"The U.S. Food and Drug Administration today approved the Roche cobas HPV Test as the first test for Human Papilloma Virus (HPV) that can be used with cervical cells obtained for a Pap test and collected in SurePath Preservative Fluid.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. There is the possibility that broad use of MENHIBRIX could reveal adverse reactions not observed in clinical trials.
A total of 7,521 infants received at least one dose of MENHIBRIX in 6 clinical studies.1-6 In 5 of these studies, 6,686 children received 4 consecutive doses of MENHIBRIX.2-6 Across all studies, approximately half of participants were female; 50% were white, 41% were Hispanic, 4% were black, 1% were Asian and 4% were of other racial/ethnic groups.
Two randomized, controlled, pivotal trials enrolled participants to receive 4 doses of MENHIBRIX or a monovalent Haemophilus b Conjugate (Hib) vaccine, administered at 2, 4, 6, and 12 to 15 months of age (Study 009/0105 and Study 011/0126). Together, these trials evaluated safety in 8,571 infants who received at least one dose of MENHIBRIX (N = 6,414) or Hib vaccine (N = 2,157).5,6
In Study 009/0105, conducted in the United States, Australia, and Mexico, 4,180 infants were randomized 3:1 to receive MENHIBRIX or a control US-licensed Hib vaccine. Safety data are available for 3,136 infants who received MENHIBRIX and 1,044 infants who received a control Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) (PRP-T, manufactured by Sanofi Pasteur SA) at 2, 4, and 6 months of age. For dose 4 administered at 12 to 15 months of age, safety data are available for 2,769 toddlers who received MENHIBRIX and 923 toddlers who received a control Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PRP-OMP, manufactured by Merck and Co., Inc.). With doses 1, 2, and 3 of MENHIBRIX or PRP-T, infants concomitantly received PEDIARIX® [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine] and Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein) (PCV7, manufactured by Wyeth Pharmaceuticals, Inc.). With dose 4 of MENHIBRIX or PRP-OMP, toddlers concomitantly received PCV7, Measles, Mumps, and Rubella Virus Vaccine Live (MMR, manufactured by Merck & Co., Inc.), and Varicella Virus Vaccine Live (manufactured by Merck & Co., Inc.).
Data on solicited adverse events were collected by parents/guardians using standardized forms for 4 consecutive days following vaccination with MENHIBRIX or control Hib vaccine (i.e., day of vaccination and the next 3 days).5 Children were monitored for unsolicited adverse events that occurred in the 31-day period following vaccination and were monitored for serious adverse events, new onset chronic disease, rash, and conditions prompting emergency department visits or physician office visits during the entire study period (6 months following the last vaccine administered). Among participants in both groups, 66% were from the United States, 19% were from Mexico, and 14% were from Australia. Forty-eight percent of participants were female; 64% were white, 22% were Hispanic, 6% were black, 1% were Asian, and 7% were of other racial/ethnic groups.
In the second pivotal study (Study 011/0126), conducted in the United States and Mexico and evaluating the same vaccines and vaccination schedule, participants were monitored for serious adverse events, new onset chronic disease, rash, and conditions prompting emergency department visits during the entire study period (6 months following the last vaccine administered). Among participants in both groups, 30% were from the United States and 70% were from Mexico.
In addition to the pivotal studies, safety data are available from 4 studies which either did not include a fourth dose of MENHIBRIX1, used a dosing regimen not approved in the United States2,3, or incorporated a comparator vaccine which was not licensed in the United States.4 In these studies, participants were monitored for unsolicited adverse events and serious adverse events occurring in the 31–day period following vaccination. In 2 of these studies3,4, participants were monitored for serious adverse events, new onset chronic disease, rash, and conditions prompting emergency department visits or physician office visits through 6 months after the last vaccination.
Solicited Adverse Events
The reported frequencies of solicited local and systemic adverse events from US participants in Study 009/010 are presented in Table 1.5 Because of differences in reported rates of solicited adverse events between US and non-US participants, only the solicited adverse event data in US participants are presented. Among the US participants included in Table 1, 48% were female; 76% were white, 10% were black, 4% were Hispanic, 2% were Asian, and 8% were of other racial/ethnic groups.
Table 1: Percentage of US Children from Study 009/010
With Solicited Local and General Adverse Events within 4 Days of Vaccinationa With
MENHIBRIX or Haemophilus b Conjugate Vaccine (Total Vaccinated Cohort)
|MENHIBRIXb||Haemophilus b Conjugate Vaccineb,c|
|Dose 1||Dose 2||Dose 3||Dose 4||Dose 1||Dose 2||Dose 3||Dose 4|
|Pain, grade 3e||3.7||3.3||2.3||1.6||11.4||5.1||3.0||5.3|
|Redness, > 30 mm||0.1||0.3||0.1||0.7||1.8||0.3||0.4||1.2|
|Swelling, > 30 mm||0.5||0.3||0.3||0.6||1.5||0.2||0.4||0.8|
|N||2,008- 2,009||1,871||1,723||1,535- 1,536||659||609- 610||569||493- 494|
|Irritability, grade 3f||3.7||4.8||3.3||2.5||7.4||5.6||4.2||4.3|
|Drowsiness, grade 3g||2.7||3.2||1.7||2.1||2.7||2.6||1.4||2.0|
|Loss of appetite, any||33.8||32.1||30.1||32.1||37.6||33.6||30.2||32.5|
|Loss of appetite, grade 3h||0.5||0.7||0.5||1.1||0.3||0.7||1.1||2.2|
|Fever, ≥ 100.4°Fi||18.9||25.9||23.0||11.0||21.4||28.2||23.7||12.6|
|Fever, ≥ 102.2°Fi||1.1||1.9||3.2||1.5||0.9||2.6||2.8||2.0|
|Fever, ≥ 104°Fi||0.0||0.1||0.3||0.3||0.0||0.0||0.4||0.2|
|Total Vaccinated Cohort = all participants who received
at least one dose of either vaccine.
