Zostavax

Pronunciation

Generic Name: Zoster Vaccine Live
Class: Vaccines
VA Class: IM100

Introduction

Live, attenuated virus vaccine.1 2 6 15 Zoster vaccine live contains attenuated varicella zoster virus (VZV) of the Oka/Merck strain and is used to boost active immunity to VZV.1 2 6 15

Uses for Zostavax

Prevention of Herpes Zoster

Prevention of herpes zoster (shingles, zoster) in immunocompetent adults ≥50 years of age.1 2 6

Herpes zoster is caused by reactivation of varicella zoster virus (VZV) infection.1 2 6 Zoster vaccine is used to boost active immunity to VZV, thereby reducing risk of VZV reactivation.1 2 3 4 15 The vaccine may also reduce frequency, severity, and/or duration of postherpetic neuralgia (PHN) in those who develop herpes zoster despite vaccination.1 2 6

Slideshow: Worried About Ebola? You’re More Likely to Get These 10 Serious Infections

US Public Health Service Advisory Committee on Immunization Practices (ACIP), American Academy of Family Physicians (AAFP), American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) recommend that all adults ≥60 years of age receive a single dose of zoster vaccine, unless contraindicated.6 20 (See Contraindications under Cautions.)

ACIP and others state the vaccine can be used in those with or without a prior episode of herpes zoster, unless a medical condition is present that is considered a contraindication or precaution for use of the vaccine.6 19

ACIP does not currently recommend routine use of zoster vaccine in adults 50 through 59 years of age since risk of getting zoster and having prolonged pain after zoster is much lower in this age group than in those ≥60 years of age and there have been shortages and supply problems with the vaccine during the last several years.26 ACIP states the vaccine may be offered to individuals 50 through 59 years of age after considering whether the individual would have poor tolerance to zoster or PHN symptoms (e.g., patient has preexisting chronic pain, severe depression, or other comorbidities; hypersensitivity to or potential drug interactions with drugs used for zoster treatment; extenuating employment-related factors).26

Not indicated for treatment of herpes zoster or PHN.1 6 Not indicated for use in individuals with acute zoster infection in an attempt to prevent development of PHN.6

Not used for prevention of primary varicella infection (chickenpox).1 Not a substitute for varicella vaccine (Varivax).6

Not recommended for individuals of any age who have previously received varicella vaccine.6 Most individuals ≥50 years of age will not have received varicella vaccine.6

Not used in children, adolescents, or adults <50 years of age.1 6

Zostavax Dosage and Administration

Administration

Sub-Q Administration

Administer by sub-Q injection into the deltoid region of the upper arm.1 6

Do not administer IM or intravascularly.1 6

Administer immediately following reconstitution to minimize loss of potency and ensure an adequate immunizing dose.1

Do not mix with any other vaccine or solution.8

Reconstitution

Lyophilized zoster vaccine must be kept frozen at -50 to -15°C.1 (See Storage under Stability.) Reconstitute immediately following removal from the freezer.1

To reconstitute, add entire contents of the vial containing diluent provided by the manufacturer to the vial of lyophilized vaccine.1 To avoid excessive foaming, slowly inject diluent into vial of lyophilized vaccine and agitate gently.1 Use only the diluent supplied by the manufacturer.1

Use sterile syringes and needles free of preservatives, antiseptics, and detergents to avoid inactivating the live virus vaccine.1 8

Gently agitate reconstituted vaccine to mix thoroughly.1 Reconstituted vaccine is a semi-hazy to translucent off-white to pale yellow suspension.1

Dosage

Adults

Prevention of Herpes Zoster
Adults ≥50 Years of Age
Sub-Q

Single dose consisting of entire contents (0.65 mL) of a reconstituted single-dose vial.1 6

Duration of protection following the recommended single dose is at least 4 years.1 3 5 6 Need for revaccination or additional (booster) doses not determined.1 (See Duration of Immunity under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No specific dosage recommendations.1

Cautions for Zostavax

Contraindications

  • History of anaphylactic/anaphylactoid reactions to gelatin, neomycin, or any other vaccine component.1 6 (See Sensitivity Reactions under Cautions.)

