Persons at greatest risk of experiencing serious vaccination complications are often those at greatest risk for death from smallpox. The risk for experiencing serious vaccination complications must be weighed against the risks for experiencing a potentially fatal smallpox infection. Serious Complications And Death Serious complications that may follow either primary live vaccinia smallpox vaccination or revaccination include: myocarditis and/or pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome), eczema vaccinatum, blindness, and fetal death in pregnant women. These complications may rarely lead to severe disability, permanent neurological sequelea and death. Based on clinical trials, symptoms of suspected myocarditis or pericarditis (such as chest pain, raised troponin/cardiac enzymes, or ECG abnormalities) occur in 5.7 per 1000 primary vaccinations. This finding includes cases of acute symptomatic or asymptomatic myocarditis or pericarditits or both. Historically, death following vaccination with live vaccinia virus is a rare event; approximately 1 death per million primary vaccinations and 1 death per 4 million revaccinations have occurred after vaccination with live vaccinia virus. Death is most often the result of sudden cardiac death, postvaccinial encephalitis, progressive vaccinia, or eczema vaccinatum. Death has also been reported in unvaccinated contacts accidentally infected by individuals who have been vaccinated. Incidence Of Serious Complications In 1968 US Surveillance Studies Estimates of the risks of occurrence of serious complications after primary vaccination and revaccination, based on safety surveillance studies conducted when live vaccinia virus smallpox vaccine (i.e., New York City Board of Health strain, Dryvax®) was routinely recommended, are as follows: Table 1A : Rates of reported complicationsa associated with primary vaccinia vaccinations (cases/million vaccinations)b
Age (yrs) < 1 1-4 5-19 ≥ 20 Overall ratesh Inadvertent inoculationc § 507.0 577.3 371.2 606.1 529.2 Generalized vaccinia 394.4 233.4 139.7 212.1 241.5 Eczema vaccinatum 14.1 44.2 34.9 30.3 38.5 Progressive vacciniad --g 3.2 --g --g 1.5 Post-vaccinial encephalitis 42.3 9.5 8.7 --g 12.3 Deathe 5 0.5 0.5 unknown -- Totalf 1549.3 1261.8 855.9 1515.2 1253.8 a See article for descriptions of complications.
b Adapted from Lane JM, Ruber FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis. 1970; 122:303-309.
c Referenced as accidental implantation.
d Referenced as vaccinia necrosum.
e Death from all complications.
f Rates of overall complications by age group include complications not provided in this table, including severe local reactions, bacterial superinfection of the vaccination site, and erythema multiforme.
g No instances of this complication were identified during the 1968 10-state survey.
h Overall rates for each complication include persons of unknown age. Table 1B : Rates of reported serious complicationsa associated with vaccinia revaccinations (cases/million vaccinations)b
Age (yrs) < 1 1-4 5- 19 ≥ 20 Overall ratesb Inadvertent inoculationc g 109.1 47.7 25.0 42.1 Generalized vaccinia g g 9.9 9.1 9.0 Eczema vaccinatum g g 2.0 4.5 3.0 Progressive vacciniad g g g 6.8 3.0 Post-vaccinial encephalitis g g g 4.5 2.0 Deathe -- -- -- -- -- Totalf g 200.0 85.5 113.6 108.2 See Table 1A for explanation of footnotes. Incidence Of Serious Complications And Emergence Of Myocarditis And/Or Pericarditis In 2002-2005 Data on the incidence of adverse events among U.S. military personnel and civilian first responders vaccinated with Dryvax®, a licensed live vaccinia virus smallpox vaccine, during vaccination programs initiated in December 2002 are shown below in Table 2. The incidence of preventable adverse events (eczema vaccinatum, contact transmission, and auto-inoculation) were notably lower in these programs when compared with data collected in the 1960s; presumably because of better vaccination screening procedures and routine use of protective bandages over the inoculation site. Myocarditis and pericarditis were not commonly reported following smallpox vaccination in the 1960s, but emerged as a more frequent event based on more active surveillance in the military and civilian programs. Table 2 : Serious adverse events in 2002-20055
Adverse event Department of Defense program (n=730,580a) as of Jan05 Department of Health and Human Services program (n=40, 422) as of Jan04b N Incidence/ million N Incidence /million Myo/pericarditis Post-vaccinal 86 117.71 21 519.52 encephalitis 1 1.37 1 24.74 Eczema vaccinatum 0 0.00 0 0.00 Generalized vaccinia 43 58.86 3 74.22 Progressive vaccinia 0 0.00 0 0.00 Fetal vaccinia 0 0.00 0 0.00 Contact transmission 52 71.18 0 0.00 Auto-inoculation (nonocular) 62 84.86 20 494.78 Ocular vaccinia 16 21.90 3 74.22 a 71% primary vaccination; 89% male; median age 28.5 yr
