Acam2000

Name: ACAM2000

Uses For ACAM2000

Smallpox vaccine is an active immunizing agent used to prevent smallpox infection. It works by causing your immune system to produce its own protection (antibodies) against the virus .

This vaccine should only be administered by or under the supervision of your doctor or another health care professional .

This medicine is available only with a doctor's prescription .

How supplied

Dosage Forms And Strengths

After reconstitution of the lyophilized preparation, each vial has approximately 100 doses of 0.0025 mL of vaccinia virus (live) containing 2.5-12.5x105 plaque forming units / dose.

ACAM2000, Smallpox (Vaccinia) Vaccine, Live, 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.

Storage And Handling

ACAM2000 should be stored 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 Vaccination Instructions]. Diluent for Smallpox Vaccine, (Vero Cells) Lyophilized, ACAM2000 should be stored at room temperature (15-30°C, 59-86°F). ACAM2000 contains live vaccinia virus that is transmissible, and should be handled as an infectious agent once vials are open. See [Instructions for Vaccine Preparation] and [Preparation / Handling Precautions and Instructions for Disposal] for details on handling and disposal.

REFERENCES

1 Fulginiti VA, Papier A, Lane JM, Neff JM, Henderson, DA. Smallpox vaccination: a review, part 1. background, vaccination technique, normal vaccination and revaccination, and expected normal reactions. Clin Infect Dis. 2003;37:241-250.

Sanofi Pasteur Biologics Co., 38 Sidney Street, Cambridge, MA 02139. Revised: October 2009

Other Medical Problems

The presence of other medical problems may affect the use of this vaccine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bone marrow transplant or
  • Cancer or
  • HIV or AIDS or
  • Immune deficiency conditions or
  • Leukemia (cancer of the blood) or
  • Lymphoma (cancer of the lymph nodes)
  • Organ transplant—Should not use in patients with these conditions .
  • Burns, severe or
  • Chest pain or
  • Chickenpox or
  • Congestive heart failure or
  • Dermatitis or
  • Diabetes or
  • Eczema or
  • Eye disease or
  • Heart attack, history of or
  • Heart disease (or family history of) or
  • High blood pressure or
  • High cholesterol in the blood or
  • Impetigo or
  • Psoriasis or
  • Shingles or
  • Stroke—May increase the chance and severity of side effects .

Administration

Vaccine Preparation

Reconstitution

  • Reconstitute only with diluent provided
  • Removed vial from cold storage and bring to room temperature before reconstitution
  • Remove the flip cap seals of the vaccine and diluent vials and wipe each rubber stopper with an isopropyl alcohol swab and allowed to dry thoroughly
  • Using aseptic technique and a sterile 1 mL syringe fitted with a 25 gauge x 5/8” needle (provided), draw up 0.3 mL of diluent and transfer the entire content of the syringe to the vaccine vial
  • Note: this 0.3 mL of diluent is not the entire content of the diluent vial
  • Gently swirl to mix but try not to get product on the rubber stopper
  • Reconstituted liquid should appear clear to slightly hazy, colorless to straw-colored, and free from extraneous matter
  • Inspect visually for particulate matter and discoloration prior to administration; if particulate matter or discoloration is observed, the vaccine should not be used and the vial should be disposed of according to biocontaminant regulations

Handling precautions and disposal

  • Personnel preparing and administering the vaccine should wear surgical or protective gloves and avoid contact of vaccine with skin, eyes or mucous membranes
  • The vaccine vial, its stopper, the diluent syringe, the vented needle used for reconstitution, the bifurcated needle used for administration, and any gauze or cotton that came in contact with the vaccine should be discarded in leak-proof, puncture-proof biohazard containers
  • These containers should then be disposed of appropriately

Percutaneous (Scarification) Administration

The site of vaccination is the upper arm over the insertion of the deltoid muscle

No skin preparation should be performed unless the skin at the intended site of vaccination is obviously dirty, in which case an alcohol swab(s) may be used to clean the area; the skin must be allowed to dry thoroughly to prevent inactivation of the live vaccine virus by the alcohol