  • History of primary or acquired immunodeficiency states, including leukemia, lymphomas of any type, other malignant neoplasms affecting the bone marrow or lymphatic system, or clinical manifestations of HIV infection (e.g., AIDS).1 6 20 (See Individuals with Altered Immunocompetence under Cautions.)

  • Immunosuppressive therapy.1 6 (See Specific Drugs under Interactions.)

  • Pregnancy or possible pregnancy.1 6 20 (See Pregnancy under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylactic reactions, reported.1

As with any vaccine, have appropriate medical treatment (e.g., epinephrine injection 1:1000) readily available in case an anaphylactic/anaphylactoid reaction occurs.1

Gelatin Allergy

Contains hydrolyzed porcine gelatin (15.58 mg per dose) as a stabilizer.1 6 Do not use in individuals with history of anaphylactic/anaphylactoid reaction to gelatin.1

Neomycin Allergy

Contains trace amounts of neomycin sulfate.1 6

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.6 8

Manufacturer and ACIP state do not use in those with history of anaphylactic/anaphylactoid reaction to neomycin, but neomycin allergy manifested as contact dermatitis is not a contraindication.1 6 8

Individuals with Altered Immunocompetence

Because zoster vaccine contains live, attenuated virus, it should not be used in individuals with altered immunocompetence, including those with primary or acquired immunodeficiencies or those receiving immunosuppressive therapy.1 6 20

Not recommended for HIV-infected individuals.6 23 ACIP, AAFP, ACOG, and ACP state the vaccine is contraindicated in HIV-infected individuals with CD4+ T-cell counts ≤200/mm3 or ≤15% of total lymphocytes.6 20

Risk for herpes zoster and its clinical complications is much greater among immunocompromised individuals than immunocompetent individuals.6 Review vaccination status of all immunocompetent individuals ≥60 years of age, particularly those who may be anticipating initiation of immunosuppressive therapy or have diseases that may lead to immunodeficiency.6 Those without previous zoster vaccination should receive a single dose of zoster vaccine at the first possible health-care visit while immunity is intact.6

Transmission of Vaccine Virus

Zoster vaccine contains live, attenuated virus.1 Transmission of vaccine virus may occur rarely between vaccinees and susceptible contacts.1 6

Transmission of zoster vaccine virus has not been documented to date; however, transmission of Oka/Merck strain of VZV has been reported rarely following administration of varicella vaccine, usually only when vaccine recipient developed a varicella-like rash.6

Weigh risk of possible vaccine virus transmission against risk of developing natural zoster infection that could be transmitted to susceptible contacts.1 6

Limitations of Vaccine Effectiveness

Does not prevent herpes zoster in all vaccine recipients.1 2 In those who develop herpes zoster, duration of pain and discomfort may be reduced.1 2

May be less effective in those ≥70 years of age than in those 60–69 years of age.1 2

Duration of Immunity

Duration of protection against herpes zoster following a single dose of zoster vaccine and need for revaccination or additional (booster) doses not fully determined.1 Data to date indicate the duration of protection is at least 4 years.1 6

Concomitant Illness

Defer vaccination in patients with active untreated tuberculosis.1

A decision to administer or delay vaccination in an individual with a current or recent acute illness depends on the severity of symptoms and etiology of the illness.1 6 8 Manufacturer suggests that vaccination be deferred in individuals with acute illness (e.g., in the presence of fever).1

ACIP states zoster vaccine may be administered to age-appropriate adults with minor acute illnesses such as diarrhea or mild upper respiratory tract infection (with or without fever), but defer vaccination in those with moderate or severe acute illness (with or without fever).6 8

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency8 21 and result in reduced or inadequate immune responses in vaccinees.8

Do not administer zoster vaccine that has been mishandled or has not been stored at the recommended temperature.1 21 Lyophilized vaccine should be stored frozen at -50 to -15°C and used within 30 minutes following reconstitution.1 (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.8 21 If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.8 21

Specific Populations

Pregnancy

Contraindicated.1

Naturally occurring VZV infection can cause fetal harm.1 6 7

Do not administer to pregnant women;1 avoid pregnancy for 3 months after vaccination.1

Inform vaccinees of the theoretical risk of transmitting the attenuated vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.1 (See Transmission of Vaccine Virus under Cautions.)

