been observed in some infants born prematurely." The package insert states, "INFANRIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." Insert from FDA website Link Here

  • Infanrix-IPV (GSK) (Canadian Insert) -  is a combination of 4 vaccines in one vial - DTaP, IPV. It was tested on children (number not specified) aged 15 months to 20 months. This vaccine was tested as a booster dose. The participants were monitored for 48 hours following vaccination. Infanrix-IPV was tested on children who were also given a HIB vaccine at the same time. The reactions experienced by the children who received the Infanrix-IPV + HIB vaccine were less frequent, when compared against the reactions experienced by children who received a control of DTP-IPV + HIB vaccine. (It needs to be noted that DTP (the control), which is sometimes also called DTwP or DwPT, is no longer considered safe enough to use on American and Canadian infants). The vaccine was also tested on 2200 infants, and the participants were monitored for some of the above listed reactions. The ages of those 2200 infants, the length of time that their health was monitored for, and the control information was not provided. The package insert states, "The potential risk of apnea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." The insert states,"adequate animal reproduction studies are not available." Link Here On the FDA website, the package insert for the American Infanrix vaccine states, "INFANRIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility."  Link Here The Canadian insert is silent on this.

  • Infanrix-IPV/HIB (GSK) (Canadian Insert) - is a combination of 5 vaccines in one vial -DTaP, IPV, HIB. The vaccine was tested through 6100 primary immunization doses administered (at 2, 4, & 6 months of age), and 2900 booster doses administered (in second year of life). It does not state the number of participants, but recognizing that infants receive three doses in the first year of life, I estimate approximately 2000 infants participated in the primary study. The participants were monitored for several of the reactions listed above. It does not specify how long the participants were monitored for, or what was used as control. The vaccine was also tested on 3500 subjects (age not specified). Participants were monitored for some of the above listed reactions, but it does not say how long participants were monitored for. The insert states, "The potential risk of apnea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." The package insert states, "Experience with INFANRIX and other INFANRIX based combinations have not revealed any cases of encephalopathy or permanent neurologic damage causally linked to vaccination. While acute encephalopathy and permanent neurologic damage have not been reported to be causally linked nor in temporal association with administration of INFANRIX®-IPV/Hib, data are limited at this time." (It is important to note that whole cell DTP vaccines became widely used 70 years ago, and due to safety concerns were replaced with DTaP vaccines 20 years ago. Recognizing the extensive history of use, there is no reason why 70 & 20 years later, data should still be limited). The insert also says, "Studies suggest that, when given whole-cell DTP vaccine, infants and children with a history of convulsions in first-degree family members (i.e. siblings and parents) have a 2.4-fold increased risk for neurologic events compared to those without such histories." (They are providing data on the former DTP vaccine, which is no longer used, because the warning may still apply to the re-formulated DTaP vaccines that are used today). On the FDA website, the package insert for the American Infanrix vaccine states, "INFANRIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." Link Here The Canadian insert is silent on this.

  • Infanrix-Hexa (GSK) (Canadian Insert) - is a combination of 6 vaccines in one vial - DTaP, IPV, HIB, Hep B. It was tested on 267 infants. The participants were monitored for some of the above listed reactions during the 8 days following vaccination. The control group received a combination of other vaccines (Infanrix + Engerix-B + OPV administered at the same time). Reactions were also monitored in 16,000 participants(ages not specified). The data given does not provide the time frame that the participants were monitored for, or which other vaccines were injected simultaneously or what was used as control. The insert states, "The potential risk of apnea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunization series to very preterm infants (born after at least 24 weeks of gestational age) and particularly for those with a previous history of respiratory immaturity." Seizure (with or without fever) was listed as occurring in less than 0.01% of the population (1 in 10,000 infants). The package insert states, "While acute encephalopathy and permanent neurologic damage have not been reported to be causally linked nor in a temporal association with administration of INFANRIX hexa data is limited at this time." The insert also states, "Studies suggest that when given whole-cell DTP vaccine, infants and children with a history of convulsions in first-degree family members (i.e., siblings and parents) have a 2.4-fold increased risk for neurologic events compared to those without such histories." The insert also states, "adequate animal reproduction studies are not available." Link Here. On the FDA website, the package insert for the American Infanrix vaccine states, "INFANRIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." Link Here The Canadian insert is silent on this.

  • Quadracel (Sanofi Pasteur) (Canadian Insert) - is a combination of 4 vaccines in one vial - DTaP, IPV. 113 infants were tested (at 2, 4, & 6 months of age), with 104 of these infants later vaccinated again as toddlers at 18 months of age. The participants were monitored for some of the above listed reactions during the 24 hours following vaccination. Control vaccine information was not provided. It was also tested on 800 children (4-6 years) who were monitored for some of the above listed reactions during the following 48-96 hours post vaccination. The package insert states, "The potential risk of apnea and the need for respiratory monitoring for 48 – 72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." The package insert states, "the following events are contraindications to administration of any pertussis-containing vaccine...Encephalopathy(e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause." The insert also states, "A review by the US Institute of Medicine (IOM) found evidence for a causal relationship between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome." Canadian Insert Here On the FDA website, the package insert for the American Quadracel vaccine states, "Quadracel has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility." Link Here The Canadian insert is silent on this. 

  • Quadracel (Sanofi Pasteur) (American Insert) - A study conducted in Puerto Rico, tested Quadracel on 2733 children (4-6 years). A control group of 621 children received Daptacel + IPOL vaccines instead. All participants received MMR and Varicella vaccines at the same time. The participants were monitored for some of the above listed reactions during the 7 days following vaccination. Participants could report unsolicited adverse events for 28 days following vaccination, and participants were monitored for serious adverse events during the 6 months following vaccination. During the 28 day period, 0.1% of Quadracel recipients and 0.2% of Daptacel+IPOL recipients experienced serious adverse events (not detailed). During the 6 month period, 0.8% of Quadracel recipients (21 of 2733) and 0.5% Daptacel+IPOL recipients (3 of 621) experienced a serious adverse event (not detailed). The insert states that none of the adverse events were assessed as related to vaccination. (A never vaccinated control group was not monitored during this period, to see if they too experienced serious medical events at a rate of 0.1-0.2% in 28 days or 0.5-0.8% in 6 months). The package insert states, "Quadracel has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility." FDA Link Here

  • Adacel (Sanofi Pasteur) (Canadian Insert) - was tested on 298 children (less than 4 years of age) and 1508 adolescents. The participants were monitored for some of the above listed reactions during the 14 days after vaccination. The reactions experienced by the children were compared to reactions experienced in Quadracel vaccine recipients (children) and Td vaccine recipients (adolescents and adults). The insert states, "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." The package insert also states, "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." The insert also states, "A review by the US Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome. Canadian insert Here On the FDA website, the package insert for the American Adacel vaccine states, "Adacel vaccine has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility." Link Here The Canadian insert is silent on this.

  • Adacel (Sanofi Pasteur) (American Insert) - the vaccine was tested in 5 trials involving a total of 4,695 adolescents (10-17 years) and 2,448 adults (18-64 years). In one trial, the participants were monitored for some of the above listed reactions during the 14 daysfollowing vaccination. Reactions were compared to a control group that received a Td vaccine. Data was also gathered for adverse events necessitating medical support, starting on day 14, until 6 months after vaccination. The reports were made by interview at a 28 day follow-up and 6 month follow-up telephone call. Two serious adverse events occurred within 28 days following vaccination. They were one severe migraine with unilateral facial paralysis and one diagnosis of nerve compression in neck and left arm. Serious adverse events during the 6 month period were reported as occurring in 1.5% of Adacel recipients and 1.4% of Td recipients (not detailed). The vaccine was also tested in 1806 adolescents (11-17 years) who were monitored for some of the above listed reactions during the 14 days following vaccination. Participants could report unsolicited events during the 28 days after vaccination, and participants were monitored for serious events during that time. In a Canadian trial, the vaccine was tested on 762 adolescents and adults. Their reactions were compared to recipients who received a TD vaccine. The reactions were deemed similar to those experienced in four prior American trials. The package insert states, "Adacel vaccine has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility." FDA Link Here

  • Adacel-Polio (Sanofi Pasteur) (Canadian Insert) - was tested in 7 clinical trials that spanned a total of 644 children (age 3-7 years) and 992 adolescents and adults (age 11-60). The length of time that the participants were monitored for was not clearly defined, though from one table it appears that three of the studies followed the participants for 7 and 14 days. In the children studies, reactions to Adacel-Polio, were stated to be comparable to reactions observed in children who received an Adacel vaccine. The package insert states, "A review by the US Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome." The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • Boostrix (GSK) (Canadian Insert) - was tested in two trials on 1243 subjects. Of those subjects, a total of  211 children (under 10 years of age) and 448 adolescents (10 - 17 years of age) received Boostrix, while 119 adolescents received either Td or aP vaccines as control. The participants were monitored for some of the above listed reactions during the 15 days after vaccination, and those reactions experienced by Boostrix recipients were deemed comparable to the control groups. The vaccine was also tested on 839 children (age 4-9 years) and 1931 children, adolescents, and adults (over 10 years of age). It lists the rate of occurrence of some of the above listed reactions, but does not specify how long participants were monitored for. On the FDA website, the package insert for the American Boostrix vaccine states, "Boostrix has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility." Link Here The Canadian insert is silent on this.

