Pharmaceutical Name

Trade (marketing or proprietary) name: ACAM2000

Generic (nonproprietary or active ingredient) name: Smallpox (Vaccinia) Vaccine, Live

Indication and Usage

Reason the product has been approved for sale on the market.

ACAM2000® is indicated for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection.

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

ACAM2000, Smallpox (Vaccinia) Vaccine, Live, is a live vaccinia virus derived from plaque purification cloning from Dryvax® (Wyeth Laboratories, Marietta, PA, calf lymph vaccine, New York City Board of Health Strain) and grown in African Green Monkey kidney (Vero) cells and tested to be free of adventitious agents. ACAM2000 is provided as a lyophilized preparation of purified live virus containing the following non-active excipients: 6-8 mM HEPES (pH 6.5-7.5), 2% human serum albumin USP, 0.5 – 0.7% sodium chloride USP, 5% mannitol USP, and trace amounts of neomycin and polymyxin B. Diluent for ACAM2000 contains 50% (v/v) Glycerin USP, 0.25% (v/v) Phenol USP in Water for Injection USP, supplied in 3 mL clear glass vials containing 0.6 mL of diluent.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Severe Immune Deficiency: Do not administer ACAM2000 to individuals with severe immunodeficiency. These individuals may include individuals who are undergoing bone marrow transplantation or individuals with primary or acquired immunodeficiency who require isolation.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Serious complications that may follow either primary or revaccination with ACAM2000 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, accidental eye infection (ocular vaccinia) which can cause ocular complications including keratitis and corneal scarring that may lead to blindness, and fetal death in pregnant women. These complications may rarely lead to severe disability, permanent neurological sequalae and death. Based on ACAM2000 clinical trials, symptoms of suspected myocarditis or pericarditis (such as chest pain, raised troponin/cardiac enzymes, or ECG abnormalities) occurred in 5.7 per 1000 primary vaccinations. This finding includes cases of acute symptomatic or asymptomatic myocarditis or pericarditis 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, post-vaccinial encephalitis, progressive vaccinia, or eczema vaccinatum. Death has also been reported in unvaccinated contacts accidentally infected by individuals who have been vaccinated.

Cardiac Disease: Ischemic cardiac events, including fatal events, and non-ischemic, dilated cardiomyopathy have been reported following ACAM2000 and other live vaccinia virus vaccines that were used historically. The relationship of these events to 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, individuals who have been diagnosed with 3 or more of the following risk factors for ischemic coronary disease may have increased risks: 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.

Ocular Complications: Accidental infection of the eye (ocular vaccinia) may result in ocular complications, including keratitis and corneal scarring that may lead to 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, high-dose corticosteroids (>10 mg prednisone/day or equivalent for ≥2 weeks), or other immunomodulatory drugs. ACAM2000 is contraindicated in individuals with severe immunodeficiency. Close contacts of vaccinees (including sexual 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: Based on data from historical use of other live vaccinia virus vaccines, the risk of serious adverse reactions following vaccination with ACAM2000 is higher in infants (<12 months of age). Vaccinated persons who have close contact with infants must take precautions to avoid inadvertent transmission of ACAM2000 live vaccinia virus to infants.

Pregnancy: ACAM2000 has not been studied in pregnant women. Based on data from historical use of other live vaccinia virus vaccines, ACAM2000 can cause fetal vaccinia and fetal death. If ACAM2000 is administered during pregnancy or within 6 weeks before becoming pregnant, the vaccinee should be apprised of the potential hazard to the fetus. Vaccinees should be counseled to avoid becoming pregnant (or getting their partner pregnant) for 6 weeks after vaccination and until the vaccination site has healed. Pregnant women who are close contacts of vaccinees may be at risk of adverse fetal outcomes because ACAM2000 live vaccinia virus can be transmitted from vaccinees.

Severe Allergic Reactions: Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of ACAM2000.
Persons who experienced a severe allergic reaction following a previous dose of ACAM2000 or following exposure to any ingredient of ACAM2000, including neomycin or polymyxin B, may be at increased risk for severe allergic reactions.

Management of ACAM2000 Complications: The CDC can assist physicians in the diagnosis and management of patients with suspected complications of ACAM2000 vaccination. Vaccinia immune globulin intravenous (human) (CNJ-016®) is indicated for the treatment of certain complications due to vaccinia vaccination. If CNJ-016 and/or other antivirals are needed or additional information is required, physicians should contact the CDC Emergency Operations Center (EOC) at 1-800-232-4636 (CDC-INFO).

Prevention of Transmission of Live Vaccinia Virus: The most important measure to prevent inadvertent auto-inoculation and contact transmission from ACAM2000 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 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, the loose gauze held in place with first aid tape may be covered with a semipermeable (semi-occlusive) dressing as an additional barrier. 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 gauze and dressing should be changed every 1 to 3 days.

