Formulary

Products Distributed by the Centers for Disease Control and Prevention*

Biologics, Therapeutic Use

Product	Producer	Licensed or IND	Distributed To	Release	Storage Conditions
Botulism Antitoxin Heptavalent (Equine) Types A-G (H-BAT)***	Cangene Corporation	IND**	clinical investigator	emergency	2-8°C
Diphtheria Antitoxin (Equine)	Instituto Butantan	IND**	clinical investigator	emergency	2-8°C
Vaccinia immune globulin (VIG)	Cangene Corporation	licensed	M.D. as required	emergency	2-8°C

Biologics, Prophylactic Use

Product	Producer	Licensed or IND	Distributed To	Release	Storage Conditions
Botulinum Toxoid pentavalent (ABCDE)	Michigan Dept. of Public Health	IND**	clinical investigator	prophylaxis	2-8°C
Vaccinia (Smallpox) vaccine	Sanofi Pasteur	licensed	M.D. as required	prophylaxis	2-8°C
Anthrax Vaccine Adsorbed	Emergent Biosolutions	licensed	M.D. as required	prophylaxis	2-8°C

Drugs

Product	Producer	Licensed or IND	Distributed To	Release	Storage Conditions
Artesunic acid	Walter Reed Army Institute of Research	IND**	clinical investigator	compassionate IND	2-10°C
Diethylcarbamazine (DEC)	WHO	IND**	clinical investigator	compassionate IND	15-30°C
Melarsoprol	Aventis	IND**	clinical investigator	compassionate IND	2-25°C
Nifurtimox	Bayer	IND**	clinical investigator	compassionate IND	2-25°C
Sodium Stibogluconate	Wellcome Foundation Ltd.	IND**	clinical investigator	compassionate IND	2-25°C
Suramin	Bayer	IND**	clinical investigator	compassionate IND	15-30°C

*Distributed by Division of Scientific Resources, Office of Infectious Diseases, CDC

**IND = Investigational New Drug (IND), Food and Drug Administration

 

FORMULARY

I. Biologic Agents Used Therapeutically

Botulism Antitoxin Heptavalent (Equine) Types A,B,C,D,E,F,G

Heptavalent Botulism Antitoxin bivalent (H-BAT) contains equine-derived antibody to the seven known botulinum toxin types (A--G). H-BAT is composed of <2% intact immunoglobulin G (IgG) and ≥90% Fab and F(ab')2 immunoglobulin fragments.  These fragments are created by the enzymatic cleavage and removal of Fc immunoglobulin components in a process sometimes referred to as despeciation (1). It is supplied under an IND protocol for the treatment of persons thought to be suffering from botulism. 

Each vial contains the following (1):

• 7,500 U anti-A
• 5,500 U anti-B
• 5,000 U anti-C
• 1,000 U anti-D
• 8,500 U anti-E
• 5,000 U anti-F
• 1,000 U anti-G

In 2010, H-BAT became the only botulism antitoxin available in the United States for naturally occurring noninfant botulism (2). It is available only from the CDC because of its limited use and its relatively short expiration date. The antitoxin is released only for suspected or actual cases of botulinum toxin poisoning and works by neutralizing unbound toxin molecules (3). The antitoxin is stored at CDC quarantine stations located in major airports around the nation, ensuring delivery to any location in the United States within hours.  Medical care providers who suspect a diagnosis of botulism in a patient should immediately call their state health department's emergency 24-hour telephone number to maintain effective botulism surveillance and to detect outbreaks as soon as possible. The state health department will contact CDC to arrange for a clinical consultation by telephone and, if indicated, release of botulism antitoxin.  State health departments requesting botulism antitoxin should contact the Emergency Operations Center (EOC) at 770-488-7100.