Remove the vaccine vial cap and bifurcated needle from individual wrapping; submerge bifurcated end of needle in reconstituted vaccine solution; the needle will pick up a droplet of vaccine (0.0025 mL) within the fork of the bifurcation

Use aseptic technique; ie, do not insert the upper part of the needle that has been in contact with fingers into the vaccine vial, and never redip 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 vaccine 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

Any excess droplets of vaccine and blood should be wiped off the skin using a dry gauze pad and discarded in a biohazard container; discard the needle in a biohazard sharps container

Close the vaccine vial by reinserting the rubber cap and return to a refrigerator or place on ice unless it will be used immediately to vaccinate another subject (see Storage)

Cover the vaccination site loosely with a gauze bandage, using first aid adhesive tape to keep it in place; this bandage provides a barrier to protect against spread of the vaccinia virus

If the vaccinee is involved in direct patient care, the gauze should be covered with a semipermeable (semiocclusive) dressing as an additional barrier; a semipermeable dressing is one that allows for the passage of air but does not allow for the passage of fluids

Wash hands with soap and warm water or with alcohol-based hand rubs such as gels or foams after direct contact with the vaccination site, the bandage or clothes, towels or sheets that might be contaminated with virus from the vaccination site; this is vital in order to remove any virus from your hands and prevent contact spread

Put the contaminated bandages in a sealed plastic bag and throw them away in the trash

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

Don’t use a bandage that blocks air from the vaccination site; this may cause the skin at the vaccination site to soften and wear away; use loose gauze secured with medical tape to cover the site

Don’t put salves or ointments on the vaccination site

See ACAM2000 prescribing information for visual photos on how to interpret vaccination response

Storage

Lyophilized powder

  • Store in freezer with an average temperature of -15°C to -25°C (+5°F to -13°F)
  • Prior to reconstitution, smallpox vaccine retains a potency of ≥1 x 10^8 PFU per dose for at least 18 months when stored at refrigerated temperatures of +2-8°C (36-46°F)
  • During shipment: Maintain temperature of -10°C or colder

Reconstituted solution

  • After reconstitution, vaccine may be administered within 6-8 hr if kept at room temperature (20-25°C, 68-77°F)
  • Unused, reconstituted vaccine may be refrigerated (2-8°C, 36-46°F) for up to 30 days, after which it should be discarded as a biohazardous material
  • Exposure of reconstituted vaccine to room temperature during vaccination sessions should be minimized by placing it in refrigerator or on ice between patient administrations

Side effects

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome) and eczema vaccinatum. Severe disability, permanent neurological sequelae, and/or death may occur. Death of unvaccinated individuals who have contact with vaccinated individuals. [See WARNINGS AND PRECAUTIONS].
  • Myocarditis and/or pericarditis, ischemic heart disease and non-ischemic, dilated cardiomyopathy [See WARNINGS AND PRECAUTIONS].
  • Ocular complications and blindness [See WARNINGS AND PRECAUTIONS].

Overall Adverse Reaction Profile

Information regarding the safety of ACAM2000 has been derived from three sources: 1) ACAM2000 clinical trial experience (Phase 1, 2 and 3 clinical trials), 2) data compiled during the era of routine smallpox vaccination using other NYCBH vaccinia vaccines and 3) adverse event data obtained during military and civilian smallpox vaccination programs (2002-2005) that used Dryvax®, a licensed live vaccinia virus smallpox vaccine.