Any exposure to zoster vaccine that occurs during pregnancy should be reported to the pregnancy registry at 800-986-8999.1 6

Lactation

Not indicated in nursing women.1

Not known whether naturally occurring VZV is distributed into milk.1 Because some viruses are distributed into milk, use caution in nursing women.1

ACIP states that antigens contained in most live vaccines, including varicella vaccine, are not distributed into milk.6 Therefore, breast-feeding is not a contraindication for zoster vaccine.6

Pediatric Use

Not indicated in children and adolescents.1

Geriatric Use

Safety and efficacy established only in adults ≥50 years of age.1 6 Median age of individuals enrolled in the largest clinical study was 69 years.1

Common Adverse Effects

Injection site reactions (erythema, pain/tenderness, swelling, pruritus, warmth, hematoma, induration), headache, extremity pain.1 6

Interactions for Zostavax

Other Vaccines

Simultaneous administration with other age-appropriate vaccines or toxoids during the same health-care visit (using different syringes and different injection sites) generally is not expected to affect immunologic responses or adverse reactions to any of the vaccines.6 However, if another parenteral live vaccine is indicated in a patient receiving zoster vaccine, the vaccines should either be administered on the same day or at least 4 weeks apart.6

Specific Drugs

Drug

Interaction

Comments

Antiviral agents active against Herpesviruses (e.g., acyclovir, famciclovir, valacyclovir)

Data not available to date regarding use of zoster vaccine in patients receiving antiviral agents active against VZV1 7 13 16

These antiviral agents may interfere with replication of the live, attenuated VZV contained in zoster vaccine6

Antiviral agents active against VZV should be discontinued at least 24 hours before administration of zoster vaccine, if possible, and should not be used for at least 14 days after vaccination6

Blood products (e.g., whole blood, packed RBCs, plasma, platelet products)

May be given simultaneously with or at any time before or after blood or other antibody-containing blood products6 8

Immune globulin (immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific hyperimmune globulin (hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG])

May be given simultaneously with or at any interval before or after immune globulin or specific hyperimmune globulin preparations6 8

Immunosuppressive agents (e.g., corticosteroids)

Use of zoster vaccine in individuals receiving immunosuppressive agents may result in disseminated disease1

Manufacturer states that zoster vaccine is contraindicated in individuals receiving immunosuppressive agents1

ACIP states zoster vaccine should be administered at least 14 days before initiation of immunosuppressive therapy; some experts advise waiting 1 month after zoster vaccination before initiating such therapy, if possible6

High-dose systemic corticosteroid therapy (prednisone or equivalent in a dosage ≥2 mg/kg daily or ≥20 mg daily given for ≥2 weeks) is considered immunosuppressive;6 8 delay administration of live vaccines for at least 1 month after such therapy is discontinued6 8

Corticosteroid therapy involving short-term (<2 weeks) or low- to moderate-dose systemic therapy (<20 mg prednisone or equivalent daily); long-term, alternate-day systemic therapy using short-acting drugs; maintenance physiologic doses (replacement therapy); topical therapy (e.g., cutaneous, ophthalmic); oral inhalation; or intra-articular, bursal, or tendon injections should not be immunosuppressive and does not require deferral of live vaccines6 8

Influenza vaccine

Parenteral inactivated influenza vaccine: Studies using seasonal parenteral inactivated influenza vaccine indicated concomitant administration with zoster vaccine in adults ≥60 years of age results in antibody responses similar to those reported when the vaccines are administered 4 weeks apart 1 6 22

Parenteral inactivated influenza vaccine: May be administered concurrently (using different syringes and different injection sites)1 6 22