  • Boostrix (GSK) (American Insert) - was tested in various clinical trials on a total of 4,949 adolescents (10-18 years). Of these adolescents, 1341 of them received a meningococcal vaccine at the same time. In one US study, 3,080 adolescents who received Boostrix, were compared to a control group of 1,034 adolescents who received Td vaccine. All participants were monitored for some of the above reactions in the 14 days following vaccination. Participants could also report unsolicited events for 31 days following vaccination. Unsolicited events were reported as occurring in 25.4% of Boostrix recipients and 24.5% of Td recipients. As well, participants were monitored for non-routine medical visits, ER visits, onset of new chronic illness, and serious adverse events, for 6 months following vaccination. In a German study, 319 children (10-12 years) were monitored for 15 days for some of the solicited events listed above, and for 31 days for unsolicited reactions. Participants were also monitored for 6 months after vaccination, for ER visits, onset of new chronic illness, and serious adverse events. Regarding serious adverse events, the insert states, "In the US and German adolescent safety studies, no serious adverse events were reported to occur within 31 days of vaccination. During the 6-month extended safety evaluation period, no serious adverse events that were of potential autoimmune origin or new onset and chronic in nature were reported to occur." (That phrasing leaves questions for me. Does that mean that participants with existing chronic autoimmune conditions which were previously stable, those stable conditions became worse following vaccination?) The insert goes on to state, "In non-US adolescent studies in which serious adverse events were monitored for up to 37 days, one subject was diagnosed with insulin-dependent diabetes 20 days following administration of BOOSTRIX. No other serious adverse events of potential autoimmune origin or that were new onset and chronic in nature were reported to occur in these studies." The inset states, "BOOSTRIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." FDA link Here

  • Boostrix-Polio (GSK) (Canadian Insert) - was tested on 908 children (age 4-9), who were monitored for several of the above listed reactions. It did not say how long they were monitored for, or if there was a comparison to control. The vaccine was also tested on 1931 subjects over 10 years of age (did not provide the distribution of children, adolescents and adults in that group). A detail of the rate of reactions was provided. The insert states, "Although an isolated and slight retardation of some ossification parameters was observed among dTpa-IPV treated [rat] fetuses on Day 20 gestation, no sustained effects were observed after parturition." The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • Imovax-Polio (Sanofi Pasteur) (Canadian Insert) - is a combination of 4 vaccines in one vial, for illnesses DTaP, IPV). This vaccine was tested on 395 participants (ages not specified. The participants were monitored for some of the above listed reactions. It did not say how long the participants were monitored for, or what vaccines were administered at the same time, or which comparator vaccine was used as control. The vaccine was also tested on 205 children (ages not specified), who were monitored for rates of fever. No other details were provided. The insert says the vaccine was also tested on 324 children (ages not specified) who received Imovax-Polio with or without DPT vaccine. The study concluded that Imovax-Polio was as well tolerated as when DPT was administered alone (DPT is no longer used in the US or Canada because of the severe side effects). The package insert states, "Although no causal relationship between IMOVAX® Polio and Guillain-Barré syndrome (GBS) has been established, GBS has been temporally related to administration of another inactivated poliovirus vaccine. An extensive review by the (US) Institute of Medicine of adverse events associated with vaccination suggested that no serious adverse events have been associated with IPV. Although no causal relationship has been established, deaths have occurred in temporal association after vaccination of infants with IPV." The package insert states, "No clinical trials with inactivated poliomyelitis vaccine have been conducted on pregnant women. Although there is no convincing evidence documenting adverse effects of inactivated poliomyelitis vaccine on the pregnant woman or the developing fetus, it is prudent on theoretical grounds to avoid vaccinating pregnant women." But, The National Advisory Committee on Immunization (NACI) says you can disregard the manufacturer's warning completely, because the package insert goes on to state, "The National Advisory Committee on Immunization (NACI) states that IPV is not contraindicated in pregnancy, but its administration should be delayed until after the first trimester, if possible, to minimize any theoretical risk. If risk of exposure is imminent, IPV should be given and is always the vaccine of choice except for outbreak control." In other words, they are saying, "Don't worry that we have no scientific data to refute the manufacturer's warning, our recommendation which is based on our belief, is that you and your baby will be okay! YAY! Vaccines for everyone!" The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here


POLIO VACCINES

  • 5 total doses given to Canadian infants and children: at 2, 4, 6 & 18 months of age, and at 4-6 years of age

  • 4 total doses given to American infants and children: at 2, 4 & 6-18 months of age, and at 4-6 years of age

The brands available in Canada, for Polio are:

  • Td Polio Adsorbed (Sanofi Pasteur) (Canadian Insert) - is a combination of 3 vaccines in one vial -Td, IPV). This vaccine is approved for use in children 7 years of age and older. This vaccine was tested on 40 participants (ages not specified) who had previously been vaccinated against diphtheria, tetanus, and polio. The participants were monitored for some of the above listed reactions during the 3 days following vaccination. The inset states, "A review by the US Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-BarrÈ syndrome. If Guillain-BarrÈ Syndrome occurred within 6 weeks of immunization with a previous dose of vaccine containing tetanus toxoid, the decision to give subsequent doses of Td POLIO ADSORBED or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks."  The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

Also, refer to the DTaP section above, for the DTaP combo vaccines that also contain Polio vaccination. These vaccines include:

  • Infanrix Hexa

  • Infanrix-IPV/Hib 

  • Infanrix-IPV

  • Quadracel

  • Pediacel

  • Adacel-Polio

  • Boostrix-Polio

  • Imovax-Polio


HAEMOPHILUS INFLUENZAE TYPE B (HIB) VACCINES

  • 4 total doses given to Canadian infants at: 2, 4, 6 & 18 months of age

  • 4 total doses given to American infants at: 2, 4, 6 & 12-18 months of age

The brands available in Canada for HIB are:

  • Act-HIB (Sanofi Pasteur) (Canadian Insert) - Very general information is provided on this insert, with few specific clinical trial details explained. The insert states that the vaccine has been tested in multiple clinical trials, carried out in multiple countries, involving more than 110,000 infants and children. The insert states that in almost all of the trials, the Act-HIB vaccine was injected with DPT or DTaP vaccines, and that reactions to Act-HIB were deemed comparable to reactions seen in participants who received DPT vaccine alone. In a later section of the insert where it provides a little more detail about the safety trials, the insert explains one specific safety trial (the number of participants is not specified). The insert then explains that participants received either Act-HIB + DPT vaccine at separate injection sites, or placebo + DPT vaccine given at separate injection sites. The participants in that trial were monitored for some of the above listed reactions during the 24 hours following vaccination. In that same section, the insert goes on to  mention a few other safety trials, specifying the number of participants enrolled in those various safety studies. The numbers of participants listed in that summary are as follows: 215 infants, 186 toddlers (18-months old), 68 infants, 62 toddlers (18-months old), and 66 toddlers (18-months old). So, if we are to believe that 110,000 infants and children did participate in various pre-licensing safety trials like the package insert alludes to, I question why the insert only highlights and details safety trial data involving a few very small groups of children, ranging from 62 participants to 215 participants. Based on those very low participant numbers, I suspect that the bulk of that "110,000 participants" number, were most likely a result of a post marketing observational study completed after the vaccine was licensed and was being used on a mass scale. If so, that 110,000 number is not actually reflective of the number of participants who were monitored during the more targeted and focused pre-licensing safety trials. The insert states, "No evaluation of Act-HIB® has been made with respect to its potential for carcinogenesis or mutagenesis." It is says that it's unknown whether the Act-HIBvaccine can cause fetal harm or affect fertility. The insert states, "The potential risk of apnea and the need for respiratory monitoring for 48 – 72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." Link Here

  • Act-HIB (Sanofi Pasteur) (American Insert) - The details are very sparse in this insert, and it appears that the insert phrases information very poorly and provides incorrect information. The insert states, "More than 7,000 infants and young children (≤2 years of age) have received at least one dose of 19 ActHIB vaccine during US clinical trials. Of these, 1,064 subjects 12 to 24 months of age who 20 received ActHIB vaccine alone reported no serious or life threatening adverse reactions." Wow! That statement could be read to mean that the majority of the participants, approximately 6,000 them, did experience a serious or life threatening adverse reaction to the vaccine. I believe their statement is actually alluding to the reality that few of the subjects participated in safety testing, and that approximately 6,000 of them participated in vaccine effectiveness testing only. It states that 110 children (15-20 months) received 3 doses of Act-HIB or a competitor HIB vaccine at 2, 4 & 6 months of age. Again, there's something wrong here. How can children who are 15-20 months of age be enrolled in an infancy study. Did they teleport those toddlers back in time so those toddlers could receive this vaccine at 2, 4, and 6 months of age? I doubt it, so I assume they've incorrectly stated the age of the participants. Whatever age those participants were, the children were monitored for some of the above listed reactions during the 48 hours following vaccination. The insert says that 1454 infants received 3 doses of Act-HIB at 2, 4 & 6 months of age. Of those participants, 418 of them also received a fourth dose at 15-18 months of age. In that trial, the Act-HIB vaccine was administered simultaneously with routine childhood vaccines, which included either Daptacel, Polio, Prevnar, Hep B, or combinations of those. The participants were monitored for some of the above listed reactions during the 3 days following vaccination. The insert states, "In Study P3T06, within 30 days following any of Doses 1-3 of DAPTACEL + IPOL + ActHIB vaccines, 50 of 1,455 (3.4%) participants experienced a serious adverse event. One SAE of seizure with apneaoccurring on the day of vaccination with the first dose of the three vaccines was determined by the investigators as possibly related." And Section 13.1 of the insert states, "ActHIB vaccine has not been evaluated for its carcinogenic or mutagenic potential or impairment of fertility." Link to FDA site Here

  • Hiberix (GSK) (Canadian Insert) - The details provided in the Adverse Events Reactions section are extremely sparse. This section provided 2 sentences of background, which read, "The following frequencies were based on the analysis of approximately 3000 infants enrolled in study Hib-097 and of approximately 1200 infants enrolled in study DTPa- HBV-IPV-011." From there, they provided a legend, and a short 12 line list that encompassed 12 potential side effects, all of which I've listed above. No information was provided for the placebo or comparator vaccine used, or how long the participants were monitored for following vaccination. The insert states, "The potential risk of apnea and the need for respiratory monitoring for 48- 72h should be considered when administering the primary immunization series to very premature infants (born 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." Section 13.1 of the American insert states, "HIBERIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." Link to FDA website Here The Canadian insert is silent on  this. Link Here

