Vaccines:

Indications for: ACAM2000

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

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.

Adult Dosage:

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.

Children Dosage:

<17yrs: not established.

ACAM2000 Contraindications:

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

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.

ACAM2000 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.

ACAM2000 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.

Adverse Reactions:

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

Generic Drug Availability:

NO

How Supplied:

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