  • General Disorders and Administrative Site Conditions: In the ACAM2000 clinical studies 97% and 92% of vaccinia-na�ve and previously vaccinated subjects, respectively, experienced one or more adverse event. Common events included injection site reactions (erythema, pruritus, pain and swelling) and constitutional symptoms (fatigue, malaise, feeling hot, rigors and exercise tolerance decreased). Across all ACAM2000 studies 10% of vaccinia-na�ve and 3% of previously vaccinated subjects experienced at least one severe adverse event (defined as interfering with normal daily activities).
  • Nervous System Disorder: Overall, 50% and 34% of vaccinia-na�ve subjects and previously vaccinated subjects, respectively, reported headaches in ACAM2000 studies. There have been reports of headache following smallpox vaccination which required hospitalization. Although < 1% of the subjects in the ACAM2000 program experienced severe headaches, none required hospitalization.
    Neurological adverse events assessed among the 2002 - 2005 military (n=590,400) and DHHS (n=64,600) programs temporally associated with smallpox vaccination included headache (95 cases), non-serious limb paresthesias (17 cases) or pain (13 cases) and dizziness or vertigo (13 cases). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 9 seizures (including 1 death), and 3 cases of Guillain-Barre syndrome. Among these 39 events, 27 (69%) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination. There have also been cases of photophobia following smallpox vaccination, some of which required hospitalization.
  • Musculoskeletal and Connective Tissue Disorders: Across all ACAM2000 studies, severe, vaccine-related myalgia was seen in 1% of vaccinia-na�ve subjects and < 1% of previously vaccinated subjects. Other adverse events included back pain, arthralgia and pain in extremity and none occurred with a frequency of more than 2% in either the vaccinia-na�ve or previously vaccinated populations.
  • Blood and Lymphatic System Disorders: The only adverse event occurring at ≥ 5% in the ACAM2000 studies were lymph node pain and lymphadenopathy. The incidence of severe lymph node pain and lymphadenopathy was < 1%.
  • Gastrointestinal (GI) Disorders: Commonly reported GI disorders among ACAM2000-treated subjects included nausea and diarrhea (14%), constipation (6%), and vomiting (4%). Severe abdominal pain, nausea, vomiting, constipation diarrhea and toothache accounted for all the severe adverse events reported and occurred in < 1% of subjects.
  • Skin and Subcutaneous Tissue Disorders: Erythema and rash were noted in 18% and 8% of subjects respectively. In ACAM2000 subjects 1% of vaccinia-na�ve and < 1% of previously vaccinated subjects experienced at least one severe adverse event. With the exception of one case of contact dermatitis and one case of urticaria, erythema and rash accounted for all severe events.

Generalized rashes (erythematous, papulovesicular, urticarial, folliculitis, nonspecific) are not uncommon following smallpox vaccination and are presumed to be hypersensitivity reactions occurring among persons without underlying illnesses. These rashes are generally self-limited and require little or no therapy, except among patients whose conditions appear to be toxic or who have serious underlying illnesses.

Inadvertent inoculation at other body sites is the most frequent complication of vaccinia vaccination, usually resulting from autoinoculation of the vaccine virus transferred from the site of vaccination. The most common sites involved are the face, nose, mouth, lips, genitalia and anus. Accidental infection of the eye (ocular vaccinia) may result in ocular complications including, but not limited to, keratitis, corneal scarring and blindness.

Major cutaneous reactions at the site of inoculation, characterized by large area of erythema and induration and streaking inflammation of draining lymphatics may resemble cellulitis. Benign and malignant lesions have been reported to occur at the smallpox vaccination site.

ACAM2000 Clinical Trial Experience

Two randomized, controlled, multi-center Phase 3 trials enrolled 2244 subjects that received ACAM2000 and 737 that received a comparison licensed live vaccinia virus vaccine, Dryvax®. Study 1 was conducted in male (66% and 63% for ACAM2000 and Dryvax®, respectively) and female (34% and 37% for ACAM2000 and Dryvax®, respectively) subjects who previously had not been vaccinated with smallpox vaccine (i.e., vaccinia-na�ve subjects). The majority of subjects were Caucasian (76% and 71% for ACAM2000 and Dryvax®, respectively) and the mean age was 23 in both groups with an age range from 18-30 years. Study 2 was conducted in male (50% and 48% for ACAM2000 and Dryvax®, respectively) and female (50% and 52% for ACAM2000 and Dryvax®, respectively) subjects who had been vaccinated with smallpox vaccine > 10 years previously (i.e., previously vaccinated subjects). The majority of subjects were Caucasian (78% for both groups) and the mean age was 49 years in both groups with an age range of 31 to 84 years.