b 36% primary vaccination; 36% male; median age 47.1 yr Myocarditis And Pericarditis In The ACAM2000 Clinical Trial Experience In clinical trials involving 2983 subjects who received ACAM2000 and 868 subjects who received Dryvax®, ten (10) cases of suspected myocarditis [0.2% (7 of 2983) ACAM2000 subjects and 0.3% (3 of 868) Dryvax® subjects] were identified. The mean time to onset of suspected myocarditis and/or pericarditis from vaccination was 11 days, with a range of 9 to 20 days. All subjects who experienced these cardiac events were naïve to vaccinia. Of the 10 subjects, 2 were hospitalized. None of the remaining 8 cases required hospitalization or treatment with medication. Of the 10 cases, 8 were sub-clinical and were detected only by ECG abnormalities with or without associated elevations of cardiac troponin I. All cases resolved by 9 months, with the exception of one female subject in the Dryvax® group, who had persistent borderline abnormal left ventricular ejection fraction on echocardiogram. The best estimate of risk for myocarditis and pericarditis is derived from the Phase 3 ACAM2000 clinical trials where there was active monitoring for potential of myocarditis and pericarditis. Among vaccinees naïve to vaccinia, 8 cases of suspected myocarditis and pericarditis were identified across both treatment groups, for a total incidence rate of 6.9 per 1000 vaccinees (8 of 1,162). The rate for the ACAM2000 treatment group were similar: 5.7 (95% CI: 1.9-13.3) per 1000 vaccinees (5 of 873 vaccinees) and for the Dryvax® group 10.4 (95% CI: 2.1-30.0) per 1000 vaccinees (3 of 289 vaccinees). No cases of myocarditis and/or pericarditis were identified in 1819 previously vaccinated subjects. The long-term outcome of myocarditis and pericarditis following ACAM2000 vaccination is currently unknown. Cardiac Disease Ischemic cardiac events, including fatalities, have been reported following smallpox vaccination; the relationship of these events, if any, to vaccination has not been established. In addition, cases of non-ischemic, dilated cardiomyopathy have been reported following smallpox vaccination; the relationship of these cases to smallpox vaccination is unknown. There may be increased risks of adverse events with ACAM2000 in persons with known cardiac disease, including those diagnosed with previous myocardial infarction, angina, congestive heart failure, cardiomyopathy, chest pain or shortness of breath with activity, stroke or transient ischemic attack, or other heart conditions. In addition, subjects who have been diagnosed with 3 or more of the following risk factors for ischemic coronary disease: 1) high blood pressure; 2) elevated blood cholesterol; 3) diabetes mellitus or high blood sugar; 4) first degree relative (for example mother, father, brother, or sister) who had a heart condition before the age of 50; or 5) smoke cigarettes may have increased risks. Ocular Complications And Blindness Accidental infection of the eye (ocular vaccinia) may result in ocular complications including keratitis, corneal scarring and blindness. Patients who are using corticosteroid eye drops may be at increased risk of ocular complications with ACAM2000. Presence Of Congenital Or Acquired Immune Deficiency Disorders Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems, including patients with leukemia, lymphoma, organ transplantation, generalized malignancy, HIV/AIDS, cellular or humoral immune deficiency, radiation therapy, or treatment with antimetabolites, alkylating agents, or high-dose corticosteroids ( > 10 mg prednisone/day or equivalent for ≥ 2 weeks). The vaccine is contraindicated in individuals with severe immunodeficiency [See CONTRAINDICATIONS]. Vaccinees with close contacts who have these conditions may be at increased risk because live vaccinia virus can be shed and be transmitted to close contacts. History Or Presence Of Eczema And Other Skin Conditions Persons with eczema of any description such as, atopic dermatitis, neurodermatitis, and other eczematous conditions, regardless of severity of the condition, or persons who have a history of these conditions at any time in the past, are at higher risk of developing eczema vaccinatum. Vaccinees with close contacts who have eczematous conditions, may be at increased risk because live vaccinia virus can shed and be transmitted to these close contacts. Vaccinees with other active acute, chronic or exfoliative skin disorders (including burns, impetigo, varicella zoster, acne vulgaris with open lesions, Darier's disease, psoriasis, seborrheic dermatitis, erythroderma, pustular dermatitis, etc.), or vaccinees with household contacts having such skin disorders might also be at higher risk for eczema vaccinatum. Infants ( < 12 Months Of Age) And Children ACAM2000 has not been studied in infants or children. The risk of serious adverse events following vaccination with live vaccinia virus is higher in infants. Vaccinated persons who have close contact with infants, e.g., breastfeeding, must take precautions to avoid inadvertent transmission of ACAM2000 live vaccinia virus to infants. Pregnancy ACAM2000 has not been studied in pregnant women. Live vaccinia virus vaccines can cause fetal vaccinia