Diphtheria Antitoxin (Equine)

Diphtheria antitoxin is a sterile, aqueous solution of the refined and concentrated proteins, chiefly globulins, containing antitoxic antibodies obtained from the blood serum of horses that have been immunized against diphtheria toxin (4). It is used to prevent or treat diphtheria by neutralizing the toxins produced by Corynebacterium diphtheriae. Diphtheria antitoxin is available under an IND protocol through the CDC and is released for actual or suspected cases of diphtheria (5). The antitoxin is stored at CDC quarantine stations located in major airports around the nation, ensuring delivery to any location in the United States within hours. All suspected cases of diphtheria and the subsequent request for antitoxin must be initiated through state or local health departments. The decision to dispense the antitoxin is made by CDC medical epidemiologists after discussion with the treating physician. This allows the CDC and the state health departments to maintain effective diphtheria surveillance and detect outbreaks as soon as possible. Clinicians requesting diphtheria antitoxin should contact the CDC diphtheria duty officer at 404-639-8257 during working hours (8:00am to 4:30pm) and the Emergency Operations Center (EOC) at 770-488-7100 at any other time.

Vaccinia Immune Globulin (VIG)

Vaccinia immune globulin is a sterile, non-pyrogenic solution of globulin derived from the plasma of adult human donors who have been vaccinated with the smallpox vaccine.  Vaccinia immune globulin is released from the CDC Strategic National Stockpile when indicated for the treatment of eczema vaccinatum, vaccinia necrosum, ocular vaccinia, or severe generalized vaccinia in persons who receive the smallpox vaccine (6).  Medical care providers wishing to obtain VIG should contact the Emergency Operations Center (EOC) at 770-488-7100.  They will be connected with CDC medical staff that can assist them in the diagnosis and management of patients with suspected complications of vaccinia vaccination.

II. Biologic Agents Used Prophylactically

Botulinum Toxoid

Pentavalent (ABCDE) botulinum toxoid is a combination of aluminum phosphate-adsorbed toxoid derived from formalin-inactivated type A,B,C,D and E botulinum toxins, with formaldehyde as a stabilizer and thimerosal used as a preservative (7). The current toxoid in distribution was manufactured by Michigan Biologic Products Institute (now BioPort) and is no longer being produced. Botulinum toxoid is not licensed; it is distributed by the CDC under an IND protocol. The toxoid is used as an adjunct in the protection of laboratorians from accidental exposure to botulinum toxins (3). It should be administered only to at risk individuals who are actively working or expect to be working with cultures of Clostridium botulinum or the toxins (7).

Vaccinia Vaccine

ACAM2000™ [PDF - 11 pages], 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).  The vaccine is manufactured by Acambis, Inc. and was licensed for use in the United States by the Food and Drug Administration (FDA) in August 2007. The Drug Service began distribution of ACAM2000™ in place of Dryvax® smallpox vaccine in February, 2008. (8) 

In 1982, Wyeth Laboratories, the only active manufacturer of licensed vaccinia vaccine in the United States, discontinued production and in 1983 distribution to the civilian population was discontinued. Smallpox vaccination has not been required for international travelers since January 1982 and International Certificates of Vaccination no longer include smallpox vaccination (9).

CDC recommends vaccinia vaccine for laboratory workers who directly handle a) cultures or b) animals contaminated or infected with, nonhighly attenuated vaccinia virus, recombinant vaccinia viruses derived from nonhighly attenuated vaccinia strains, or other Orthopoxviruses that infect humans (e.g., monkeypox, cowpox, vaccinia, and variola). Other health-care workers (e.g., physicians and nurses) whose contact with nonhighly attenuated vaccinia viruses is limited to contaminated materials (e.g., dressings) but who adhere to appropriate infection control measures are at lower risk for inadvertent infection than laboratory workers. However, because a theoretical risk for infection exists, vaccination can be offered to this group (9).

There is no evidence that smallpox vaccination has any therapeutic value in the treatment or prevention of recurrent herpes simplex infection, warts, oral thrush, or any other diseases (9). Requests for smallpox vaccine for these unapproved uses cannot be granted.

Anthrax Vaccine

Anthrax Vaccine Adsorbed (AVA) is the only licensed human anthrax vaccine in the United States and is produced by Emergent Biosolutions.  AVA is prepared from a cell-free filtrate of B. anthracis culture that contains no dead or live bacteria (10).