  • Hiberix (GSK) (American Insert) - The insert states that 2963 infants (2, 4 & 6 months old) were vaccinated with 3 total doses of Hiberix at those ages. A separate group of 520 control participants received a competitor HIB vaccine also at 2, 4 & 6 months of age, and a third group of 520 control participants received a DTaP-IPV/HiB vaccine at 2, 4 & 6 months of age. For the Hiberix group and competitor group, the participants received routine vaccines simultaneously, including Pediarix + Prevnar vaccines during doses 1, 2 & 3, and Roatarix vaccine with doses 1 & 2. The DTaP-IPV/Hib group received routine vaccine simultaneously, including Prevnar 13 + Engerix B vaccines with doses 1, 2 & 3, and Rotarix vaccines with doses 1 & 2. The participants were monitored for some of the above listed reactions during the 4 days following vaccination. The insert explains that the vaccine was tested in 7 additional trials conducted in various countries. 530 children (11-25 months) received a booster dose of Hiberix with simultaneous routinely recommended vaccines of their country. 478 control participants received one of two possible competitor Hib vaccines. It does not say how long the participants were monitored for, nor did it provide a table or description explaining the reactions experienced. In a German study, a booster dose of Hiberix was tested on 371 children (mean age 16 months). Hiberix was administered simultaneously with DTaP-HBV-IPV vaccine. The participants were monitored for some of the above listed reactions during the 4 days following vaccination. The insert states, "In Study 1, one of 2,963 subjects who received HIBERIX and coadministered vaccines given at 2, 4, and 6 months of age experienced a SAE which was in temporal association with vaccination and had no alternative plausible causes (convulsion on Day 14 after Dose 1)."The insert states, "Apnea following intramuscular vaccination has been observed in some infants born prematurely." Section 13.1 of the insert states, "HIBERIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." Link to FDA website Here

  • See also Infanrix Hexa and Pediacel  in the DTaP section above


PNEUMOCOCCUS VACCINES:

  • 3 total doses given to Canadian infants at: 2, 4, & 12 months of age

  • 4 total doses given to American infants at: 2, 4, 6 & 12 months of age

The brands available for pneumococcus are:

  • Prevnar 13 (Pfizer) (Canadian Insert) - the insert states that safety was assessed through 13 controlled clinical trials, involving 4729 health infants (age 6 weeks to 16 months). It appears from statements made that the "new" formulation of this vaccine, Prevnar 13, was compared against the previous version, Prevnar 7. It does not say how long the children were monitored for post vaccination. The participants were monitored for some of the above listed reactions. It states that all trials and all children received routine vaccines simultaneously with Prevnar. The insert states, "During the 13 controlled clinical trials, death occurred in 4 (out of 7,489) infants. All 4 cases were attributable to Sudden Infant Death Syndrome (SIDS). Three (out of 4,729 cases receiving 15,739 doses) cases were among Prevnar 13 recipients, and 1 (out of 2,760 cases receiving 9,030 doses) was in the Prevnar (7-valent) group. None of these cases were assessed by the investigator as causally related to vaccination."  (Again, we do not know if never vaccinated infants experience SIDS deaths at a comparable rate). The vaccine was also tested on 592 children and adolescents (age 5 to 17 years). The participants were monitored for some of the above listed reactions during the 7 days following vaccination. There was no mention of whether the vaccine was administered simultaneously with other vaccines, or was compared to a different vaccine as the control. The vaccine was also tested in 158 children (6-17 years) with sickle cell disease, stating that reactions were comparable to those experienced in healthy children. The vaccine was also tested in 150 HIV infected children (age 6-17 years). Those children were monitored for some of the above listed reactions during the 14 days following injection. The insert states, "the potential risk of apnea should be considered when administering the primary immunization series to premature infants. The need for monitoring for at least 48 hours after vaccination should be considered for very premature infants (born ≤ 30 weeks of gestation)"... The insert also states, "Increased reporting rates of convulsions (with or without fever) and hypotonic-hyporesponsive episode (HHE) were observed with concomitant administration of Prevnar 13 and Infanrix hexa." The insert on the FDA website states, "Prevnar 13 has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility. In a study in rabbits, no vaccine-related effects were found regarding reproductive performance including female fertility." FDA Link Here The Canadian insert is silent on this but does describe the rabbit study. Link Here

  • Prevnar 13 (Pfizer) (American Insert) - This insert quotes the same 13 studies on 4,729 infants and the same study on 592 children and adolescents that were referenced in the Canadian insert. The American insert provided some additional information as follows. The 13 infant studies compared reactions from Prevnar 13, to reactions experienced by a group of 2,760 control subjects who received at least one dose of Prevnar (the previous formulation). Reactions between the two groups were deemed comparable. It states that 7 of those infant studies had data for a 6 month follow-up. It read that in 3 of the US studies the Prevnar vaccine was administered simultaneously with routine vaccines and participants were monitored for some of the above listed reactions during the 7 days following vaccination. Unsolicited reactions could be reported from day one of receipt of the first vaccine, until 1 month after receipt of the third infant dose (5 months time). In the toddler group, parents could report unsolicited reactions for 1 month following receipt of the toddler dose. It explains that unsolicited reactions, serious adverse events, newly diagnosed medical conditions and hospitalizations, occurring since the last visit, could be reported during the clinic visit of the forth-study dose, as well, during a follow-up telephone interview occurring 6 months after the forth-study dose (16 months time). The insert states, "Serious adverse events were collected throughout the study period for all 13 clinical trials. This reporting period is longer than the 30-day post-vaccination period used in some vaccine trials. The longer reporting period may have resulted in serious adverse events being reported in a higher percentage of subjects than for other vaccines...The most commonly reported serious adverse events were in the ‘Infections and infestations’ system organ class including bronchiolitis (0.9%, 1.1%), gastroenteritis, (0.9%, 0.9%), and pneumonia (0.9%, 0.5%) for Prevnar 13 and Prevnar respectively. There were 3 (0.063%) deaths among Prevnar 13 recipients, and 1 (0.036%) death in Prevnar recipients, all as a result of sudden infant death syndrome (SIDS). These SIDS rates are consistent with published age specific background rates of SIDS from the year 2000. Among 6,839 subjects who received at least 1 dose of Prevnar 13 in clinical trials conducted globally, there was 1 hypotonic-hyporesponsive episode adverse reaction reported (0.015%). Among 4,204 subjects who received at least 1 dose of Prevnar in clinical trials conducted globally, there were 3 hypotonic-hyporesponsive episode adverse reactions reported (0.071%). All 4 events occurred in a single clinical trial in Brazil in which subjects received whole cell pertussis vaccine at the same time as Prevnar 13 or Prevnar." The insert also states, "Apnea following intramuscular vaccination has been observed in some infants born prematurely." The inserts states, "Prevnar 13 has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility. In a study in rabbits, no vaccine-related effects were found regarding reproductive performance including female fertility." Link Here

  • Synflorix (GK) (Canadian Insert) - safety was based on clinical trials involving 22,500 healthy children and 137 premature infants receiving the primary vaccination series (3 doses). Of those participants, 19,500 healthy children and 116 premature infants received a booster dose in the second year of life. The vaccine was also tested in 400 children (age 2-5 years). In all trials, Synflorix was administered simultaneously with other vaccines. Participants were monitored for some of the above listed reactions during the 4 days following vaccination and reactions in Synflorix recipients were compared to a group that received the competitor pneumococcal vaccine Prevnar, as control. 21 deaths were reported during the infant trials, one of which was deemed to be caused by the vaccine. The insert also states, "Fatal [serious adverse events] SAEs were reported for 5 HIV+/+ infants and 3 HIV+/- infants during the post- primary phase and for 1 HIV+/- infant during the post-booster phase. Among these fatal SAEs, 1 HIV+/- infant was assessed by the investigator to be causally related to vaccination (sudden infant death syndrome) given the time interval between vaccination and the onset of the event (3 days)." The insert also states, "The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunization series to very premature infants (born 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." The insert discusses occurrences of large swelling reactions, describing that 2 cases resulted in swelling which lasted 32 and 33 days. It also stated, "Serious Adverse Events (SAE) following vaccination in healthy populations: Fifteen out of 22,429 subjects (0.07%) receiving primary vaccination with SYNFLORIX and three out of 1461 7-valent PCV vaccinees (0.2%) experienced an SAE that was assessed by the investigator as causally related to vaccination." Details of each SAE were not provided. The insert states, "SYNFLORIX has not been evaluated for the potential to cause carcinogenicity or genotoxicity...No studies on reproductive and developmental toxicity have been performed. This vaccine is not intended for women of child-bearing potential." Link Here

  • Pneumovax 23 (Merck) (Canadian & American Inserts) - This vaccine is approved for use in children over 2 years of age. There was no safety data provided for children or adolescents in either the Canadian or American package insert. The only clinical trial safety data provided was for the adult population. The insert stated that adverse reactions in the population >65 increased at re-vaccination, and that the reactions in the >65 group were comparable to those reactions seen in the 50-64 population. The inserts said that the adult participants were monitored for 3 days. The American insert stated that participants received either a saline placebo, followed later by Pneumovax 23 vaccine, OR  they received Pneumovax 23, followed later by saline placebo, at 30 day intervals. The American insert explained that Initial vaccination was evaluated in a total of 444 subjects and revaccination was evaluated in 564 subjects. Both the Canadian and American inserts are silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Canadian Insert Here, FDA link Here


ROTAVIRUS VACCINES:

  • 2 total doses given to Canadian infants at: 2 & 4 months of age

  • 3 total doses given to American infants at: 2, 4, & 6 months of age

The vaccines for Rotavirus appear to provide more safety data than is provided in the other vaccine inserts. The Rotavirus package inserts each provide a listing of several clinical studies and observational studies, following the health of 10,000s and 100,000s of children. Post marketing observational studies are studies conducted after a vaccine is licensed and being used on the public in a mass scale.