and fetal death. If ACAM2000 is administered during pregnancy, the vaccinee should be apprised of the potential hazard to the fetus [See Use in Specific Populations]. Vaccinees with close contacts who are pregnant may be at increased risk because live vaccinia virus can shed and be transmitted to close contacts. Allergy To ACAM2000 Smallpox Vaccine Or Its Components ACAM2000 contains neomycin and polymyxin B. Persons allergic to these components may be at higher risk for adverse events after vaccination. Both the vaccine and diluent vial stoppers do not contain latex material. Management Of Smallpox Vaccine Complications The CDC can assist physicians in the diagnosis and management of patients with suspected complications of vaccinia (smallpox) vaccination. Vaccinia Immune Globulin (VIG) is indicated for certain complications of vaccination live vaccinia virus smallpox vaccine. If VIG is needed or additional information is required, physicians should contact the CDC at (404) 639-3670, Monday through Friday 8 AM to 4:30 PM Eastern Standard Time; at other times call (404) 639-2888. Prevention Of Transmission Of Live Vaccinia Virus The most important measure to prevent inadvertent auto-inoculation and contact transmission from vaccinia vaccination is thorough hand washing after changing the bandage or after any other contact with the vaccination site. Individuals susceptible to adverse effects of vaccinia virus, i.e., those with cardiac disease, eye disease, immunodeficiency states, including HIV infection, eczema, pregnant women and infants, should be identified and measures should be taken to avoid contact between those individuals and persons with active vaccination lesions. Recently vaccinated healthcare workers should avoid contact with patients, particularly those with immunodeficiencies, until the scab has separated from the skin at the vaccination site. However, if continued contact with patients is unavoidable, vaccinated healthcare workers should ensure the vaccination site is well covered and follow good hand-washing technique. In this setting, a more occlusive dressing may be used. Semipermeable polyurethane dressings are effective barriers to shedding of vaccinia. However, exudate may accumulate beneath the dressing, and care must be taken to prevent viral spread when the dressing is changed. In addition, accumulation of fluid beneath the dressing may increase skin maceration at the vaccination site. Accumulation of exudate may be decreased by first covering the vaccination with dry gauze, then applying the dressing over the gauze. The dressing should be changed every 1-3 days [See Self Inoculation and Spread to Close Contacts and Care of the Vaccination Site and Potentially Contaminated Materials]. Blood And Organ Donation Blood and organ donation should be avoided for at least 30 days following vaccination with ACAM2000. Limitations Of Vaccine Effectiveness ACAM2000 smallpox vaccine may not protect all persons exposed to smallpox. Patient Counseling Information Please refer patient to the Medication Guide prepared for ACAM2000 Smallpox Vaccine. Serious Complications Of Vaccination Patients must be informed of the major serious adverse events associated with vaccination, including myocarditis and/or pericarditis, progressive vaccinia in immunocompromised persons, eczema vaccinatum in persons with skin disorders, auto- and accidental inoculation, generalized vaccinia, urticaria, erythema multiforme major (including Stevens-Johnson syndrome) and fetal vaccinia in pregnant women. Protecting Contacts At Highest Risk For Adverse Events Patients must be informed that they should avoid contact with individuals at high risk of serious adverse effects of vaccinia virus, for instance, those with past or present eczema, immunodeficiency states including HIV infection, pregnancy, or infants less than 12 months of age. Self-inoculation And Spread To Close Contacts Patients must be advised that virus is shed from the cutaneous lesion at the site of inoculation from approximately Day 3 until scabbing occurs, typically between Days 14-21 after primary vaccination. Vaccinia virus may be transmitted by direct physical contact. Accidental infection of skin at sites other than the site of intentional vaccination (self-inoculation) may occur by trauma or scratching. Contact spread may also result in accidental inoculation of household members or other close contacts. The result of accidental infection is a pock lesion(s) at an unwanted site(s) in the vaccinee or contact, and resembles the vaccination site. Self-inoculation occurs most often on the face, eyelid, nose, and mouth, but lesions at any site of traumatic inoculation can occur. Self-inoculation of the eye may result in ocular vaccinia, a potentially serious complication. Care Of The Vaccination Site And Potentially Contaminated Materials Patients must be given the following instructions:
- The vaccination site must be completely covered with a semipermeable bandage. Keep site covered until the scab falls off on its own.
