Drug Criteria & Outcomes
Vaccine Update
By Lauren B. Sulcer, PharmD Candidate
Auburn University Harrison School of Pharmacy
Richard Cramer, PharmD, Drug Information Coordinator, Huntsville (AL) Hospital
Vaccine development and appropriate use are essential components of preventive medicine, providing the reality of not only disease prevention, but also complete disease eradication. A renewed interest in vaccines by the pharmaceutical industry has resulted in substantially increased vaccine development with nine new vaccines gaining FDA approval since the beginning of 2005.
Two of these newly approved vaccines have indications for disease states for which vaccinations have not previously been available.1 Health-system pharmacists should evaluate patient populations in their practice setting and review these new vaccines for formulary status. This article serves to discuss the two brand new vaccines, briefly review the other eight newly released vaccines, and mention three vaccines that are currently pending FDA licensure.
Hot Off the Press
Until now, human papillomavirus (HPV) and herpes zoster virus (HZV) have been viruses that were treated in a reactive manner. Both of these viruses have traditionally had a widespread impact: In 2005, approximately 20 million people were infected with HPV and 500,000 with HZV, with 100,000-200,000 new cases of HZV each year.2,3 With the development of Gardasil® for HPV and Zostavax® for HZV, these viruses now can be approached proactively, preventing onset of potentially debilitating disease in certain patient populations.
Gardasil was approved in June 2006 for prevention of cervical cancer and genital warts in females ages 9-26. Gardasil targets the four HPV types responsible for approximately 70% of cervical cancer and 90% of genital warts. This vaccine is given as three separate 0.5 mL intramuscular doses to the deltoid muscle with the first injection given on an elected date, the second injection one month after the first, and the third injection six months after the first dose. Because the dosing schedule is similar to that of the hepatitis B vaccine, studies were conducted on the concomitant use of these vaccines. Data suggest that concomitant administration of the two vaccines is acceptable when given on the same visit, but different injection sites should be used.
Gardasil has a pregnancy Category B designation and a pregnancy registry is maintained by Merck & Co. to evaluate and monitor fetal outcomes in patients who are exposed to Gardasil during pregnancy. While the most appropriate target population has not yet been determined, females ages 10-13 may become the focus in an attempt to vaccinate girls before sexual activity begins.
This vaccine is not intended for treatment of active cervical cancer or genital warts, only prevention. The need for revaccination with Gardasil is unknown and studies are currently under way to determine the duration of immunogenicity.2 The cost associated with one dose of this vaccine is $120.
Zostavax is indicated for prevention of zoster virus, which causes shingles, and was approved by the FDA in May. Preliminary clinical trials studied the use of this vaccine in patients who had no history of zoster virus and who had not previously received the varicella vaccine. Zostavax is a live, attenuated vaccine intended for use in patients 60 years of age and older who are at an increased risk of developing zoster virus by having a history of varicella virus, but who have not received the varicella vaccine. Chronic disease states can also predispose patients to an increased risk of contracting zoster virus.
This vaccine is administered as a one-time subcutaneous injection and is not intended for treatment of shingles or postherpetic neuralgia. Zostavax has a category C pregnancy designation and is contraindicated in the following patients: those with a history of anaphylaxis to gelatin or neomycin, those who are immunocompromised or taking immunosuppressive medications, and those with active, untreated tuberculosis. This vaccine should be stored in the freezer at -15° C (5° F).5 Duration of protection against zoster virus has not yet been determined.4 Zostavax is expected to cost approximately $150 per dose.
New Takes on Old Products
Over the years there have been vaccines that were approved, used, and then removed from the market due to adverse events associated with their use. An example would be Rotashield™, which was the first rotavirus vaccine. It was licensed for use in 1998, but was subsequently removed from the market in 1999 due to the vaccine's contribution to an increased risk of intussusception, or gastrointestinal obstruction, with a frequency of about one in every 12,000 vaccinated infants.5 Thus, no rotavirus vaccine has been available for use in the past seven years.
In February 2006, Merck & Co. received approval for a new live oral rotavirus vaccine called RotaTeq®. Preliminary clinical trials indicate that RotaTeq did not pose an increased risk of intusssusception relative to placebo. Because the patients most severely affected by rotavirus are infants and young children, this vaccine is indicated for use at 2, 4, and 6 months of age. It is given as a ready-to-use liquid and should be dosed starting at 6-12 weeks of age and then repeated twice at least four weeks apart. RotaTeq was administered concomitantly with diphtheria and tetanus toxoids and acellular pertussis (DTap), inactivated poliovirus vaccine (IPV), H. influenza type B conjugate vaccine (Hib), hepatitis B vaccine, and pneumococcal conjugate vaccine during clinical trials.