The brands available in Canada, for rotavirus are:

  • Rotarix (GSK) (Canadian Insert) - An overview of 23 clinical studies stated that the health of 51,000 infants was monitored. The overview description didn't provide the time frame for which the participant's health was monitored. The package insert also states, "In a total of four clinical trials, approximately 3,800 doses of ROTARIX® liquid formulation were administered to approximately 1,930 infants. Those trials have shown that the safety and reactogenicity profile of the liquid formulation is comparable to the lyophilized formulation...In three placebo controlled clinical trials (Finland, India and Bangladesh), in which, ROTARIX® lyophilized formulation was administered alone (administration of routine pediatric vaccines was staggered), the incidence and severity of the solicited events (collected 8 days post vaccination), diarrhea, vomiting, loss of appetite, fever, irritability and cough/runny nose, were not significantly different in the group receiving ROTARIX when compared to the group receiving placebo." Though they mention the word placebo here, I question whether or not it was a genuine saline placebo or whether the placebo used vaccine ingredients or a competitor vaccine. There have been occurrences where the manufacturer calls something a placebo, but that control used was actually a different vaccine or a solution that contained vaccine ingredients. In addition to the overview, they provide a listing of other safety evaluations completed, where it appears the health of 63,225 children, was monitored for 31 days post vaccination, to monitor for a severe adverse event called intussusception (a different rotavirus vaccine was recalled for causing this medical condition). Placebo information was not provided. The package insert states, "The risk of intussusception has been evaluated in a large safety trial (including 63,225 infants) conducted in Latin America and Finland. No increased risk of intussusception was observed in this clinical trial following administration of ROTARIX® when compared with placebo...However, post-marketing safety studies indicate an increased incidence of intussusception after vaccination, mostly within 7 days of the first dose...It has not been established whether ROTARIX® affects the overall risk of intussusception" The insert also states, "In 11 other clinical studies (N=12,220) there were 7 cases of intussusception reported, 5 cases in HRV vaccinees and 2 cases in placebo recipient. It is to be highlighted that none of these studies were powered to compare the incidence of intussusception in the ROTARIX® and placebo groups." The insert also says, "In 8,262 infants enrolled and vaccinated in 10 completed trials, a total of 18 deaths were reported: 12 deaths in ROTARIX® (0.19%, N=6,290) and 6 in placebo (0.30%, a N=1,972). In the large safety study (Rota-023), 99 deaths occurred during the study : 56 in ROTARIX® group (N=31,673) and 43 in the placebo group (N=31,552). None of the cases were assessed as related to vaccination." Link Here. The package insert on the FDA website states, "ROTARIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." FDA Link Here The Canadian insert is silent on this.

  • Rotarix (GSK) (American Insert) - the vaccine was tested in 7 trials involving a total of approximately 7,984 infants (ages not specified) who were monitored for some of the above listed reactions during the 8 days following vaccination. Unsolicted events could be reported for 31 days, and serious adverse events (SAE)  were monitored for 31 days following vaccination. An additional trial was conducted on 63,225 infants to look at the risk of intussusception. Of the 8 total studies sited on the insert, it states that 36,755 infants received Rotarix, and 34,454  received placebo. It does not state if the placebo was saline or a competitor rotavirus vaccine. Regarding the risk of intussusception the insert states, "Following administration of a previously licensed oral live rhesus rotavirus-based vaccine, an increased risk of intussusception was observed. The risk of intussusception with ROTARIX was evaluated in a pre-licensure randomized, placebo-controlled safety study (including 63,225 infants) conducted in Latin America and Finland. No increased risk of intussusception was observed in this clinical trial following administration of ROTARIX when compared with placebo. In a postmarketing, observational study conducted in Mexico, cases of intussusception were observed in temporal association within 31 days following the first dose of ROTARIX, with a clustering of cases in the first 7 days. Other postmarketing observational studies conducted in Brazil and Australia also suggest an increased risk of intussusception within the first 7 days following the second dose of ROTARIX. In worldwide passive postmarketing surveillance, cases of intussusception have been reported in temporal association with ROTARIX." The  insert also states, "During the entire course of 8 clinical studies, there were 68 (0.19%) deaths following administration of ROTARIX (N = 36,755) and 50 (0.15%) deaths following placebo administration (N = 34,454). The most commonly reported cause of death following vaccination was pneumonia, which was observed in 19 (0.05%) recipients of ROTARIX and 10 (0.03%) placebo recipients." The package insert states, "Infants with a history of intussusception should not receive ROTARIX. In postmarketing experience, intussusception resulting in death following a second dose has been reported following a history of intussusception after the first dose." It states, "Infants with Severe Combined Immunodeficiency Disease (SCID) should not receive ROTARIX. Postmarketing reports of gastroenteritis, including severe diarrhea and prolonged shedding of vaccine virus, have been reported in infants who were administered live, oral rotavirus vaccines and later identified as having SCID." It also states, "Rotavirus shedding in stool occurs after vaccination with peak excretion occurring around Day 7 after Dose 1. One clinical trial demonstrated that vaccinees transmit vaccine virus to healthy seronegative contacts." The insert states, "ROTARIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility." FDA link Here

  • Rotateq (Merck) (Canadian Insert) - The overview states that 71,725 infants were evaluated in 3 placebo-controlled clinical trials (Study 006, Study 007, and Study 009) including 36,165 infants who received RotaTeq® and 35,560 infants who received placebo. Information on whether the placebo was saline or a competitor rotavirus vaccine was not provided. Parents/guardians were contacted on days 7, 14, and 42, and 6 weeks thereafter for 1 year after the 1st dose. Participants were monitored after each dose for intussusception and any other serious adverse events. The conclusion of the trial was, "RotaTeq® did not increase the risk of intussusception relative to placebo." The package insert also states, "In a prospective post-marketing observational study conducted in the U.S. using a large medical claims database, the risk of intussusception resulting in emergency department visits or hospitalizations during the 30 days following any dose of vaccine was analyzed among 85,150 infants receiving one or more doses of RotaTeq®. During the 0–30 day follow-up period after vaccination, there was no statistically significant difference in the rate of intussusception compared with the expected background rate. A Vaccine Safety Datalink Study in the U.S. assessed the rate of intussusception in the 1–7 and 1–30 day period after vaccination with RotaTeq®. There was no statistically significant increased risk of intussusception after any dose or after the first dose in either the 1–7 day or 1–30 day period after vaccination compared with the rate in concurrent, unvaccinated controls. However, a self controlled case series analysis was undertaken in Australian infants immunized between June 2007 and December 2009 to evaluate cases of intussusception in the 21 day period following any vaccination with rotavirus vaccines. Preliminary data from this study indicates the likelihood of a small increased risk of intussusception following the first dose of RotaTeq®  In worldwide post-marketing surveillance, cases of intussusception have been reported in temporal association with RotaTeq." The insert also states, "Serious adverse events occurred in 2.4% of recipients of RotaTeq® when compared to 2.6% of placebo recipients within the 42-day period of a dose in the phase 3 clinical studies of RotaTeq®. The most frequently reported serious adverse events for RotaTeq® compared to placebo were: bronchiolitis (0.6% RotaTeq® vs. 0.7% Placebo), gastroenteritis (0.2% RotaTeq® vs. 0.3% Placebo), pneumonia (0.2% RotaTeq® vs. 0.2% Placebo), fever (0.1% RotaTeq® vs. 0.1% Placebo), and urinary tract infection (0.1% RotaTeq® vs. 0.1% Placebo). Deaths: Across the clinical studies, 52 deaths were reported. There were 25 deaths in the RotaTeq® recipients compared to 27 deaths in the placebo recipients. The most commonly reported cause of death was sudden infant death syndrome (SIDS), which was observed in 8 recipients of RotaTeq® and 9 placebo recipients." The insert also states, "Seizures reported as serious adverse experiences occurred in <0.1% (27/36,150) of vaccine and <0.1% (18/35,536) of placebo recipients (not significant). Ten febrile seizures were reported as serious adverse experiences, 5 were observed in vaccine recipients and 5 in placebo recipients." The insert also states, "Administration of other licensed vaccines was permitted in all studies. The insert also states, "RotaTeq® has not been evaluated for its carcinogenic or mutagenic potential or its potential to impair fertility." Link Here


MENINGICOCCAL VACCINES:

  • 3 total doses given to Canadian infants and adolescents: at 4 & 12 months of age, and in grade 9

  • 2 total doses are given to American children and adolescents at: 11 & 16 years of age

The brands available in Canada, for meningicoccal are:

  • Bexsero (GSK) (Canadian Insert) - was tested in 8 trials on 4,843 infants and children(less than 2 years of age), and 1,584 adolescents and adults (11+ years). The participants were monitored for some of the above listed reactions during the 7 days following vaccination. The Bexsero reaction data was compared to reactions experienced from different vaccines (Prevnar, Infanrix-Hexa, Menjugate), and the various reactions were considered mild to moderate in severity and were deemed comparable between the different groups. Some of the severe reactions in the Bexero group were listed as follows, unusual crying - high-pitched screaming unlike the child's usual crying, lasting for 3 hours or longer, occurred in 5% of Bexsero recipients, fever above 40° occurred in 1% of Bexero recipients, and 1% of Bexsero recipients needed medical assistance for their fevers. This insert includes a Consumer Information section, and within this section it states, "Side effects that have been reported during marketed use include: ...Collapse (sudden onset of muscle floppiness), less responsive than usual or lack of awareness, and paleness or bluish skin discoloration in young children;" The insert also states, "There are no data on fertility in humans." Link Here. The package insert also states, "Adverse reactions (following primary immunization or additional dose) considered as being at least possibly related to vaccination have been categorized by frequency," at which point it lists the following adverse events, seizures, eczema, Kawasaki syndrome. The American package insert on the FDA website states, "BEXSERO has not been evaluated for carcinogenic or mutagenic potential or impairment of male fertility."Link Here The Canadian insert is silent on this.