Common Adverse Events Reported In ACAM2000 Clinical Program

Adverse events reported by ≥ 5% of subjects in either the ACAM2000 or the comparison treatment group during Phase 3 studies are presented by type of adverse events, by baseline vaccination status (vaccinia-na�ve versus previously vaccinated) and by treatment group. Severe vaccine-related adverse events, defined as interfering with normal daily activities, in vaccinia-na�ve subjects were reported by 10% of subjects in the ACAM2000 group and 13% in the comparison group. In the previously vaccinated subjects, the incidence of severe vaccine-related adverse events was 4% for the ACAM2000 groups and 6% for the comparison group.

Table 3 : Adverse Events Reported by ≥ 5% of Subjects in ACAM2000 or Dryvax®

  Study 1 Vaccinia-Naive Subjects Study 2 Previously Vaccinated Subjects
ACAM2000
N=873
n (%)
Dryvax®
N=289
n (%)
ACAM2000
N=1371
n (%)
Dryvax®
N=448
n (%)
At least 1 adverse event 864 (99) 288 (100) 1325 (97) 443 (99)
Blood and lymphatic system disorders 515 (59) 204 (71) 302 (22) 133 (30)
Lymph node paina* 494 (57) 199 (69) 261 (19) 119 (27)
Lymphadenopathy 72 (8) 35 (12) 78 (6) 29 (6)
Gastrointestinal disorders 273 (31) 91 (31) 314 (23) 137 (31)
Nauseaa 170 (19) 65 (22) 142 (10) 63 (14)
Diarrheaa 144 (16) 34 (12) 158 (12) 77 (17)
Constipationa 49 (6) 9 (3) 88 (6) 31 (7)
Vomitinga 42 (5) 10 (3) 40 (3) 18 (4)
General disorders and administration site conditions 850 (97) 288 (100) 1280 (93) 434 (97)
Injection site pruritusa 804 (92) 277 (96) 1130 (82) 416 (93)
Injection site erythemaa 649 (74) 229 (79) 841(61) 324 (72)
Injection site paina 582 (67) 208 (72) 505 (37) 209 (47)
Fatiguea 423 (48) 161 (56) 468 (34) 184 (41)
Injection site swelling 422 (48) 165 (57) 384 (28) 188 (42)
Malaisea 327 (37) 122 (42) 381 (28) 147 (33)
Feeling hota 276 (32) 97 (34) 271 (20) 114 (25)
Rigorsa 185 (21) 66 (23) 171 (12) 76 (17)
Exercise tolerance decreaseda 98 (11) 35 (12) 105 (8) 50 (11)
Musculoskeletal and connective tissue disorders 418 (48) 153 (53) 418 (30) 160 (36)
Myalgiaa 404 (46) 147 (51) 374 (27) 148 (33)
Nervous system disorders 444 (51) 151 (52) 453 (33) 174 (39)
Headachea 433 (50) 150 (52) 437 (32) 166 (37)
Respiratory, thoracic, and mediastinal disorders 134 (15) 40 (14) 127 (9) 42 (9)
Dyspneaa 39 (4) 16 (6) 41 (3) 18 (4)
Skin and subcutaneous tissue disorders 288 (33) 103 (36) 425 (31) 139 (31)
Erythemaa 190 (22) 69 (24) 329 (24) 107 (24)
Rasha 94 (11) 30 (10) 80 (6) 29 (6)
a Event was listed on a checklist included in subject diaries; therefore should be considered solicited. In addition to events listed above the following were also included as part of the checklist: chest pain and heart palpitations, but these events did not occur in ≥ 5% of subjects.

Read the entire FDA prescribing information for ACAM2000 (Smallpox (Vaccinia) Vaccine, Live)

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What should I expect at the vaccination site and in the weeks following vaccination?

  • If vaccination is successful, a red and itchy bump forms at the vaccination site in 2 to 5 days. Over the next few days, the bump becomes a blister and fills with pus. During the second week, the blister dries up and a scab forms. The scab falls off after 2 to 4 weeks, leaving a scar. People vaccinated for the first time may have a larger reaction than those being revaccinated.

