Acam2000

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  • Vaccines
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Acam2000 Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Smallpox (vaccinia) vaccine, live; contains 2.5–12.5×10^5 plaque forming units; per 0.0025mL dose; lyophilized pwd for percutaneous scarification after reconstitution; contains trace amounts of neomycin, polymyxin B.

    How Supplied

    Multiple-dose vial (3mL)—1 (w. bifurcated needles, tuberculin syringes)

    How Supplied

    • ACAM2000 is supplied in multiple-dose 3 mL clear glass vials containing lyophilized powder (freeze-dried vaccine). After reconstitution with 0.3 mL of diluent, the vial contains approximately 100 nominal doses of 0.0025 mL of vaccinia virus (live), 1.0 - 5.0x108 PFU/mL or 2.5-12.5x105 PFU/dose. 

    • Diluent for ACAM2000, 50% (v/v) Glycerin USP, 0.25% (v/v) Phenol USP in Water for Injection USP, is supplied in 3 mL clear glass vials containing 0.6 mL of diluent. 

    • Bifurcated needles are supplied in boxes (5 x 5 x 1 in) containing 100 needles.

    • 1 mL tuberculin syringes with 25 gauge x 5/8” needles are supplied for vaccine reconstitution.

    • Both the vaccine and diluent vial stoppers are not made with natural rubber latex.

    Storage

    • Store in a freezer with an average temperature of -15°C to -25°C (+5°F to -13°F).

    • Prior to reconstitution, ACAM2000 vaccine retains a potency of 1.0x108 PFU or higher per dose for at least 18 months when stored at refrigerated temperatures of +2-8°C (36-46°F).

    • During shipment, ACAM2000 should be maintained at a temperature of -10°C or colder.

    • After reconstitution, ACAM2000 vaccine may be administered during a 6 to 8 hour workday at room temperature (20-25°C, 68-77°F). Reconstituted ACAM2000 vaccine may be stored in a refrigerator (2-8°C, 36-46°F) no longer than 30 days, after which it should be discarded [see Dosage and Administration (2.3)]. Diluent for Smallpox Vaccine, (Vero Cells) Lyophilized, ACAM2000 should be stored at room temperature (15-30°C, 59- 86°F).

    Manufacturer

    Emergent BioSolutions Inc.

    Generic Availability

    NO

    Mechanism of Action

    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.

    Acam2000 Indications

    Indications

    Active immunization against smallpox disease for persons determined to be at high risk for smallpox infection.

    Acam2000 Dosage and Administration

    Adult

    See full labeling. ≥17yrs: Give by percutaneous route (scarification) into the upper arm (deltoid) only after proper training. Clean the inj site area using an alcohol swab(s), if necessary. Allow skin to dry thoroughly to prevent inactivation of the live vaccine virus by the alcohol. Pick up a droplet (0.0025mL) of reconstituted vaccine soln using a bifurcated needle and deposit onto the vaccination site. Rapidly make 15 jabs of the needle perpendicular to the skin through the droplet to puncture skin, within a diameter of about 5mm. Vaccination site may be covered with loose gauze bandage or semipermeable dressing. Repeat vaccination every 3yrs in those at continued high risk of exposure.

    Adult

    Reconstitution

    • Remove vaccine vial from freezer and bring to room temperature before reconstitution.

    • Reconstitute ACAM2000 by adding 0.3 mL of diluent to the vial containing lyophilized vaccine. The reconstituted vaccine should be a clear to slightly hazy, colorless to straw-colored liquid free from extraneous matter.

    • Do not use the vaccine if particular matter or discoloration is observed.

    Preparation / Handling Precautions and Instructions for Disposal

    • Personnel preparing and administering the vaccine should wear surgical or protective gloves and avoid contact of vaccine with skin, eyes or mucous membranes.

    Vaccination Instructions

    • Bring reconstituted vaccine to room temperature prior to administration.

    • Visually examine the vial contents to verify the absence of particulates and gently swirled.