Pneumococcal vaccine

Study using pneumococcal 23-valent vaccine (PPSV23; Pneumovax 23) indicated concomitant administration of zoster vaccine in adults ≥60 years of age results in a significantly reduced antibody response to zoster vaccine compared to that reported when the vaccines are administered 4 weeks apart1 25

Consider administering ≥4 weeks apart1

Stability

Storage

Parenteral

For Injection, for Sub-Q Use

To maintain potency during shipment and storage, keep lyophilized zoster vaccine frozen at -50 to -15°C and protect from light.1

Any freezer (e.g., frost-free) that reliably maintains an average temperature of -50 to -15°C and has a separate sealed freezer door is acceptable;1 use of dry ice may expose the vaccine to temperatures colder than -50°C.1

When optimal handling conditions are not feasible (e.g., during transportation), the lyophilized vaccine may be stored for ≤72 hours at 2–8°C;1 discard the refrigerated vaccine if it has not been used within 72 hours after removal from storage at -50 to -15°C.1

Store vial containing the diluent supplied by the manufacturer separately either at room temperature (20–25°C) or in a refrigerator (2–8°C).1

Contact the manufacturer at 800-637-2590 for information regarding vaccine stability under conditions other than those recommended.1

Use immediately following reconstitution; discard reconstituted vaccine if not used within 30 minutes.1 Do not freeze.1

Zoster vaccine does not contain thimerosal or any other preservatives.1 6

Actions

  • Zoster vaccine is a lyophilized preparation containing live, attenuated VZV of the Oka/Merck strain.1 2 3 4 6 15

  • Vaccination with a single dose of zoster vaccine boosts active immunity to VZV, thereby reducing reactivation of VZV and development of herpes zoster and complications of the disease.1 2 3 4 6 15

  • Contains same antigen as varicella vaccine (Varivax); however, zoster vaccine is about 14 times more potent than varicella vaccine.1 6 10

  • The higher potency of varicella antigen contained in zoster vaccine is required to elicit a clinically important increase in cell-mediated immunity to VZV in older adults.2 3

  • Herpes zoster (shingles, zoster) and varicella (chickenpox) are distinct clinical entities caused by the same virus, VZV.3 6 7 13 16 During primary infection, VZV causes chickenpox; the virus invades sensory neurons and becomes latent in sensory nerve ganglia, establishing a source of potential secondary infection.1 2 3 6 7 13 15 16

  • Herpes zoster is characterized by unilateral, painful, vesicular cutaneous eruption with a dermatomal distribution.1 2 6 13 15 16 Pain may occur during the prodrome, the acute eruptive phase, and the postherpetic phase of the infection (PHN).1 2 6 13 16 Serious complications of the disease (e.g., scarring, bacterial superinfection, allodynia, cranial and motor neuron palsies, pneumonia, encephalitis, visual impairment, hearing loss, death) may occur.1 6 13 15 16

  • A single dose of zoster vaccine boosts VZV antibody levels 2.3-fold in adults 50–59 years of age or 1.7-fold in adults ≥60 years of age.1

  • Minimum antibody titer that correlates with protection against herpes zoster not established.1 6 15

Advice to Patients

  • Provide copy of manufacturer’s patient information.1 19 Prior to administration of the vaccine dose, also provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative (VISs are available at ).24

  • Advise patient of the risks and benefits of vaccination with zoster vaccine.1 19

  • Advise patient that they should not receive zoster vaccine if they have a history of anaphylactic/anaphylactoid reactions to any of its ingredients (e.g., gelatin, neomycin).1 19

  • Advise patient that they should not receive zoster vaccine if they have a disease that weakens the immune system (e.g., leukemia, lymphoma, HIV/AIDS), are receiving treatment that may weaken the immune system (e.g., corticosteroids), or have active, untreated tuberculosis.1 19

  • Advise patient that zoster vaccine may not provide protection against herpes zoster in all vaccinees.1 19

  • Advise patient that zoster vaccine can prevent shingles (not chickenpox) and cannot be used to treat shingles once the condition develops.1 19