Although the data associated with the immunogenicity and pertussis were inconclusive, there was no evidence to suggest that a decreased antibody response would be experienced with any of the other vaccines that were administered concomitantly with RotaTeq. While concomitant immunosuppression has not been studied with the use of this product, caution should always be used when administering live vaccines to patients with impaired immune function; use of live vaccines in immunocompromised patients is often a contraindication.
Estimates suggest rotavirus gastroenteritis affects 2.7 million children younger than age 5 every year in the United States. In the REST Phase III clinical trial, RotaTeq prevented 98% of severe cases, and 74% of all cases caused by targeted serotypes and reduced hospitalizations by 96% and emergency department visits by 94%. The Advisory Committee on Immunization Practices (ACIP) to the Centers for Disease Control and Prevention (CDC) has not released recommendations on standards of immunization with RotaTeq at this time; the need for routine vaccination against rotavirus in infants is being considered.6 The expected cost of vaccine is $63 per dose.
Vaccination against meninogoccal disease has been available since the early 1980s with a product called Menomune®. However, in January 2005, a new meningococcal vaccine, Menactra® was approved. This new vaccine showed a fourfold or more increase of bacterial antibody and is believed to provide longer-lasting protection than Menomune.7 The cost associated with Menactra is about $82 per dose, which is similar to the cost of Menomune. Menactra is indicated for use in patients ages 11-55 and is given as a single 0.5 mL intramuscular deltoid injection.
This vaccine has a pregnancy category C designation and should not be given to patients with a history of hypersensitivity to natural rubber latex.8 In September 2005, the FDA issued a statement reporting several cases of Guillain-Barré Syndrome occurring after administration of Menactra, but indicated that clear causation had not yet been determined.9 In light of these reports, no changes were made with respect to the vaccine's indications, but Menactra should be avoided in patients with a history of Guillain-Barré Syndrome.8
Another new vaccine product that was released in September 2005 combines two previously used vaccines in an attempt to minimize the injection burden associated with childhood vaccinations. ProQuad® is a live combination vaccine that protects against measles, mumps, rubella, and varicella. Although products like MMR®II already are on the market combining measles, mumps, and rubella vaccines, ProQuad is the first combination vaccine to add varicella to the combination formulation. This combination product costs $41 per dose, which is more cost-effective than administering each of the vaccine components separately. ProQuad is indicated for children aged 12 months to 12 years and is given as a single 0.5 mL subcutaneous injection. Contraindications to this product include a history of anaphylaxis to gelatin or neomycin, blood dyscrasias, leukemia, lymphoma, malignant neoplasms, patients who are immunocompromised or on immunosuppressive medications, acute untreated tuberculosis, and patients experiencing acute febrile illness.10
Two more combination products called Boostrix® and Adacel™ were released in the spring of 2005, gaining approval in May and June, respectively. Both of these vaccines are active booster immunizations for the prevention of tetanus, diphtheria, and pertussis (Tdap). They are targeted especially for adolescents due to the recent increase in incidence of pertussis in this age group.11 While Boostrix is indicated for use in patients ages 10-18, Adacel has a more broad age range and is indicated for use in patients ages 11-64. ACIP now recommends that adolescents aged 11-18 years receive a single dose of TDap instead of tetanus and diphtheria toxoids vaccine (Td).
Contraindications to both these vaccines include hypersensitivity to any component included in the formulations. Like with any vaccine containing pertussis, use of Boostrix and Adacel is contraindicated in patients with a history of encephalopathy within days of a previous administration, as well as progressive neurological disorders, uncontrolled epilepsy, or progressive encephalopathy.11-13 According to the CDC, both Boostrix and Adacel are appropriate for interchangeable use when TDap vaccinations are indicated. The cost associated with these vaccines is similar (Boostrix cost $33 per dose; Adacel costs about $38 per dose).11
In the fall of 2005, Havrix® and Vaqta® were approved for active immunization against hepatitis A. Both are indicated for use in patients 12 months of age and older and both are given as intramuscular injections to the deltoid muscle. Booster doses are required between 6 and 18 months for both Havrix and Vaqta for all patient age groups to ensure highest possible antibody titers.14,15 The two vaccines have similar immunogenicity against hepatitis A and neither has been associated with significant adverse events. Both vaccines are available in two formulations, which differ depending on the patient's age and both are given with a two-dose schedule.16 There does not seem to be a clear reason for choosing one of these vaccines over the other at this time based on preliminary clinical trials. Vaqta costs about $32 for pediatric doses and about $64 per adult dose. The pediatric dose of Havrix is approximately $28 and the adult dose is $47.
