CurrentAetnaPolicy 0483

Anthrax (Clinical Policy Bulletin)

This Aetna clinical policy bulletin governs medical necessity and coverage for anthrax immunization (pre- and post-exposure), monoclonal antibodies, and human anthrax immune globulin for members when indications meet ACIP and Aetna criteria; it applies to Aetna members and providers submitting claims to Aetna.

Policy Summary

PayerAetna

PolicyAnthrax (Clinical Policy Bulletin)

Policy CodePolicy 0483

Change TypeNo material change

Effective Date01/08/2002

Next Review Date05/09/2024

Key ActionRequest coverage for anthrax vaccine (CPT 90581) only when member meets ACIP/Aetna selection criteria and include documentation of indication and relevant ICD-10 codes.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2IM+3SCprimary series doses

Annualbooster frequency

60 dayspost-exposure antibiotic duration (inhalation)

A22.1, Z20.810, 90581example codes

3FDA antitoxin products discussed

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Coverage Criteria

Pre-Exposure Vaccination (Medically Necessary)

Covered when ALL of the following are met:

Pre-exposure indications per ACIP: Member is in an ACIP-recommended high-risk group: decontamination personnel or persons who work directly with the organism in the laboratory; military personnel deployed to high-risk areas; persons handling potentially infected animal products in high-incidence areas; persons working with imported animal hides/furs where standards are insufficient; environmental investigators/remediation workers who might repeatedly enter contaminated areas; responder units engaged in activities that might lead to aerosolized B. anthracis exposure (routine pre-event vaccination of emergency responders is not recommended due to lack of calculable risk).

Immunization series: 2 intramuscular doses 4 weeks apart, then 3 subcutaneous doses at 6, 12, and 18 months with annual boosters thereafter (ACIP).

Post-Exposure Vaccination (Medically Necessary)

Covered when ALL of the following are met:

Post-exposure indications per ACIP: Member has sustained an exposure consistent with ACIP post-exposure recommendations: aerosol exposure to B. anthracis spores OR cutaneous or gastrointestinal exposure to B. anthracis; vaccination is administered in combination with appropriate antibiotic chemoprophylaxis (per ACIP guidance).

ACIP recommends 3 doses of vaccine as part of post-exposure prophylaxis and 60 days of antimicrobial prophylaxis following inhalation exposure; initial antibiotic choice can be doxycycline or ciprofloxacin until susceptibilities are known, with switch to penicillin VK or amoxicillin if appropriate.

Monoclonal antibodies and Immune Globulin (Medically Necessary)

Covered when ALL of the following are met:

Specific therapeutics: Raxibacumab injection is medically necessary for prevention and treatment of inhalational anthrax; obiltoxaximab (Anthim) injection is medically necessary in combination with appropriate antibacterial drugs for treatment of inhalational anthrax and is medically necessary for prevention when alternative therapies are not available or not appropriate; intravenous human anthrax immune globulin (Anthrasil) is medically necessary to treat inhalational anthrax in combination with appropriate antibacterial drugs.

FDA approvals and indications per policy; document concurrent use of antibacterial therapy when applicable.

Experimental and Investigational (Not Covered)

Unproven uses: Anthrax vaccine for all other indications and intravenous anthrax immune globulin for treatment of systemic anthrax soft tissue infection related to drug injection are considered experimental and investigational because effectiveness has not been established.

Not medically necessary per policy (experimental/investigational).

Clinical coverage context

Clinical positions and evidence summaries relevant to use of vaccine and antitoxin/immune products

Vaccination during lactation: Breastfeeding is neither a precaution nor a contraindication to anthrax vaccination; vaccination need not be deferred for breastfeeding mothers at occupational risk.

ACIP guidance; no data suggest increased risk.

Vaccine contraindications: Anthrax Vaccine Adsorbed (AVA) is contraindicated in persons with a prior anaphylactic reaction to AVA or any vaccine component, and in persons who have recovered from anthrax because of observed more severe adverse events in such recipients.

ACIP guidance.

Vaccination during acute illness: Postpone vaccination in persons with moderate or severe acute illness until recovery; vaccination may proceed in persons with mild illness with or without low-grade fever.

ACIP guidance to avoid confounding adverse events with underlying illness.