  • Advise patient of the theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.1 19

  • Importance of informing clinicians if patients had allergic reactions to another vaccine or if they expect to be in close contact with neonates, pregnant women who have not had chickenpox or been vaccinated against chickenpox, or individuals with a weakened immune system.19

  • Importance of contacting clinicians if a hypersensitivity reaction (e.g., difficulty breathing or swallowing) occurs following the vaccine dose.1 19 Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .1 6

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 19 Importance of avoiding pregnancy for 3 months following vaccination.1 If any exposure to zoster vaccine occurs during pregnancy, vaccinees and their clinicians are encouraged to contact the pregnancy registry at 800-986-8999.1 19

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Zoster Vaccine Live

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injectable suspension, for subcutaneous use

≥19,400 plaque-forming units (PFU) of Oka/Merck strain of varicella zoster virus per 0.65 mL

Zostavax

Merck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 2, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Merck & Co. Zostavax (zoster vaccine live suspension for subcutaneous injection) prescribing information. Whitehouse Station, NJ; 2011 Jun.

2. Oxman MN, Levin MJ, Johnson GR et al; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005; 352:2271-84. [PubMed 15930418]

3. Arvin A. Aging, immunity, and the varicella-zoster virus. N Engl J Med. 2005; 352:2266-7. [PubMed 15930416]

4. Gilden DH. Varicella-zoster virus vaccine--grown-ups need it, too. N Engl J Med. 2005; 352:2344-6. [PubMed 15930426]

5. Anon. Herpes zoster vaccine (zostavax). Med Lett Drugs Ther. 2006; 48:73-4. [PubMed 16977285]

6. Centers for Disease Control and Prevention. Prevention of herpes zoster. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008; 57(RR-5):1-30.

7. Whitley RJ. Varicella-Zoster Virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 6th ed. New York: Churchill Livingstone; 2005:1780-6.

8. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-64.

9. Supplementary Appendix to Oxman MN, Levin MJ, Johnson GR et al; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005; 352:2271-84. [PubMed 15930418]

10. Merck & Co. Varivax (varicella virus vaccine live) prescribing information. Whitehouse Station, NJ; 2009 Jun.

12. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007; 56(RR-4):1-40.

13. Gnann JW, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002; 347:340-5. [PubMed 12151472]

15. Hambleton S, Gershon AA. Preventing varicella-zoster disease. Clin Microbiol Rev. 2005; 18:70-80. [PubMed 15653819]

16. Dworkin RH, Johnson RW, Breuer J et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007; 44:S1-S26. [PubMed 17143845]

17. Merck & Co. North Wales, PA: Personal communication.

18. A phase III clinical trial to study the safety, tolerability and immunogenicity of zoster vaccine live (Oka/Merck) in subjects with a history of herpes zoster. From ClinicalTrials.gov web site. (). Accessed 2007 Jan 8.

19. Merck & Co. Zostavax (zoster vaccine live) patient information. Whitehouse Station, NJ; 2008 Apr.

20. Centers for Disease Control and Prevention. Recommended adult immunization schedule–United States, 2011. Updates available at CDC website.

21. Centers for Disease Control and Prevention. Vaccine storage and handling guide. 2011 Oct. From CDC website.

22. Kerzner B, Murray AV, Cheng E et al. Safety and immunogenicity profile of the concomitant administration of zostavax and inactivated influenza vaccine in adults aged 50 and older. J Am Geriatr Soc. 2007; 55:1499-507. [PubMed 17908055]

23. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58:1-207; quiz CE1-4.

24. Centers for Disease Control and Prevention. Shingles vaccine information statement. 2009 Oct 6. From CDC website.

25. Macintyre CR, Egerton T, McCaughey M et al. Concomitant administration of zoster and pneumococcal vaccines in adults ≥60 years old. Hum Vaccin. 2010; 6:894-902. [PubMed 20980796]

26. Centers for Disease Control and Prevention. Herpes zoster vaccination for health care professionals. From CDC website. 2011 Sep.

Hide
(web4)