  • Bexsero (GSK) (American Insert) - was tested in a total of 4 clinical trials (3 controlled and one uncontrolled) on 3,058 children and adults (10-25 years). One of those trials was conducted in the US and Poland, involving 120 children and adults (distribution of ages not provided) who received at least 1 dose of Bexsero, with 112 participants receiving 2 doses 2 months apart. In a control group, 97 participants received a saline placebo, followed by a Menveo vaccine. One of those four trials involved 1622 adolescents (11-17 years), and was conducted in Chile. Those recipients received at least 1 dose of Bexsero, with a subset group of 810 recipients receiving 2 doses at 1 or 2 months apart. A control group of 128 subjects received at least 1 dose of placebo containing aluminum hydroxide (a vaccine ingredient). A subgroup of 128 subjects received 2 doses of Bexsero 6 months apart. One of those four trials was an uncontrolled study, conducted in Canada and Australia, where the  vaccine was tested on 342 adolescents (11-17 years) who received at least 1 dose, with 338 participants receiving 2 doses 1 month apart. The insert is not clear in explaining how long those four trials monitored the participants for reactions listed above. One trial shows the participants were monitored for 7 days. Serious adverse events, medically attended adverse events, and adverse events leading to premature withdrawal were collected throughout the study period, in Chile for 12 months, US/Poland 8 monthsand Canada/Australia 2 months. Of the 4 clinical trials involving 3,058 participants (10-25 years), 66 (2.1%) of participants reported a serious adverse event at any time during the study. In the 3 controlled studies involving 2,716 Bexsero recipients and 2,078 control recipients, serious adverse events were reported in 23 (0.8%) of Bexsero recipients and 10 (0.5%) of control recipients in the 30 days following vaccination. The package insert states, "BEXSERO has not been evaluated for carcinogenic or mutagenic potential or impairment of male fertility." FDA link Here

  • Menveo (GSK) (Canadian Insert) - The safety introduction states, "In most studies, solicited local reactions and systemic adverse events were monitored daily for 7 daysfollowing vaccination and recorded on a diary card. Participants were monitored for at least 28 days for unsolicited adverse events requiring a physician visit, Emergency Department visit or which led to a subject’s withdrawal from the study." The vaccine was tested in 3 trials on 8,735 infants (2, 4, 6 and 12-16 months of age), where routine vaccines were given simultaneously (DTaP, IPV, Hep B, HIB, Rotavirus, Pneumoccocal) or (Pneumoccocal, MMRV, Hep). Reactions were compared to a group of 2,864 children who received routine vaccines only. Reactions between the different groups were deemed to be comparable. The table detailed that 1 or 2 children in each of the different vaccinated groups experienced persistent crying lasting for 3 hours or longer. The vaccine was also tested in 3 randomized trials, one of which involved 1,985 children (7- 23 months), who received Menveo with simultaneous MMRV vaccine. The vaccine was also tested in 4 trials on 3,181 children (aged 2-10). Reactions were compared to those experienced in a group of 2,190 children who received a comparator vaccine (either Menomune, Menactra, or Mencevax). The vaccine was also tested in 6,185 adolescents and adults (age 11-55). The reactions experienced were compared to groups that either received Menveo + simultaneous routine vaccines (Boostrix or Boostrix + HPV), or received comparator vaccines (either Menomune or Menactra). The insert states that rates of solicited adverse reactions were comparable to groups receiving only routine vaccines or comparator vaccines. The insert states, "As with all injectable pediatric vaccines, the potential risk of apnea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." Regarding serious adverse events, the package insert states, "The most common serious adverse events reported in these three [infant] studies were wheezing, pneumonia, gastroenteritis and convulsions, and most occurred at highest frequency after the infant series." It also says, "Across the submitted studies of individuals 2 through 23 months of age, within 28 days of vaccination, two deaths were reported in the Menveo treatment groups (one case of sudden death and one case of sepsis), while no deaths were reported in the control group." For the 2-10 year population, the insert states, "In the subjects receiving either one or two doses of Menveo, there were 6 subjects with pneumonia, 3 subjects with appendicitis, and 2 subjects with dehydration...The serious adverse events occurring within the first 30 days of vaccination were as follows: Menveo (6/2883 [0.2%]) – appendicitis, pneumonia, staphylococcal infection, dehydration, febrile convulsion, and tonic convulsion"In the 11-55 year age bracket, the insert states, "During the 6 months following immunization, serious adverse events reported by more than one subject were as follows: Menveo - appendicitis (3 subjects), road traffic accident (3 subjects), and suicide attempt (5 subjects)...The events that occurred during the first 30 days post immunization with Menveo were: vitello-intestinal duct remnant; Cushing’s syndrome; viral hepatitis; pelvic inflammatory disease; intentional multiple drug overdose; simple partial seizure; and suicidal depression." The package insert states, "There are no data to demonstrate whether or not Menveo affects reproductive capacity" Link Here. The American package insert on the FDA website states, "MENVEO has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility." Link Here The Canadian insert is silent on this.

  • Menveo (GSK) (American Insert) - The same clinical trials were referenced, as described in the Canadian package insert, and the information was presented in a similar way. One difference noted was in the serious adverse event section. In the 2-23 month age group the American insert describes that 3 Menveo recipients (of 12,049 total) were diagnosed with Kawaski disease, compared to zero control recipients (of 2,877 total). Symptom onset began within 42 days after vaccination. The package insert also states, "One case of acute disseminated encephalomyelitis with symptom onset 29 days post-dose 4 was observed in a participant given MENVEO co-administered with routine US childhood vaccines at 12 months of age (including MMR and varicella vaccines)." The insert also states, "Guillain-Barré syndrome (GBS) has been reported in temporal relationship following administration of another U.S.-licensed meningococcal quadrivalent polysaccharide conjugate vaccine." And that, "Apnea following intramuscular vaccination has been observed in some infants born prematurely." The insert states, "MENVEO has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility." ink Here

  • Menactra (Sanofi Pasteur) (Canadian Insert) - was tested in 4 clinical trials involving 3,569 infants and toddlers (9 months and 12-15 months old), with 2,455 of those children receiving routine vaccines simultaneously with their second dose. The participants were monitored for some of the above listed reactions during the 7 days, 30 days and 6 months post vaccination. In the reaction table, it explains that 1.8% of infants at the 9 month dose, and 2.2% of infants at the 12 month dose, experienced abnormal crying, lasting longer than 3 hours. Reactions were compared to a group of 797 children who received routine vaccines only. Reactions reported between the various vaccinated groups were deemed to be similar. The vaccine was also tested in 3 clinical trials on 2,400 children (age 2-10 years). The participants reactions were compared to a group of 2,200 children who received a comparator vaccine (Menomune). All participants were monitored for some of the above listed reactions during the 7 days, 28 days and 6 months post vaccination, and reactions between the two groups were deemed to be comparable.  The vaccine was also tested in 6 clinical trials on 7,640 adolescents and adults (aged 11-55 years). The reactions experienced in this group were compared to a group of 3,041 adolescents and adults who received a comparator vaccine (Menomune). All participants were monitored for some of the above listed reactions during the 7 days following vaccination, and reactions rates were deemed comparable and mild in intensity. Link Here. The American package insert on the FDA website states, "Menactra has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility." Link Here The Canadian insert is silent on this.

  • Menactra (Sanofi Pasteur) American Insert) - A total of 4 trials involving 3,721 infants, (age 9 and 12 months) tested the vaccine by administering 1 dose of Menactra at both 9 and 12 months of age. With the second dose, infants received either MMRV or MMR + V, with pneumococcal + Hep A vaccines simultaneously. A control group of 997 infants received MMRV or MMR + V, with pneumococcal + Hep A vaccines, excluding Menactra. One of those studies was the  primary safety evaluation, involving 1,256 infants, and 552 control infants. A table details the reactions (some of the listed above)  experienced after the various vaccine combinations. The vaccine was also tested in 8 trials, involving 10,057 Menactra recipients (2-55 years), and 5,266 control participants who received comparator vaccine Menomumne. Within those trials, the distribution of ages was approximately 2,414 children (2-10 years), 1,629 children and adolescents (11-14 years), 4,063 adolescents and adults (15-25 years), and for the control group, 2,228 children, 490 children and adolescents, and 1580 adolescents and adults. The three primary safety evaluations within those 8 trials, involved 1,713 children (2-10 years) who received Menactra and 1,519 controls who received Menomune, and 2,270 adolescents (11-18 years) who received Menactra and 972 controls who received Menomune. All participants were monitored for 7 days for some of the above listed reactions, as well as 30 days (28 for infants and toddlers) for unsolicited adverse events, and 6 months for ER visists, unexpected visits to a physician's office, and serious adverse events. Tables throughout the insert detail the rates of reactions experienced by the different vaccinated groups. Regarding serious adverse events, the insert states that at 9 months of age, 2.0-2.5% of participants experienced a serious adverse event, with the higher rate occurring in the group receiving simultaneous routine vaccines. In the 12 month age group, 1.6-3.6% of recipients experienced a serious adverse event, depending on the number of vaccines received. In the 2-10 year age group, the rate of serious adverse event was 0.6% in the group that received Menactra and 0.7% in the group that received Menomune. In the 11-18 year age group, 1% of Menactra recipients experienced a serious adverse event compared to 1.3% of Menomune recipients. A description of the serious adverse events was not provided. The insert states, "Menactra has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility." Link Here