    • Give by percutaneous route (scarification) into the upper arm (deltoid) only after proper training. Do not inject by the intradermal, subcutaneous, intramuscular, or intravenous route.

    • Clean the injection site area using an alcohol swab(s), if necessary. Allow skin to dry thoroughly to prevent inactivation of the live vaccine virus by the alcohol. 

    • Pick up a droplet (0.0025mL) of reconstituted vaccine solution within the fork of the bifurcated needle and deposit onto the vaccination site. Never re-dip the needle into the vaccine vial if the needle has touched skin.

    • Deposit the droplet of vaccine onto clean, dry skin of the arm prepared for vaccination. The needle is held between thumb and first finger perpendicular to the skin. The wrist of the hand holding the needle of the vaccinator rests against the patient’s arm. Rapidly make 15 jabs of the needle perpendicular to the skin through the droplet to puncture the skin, within a diameter of about 5 mm. The jabs should be vigorous enough so that a drop of blood appears at the vaccination site.

    • Repeat vaccination every 3yrs in those at continued high risk of exposure.

    • Cover the vaccination site loosely with a gauze bandage.

    • Wash hands after administration. Wash separately clothes, 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.

    • Don’t put salves or ointments on the vaccination site.

     

    Instructions for Interpreting Vaccination Response 

    Primary Vaccinees

    • Individuals who received ACAM2000 for the first time (primary vaccination), the expected response is the development of a major cutaneous reaction at the site of inoculation. 

    • The lesion evolves with an appearance of a papule at the site of vaccination after 2 to 5 days. The papule becomes vesicular, then pustular, and reaches maximum size at 8 to 10 days after vaccination.

    • A successful ‘take’ and acquisition of protective immunity is the formation of a major cutaneous reaction by day 6 to 8.

    Previously Vaccinated Individuals (Revaccination)

    • A successful ‘take’ and acquisition of protective immunity is the formation of a major cutaneous reaction by day 6 to 8; similar to primary vaccines.

    • Previously vaccinated individuals who do not have a cutaneous response on revaccination do not require revaccination to try to elicit a cutaneous response.

    Vaccination Failures

    • Individuals who are not successfully vaccinated (i.e., vaccination failures) after primary vaccination may be revaccinated again in an attempt to achieve a satisfactory take. 

     

    Booster Schedule

    • Individuals at continued high risk of exposure to smallpox (e.g., research laboratory workers handling variola virus) should receive repeat ACAM2000 vaccination every three years.

    Smallpox Vaccination Recommendations from US Government Agencies

    Children

    <17yrs: not established.

    Acam2000 Contraindications

    Contraindications

    Severe immunodeficiency, including those who are undergoing bone marrow transplantation or those with primary or acquired immunodeficiency who require isolation.

    Acam2000 Boxed Warnings

    Boxed Warning

    Risk for serious complications including: myocarditis and/or pericarditis in healthy adults; encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson Syndrome), eczema vaccinatum resulting in permanent sequelae or death, ocular complications, blindness, and fetal death following either primary vaccination or revaccination. Increased risk of these complications, which may result in severe disability, permanent neurological sequelae and/or death, with the following conditions: cardiac disease or history of, eye disease treated with topical steroids, congenital or acquired immune deficiency disorders (including those taking immunosuppressants), eczema or history of, other exfoliative skin conditions, infants <12mos of age, pregnancy. Risk of transmitting live vaccinia virus to persons who have close contact with the vaccinee; the risks in close contacts are the same as the vaccinee. Weigh risk of serious vaccination complications against the risk of a potentially fatal smallpox infection.

    Boxed Warning

    • Risk for serious complications including myocarditis and/or pericarditis in healthy adults (at an approximate rate of 5.7 per 1000, 95% CI: 1.9-13.3) receiving ACAM2000.

    • Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson Syndrome), eczema vaccinatum resulting in permanent sequelae or death, ocular complications, blindness, and fetal death have occurred following either primary vaccination or revaccination. 