N = number of participants who completed the symptom sheet for a given symptom at the specified dose.
a Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b Co-administered with PEDIARIX and PCV7 at doses 1, 2, 3 and PCV7, MMR and varicella vaccines at dose 4.
c US-licensed monovalent Haemophilus b Conjugate Vaccine manufactured by Sanofi Pasteur SA for doses 1, 2, and 3 (PRP-T) and by Merck & Co., Inc for dose 4 (PRP-OMP).
d Local reactions at the injection site for MENHIBRIX or Haemophilus b Conjugate Vaccine.
e Cried when limb was moved/spontaneously painful.
f Crying that could not be comforted/prevented normal daily activities.
g Prevented normal daily activities.
h Not eating at all.
i Across both treatment groups, 54%, 56%, and 59% of participants had temperatures measured rectally following doses 1, 2, and 3, respectively; 45%, 44%, and 40% of participants had temperatures measured by the axillary route for doses 1, 2, and 3, respectively. For dose 4, > 90% of participants had temperatures measured via the axillary route.
The reported rates of some solicited adverse events in participants from Australia and Mexico varied from those in the United States.5 For example, in Australia, pain after dose 1 was reported in 28.4% of participants who received MENHIBRIX and 33.3% of control participants, while in Mexico pain after dose 1 was reported in 73.7% of participants who received MENHIBRIX and 79.4% of control participants. Fever after dose 1 was reported in 10.4% of participants who received MENHIBRIX and 10.7% of control participants in Australia, while it was reported in 44.0% of participants who received MENHIBRIX and 35.7% of control participants in Mexico. The reported incidences of pain and fever in US participants after dose 1 are provided in Table 1.
Unsolicited Adverse Events
Among participants who received MENHIBRIX or Hib control vaccine co-administered with US-licensed vaccines at 2, 4, 6 and 12 to 15 months of age1,3-5, the incidence of unsolicited adverse events reported within the 31-day period following study vaccination (doses 1, 2, and 3) was comparable between MENHIBRIX (61.9%; 2,578/4,166) and PRP-T (62.5%; 1,042/1,666). The incidence of unsolicited adverse events reported within the 31-day period following dose 4 was also comparable between MENHIBRIX (42.5%; 1,541/3,630) and PRP-OMP (41.4%; 520/1,257).
Serious Adverse Events
Following doses 1, 2, and 31,3-6, 1.8% (137/7,444) of participants who received MENHIBRIX and 2.1% (59/2,779) of participants who received PRPT reported at least one serious adverse event within the 31-day period. Up to 6 months following the last vaccine administered (doses 1, 2, and 3) or until administration of dose 43-6, 4.8% (365/7,362) of participants who received MENHIBRIX and 5.0% (134/2,697) of participants in the PRP-T group reported at least one serious adverse event.
Following dose 43-6, 0.5% (35/6,640) of participants who received MENHIBRIX and 0.5% (12/2,267) of participants who received PRP-OMP reported at least one serious adverse event within the 31-day period. Up to 6 months following the last vaccine administered (dose 4), 2.5% (165/6,640) of participants who received MENHIBRIX and 2.0% (46/2,267) of participants who received PRP-OMP reported at least one serious adverse event.
The following adverse events have been spontaneously reported during post-approval use of HIBERIX® (Haemophilus b Conjugate Vaccine [Tetanus Toxoid Conjugate]) in the United States and other countries. These events are relevant because the Haemophilus b capsular polysaccharide tetanus toxoid conjugate is included as a component antigen in both MENHIBRIX and HIBERIX. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish a causal relationship to vaccine exposure.
The following adverse events were included based on one or more of the following factors: seriousness, frequency of reporting, or strength of evidence for a causal relationship to HIBERIX.
General Disorders and Administration Site Conditions: Extensive swelling of the vaccinated limb, injection site induration.
Immune System Disorders: Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema.
Respiratory, Thoracic, and Mediastinal Disorders: Apnea.
Skin and Subcutaneous Tissue Disorders: Rash, urticaria.
Read the MenHibrix (meningococcal groups c and y and haemophilus b tetanus toxoid conjugate vaccine) Side Effects Center for a complete guide to possible side effects
Concomitant Vaccine Administration
In clinical studies, MENHIBRIX was administered concomitantly with routinely recommended pediatric US-licensed vaccines [see ADVERSE REACTIONS and Clinical Studies].
If MENHIBRIX is administered concomitantly with other injectable vaccines, they should be given with separate syringes and at different injection sites. MENHIBRIX should not be mixed with any other vaccine in the same syringe or vial.
Interference With Laboratory Tests
Haemophilus b capsular polysaccharide derived from Haemophilus b Conjugate Vaccines has been detected in the urine of some vaccinees.7 Urine antigen detection may not have a diagnostic value in suspected disease due to H. influenzae type b within 1 to 2 weeks after receipt of a H. influenzae type b-containing vaccine, including MENHIBRIX.
Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to MENHIBRIX.
All NCT numbers are as noted in the National Library of Medicine clinical trial database (see www.clinicaltrials.gov).
1. NCT00127855 (001).
2. NCT00129116 (003/004).
3. NCT00129129 (005/006).
4. NCT00134719 (007/008).
5. NCT00289783 (009/010).
6. NCT00345579/NCT00345683 (011/012).
Last reviewed on RxList: 10/22/2015
Additional MenHibrix Information
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