  • Menjugate (GSK) (Canadian Insert) - The trials are listed as follows: In 2 clinical trials,involving a total of 642 infants (monitored at age 2, 3 and 4 months, or 2, 4, and 6 months) each infant received up to three total doses of Menjugate, with simultaneous Pentacel vaccine (DTaP+HIB+IPV). The participants were monitored for some of the above listed reactions during the 7 days following vaccination. In another clinical trial, 175 infants (age 2, 4, and 6 months), received a total of three doses of Menjugate and simultaneous Pentacel vaccine. Their reactions were compared to a control group that received 3 total doses of hepatitis B vaccine and simultaneous Pentacel vaccine.  Reactions were summarized as being predominantly mild, and comparable to reactions experienced following administration of  control vaccines. The insert states, "In infants and children aged 12 through 23 months, symptoms including crying, irritability, drowsiness, impaired sleeping, anorexia, diarrhea and vomiting were common after vaccination but there was no evidence that these were related to Menjugate rather than concomitant vaccines, particularly DTP." (That is an incredible statement! Unlike most package inserts, this one actually acknowledges that by administering routine vaccines simultaneously with the test vaccine, they impaired their ability to determine the adverse effects specific to the Menjugate vaccine)  A trial involving 6,700 infants through adults (didn't specify breakdown of ages), monitored participants for severe adverse events (SAE). The insert states, "There were four SAEs which were considered to be at least possibly related to vaccine. These were one report each of: hypotonia, screaming syndrome, maculopapular rash and agitation, all of which occurred in an open label infant study conducted in the United Kingdom (UK), in which Menjugate was administered concomitantly with DTP, Hib and OPV vaccines. Because these reactions have been reported previously in conjunction with DTP vaccines alone, a causal relationship between these experiences and Menjugate administration cannot be established." Data from 11 clinical trials was summarized, stating that Menjugate was tested on 942 toddlers (1-2 years), 198 children (3-5 years) and 269 children adolescents, and adults (11-64 years). The participants were monitored for some of the above listed reactions during the 7 days following. Comparator information was not provided. The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • NeisVac-C (Pfizer) (Canadian Insert) - In this package insert the details are very sparse, though they did provide a table of reactions and rates of occurrence. Examples of the phrasing used include, "clinical studies [were] performed in all age groups, signs and symptoms were actively monitored and recorded." It did not specify the number of participants in each age group that tested the vaccine, nor did they provide a time frame that reactions were monitored for. Comparator vaccine information was not given. It stated that for infants, toddlers, and some children, NeisVac-C was administered with one or two multivalent vaccines simultaneously (didn't specify which). The insert states, "In infants and toddlers, and partially in children, NeisVac-C® has been administered concomitantly with one or two other routine multivalent pediatric vaccines. In some studies, NeisVac-C® and another vaccine were administered in the same limb. Therefore, the adverse reactions listed in the table above, for the respective age groups, may represent a cumulative effect of the administration of these vaccines." The insert states, "The potential risk of apnea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunization series to very premature infants (born 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity." The insert also states, "In rare cases, in patients with pre-existing nephrotic syndrome (kidney disease), reoccurrence has been reported to present within a few months following vaccination with meningococcal group C polysaccharide conjugated vaccines. Signs of reoccurrence include angioedema (see definition in list above), proteinurea (protein in urine) and/or abnormal weight gain." (This insert is acknowledging that vaccine side effects can present months after vaccination, and yet vaccine safety testing rarely follows the participants for more than two weeks). The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • Nimenrix (Pfizer) (Canadian Vaccine) - The vaccine was tested on 3,079 toddlers (age 12-23 months) who either received Nimenrix alone, or Nimenrix with a first dose of Priorix Tetra. All participants were monitored for some of the above listed reactions during the 4 days following vaccination. The vaccine was also tested on 1,899 children (2 - 10 years of age). Participants received Nimenrix or the comparator MenC-CRM vaccine as control, and all participants were monitored for 4 days following vaccination. The vaccine was also tested on 2,317 adolescents (11-17 years of age). Participants received Nimenrix or the competitor vaccine Menactra as control, and all participants were monitored for 4 days following vaccination. The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential. Link Here


INFLUENZA VACCINES

  • 2 doses given 1 month apart to American and Canadian infants

  • 1 dose annually, for everyone else even during pregnancy, for the duration of life

The brands available in Canada for influenza are:

  • Agriflu (Seqirus) (Canadian Insert) -  The insert states, "safety data are limited in 6 to 35 months old children." Agriflu was tested on 93 infants and toddlers (age 6-36 months). It was also tested on 402 children (age 3-8 years) and 400 children and adolescents (age 9-17 years). The participants were monitored for some of the above listed reactions during the 4 days following vaccination. The insert states, "Limited data are available from vaccinations with AGRIFLU® in pregnant women... NACI considers influenza vaccination safe during pregnancy. NACI recommends influenza vaccination in pregnant women with high-risk conditions at any stage during pregnancy." It also states, "A trend toward a lower gestation index and fewer animals [rabbits] with surviving litters in the AGRIFLU® groups compared to control groups did not reach statistical significance, and was not considered to be related to toxicity of the vaccine. The clinical relevance, if any, of this finding is not known because, on a body weight basis, each dose administered to rabbits was approximately 15 times the human dose, and studies in pregnant women have not been conducted." The insert also states, "AGRIFLU® has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility." Link Here

  • Agriflu (Seqirus) (FDA - Reproduction Toxicity Study) - Though I couldn't find the American package insert for Agriflu on the FDA website, details of the Agriflu reproduction toxicity study were provided there. FDA documents show that the vaccine was tested on rabbits, with 3 doses given prior to mating, and two more 2 doses given during pregnancy. The rabbits were vaccinated with Agriflu vaccine at 15 times the human dose. A control group of rabbits was injected with saline at 5 different times, following the same schedule as the Agriflu vaccinated group. The study describes that for both the control pups and vaccinated pups that were born naturally, instead of by caesarean, those pups died at an increased rate. So many pups died in the natural delivery arm of the initial trial, that there was not enough data to work with. As a result, a second study was conducted to repeat the natural delivery arm. The study goes on to state, "Animals were dosed on study days (DS) -1, -15 and -29 prior to mating and on gestation days 7 and 20 either with Agrippal vaccine, 0.5 ml, I.M., 45 ug antigen or saline control. Animals were allowed to rear their offspring. Three does died in the vaccine treated group, however data are within the range reported in historical data. Beginning on DG7 – DG 26, mean absolute and relative feed consumptions values in the vaccine treated group were significantly reduced compared to the control group values. There were slight differences in reproductive parameters, i.e., the number of rabbits achieving pregnancy in the vaccine treated group was slightly decreased compared to the control group, 21 and 25 does, respectively, there were differences in the fertility index (92.6% in control group and 80.0% in the vaccine group) and gestation index (100% in control group and 85.7% in the vaccine group) . The pregnancy rate was 92.6% in control group compared to 77.8% in vaccine treated group. In addition, the number of liveborn pups in the vaccine treated group (82.0%) was reduced compared to the number of liveborn pups in the control group (92.0 %). Importantly, when calculating the viability indices based on the numbers of pups dead/euthanized between DL 1-7, the results are 52.5% (control group) and 66.4% (vaccine group). These values are markedly lower than the viability index observed for the same interval in the historical control data base (87.3% (81.6-96.7), historical data from 3 studies)." Study Here FDA Link Here

  • Fluad Pediatric (Seqirus) (Canadian insert) - Fluad was tested on 1,800 infants and toddlers (age 6 months to less than 2 years). 2,083 infants and toddlers received a comparator influenza vaccine as control, and 208 infants and toddlers received a non-influenza vaccine, also as control. All participants were monitored for some of the above listed reactions following vaccination. Frequency of reactions was provided. The insert does not explain how long participants were monitored for. The insert states "In addition, the following unsolicited adverse events of note were reported within 3 weeks of vaccination as at least possibly related: 1 case of febrile convulsion, 13 cases of rash, and 1 case of anaphylactic reaction." The insert also states, "FLUAD® has not been evaluated for reproductive and developmental toxicity, carcinogenic or mutagenic potential." Link Here

  • Flulaval-Tetra (GSK) (Canadian Insert) - the vaccine was tested in multiple clinical trials on more than 1,960 infants and toddlers (6-35 months) and more than 3,500 children and adolescents (3-17 years). In one of those studies, 1,207 infants and toddlers received Flulaval, while a group of 1,217 peers received the comparator influenza vaccine Fluzone, as control. All participants were monitored for some of the above listed reactions during the 7 days following vaccination. The insert states, "Unsolicited adverse events that occurred within 28 days (day 0-27) of any vaccination were recorded based on spontaneous reports or in response to queries about changes in health status. The incidence of unsolicited adverse events reported in subjects who received FLULAVAL® TETRA (N = 1207), FLUZONE® QUADRIVALENT (N = 1217) was 45.5% and 44.1%, respectively. Unsolicited events reported for FLULAVAL® TETRA considered as possibly related to vaccination and occurring in 0.1% of subjects included upper respiratory tract infection, cough, diarrhea, nasopharyngitis and otitis media." The insert describes that one of those studies tested Flulaval on 913 children and adolescents, with 1,826 peers receiving one of two possible comparator influenza vaccines, either Fluarix or a trivalent influenza vaccine, as control. Those participants were monitored for 7 daysfollowing vaccination. Again, iunsolicited reports could be made during the 28 daysfollowing vaccination. The insert states, "The incidence of unsolicited adverse events reported in subjects who received FLULAVAL® TETRA (N = 932), FLUARIX® (N = 929), or TIV (B Yamagata) (N = 932) was 30%, 31%, and 30%, respectively. Unsolicited events reported for FLULAVAL® TETRA considered as possibly related to vaccination and occurring in 0.1% of subjects included influenza-like illness, injection site hematoma, injection site pruritus, rash, and upper respiratory tract infection." One of the studies tested the vaccine on 2,584 children (3-8 years), and compared their reactions to a group of 2,584 children who received the Hepatitis A vaccine called Havrix. All participants were monitored for some of the above listed reactions during the 7 days following vaccination. Again, unsolicited reactions could be reported up to 28 days after vaccination. The insert states, "The incidence of unsolicited adverse events reported was similar among the groups (33% for both FLULAVAL® TETRA and HAVRIX®). The insert states, "FLULAVAL® TETRA has not been evaluated for carcinogenic or mutagenic potential." The insert also states, "The safety of FLULAVAL® TETRA when administered to pregnant women has not been evaluated. Animal studies with FLULAVAL® TETRA do not indicate direct or indirect harmful effects with respect to reproductive and developmental toxicity." Link Here

  • Flulaval-Tetra (GSK) (American Insert) - In the same study described above (involving 1,207 infants and toddlers (6-35 months) receiving Flulaval and 1,217 peers receiving Fluzone), the insert explains that, "Subjects were followed for safety for 6 months; solicited local adverse reactions and systemic adverse events were collected for 7 days (day of vaccination and the next 6 days) post vaccination." This insert describes a study involving 1,055 children (3-17 years) who received Flulaval, and 1,061 peers who received the comparator influenza vaccine Fluzone, as control. The participants were monitored for some of the above listed reactions during the 4 days following vaccination. The insert states, "The incidence of unsolicited adverse events that occurred within 28 days (Day 0 to 27) of any vaccination reported in subjects who received FLULAVAL (n = 1,055) or FLUZONE 179 (n = 1,061) was 40% and 37%, respectively. The unsolicited adverse events that occurred most frequently (≥0.1% of subjects for FLULAVAL) and considered possibly related to vaccination included diarrhea, influenza-like illness, injection site hematoma, injection site rash, injection site warmth, rash, upper abdominal pain, and vomiting." Section 13.1 of the insert states, "FLULAVAL has not been evaluated for carcinogenic, mutagenic potential, or male infertility in animals. Vaccination of female rats with FLULAVAL had no effect on fertility." FDA Link Here