Immunizations that are recommended solely to meet requirements for employment or incarceration are not covered. In addition, HMO plans typically exclude coverage for immunizations provided solely for the purpose of travel. Coverage of preventive immunizations is available only to members who have preventive service benefits; check contract language, limitations, and exclusions for specific coverage details.

No additional explicit exclusions are listed in this section. The authors note important limitations in the evidence base — including a paucity of human clinical data, lack of standardization across case reports, reliance on Animal Rule studies for product approvals, and challenges extrapolating animal results to humans — which may restrict use when human efficacy data are required.

This Clinical Policy Bulletin is intended as a general description of plan benefits to assist in administering those benefits. It does not constitute a contract, a guarantee of coverage, or medical advice; providers remain responsible for treatment decisions and should consult plan provisions and contract language for definitive coverage determinations.

Anthrax vaccine use outside the indications supported by the Advisory Committee on Immunization Practices (ACIP) and those specified in this policy is considered experimental and investigational and therefore not medically necessary.

The document does not label any FDA‑approved antitoxin products or Anthrasil as not medically necessary. However, it emphasizes that approvals were based largely on animal efficacy data with limited human clinical evidence, and that obiltoxaximab has not been used to treat anthrax in humans — factors that should be considered when evaluating medical appropriateness.

Coding

Covered CPT Codes (if selection criteria met)CPTCovered

90581

Anthrax vaccine, for subcutaneous or intramuscular use.

ICD-10 Codes (covered if selection criteria met)ICD-10Covered

A22.1	Pulmonary anthrax
Z20.810	Contact with and (suspected) exposure to anthrax
Z23	Encounter for immunization

Therapeutics without specific codesHCPCS

no specific HCPCS	Obiltoxaximab (Anthim) - no specific code listed
no specific HCPCS	Intravenous human anthrax immune globulin (Anthrasil) - no specific code listed

Provider Actions and Billing Guidance

Documentation Required

Antitoxin / Immune globulin coverage

Use of FDA‑approved anthrax antitoxin and immune globulin products is covered as described below when medically necessary for prevention or treatment of inhalational anthrax in accordance with the policy: raxibacumab (for prevention and treatment), obiltoxaximab (Anthim) (for treatment in combination with appropriate antibacterial drugs; prevention when alternatives not available/appropriate), and intravenous human anthrax immune globulin (Anthrasil) (to treat inhalational anthrax in combination with appropriate antibacterial drugs). Antitoxins/immune globulin are adjunctive to antibacterial therapy except when used as an alternative during circumstances such as multidrug‑resistant B. anthracis or intolerance to antimicrobials. Animal and limited human data support use; benefits are greatest with early administration.

Covered products: raxibacumab, obiltoxaximab (Anthim), intravenous human anthrax immune globulin (Anthrasil).
Indications: prevention and/or treatment of inhalational anthrax per FDA approval and policy criteria.
Adjunctive use: typically given with appropriate antibacterial drugs; may be considered when antimicrobials are not available, not appropriate, or resistance is suspected.

Background

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. It presents primarily in three clinical forms: cutaneous (skin), inhalational, and gastrointestinal. Inhalational anthrax is frequently fatal if untreated; antibiotics are effective against germinated bacteria but do not eliminate dormant spores, which can persist and lead to prolonged incubation periods. Vaccination (Anthrax Vaccine Adsorbed) is employed for pre-exposure prophylaxis in defined high-risk occupational groups and as part of post-exposure prophylaxis together with appropriate antimicrobial therapy.

Definitions

inv-27: Anthrax (Bacillus anthracis) — definition and clinical presentation

DefinitionAn acute infectious disease caused by the spore-forming bacterium Bacillus anthracis that can present as cutaneous, inhalational, or gastrointestinal disease and primarily occurs after occupational or animal-product exposures.

Common animal reservoirsOccurs most commonly in wild and domestic herbivores (cattle, sheep, goats, camels, antelopes) and can infect humans via contact with infected animals or animal products.

Clinical presentationsThree principal forms: cutaneous (skin), inhalation (pulmonary), and gastrointestinal anthrax; inhalation anthrax is often the most severe and can be fatal without treatment.

Occupational risk settingsRisk groups include laboratory personnel working with B. anthracis, decontamination personnel, handlers of potentially infected animal products, and certain military deployments to high-risk areas.

Public health relevanceConsidered a potential biological warfare agent; vaccination and public health measures are used for prevention in high-risk populations.