- The vaccination site must be kept dry. Normal bathing may continue, but cover the vaccination site with waterproof bandage when bathing. The site should not be scrubbed. Cover the vaccination site with loose gauze bandage after bathing.
- Don't scratch the vaccination site. Don't scratch or pick at the scab.
- Do not touch the lesion or soiled bandage and subsequently touch other parts of the body particularly the eyes, anal and genital areas that are susceptible to accidental (auto-) inoculation.
- After changing the bandage or touching the site, wash hands thoroughly with soap and water or > 60% alcohol-based hand-rub solutions.
- To prevent transmission to contacts, physical contact of objects that have come into contact with the lesion (e.g. soiled bandages, clothing, fingers) must be avoided.
- Wash separately clothing, towels, bedding or other items that may have come in direct contact with the vaccination site or drainage from the site, using hot water with detergent and/or bleach. Wash hands afterwards.
- Soiled and contaminated bandages must be placed in plastic bags for disposal.
- The vaccinee must wear a shirt with sleeves that covers the vaccination site as an extra precaution to prevent spread of the vaccinia virus. This is particularly important in situations of close physical contact.
- The vaccinee must change the bandage every 1 to 3 days. This will keep skin at the vaccination site intact and minimize softening.
- Don't put salves or ointments on the vaccination site.
- When the scab fall off, throw it away in a sealed plastic bag and wash hands afterwards.
Use In Specific Populations Pregnancy Pregnancy Category D ACAM2000 has not been studied in pregnant women. Live vaccinia virus vaccines can cause fetal harm when administered to a pregnant woman. Congenital infection, principally occurring during the first trimester, has been observed after vaccination with live vaccinia smallpox vaccines, although the risk may be low. Generalized vaccinia of the fetus, early delivery of a stillborn infant, or a high risk of perinatal death has been reported. The only setting in which vaccination of pregnant women should be considered is when exposure to smallpox is considered likely. If this vaccine is used during pregnancy, or if the vaccinee lives in the same household with or has close contact with a pregnant women, the vaccinee should be apprised of the potential hazard to the fetus. Healthcare providers, state health departments, and other public health staff should report to the National Smallpox Vaccine in Pregnancy Registry all cases in which persons who received ACAM2000, or were exposed to a woman who received ACAM2000 within 28 days after vaccination, during pregnancy, or within 42 days prior to conception. Civilian women should contact their healthcare provider or state health department for help enrolling in the registry. Clinicians or public health staff should report civilian cases through their state health department or to CDC, telephone 404-639-8253 or 877 554 4625. Military cases should be reported to the DoD, telephone 619 553-9255, Defense Switched Network (DSN) 553-9255, fax 619 767-4806 or e-mail [email protected]
Nursing Mothers ACAM2000 has not been studied in lactating women. It is not known whether vaccine virus or antibodies are secreted in human milk. Live vaccinia virus can be inadvertently transmitted from a lactating mother to her infant. Infants are at high risk of developing serious complications from live vaccinia smallpox vaccination. Pediatric Use The safety and effectiveness of ACAM2000 have not been established in the age groups from birth to age 16. The use of ACAM2000 in all pediatric age groups is supported by evidence from the adequate and well-controlled studies of ACAM2000 in adults and with additional historical data with use of live vaccinia virus smallpox vaccine in pediatrics. Before the eradication of smallpox disease, live vaccinia virus smallpox vaccine was administered routinely in all pediatric age groups, including neonates and infants, and was effective in preventing smallpox disease. During that time, live vaccinia virus was occasionally associated with serious complications in children, the highest risk being in infants younger than 12 months of age. [See WARNINGS AND PRECAUTIONS]. Geriatric Use Clinical studies of ACAM2000 did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. There are no published data to support the use of this vaccine in geriatric (persons > 65 years) populations. 5 Poland GA, Grabenstein JD, Neff JM. The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation program. Vaccine. 2005;23:2078-2081. Last reviewed on RxList: 9/29/2014
This monograph has been modified to include the generic and brand name in many instances.