  • Fluviral (GSK) (Canadian Insert) - The vaccine quotes the same infant/toddler, children/adolescent studies completed for the Flulaval vaccine, described above. So I'm not sure if Fluviral and Flulaval are the same, or are nearly identical vaccines. They are both manufactured by the same company GlaxoSmithKline. Refer above for the details provided there. The insert states, "Safety of FLUVIRAL when administered to pregnant women has not been evaluated. Animal studies with FLUVIRAL® do not indicate direct or indirect harmful effects with respect to reproductive and developmental toxicity."Link Here

  • Fluzone - (Sanofi Pasteur) (Canadian Insert) - Fluzone was tested on 1,223 infants and toddlers (age 6-35 months) and 1,669 children (age 3-8 years). The reactions experienced by those age groups were compared to peer groups who received trivalent influenza vaccines as control. All  participants were monitored for some of the above listed reactions during the 7 days following vaccination. The insert states, "Animal reproductive studies have not been conducted with FLUZONE® Quadrivalent. It is also not known whether FLUZONE® Quadrivalent can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity....NACI states that influenza vaccination is recommended for pregnant women....Sanofi Pasteur Inc. is conducting a prospective pregnancy exposure registry to collect data on pregnancy outcomes and newborn health status following vaccination with FLUZONE® Quadrivalent during pregnancy. Healthcare providers are encouraged to enroll women who receive FLUZONE® Quadrivalent during pregnancy in Sanofi Pasteur Inc.'s vaccination pregnancy registry by calling 1-888-621-1146." The insert also states, "Guillain-Barré syndrome (GBS) has been reported after influenza vaccination. However, it is not known whether influenza vaccination specifically might increase the risk for recurrence of GBS. Therefore, NACI and the US Advisory Committee on Immunization Practices (ACIP) state it is prudent to avoid vaccinating persons who are not at high risk for severe influenza complications and who are known to have experienced GBS within 6 weeks after a previous influenza vaccination." The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • Fluzone (Son Pasteur) (American Insert) - the same studies listed on the Canadian insert were discussed on the American insert. This insert also states, "Participants were monitored for unsolicited adverse events for 28 days after each dose and serious adverse events (SAEs) during the 6 months following the last dose." Section 13.1 of the insert states, "Fluzone Quadrivalent has not been evaluated for carcinogenic or mutagenic potential. A reproductive study of female rabbits vaccinated with Fluzone Quadrivalent was performed and revealed no evidence of impaired female fertility." Link Here

  • Flumist (AstrAeneca) (Canadian insert) - NOTE: I learned from an Alberta Health Nurse that this vaccine is still being used in Alberta, Canada, whereas it is no longer used in the US because studies showed it to be completely ineffective.CDC Link Here The package insert explains that the vaccine was tested in multiple studies, 7 placebo controlled and 4 active controlled (where a different vaccine was used as the control). The insert specifies that 1,386 children and adolescents (age 2-17 years) participated, and another 28,500 children and adolescents (age 2-17 years) participated. It explains that participants were monitored for some of the above listed reactions during the 10 days following vaccination. Based on the insert summary, I infer that participants were able to report unsolicited events during the 28 daysfollowing vaccination, and were monitored for serious adverse events during the 6 months following vaccination. The insert states, "FLUMIST and FLUMIST QUADRIVALENT have not been evaluated for carcinogenic or mutagenic potential or potential to impair fertility." Link Here

  • Vaxigrip (Sanofi Pasteur) (Canadian Insert) - The vaccine is approved for use in all populations, 6 months of age and older. However the insert does not provide any safety testing data for infants, children or adolescents. The insert states, "Guillain-Barré syndrome has been reported after influenza vaccination. However, it is not known whether influenza vaccination specifically might increase the risk for recurrence of GBS. Therefore, the NACI and the Advisory Committee on Immunization Practices (ACIP) state it is prudent to avoid vaccinating persons who are known to have experienced GBS within 6 weeks after a previous influenza vaccination." The insert also states, "Animal reproduction studies have not been conducted with VAXIGRIP®. It is not known whether VAXIGRIP® can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity...NACI states that influenza vaccination is recommended for all pregnant women." The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here


MEASLES, MUMPS, RUBELLA VACCINES

(and Chicken Pox)

Combination of three or four vaccines in one vial

  • 2 total doses are given to American and Canadian children at: age 1 and at 4-6 years

The brands available in Canada, for measles, mumps, and rubella include:

  • Priorix (GSK) (Canadian Insert) - this is 3 vaccines in 1 vial - for measles, mumps, and rubella. In this package insert the details are very sparse, though they did provide some information regarding rate of occurrence for some of the reactions listed above. The summary sates that the vaccine was tested on 12,000 subjects (didn't provide a breakdown of ages). The participants reported reactions during the  42- day follow-up period. Comparator vaccine information (used as control) was not provided. The package insert states, "A total of 10 serious adverse events that were considered as at least possibly related to vaccination have been reported after the first vaccine dose." Details of those serious adverse events were not provided. The insert also states, "Individuals with current thrombocytopenia may develop more severe thrombocytopenia following vaccination with measles-mumps-rubella vaccines." According to the Mayo Clinic, thrombocytopenia is a condition in which you have a low blood platelet count. It is often the result of a different disorder, such as leukaemia, or an immune system disorder. If the condition is severe, it can result in dangerous internal bleeding. The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility.  Link Here

  • Priorix-Tetra (GSK) (Canadian Insert) - this is 4 vaccines in 1 vial - for measles, mumps, rubella, and varicella (chicken pox). Details are very sparse in this insert as well. The insert states that 6,700 doses were administered (I believe 1 dose per child), and the vaccine was tested on children aged 9 months to 27 months. The study(ies) were designed to look for many of the reactions listed above during the 42 days following vaccination. Comparator vaccine information (used as control) was not provided. The insert states, "There is an increased risk of fever and febrile convulsions 5 to 12 days after the first dose of PRIORIX-TETRA® as compared with 2 separate injections of MMR and varicella vaccines." It says that post marketing studies compared risk of febrile seizure after receipt of Priorix-Tetra (82,436 children), to reactions experienced by other vaccines including MMRV recipients (82,656 children), MMR recipients (149,259 children), MMR+Varicella recipients (39,293 children) and a control group of pooled MMR recipients and MMR+V recipients (82,469 children). The study suggests that one additional seizure occurs, per 2,747 subjects vaccinated with Priorix-Tetra, compared to those who received MMR or MMR+V. The insert also states, "Cases of worsening of thrombocytopenia and recurrence of thrombocytopenia in subjects who suffered thrombocytopenia after the first dose have been reported following vaccination with live measles, mumps and rubella vaccines" So based on the thrombocytopenia definition provided by the Mayo clinic, that thrombocytopenia results from an immune system disorder, and based on the manufacturers statement, that vaccinees "who suffered thrombocytopenia after the first dose," those two statements together imply that the live measles, mumps, and rubella vaccine causes immune system disorder. The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • MMR-II (Merck) (Canadian Insert) - this is 3 vaccines in 1 vial - for measles, mumps, and rubella. It was tested on 1,279 children (age not specified). The studies were designed to look for most of the reactions listed above, as well as various infections, respiratory disorders (including congestion, runny nose, wheezing, etc), skin disorders (including eczema, diaper rash, heat rash, etc) during the 42 days following vaccination. Two formulations of the MMR vaccine we compared against each other to determine if rates of reaction were similar. The insert states, "Individuals with current thrombocytopenia may develop more severe thrombocytopenia following vaccination. In addition, individuals who experienced thrombocytopenia with the first dose of M-M-R® II (or its component vaccines) may develop thrombocytopenia with repeat doses."  In addition to studying MMR-II, for the reactions listed above, the Merck website states that in post market study of prior MMR formulations, additional adverse reactions were noted as being possibly caused by the vaccine (causation has not been determined). Those reactions are listed as follows: encephalitis; encephalopathy; subacute sclerosing panencephalitis (SSPE); Guillain-Barré Syndrome (GBS); acute disseminated encephalomyelitis (ADEM); transverse myelitis; febrile convulsions; afebrile convulsions or seizures; ataxia; polyneuritis; polyneuropathy; ocular palsies; Stevens-Johnson syndrome; Henoch-Schönlein purpora; nerve deafness; retinitis; optic neuritis, papillitis; retrobulbar neuritis, and death. Regarding the cases of death, the insert states the following, "Death from various, and in some cases unknown, causes has been reported rarely following vaccination with measles, mumps, and rubella vaccines; however, a causal relationship has not been established in healthy individuals." (Unless they finally choose to conduct a study looking at long term health outcomes and death rates, between a vaccinated and never vaccinated population, we will continue to NOT know whether such an outcome is caused by the vaccine). According the US Table of Vaccine injuries, which lists the recognized vaccine injuries that are granted immediate compensation (as long as symptoms begin within the specified timelines following vaccination), the Table of Injuries now includes Immune thrombocytopenic purpura, and chronic arthritis as injuries resulting from the MMR vaccine. Both of those conditions are autoimmune diseases. Table of Injuries Link Hereand Here. Canadian package insert Link Here The package insert on the FDA website states, "MMR II has not been evaluated for carcinogenic or mutagenic potential, or potential to impair fertility." Link Here The Canadian insert is silent on this.

  • MMR-II (Merck) (American Insert) - this is 3 vaccines in 1 vial - for measles, mumps, and rubella. The package insert states, "If vaccination of postpubertal females is undertaken, pregnancy should be avoided for three months following vaccination." It also states, "Postpubertal females should be informed of the frequent occurrence of generally self-limited [but not always self-limited] arthralgia and/or arthritis beginning 2 to 4 weeks after vaccination."  To list the severe adverse events that Merck identifies as being possibly caused by the vaccine, those are: pancreatitis; diabetes mellitus; thrombocytopenia; diabetes mellitus; thrombocytopenia; purpora; arthritis; encephalitis; encephalopathy; measles inclusion body encephalitis; subacute sclerosing panencephalitis, Guillain-Barré Syndrome (GBS); acute disseminated encephalomyelitis (ADEM); transverse myelitis; febrile convulsions; afebrile convulsions or seizures; ataxia; polyneuritis; polyneuropathy; ocular palsies; aseptic meningitis; pneumonia; Stevens-Johnson syndrome; erythema multiforme; nerve deafness; retinitis; optic neuritis; papillitis; retrobulbar neuritis; and death. Regarding arthritis, the package insert states, "Following vaccination in children, reactions in joints are uncommon and generally of brief duration. In women, incidence rates for arthritis and arthralgia are generally higher than those seen in children (children: 0-3%; women: 12-26%), and the reactions tend to be more marked and of longer duration. Symptoms may persist for a matter of months or on rare occasions for years.Regarding deaths, the package insert states, "Death from various, and in some cases unknown, causes has been reported rarely following vaccination with measles, mumps, and rubella vaccines; however, a causal relationship has not been established in healthy individuals." The insert also states, "M-M-R II has not been evaluated for carcinogenic or mutagenic potential, or potential to impair fertility."Link Here Again, the US Table of Injuries now includes Immune thrombocytopenic purpura, and chronic arthritis as injuries caused by the MMR vaccine. Both of those conditions are autoimmune diseases. Table of Injuries Link Here and Here.