Fluarix™ was approved in May 2005 for active immunization of patients 18 years of age and older against influenza disease caused by influenza virus types A and B.17 This 0.5 mL single-dose vaccine is given by intramuscular injection to the deltoid muscle. Fluarix does not contain thimerosal or other preservatives, as most other flu vaccines do. FluLaval™ is another vaccine directed against influenza virus and is indicated for use in patients 18 years of age and older. FluLaval was granted fast-track status by the FDA in late 2005, but is still pending licensure by the FDA.18 The current hope is that Fluarix and FluLaval together will provide 30 million doses of seasonal influenza vaccine for the 2006-2007 flu season.17,18
Coming Down the Pipeline
One new combination vaccine and one single-entity product are currently under review by the FDA. Pentacel™, the combination product, is directed toward preventing Hib, DTap, and IPV. The age indications associated with this vaccine are 2, 4, 6, and 15-18 months. Ceravix™ is similar to Gardasil and is intended for prevention of HPV. Both of these vaccines have submitted licensing applications and are pending licensure by the FDA.1
Final Words
New vaccines are continuously being developed and current awareness of vaccine availability on the part of pharmacists is crucial for identifying potential candidates for receiving these vaccines. Complete disease eradication has already occurred in the case of smallpox disease and polio has been eradicated in the Americas, with efforts for worldwide eradication of polio in progress.19 Increased emphasis on vaccine development suggests continued progress in preventive medicine, which introduces more and more opportunities for the prevention and eradication of disease. With continued medical advances and new vaccine approval, commonly experienced diseases of our generation may only be mentioned in history books for generations to come.
References
- Red Book Online. American Academy of Pediatrics. Status of Licensure and Recommendations for New Vaccines. Available at: http://aapredbook.aappublications.org/news/vaccstatus.shtml. Accessed June 10, 2006.
- Gardasil®. Patient Information. Whitehouse Station, NJ: Merck & Co. Inc.; 2006.
- Meeting of the Advisory Committee on Immunization Practices. Centers for Disease Control and Prevention. National Immunization Program. Available at: www.cdc.gov/NIP/ACIP/minutes.htm. Accessed June 15, 2006.
- Zostavax®. Package Insert. Whitehouse Station, NJ: Merck & Co. Inc.; 2006.
- Rotavirus Vaccine Program. Available at: www.rotavirusvaccine.org. Accessed June 14, 2006.
- RotaTeq®. Package Insert. Whitehouse Station, NJ: Merck & Co. Inc.; 2006.
- Bilukha OO, Rosenstein N, National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC). Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2005;54(RR-7):1-21.
- Menactra®. Package Insert. Swiftwater, PA: Aventis Pasteur, Inc.; 2005.
- Food and Drug Administration. FDA and CDC Issue Alert on Menactra Meningococcal Vaccine and Guillain Barre Syndrome. Available at: www.fda.gov/bbs/topics/NEWS/2005/NEW01238.html. Accessed June 12, 2006.
- ProQuad®. Package Insert. Whitehouse Station, NJ: Merck & Co. Inc.; 2006.
- Broder KR, Cortese MM, Iskander, et al. Preventing tetanus, diphtheria, and pertussis among adolescents: Use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. MMWR Recomm Rep 2006;55(RR-3):1-34.
- Boostrix®. Package Insert. Research Triangle Park, NC: GlaxoSmithKline; 2006.
- Adacel®. Package Insert. Swiftwater, PA: Aventis Pasteur Inc.; 2005.
- Havirx®. Package Insert. Research Triangle Park, NC: GlaxoSmithKline; 2006.
- Vaqta®. Package Insert. Whitehouse Station, NJ: Merck & Co. Inc.; 2005.
- Advisory Committee on Immunization Practices (ACIP), Fiore AE, Wasley A, et al. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-7):1-23.
- Fluarix®. Package Insert. Research Triangle Park, NC: GlaxoSmithKline; 2005.
- GlaxoSmithKline submits Biologics License Application for FDA approval of Flulaval™. Available at: www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=773. Accessed June 26, 2006.
- Global Polio Eradication Initiative. Available at: www.polioeradication.org/. Accessed June 26, 2006.
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