    • Increased risk of these complications, which may result in severe disability, permanent neurological sequelae and/or death, with the following conditions: 

      • Cardiac disease or history of

      • Eye disease treated with topical steroids

      • Congenital or acquired immune deficiency disorders (including those taking immunosuppressants)

      • Eczema or history of, or other exfoliative skin conditions

      • Infants <12 months of age

      • Pregnancy

    • Risk of transmitting live vaccinia virus to persons who have close contact with the vaccinee; the risks in close contacts are the same as the vaccinee. 

    • Weigh risk of serious vaccination complications against the risk of a potentially fatal smallpox infection.

    Acam2000 Warnings/Precautions

    Warnings/Precautions

    See Boxed Warning. Known cardiac disease (eg, previous MI, angina, CHF, cardiomyopathy, chest pain, shortness of breath with activity, stroke or TIA, other heart conditions). Diagnosed with ≥3 risk factors for ischemic coronary disease (eg, high BP, elevated blood cholesterol, diabetes, family history of heart condition <50yrs of age, smokers). Accidental infection of the eye may result in ocular complications (eg, keratitis, corneal scarring, blindness). Do not inject by the intradermal, SC, IM, or IV route. Avoid contact with skin, eyes, or mucous membranes. Avoid blood and organ donation for at least 30 days after vaccination. Vaccination may not protect all recipients. Elderly (>65yrs): not studied. Pregnancy (Cat. D): may cause fetal vaccinia or fetal death. Nursing mothers: can be transmitted to infants.

    Warnings/Precautions

    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. 

    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.

    • Increased risk for adverse events in patients with known cardiac disease (eg, previous MI, angina, CHF, cardiomyopathy, chest pain, shortness of breath with activity, stroke or TIA, other heart conditions). 

    • Increased risk for adverse events in patients 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 may result in ocular complications (eg, keratitis, corneal scarring, blindness). 

    • Increased risk for ocular complications in patients who are using corticosteroid eye drops.

    Presence of Congenital or Acquired Immune Deficiency Disorders

    • See Contraindications. ACAM2000 is contraindicated for use in individuals with severe immunodeficiency.

    • 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.

    • Increased risk for vaccinees with close contacts who have the conditions listed above.

    History or Presence of Eczema and Other Skin Conditions

    • Increased risk for developing eczema vaccinatum in patients 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.

    • Increased risk for vaccinees with close contacts who have eczematous conditions or other active acute, chronic, or exfoliative skin disorders (eg, burns, impetigo, varicella zoster, acne vulgaris with open lesions, Darier’s disease, psoriasis, seborrheic dermatitis, erythroderma, pustular dermatitis, etc.).

    Infants (< 12 months of Age) and Children

    • ACAM2000: not studied in infants or children.

    • Increased risk for serious adverse events 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: not studied in pregnancy. Live vaccinia virus vaccines can cause fetal vaccinia and fetal death.

    • Pregnant women who are close contacts of vaccinees 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

    • Contains  neomycin and polymyxin B.

    Prevention of Transmission of Live Vaccinia Virus

    • Thoroughly wash hands after changing the bandage or after any other contact with the vaccination site to prevent inadvertent auto-inoculation and contact transmission from vaccinia vaccination.

    • 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. 

    • Change dressing every 1 to 3 days.

    Blood and Organ Donation

    • Avoid blood and organ donation for at least 30 days after administration.

    Limitations of Vaccine Effectiveness

    • May not protect all persons exposed to smallpox.

    Pregnancy Considerations

    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.  

    • The only setting in which vaccination of pregnant women should be considered is when exposure to smallpox is considered likely. 

    Nursing Mother Considerations

    • ACAM2000 has not been studied in lactating women.

    • 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 Considerations

    • The safety and effectiveness of ACAM2000 have not been established in the age groups from birth to age 16.

    Geriatric Considerations

    • There are no published data to support the use of this vaccine in geriatric (persons >65 years) populations.