  • Proquad (Merck) (Canadian Insert)- (frozen formulation) - this is 4 vaccines in 1 vial - for measles, mumps, rubella, and varicella (chicken pox). It was tested in clinical trials involving a total of 6,038 children (age12 months through 23 months of age). There are two formulations of Proquad, a refrigerated formulation and a frozen formulation. Participants were monitored for many of the above listed reactions, and additional reactions including agitation, clinging, emotional changes, febrile seizure, dermatitis, eczema, diaper rash, heat like rash during the 42 days after injection. The reactions experienced by the two formulations were deemed comparable. Safety of the frozen formulation was compared to a control group of participants who received MMR-II + Varivax simultaneously  An observational study was conducted involving 69,237 children (12 months to 12 years), the primary focus of which was to monitor rates of febrile seizure following Proquad vaccination. A historical comparison group of 69,237 matched children, who had been given MMR-II + VARIVAX simultaneously, were used as the control. A health comparison in the 30daysfollowing vaccination was conducted. The conclusion of that study was that a two fold increased risk of febrile seizure occurred at 5-12 day post vaccination, in the Proquad group. The insert states, "Due caution should be employed in administration of ProQuad to persons with individual or family history of convulsions, a history of cerebral injury or any other condition in which stress due to fever should be avoided." The insert also describes various clinical trials conducted to  evaluate Proquad administration with administration of routine vaccines simultaneously, looking for affect on production of anti-body response, and in some cases, rates of adverse effects listed above. The insert also states, "Post-marketing experience with VARIVAX suggests that transmission of varicella vaccine virus may occur rarely between healthy vaccine recipients and contacts susceptible to varicella...Vaccine recipients should attempt to avoid, whenever possible, close association with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination." The insert also states, "In females of childbearing age, pregnancy should be avoided for 3 months following vaccination." It also states,"In clinical trials, no cases were reported regarding the development or worsening of thrombocytopenia in individuals vaccinated with ProQuad. However, cases of thrombocytopenia have been reported in post-marketing experience after primary vaccination with ProQuad. In addition, cases of thrombocytopenia have been reported after primary vaccination or revaccination with measles vaccine; with measles, mumps, and rubella vaccine; and with varicella vaccine. Post-marketing experience with live measles, mumps, and rubella vaccine indicates that individuals with current thrombocytopenia may develop more severe thrombocytopenia following vaccination." The package insert describes that in one trial, an adverse reaction of herpes zoster (shingles), occurred in 2 of 2,108 vaccinated, and 12 of 9,543 in another trial. That works out to 0.9-1.3 cases of shingles per 1000 children vaccinated. (Note that in the pre-vaccine era, shingles was not an illness experienced in childhood, instead, it was an illness experienced by the elderly population. Shingles is a far more serious illness compared to chicken pox). The insert states that in clinical trials of both Proquad and Varivax, physician's advised against use of of aspirin, to avoid a potential reaction called Reye syndrome.  Canadian Insert Here Again, the US Table of Injuries now includes Immune thrombocytopenic purpura, and chronic arthritis as injuries caused by the MMRV vaccine. Both of those conditions are autoimmune diseases. Table of Injuries Link Here and Here. The insert on the FDA website states, "ProQuad has not been evaluated for its carcinogenic, mutagenic, or teratogenic potential (birth defects), or its potential to impair fertility." Link Here The Canadian insert is silent on this.

  • Proquad (Merck) (American Insert) - this is 4 vaccines in 1 vial - for measles, mumps, rubella, and varicella (chicken pox). Much of the information provided on the American insert was the same as that stated above from the Canadian insert. It states that the vaccine was tested in 4 clinical trials involving 4,497 children (12-23 months). The trials refrained from simultaneous administration of routine vaccine. Safety was compared to a group of 2,038 children who received MMR-II+Varivax simultaneously. Participants were monitored for some of the reactions listed above, during the 42 days following vaccination and rates of reactions were deemed comparable. It states that in these trials, 2 of 2108 children who were followed for 1 year, experienced herpes zoster (shingles). In another trial, 2,780 children (12-23 months of age) were vaccinated with Proquad, and then received a second dose 3-9 months later. The participants were monitored for some of the above listed reactions during the 28 days following vaccination. In a double blind trial, 799 children (4-6 years) who had received MMR-II+Varivax simultaneously 1 month prior to study entry, were randomized to receive either Proquad+placebo (399 participants), or MMR+placebo (205 participants), or MMR-II+Varivax (195 patricians). Participants were monitored for some of the above listed reactions during the 42 days following vaccination. The American insert also states, "This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. Although there is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), no cases of transmission of CJD or viral disease have ever been identified that were associated with the use of albumin. The [chick embryo culture, RA 27/3, WI-38 & MRC5 [aborted human fetal] cells, [vaccine] virus pools, bovine serum, and human albumin used in manufacturing are all evaluated and tested to provide assurance that the final product is free of potential adventitious agents." This insert also states, "Avoid the use of salicylates (aspirin) or salicylate-containing products in children and adolescents 12 months through 12 years of age, for six weeks following vaccination with ProQuad due to the association of Reye syndrome with aspirin therapy and wild-type varicella infection." It states, "Few subjects (<0.1% of 4497 subjects) who received ProQuad discontinued the study due to an adverse reaction." The insert states, "ProQuad has not been evaluated for its carcinogenic, mutagenic, or teratogenic potential, or its potential to impair fertility." Link Here Again, the US Table of Injuries now includes Immune thrombocytopenic purpura, and chronic arthritis as injuries caused by the MMRV vaccine. Both of those conditions are autoimmune diseases. Table of Injuries Link Hereand Here


CHICKEN POX VACCINES

  • 2 total doses are given to American and Canadian children at: age 1 and at 4-6 years

The brands available for chicken pox are:

  • Varivax III (Merck) (Canadian insert) - was tested on 8,900 children. The participants were monitored for many of the above listed reactions during the 42 days following vaccination. Comparator vaccine information (used as control) was not provided. The vaccine was also tested on 1,600 adolescents and adults (age groups not specified). The participants were monitored for many of the above listed reactions during the 42 daysfollowing vaccination. Comparator vaccine information was not provided. A post-marketing study was conducted, involving approximately 86,000 children (12 months to 12 years of age) and 3,600 adolescents and adults (13 years of age and older), to evaluate short-term safety (follow-up of 30 or 60 days). The package insert states, "No serious vaccine-related adverse events were reported. As with any vaccine, there is the possibility that broad use of the vaccine could reveal adverse reactions not observed in clinical trials." The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. Link Here

  • Varivax III (Merck) (American Insert - the refridgerated formulation) - the insert states that the vaccine was tested in trials involving a total of 11,000 children, adolescents, and adults (distribution of ages not specified). In those trials (some or all, the insert is not clear) participants were monitored for some of the above listed reactions for 42 days. One of the trials was a double blind placebo controlled study. It does not state if the placebo was saline, or a competitor varicella vaccine. That trial involved 914 children and adolsecents, and states that the only reaction that occured at a greater rate in the Varivax recipients was pain and redness at the injection site.  One trial compared the refridgerated forumlation in 635 children (12-23 months), to recipients of the frozen formulation in 323 children. The children were monitored for some of the above listed reactions for 42 days. It states that 6 participants reported a serious adverse event (details not provided). To quote the insert, "If vaccination of postpubertal females is undertaken, pregnancy should be avoided for three months following vaccination." It also states, "Post-marketing experience suggests that transmission of vaccine virus may occur rarely between healthy vaccinees who develop a varicella-like rash and healthy susceptible contacts. Transmission of vaccine virus from a mother who did not develop a varicella-like rash to her newborn infant has been reported. Due to the concern for transmission of vaccine virus, vaccine recipients should attempt to avoid whenever possible close association with susceptible high-risk individuals for up to six weeks following vaccination with VARIVAX." The package insert states, "Avoid use of salicylates (aspirin) or salicylate-containing products in children and adolescents 12 months through 17 years of age for six weeks following vaccination with VARIVAX because of the association of Reye syndrome with aspirin therapy and wild-type varicella infection." The insert is silent on whether or not the vaccine was tested for carcinogenic or mutagenic potential, or the potential to impair fertility. FDA link Here

  • See also Proquad and Priorix-Tetra in the measles mumps rubella section above


HUMAN PAPILLOMAVIRUS (HPV) VACCINES

  • 3 total doses given within 6 months to Canadian children starting at: age 9, 10 or 11

  • 3 total doses given to American children at: age 11 or 12

  • See Ch6: Part 1-6 for a detailed overview of HPV illness and vaccination

The brands available for HPV are:

  • Gardasil (Merck)

  • Gardasil 9 (Merck)

  • Cervarix (GSK)

CONTINUE to the next article Ch6: Part 1

Article Sources Here

  • FDA - Definition for Fast Track Review and Approval Process Here

  • FDA - Length of Phase III Drug Trials Here

  • US Government Table of Vaccine Injuries - explaining that vaccination can cause Hyptonic-Hypotensive Episodes which may involve cardiac or respiratory arrest Here

  • US Vaccine Court Ruling concludes that vaccination likely caused a child's SIDS death Here

  • US Government Table of Vaccine Injuries Here and Here

  • Approved Canadian Vaccines Link Here

  • Approved American Vaccines and Package Inserts Link Here

  • Link to Canadian Package inserts Here

  • Alberta and American Vaccination Schedules

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