Blood and Organ Donation: Blood and organ donation should be avoided for 6 weeks following vaccination with ACAM2000.

Limitations of Vaccine Effectiveness: ACAM2000 may not protect all recipients.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Erythema (skin redness), Pruritus (itchy skin), Pain/Swelling, Fatigue, Malaise (discomfort), Feeling hot/Rigors, Exercise tolerance decreased, Headache, Limb paresthesias, Dizziness/Vertigo, Meningitis, Encephalitis/myelitis, Bell palsy, Seizures including death, Guillain-Barré syndrome, Accidental infection of the eye (ocular vaccinia), Blindness, Photophobia, Myalgia (muscle pain), Back pain, Arthralgia (joint pain), Pain in extremity, Lymphadenopathy/pain, Nausea/Vomiting, Diarrhea/Constipation, Severe abdominal pain, Toothache, Dermatitis (eczema), Urticaria (hives), Generalized rashes, Inadvertent inoculation at other body sites (face, nose, mouth, lips, genitalia, and anus), Keratis, Corneal scarring, Benign/Malignant lesions, Progressive vaccinia (vaccinia recrosum), Generalized vaccinia, Severe vaccinial skin infections, Stevens-Johnson syndrome, Fetal vaccinia, Fetal death, Myocarditis, Pericarditis, Eczema vaccinated resulting in permanent sequelae or death.

Limitations of Effectiveness

ACAM2000 smallpox vaccine may not protect all persons exposed to smallpox.

Specific Populations

Pregnancy

ACAM2000 has not been studied in pregnant women. Based on data from historical use of other live vaccinia virus vaccines, ACAM2000 can cause fetal harm when administered to a pregnant woman. ACAM2000 is not recommended for administration to pregnant women in non-emergency situations. If ACAM2000 is used during pregnancy or within 6 weeks before becoming pregnant, or if the vaccinee lives in the same household with or has close contact with a pregnant woman, the pregnant individual should be apprised of the potential hazard to the fetus.

Disease caused by smallpox (variola virus) can cause severe illness during pregnancy. Adverse pregnancy outcomes including spontaneous abortion and stillbirth have occurred after smallpox and mpox maternal infections.

Congenital infection, principally occurring during the first trimester, was observed after vaccination with live vaccinia smallpox vaccines during the era of routine smallpox vaccination. Generalized vaccinia of the fetus, early delivery of a stillborn infant, and perinatal death have been reported from the historical experience with other live vaccinia smallpox vaccines.

Breastfeeding

ACAM2000 has not been studied in lactating women. It is not known whether ACAM2000 is excreted in human milk. No human or animal data are available to assess the effects of ACAM2000 on the breastfed infant or on milk production/excretion. Persons vaccinated with ACAM2000 and who have close contact with infants (e.g., breastfeeding) must take precautions to avoid inadvertent transmission of live vaccinia virus to infants, which may result in serious complications

Fertility

An individual vaccinated with ACAM2000 should be counseled to avoid becoming pregnant (or getting their partner pregnant) for 6 weeks after vaccination. ACAM2000 has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male or
female fertility in animals.

Pediatric

ACAM2000 has not been studied in the pediatric population. The safety and effectiveness of ACAM2000 in all pediatric age groups is based on the safety and effectiveness of ACAM2000 in adults, historical data on safety and effectiveness of live vaccinia virus smallpox vaccines in pediatric populations, and efficacy of ACAM2000 in protecting non-human primates from lethal challenge with mpox virus. Before the eradication of smallpox disease, live vaccinia virus smallpox vaccines were administered routinely in all pediatric age groups, including neonates and infants, and were 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.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

Vaccinia virus is a member of the same taxonomic group (the Orthopoxvirus genus) as variola (which causes smallpox) and mpox viruses. Immunity induced by vaccinia virus cross-protects against variola and mpox viruses. Vaccinia virus causes a localized virus infection of the epidermis at the site of inoculation, surrounding dermal and subcutaneous tissues, and draining lymph nodes. Virus may be transiently present in blood and infects reticuloendothelial and other tissues. Langerhans cells in the epidermis are specific targets for the early stage of virus replication. The formation of a pustule (‘pock’ or ‘take’) at the site of inoculation provides evidence of protective immunity. The virus replicates within cells and viral antigens are presented to the immune system. Neutralizing antibodies and B and T cells provide long-term memory. The level of neutralizing antibody that protects against smallpox or mpox is unknown but >95% of persons undergoing primary vaccination develop neutralizing or hemagglutination inhibiting antibodies to vaccinia.

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