    Acam2000 Pharmacokinetics

    See Literature

    Acam2000 Interactions

    Interactions

    Concomitant use with corticosteroid eye drops may increase risk of ocular complications. May induce false (+) tests for syphilis. May induce false (–) results for tuberculin skin test, and possibly, blood tests for tuberculosis; if possible, delay tuberculin test for 1 month after vaccination. Do not put salves or ointments on the vaccination site.

    Acam2000 Adverse Reactions

    Adverse Reactions

    Inoculation site signs/symptoms, lymphadenitis, constitutional symptoms (eg, malaise, fatigue, fever, myalgia, headache), urticaria, folliculitis.

    Acam2000 Clinical Trials

    Clinical Trials

    Approval of ACAM2000 was based on data 2 randomized, multicenter, active-controlled clinical trials; one study included patients who previously did not receive the smallpox vaccine (Study 1) and the other study included patients who received the smallpox vaccine over 10 years previously (Study 2).

    In both trials, the coprimary efficacy endpoints were the proportion of subjects with a successful vaccination/revaccination and the geometric mean neutralizing antibody titer (GMT) on Day 30.

    Successful primary vaccination was defined as a major cutaneous reaction on Day 7 or 10 (Days 6 to 11, with allowable visit window). Successful revaccination was defined as development of any cutaneous lesion on Day 7 (± 1 day) of a measurable size. Successful revaccination was determined by a panel of experts who reviewed digital photographs of the cutaneous lesions.

    Study 1

    • 1037 vaccinia-naïve patients 18 to 30 years of age were randomly assigned 3:1 to receive ACAM2000 or comparator. All patients were evaluated for their cutaneous response and a random subset was selected for evaluation of neutralizing antibody response.

    • 96% of patients treated with ACAM2000 achieved vaccination success vs 99% of patients treated with comparator. ACAM2000 achieved noninferiority to the comparator for vaccination success with regard to eliciting a major cutaneous reaction.

    • For neutralizing antibody response, GMT was 166 for ACAM2000 vs 255 for comparator. The Log10 mean was 2.2 for ACAM2000 vs 2.4 for comparator. ACAM2000 did not achieve noninferiority to the comparator for neutralizing antibody response.

    Study 2

    • 1647 previously-vaccinated patients 31 to 84 years of age were randomly assigned 3:1 to receive ACAM2000 or comparator. All patients were evaluated for their cutaneous response and a random subset was selected for evaluation of neutralizing antibody response.

    • 84% of patients treated with ACAM2000 achieved vaccination success vs 98% of patients treated with comparator. ACAM2000 did not achieve noninferiority to the comparator for vaccination success with regard to eliciting a major cutaneous reaction.

    • For neutralizing antibody response, GMT was 286 for ACAM2000 vs 455 for comparator. The Log10 mean was 2.5 for ACAM2000 vs 2.6 for comparator. ACAM2000 achieved noninferiority to the comparator for neutralizing antibody response.

    Acam2000 Note

    Not Applicable

    Acam2000 Patient Counseling

    Patient Counseling

    Serious Complications of Vaccination

    • Inform patients 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

    • Inform patients to avoid contact with individuals at high risk of serious adverse effects of vaccinia virus (eg, patients 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

    • Advise patients that viral shedding occurs from the cutaneous lesion at the site of inoculation from approximately Day 3 until scabbing, 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.

    • Self-inoculation occurs most often on the face, eyelid, nose, and mouth, but lesions at any site of traumatic inoculation can occur.

    Patients Must Be Given The Following Instructions:

    • Completely cover the vaccination site with a semipermeable bandage. Keep site covered until the scab falls off on its own.

    • Keep the vaccination site dry. May continue normal bathing, but cover the site with waterproof bandage when bathing. Do not scrub the site. Cover the site with loose gauze bandage after bathing.

    • Do not scratch the vaccination site. Do not 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, avoid physical contact of objects that have come into contact with the lesion (e.g. soiled bandages, clothing, fingers). 

    • 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.

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