Immunizations Update in the Pediatric Population

With the FDA’s approval of Gardasil 9, this vaccine will now be available as a preventive measure against up to 90% of genital, anal, vulvular, and vaginal cancers, thereby offering additional protection for pediatric patients from the human papillomavirus (HPV). Along with questions about HPV, pharmacists must prepare to respond to parents’ concerns regarding egg allergies and if vaccines cause autism. Correctly and empathetically answering may help parents embrace vaccinations as the most important method of protecting their children from preventable illnesses.

Because of the recent outbreak of meningococcal disease serogroup B, pharmacists must be aware of recent FDA-approved vaccines. This article covers the updates and trends affecting pediatric immunizations and vaccinations, provides a cursory overview of Merck’s December 2014 approval of Gardasil 9, addresses egg allergy and autism concerns regarding vaccines, and discusses various meningococcal vaccines.

Guarding Patients with Gardasil 9

Before December 2014, children could receive either Cervarix or Gardasil as vaccination against HPV. Whereas Cervarix is indicated for prevention of cervical cancer,¹ Gardasil is indicated for prevention of genital warts (caused by HPV types 6 and 11), as well as cervical, anal, vaginal, and vulvular cancers (caused by HPV types 16 and 18).² Then, in December 2014, Merck’s Gardasil 9 was approved by the FDA. Unlike Cervarix and Gardasil, Gardasil 9 offers protection from 5 additional HPV types that cause about 20% of cervical cancers (Table 1^1-4).^3,4

In a recent study of the efficacy of the additional protection, more than 14,000 females aged 16 to 26 years received either Gardasil or Gardasil 9. Gardasil 9 was 97% more effective than Gardasil in protecting women from cervical, vulvular, and vaginal cancers. The results of a second study evaluating antibody responses show that 1200 males and 2800 females between 9 and 15 years of age responded similarly to the females in the first study.

Gardasil 9 is administered in 3 separate vaccinations, with the second and third doses taking place 2 months and 6 months, respectively, after the initial dose. The most common adverse effects with Gardasil 9 are headache and injection site reactions (ie, pain, swelling, and redness). Because some vaccines may also cause syncope, resulting in falls with injuries, observing the patient for 15 minutes after administration is recommended.⁴

Thanks to the advancement of medical technology, patients with documented egg allergies are no longer exempt from receiving their annual influenza vaccine. The egg-free influenza vaccine, Flublok, by Protein Sciences Corporation, received FDA approval in 2013; however, Flublok is only recommended in patients 18 years and older.⁵ Despite the age restriction, the Advisory Committee on Immunization Practices developed guidelines for practitioners to use for patients with reported egg allergies who receive the influenza vaccine (Table 2).⁶

Mitigating Concerns about MMR and Autism Spectrum Disorder

Within the past few months, many people have been outspoken in their support for or views against vaccinating children, with autism being included in discussions on the latter due to thimerosal, a preservative found in several vaccines. Created in 1927, thimerosal contains almost 50% mercury by weight and is broken down to ethyl-Hg hydroxide and ethyl-Hg chloride in aqueous saline solutions that can be toxic to human cells. Additional concerns have been raised due to thimerosal’s presence in some vaccines in the United States.⁷

In April 2015, however, the Journal of the American Medical Association definitively proved that there is no clinical relationship between administration of the MMR vaccine and autism cases. The results of a retrospective cohort study of 95,272 children with older siblings showed that the MMR vaccine was not associated with an increased risk of developing autism spectrum disorder (ASD) at any age. By analyzing children who have a sibling with and without ASD, in relation to their own risk of being so diagnosed, no clinical or statistical significance in relation to occurrence was found (Table 3). The study concluded there is “no harmful association between MMR vaccine receipt and ASD, even among children already at higher risk for ASD.”⁸

When addressing the concerns parents or caregivers have, it is important to be empathetic and acknowledge their concerns, but then be clear that studies have shown no clinical or statistical correlation between vaccinations and ASD occurrence. Most vaccines do not contain thimerosal; for vaccines that do contain it, practitioners can offer to administer a version that does not contain any thimerosal, if it is available.

Managing Serogroup B Meningococcal Disease with New Vaccines

Prior to 2013, the FDA approved 3 vaccines to combat Neisseria meningitidis serogroups C and Y. Between March 2013 and March 2014, however, Princeton University experienced an outbreak of 8 confirmed cases of serogroup B meningococcal disease, and Drexel University had an outbreak, as well. Because no serogroup B meningococcal vaccines were created and FDA-approved yet, the FDA granted accelerated approval for the prevention of N meningitidis serogroup B in patients between the ages of 10 and 25 years (Online Table 4).⁹

Table 4: Comparison of Trumenba and Bexsero in the Prevention of Neisseria meningitidis Serogroup B Infections

Vaccine

Trumenba¹⁰

Bexsero¹¹

Approval Date

October 2014

January 2015

Directions

0.5 mL IM at 0, 2, and 6 months

0.5 mL IM at 0 and 2 months

Common Adverse Effects

Injection site pain; fatigue; headache; muscle pain; chills

Injection site pain; myalgia; redness; fatigue; headache; stiffness; nausea; arthralgia

Use in patients with latex allergy?

Yes

No

Brian J. Catton, PharmD, is the chair of the New Practitioner Network for the New Jersey Pharmacists Association, from which he received the 2014 Distinguished Young Pharmacist Award. His topics of interest include pediatrics, disease state management, professional development, and vaccinations.

References

• Cervarix [package insert]. Research Triangle Park, NC: GlaxoSmithKline Biologicals; 2009.
• Gardasil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme, Corp; 2006.
• FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV [news release]. Silver Spring, MD: US Food and Drug Administration; December 10, 2014. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm. Accessed May 6, 2015.
• Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme, Corp; 2014.
• Flublok [package insert]. Meriden, CT: Protein Sciences Corporation; 2013.
• Influenza vaccination of people with a history of egg allergy. Immunization Action Coalition website. www.immunize.org/catg.d/p3094.pdf. Published January 2015. Accessed May 6, 2015.
• Geier DA, King PG, Hooker BS, et al. Thimerosal: clinical, epidemiologic and biochemical studies. Clin Chim Acta. 2015;444:212-220. doi: 10.1016/j.cca.2015.02.030.
• Jain A, Marshall J, Buikema A, Bancroft T, Kelly JP, Newschaffer CJ. Autism occurrence by MMR vaccine status among US children with older siblings with and without autism. JAMA. 2015;313(15):1534-1540. doi: 10.1001/jama.2015.3077.
• Meningococcal, Serogroup B Meningococca Vaccine & Outbreaks. Centers for Disease Control and Prevention website. www.cdc.gov/meningococcal/outbreaks/vaccine-serogroupb.html. Updated January 26, 2015. Accessed May 6, 2015.
• Trumenba [package insert]. Philadelphia, PA: Pfizer Inc; 2014.
• Bexsero [package insert]. Cambridge, MA: Novartis AG; 2015.