CDC provides anthrax vaccine for laboratory workers conducting research under federally funded projects who require routine vaccination based on their occupational risk.

Routine vaccination with AVA is indicated for persons engaged a) in work involving production quantities or concentrations of B. anthracis cultures and b) in activities with a high potential for aerosol production. Laboratorians using standard Biosafety Level 2 practices in the routine processing of clinical samples are not at increased risk for exposure to B. anthracis spores.  The risk for persons who come in contact in the workplace with imported animal hides, furs, bone meal, wool, animal hair, or bristles has been reduced by changes in industry standards and import restrictions. Routine preexposure vaccination is recommended only for persons in this group for whom these standards and restrictions are insufficient to prevent exposure to anthrax spores.  Routine vaccination of veterinarians in the United States is not recommended because of the low incidence of animal cases. However, vaccination might be indicated for veterinarians and other high-risk persons handling potentially infected animals in areas with a high incidence of anthrax cases (10).

III. Drug Products Used Therapeutically

Artesunate

Artesunate, an investigational drug, is in the class of medications known as artemesinins, which are derivatives from the “quinghaosu” or sweet wormwood plant (Artemisia annua).   It is a sesquiterpene lactone with an internal peroxide linkage.  Artesunate may be used to treat documented cases of malaria that require a parenteral medication (11).

Diethylcarbamazine

Diethylcarbamazine citrate (DEC, Hetrazan®), an investigational drug, is an antihelmintic agent that does not resemble other antiparasitic compounds. It is a synthetic organic compound which is highly specific for several parasites and does not contain any toxic metallic elements. DEC is indicated for treatment of individual patients with certain filarial diseases. These diseases include: lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori; tropical pulmonary eosinophilia; and loiasis. DEC continues to be the mainstay for treatment of patients with lymphatic filariasis and loiasis (14, 15).

Melarsoprol

Melarsoprol (Mel B, Arsobal®), an investigational drug, is an organoarsenic compound with trypanocidal effects. It is indicated for the treatment of African (Gambian and Rhodesian) sleeping sickness (trypanosomiasis) with neurologic involvement. It has been used outside the United States since 1949 (16). Cases of African sleeping sickness are rarely imported into the United States.

Nifurtimox

Nifurtimox (Bayer 2502, Lampit®), an investigational drug, is a nitrofurfurylidene derivative. It was developed for the treatment of Trypanosoma cruzi, the causative agent of Chagas' disease. The drug is distributed by CDC to treat patients with acute, subacute, or early chronic Chagas' disease (17). Although vector-borne transmission of T. cruzi is very rare in the United States, it is estimated that there may be 100,000 imported cases in this country.

Sodium Stibogluconate

Pentostam® (sodium stibogluconate; sodium antimony gluconate) is a pentavalent antimony compound used for treatment of all forms of leishmaniasis. The 3 major clinical syndromes in humans are visceral (kala-azar), cutaneous (Oriental sore), and mucosal leishmaniasis. Pentostam is a well-established antileishmanial agent that is used in many countries of the world and is available to U.S. licensed physicians under an IND protocol through the CDC (18, 19).

Suramin

Suramin (Bayer 205, Germanin®, Moranyl®, Fourneau 309, Belganyl®, Naphuride®, Antrypol®) was introduced in 1920 for the treatment of African trypanosomiasis (sleeping sickness). Suramin is considered the drug of choice for the therapy of early Trypanosoma brucei rhodesiense sleeping sickness when the central nervous system is not involved. Pentamidine is the drug of choice for early sleeping sickness due to Trypanosoma brucei gambiense.

Suramin has also been used to destroy the adult worm (Onchocerca volvulus) in onchocerciasis but, due to its toxicity, it is rarely used for this. Ivermectin is considered the primary agent for treatment of onchocerciasis. Suramin has also demonstrated antitumor activity against prostatic, ovarian, and adrenocortical carcinoma. However, appropriate dose, efficacy, and safety have not been established for treatment of neoplasms.  The CDC supplies suramin under an IND protocol to licensed physicians (20).

Use of trade names is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.