  • If you need medical care in the month after your vaccination, tell your healthcare provider you just got a smallpox vaccination.

  • Certain people, such as laboratory workers who work with smallpox, are at risk of being exposed to smallpox over a long period of time. These people may need a booster vaccination every 3 years to maintain protection against smallpox.

What are the possible side effects of ACAM2000?

ACAM2000 may cause serious heart problems, including myocarditis and pericarditis. This can happen within 3 to 4 weeks after you get the vaccine.

Call your healthcare provider or get emergency help right away if you have:

    • chest pain or pressure
    • fast or irregular heartbeat
    • breathing problems

Most people who get myocarditis and/or pericarditis seem to get better after a few weeks. But heart problems may last longer in some people, and in rare cases, could lead to death.

Other serious side effects include:

    • swelling of the brain or spinal cord
    • problems with the vaccination site blister, such as it becoming infected
    • spreading of the vaccine virus to other parts of your body or to another person
    • severe allergic reaction after vaccination
    • accidental infection of the eye (which may cause swelling of the cornea causing watery painful eyes and blurred vision, scarring of the cornea, and blindness)

Common side effects include:

    • itching
    • swollen lymph nodes
    • sore arm
    • fever
    • headache
    • body ache
    • mild rash
    • fatigue

The risks for serious vaccine side effects are greater for people who:

    • have skin problems called eczema or atopic dermatitis
    • have skin problems, such as burns, impetigo, contact dermatitis, chickenpox, shingles, psoriasis, or uncontrolled acne
    • have had heart problems
    • have serious heart or blood vessel problems including angina, previous heart attack, artery disease, congestive heart failure, stroke, or other cardiac problems
    • smoke or have high blood pressure, high cholesterol, diabetes, high blood sugar, or a family history of heart problems
    • are breastfeeding
    • are pregnant, could be pregnant, or plan to become pregnant
    • are less than 1 year old
    • are taking steroid eye drops or ointment
    • have had problems after previous doses or are allergic to ACAM2000 or any part of ACAM2000 such as antibiotics neomycin or polymixin B

Tell your healthcare provider if you have any of the above conditions.

The virus from your vaccination can spread to other people and cause serious side effects. It is important to tell your healthcare provider if you:

  • live or work with a person who has skin problems (like eczema, dermatitis, burns, psoriasis, bad acne) or is suffering from impetigo, chicken pox or shingles
  • live or have close contact with a baby, or a person who is pregnant or breastfeeding
  • live or have close contact with a person who has an immune deficiency or cardiac disease

See "How do I care for the ACAM2000 vaccination site?"

Tell your healthcare provider about any side effect that bothers you or that does not go away.

To report SUSPECTED ADVERSE REACTIONS, contact your health provider and Acambis Inc. at 866-440-9440 (toll free) or 617-866-4500 or VAERS at 800-822-7967 and http://vaers.hhs.gov

Precautions

Routine nonemergency vaccination is contraindicated in individuals with eczema or a past history of eczema; individuals whose household contacts have eczema or other acute, chronic or exfoliative skin conditions; persons receiving immunosuppressive doses of corticosteroids, radiation or immunosuppressive drugs; immunodeficient individuals (including HIV); immunosuppressed persons; and pregnant women. Vaccination is also contraindicated in household contacts of these individuals.

Routine nonemergency vaccination is contraindicated in infants less than 12 months, individuals with eczema or a past history of eczema; individuals whose household contacts have eczema or other acute, chronic or exfoliative skin conditions; persons receiving immunosuppressive doses of corticosteroids, radiation or immunosuppressive drugs; immunodeficient individuals (including HIV); immunosuppressed persons; and pregnant women. Vaccination is also contraindicated in household contacts of these individuals.

Nonemergency vaccination is not recommended in children less than 18 years or in geriatric individuals.

Routine vaccination should be deferred in individuals with a history of heart disease (including prior myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke, transient ischemic attack, chest pain or exercise induced shortness of breath).

Routine vaccination should also be deferred in individuals with at least three of the following risk factors: cigarette smoker, hypertension, hypercholesterolemia, diabetes, and/or a first-degree relative with onset of heart disease before the age of 50.

There are no absolute contraindications to the vaccination of any individual with a high-risk exposure or during an outbreak emergency. If the person has a relative contraindication, the risk for serious vaccine complications should be weighed against the risk of a potentially fatal smallpox infection.

The natural rubber stopper in the vial may cause allergic reactions if handled by or administered to persons with a latex allergy.

After vaccination is completed, any vaccine remaining on the skin should be blotted off with clean, dry gauze or cotton.

The vial, stopper, needle to release the vacuum, diluent syringes, vented needle for reconstitution, bifurcated needle for administration, and any gauze or cotton coming into contact with the vaccine should be disposed of as biohazardous waste.

Susceptible individuals (with eczema, immunodeficiency or immunosuppression, including HIV) should be identified and measures taken to avoid contact with persons who have active vaccination lesions.

Contact spread of vaccinia from recently vaccinated persons has been reported. Vaccinia virus is present at the vaccination site from the time of papule development (2 to 5 days after vaccination) until scab separation from the skin lesion (14 to 21 days after vaccination). During this time, measures should be taken to prevent the spread of the virus to another person or another part of the body.

The vaccination site may be left uncovered or covered with a porous bandage such as gauze, until the scab has fallen off and the skin has healed. An occlusive bandage should not be used routinely. Bandages should be changed every 1 to 2 days to prevent maceration of the vaccination site due fluid accumulation. Topical creams or ointments should not be applied to the vaccination site. Contaminated bandages should be put in sealed plastic bags before disposal in the trash. Clothing or other cloth materials may be decontaminated by laundering in hot water with bleach. The vaccination site should be kept dry, although normal bathing may continue.

Recently vaccinated healthcare personnel should avoid contact with patients, especially immunodeficient patients, until the scab has fallen off. However, if contact is unavoidable, the vaccination site should be well covered and good handwashing technique should be practiced. A more occlusive dressing such as semipermeable polyurethane (e.g., Opsite(R)) is an effective barrier. Care should be taken to prevent viral contamination from the accumulated exudate when the dressing is removed. Fluid accumulation beneath the dressing may increase the maceration of the vaccination site. Accumulation may be decreased by covering the vaccination with dry gauze, than applying the dressing over the gauze. The dressing should be changed at least daily.

Thorough hand washing is vital to preventing inadvertent autoinoculation and contact transmission.

Other Comments

If a major (primary) reaction is not observed within 6 to 8 days, the individual should be revaccinated with vaccine from a different vial or lot.

Smallpox vaccine Pregnancy Warnings

A National Smallpox Vaccine in Pregnancy Registry has been established by the Centers for Disease Control, Food and Drug Administration, and Department of Defense to collect reports of exposure to vaccine during pregnancy. As of April 2003, there have been 103 reports of inadvertent exposure. Of 6 women who were exposed to vaccine during pregnancy or conceived within 4 weeks after vaccination, two had miscarriages. Two pregnant women had close contacts who were recently vaccinated; however, neither had symptoms of vaccinia exposure.

Smallpox vaccine has been assigned to pregnancy category C by the FDA. Animal studies have not been reported. The vaccine is not known to be teratogenic. Vaccinia virus may very rarely cause fetal infections after vaccination, resulting in stillbirth or neonatal death. Less than 50 cases of fetal vaccinia have been reported. In a nonemergency situation, pregnant women or women who may become pregnant within 4 weeks of vaccination, who have not been exposed to smallpox, should not be routinely vaccinated until after delivery. Close contacts of pregnant women (household or sexual contacts) should also not be routinely vaccinated. However, the vaccine should be administered to pregnant women who have been exposed to smallpox. There are no contraindications to receiving the vaccine in case of an outbreak emergency. Because the risk of maternal serious illness or death, prematurity, miscarriage, or stillbirth from a smallpox infection are greater than the risk of the vaccination, smallpox vaccine is recommended and should be offered to pregnant women in case of an outbreak emergency.

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