Policy Summary

PayerAetna

PolicyAnthrax (Clinical Policy Bulletin)

Policy CodePolicy 0483

Change TypeNo material change

Effective Date01/08/2002

Next Review Date05/09/2024

Key ActionRequest coverage for anthrax vaccine (CPT 90581) only when member meets ACIP/Aetna selection criteria and include documentation of indication and relevant ICD-10 codes.

SourceLink

On This Page

Antitoxin approvals and evidence: Raxibacumab, obiltoxaximab (Anthim), and human anthrax immune globulin (Anthrasil) are FDA‑approved for treatment of inhalational anthrax and for prevention when alternatives are unavailable or inappropriate; approvals were supported primarily by Animal Rule efficacy studies with human safety cohorts summarized in the literature and product labels.

Animal survival endpoints and human safety data referenced.

Adjunctive therapy evidence: Systematic reviews and animal studies show improved survival with antitoxin monotherapy versus placebo and variable benefit when combined with antimicrobials; limited human data suggest adjunctive antitoxin treatment may improve survival and may be considered when antimicrobials are not effective, not tolerated, or unavailable; earlier administration is associated with better outcomes.

Evidence limited; timing of antitoxin administration affects outcomes.

Clinical practice guidance summary: Clinical guidance (e.g., UpToDate) recommends urgent IV combination antimicrobials, consideration of an antitoxin (raxibacumab, obiltoxaximab, or anthrax immunoglobulin), drainage of pleural effusions, supportive care, and consideration of adjunctive glucocorticoids for suspected systemic anthrax; antimicrobial selection should account for toxin production, resistance potential, meningitis risk, and latent spores.

Practice guidance summarized.

Prior Authorization

Prior authorization guidance

Follow plan‑specific prior authorization procedures where applicable. This policy does not state an explicit universal prior authorization requirement for antitoxins, vaccines, or immune globulin; however, providers should verify member benefits and obtain any required prior authorizations per the member’s plan before administering or billing for these products.

Verify member eligibility and benefit coverage before treatment.
Obtain prior authorization when required by the member’s specific Aetna plan.
Claims should include documentation supporting medical necessity.

Note

Clinical Policy Bulletins are developed

Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and provide guidance on coverage criteria and coding; they do not guarantee coverage and do not replace the treating provider’s responsibility for medical advice and verifying member benefits.

CPBs are guidance documents — they are not a contract or guarantee of benefits.
Providers must confirm member‑specific coverage, limitations, and exclusions before providing services.

Documentation Required

Required clinical documentation

Providers must document the clinical circumstances supporting use of antitoxin, immune globulin, antibiotics, and/or vaccination. Documentation should include: severity and type of anthrax exposure or infection, timing of exposure, clinical signs and symptoms, diagnostic test results, antimicrobial susceptibilities (if available), rationale for adjunctive antitoxin or immune globulin therapy, contraindications to vaccination (e.g., prior anaphylaxis to AVA), and whether vaccination is deferred for moderate/severe acute illness.

Record severity of acute illness; defer vaccination for moderate/severe illness until recovery; mild illness may proceed.
Document prior anaphylactic reaction to AVA or vaccine components as contraindication.
Include antibiotic selection, duration, and any susceptibility data when applicable.

Billing Rule

Post-exposure antibiotic and vaccine sequencing

Post‑exposure management frequently includes a course of antibiotic chemoprophylaxis together with anthrax vaccination for optimal protection after aerosol exposure. ACIP recommends 60 days of antimicrobial prophylaxis plus a 3‑dose post‑exposure vaccine series for previously unvaccinated persons after aerosolized exposure. Initial antibiotic choice (e.g., doxycycline or ciprofloxacin) may be switched to penicillin VK or amoxicillin when susceptibilities indicate penicillin susceptibility.

ACIP post‑exposure recommendation: 60 days of antimicrobials + 3 doses of anthrax vaccine for aerosol exposure.
Initial PEP antibiotic choices include doxycycline or ciprofloxacin; switch to penicillins if susceptibilities support.
Vaccination may provide added protection; duration of vaccine protection after the shortened post‑exposure regimen is uncertain.

Documentation Required

Therapy sequencing considerations

Therapy sequencing: antitoxin therapy is adjunctive to antimicrobial therapy in most cases and has not consistently shown additional survival benefit over antimicrobials alone in all studies; animal data show improved survival with antitoxin monotherapy versus placebo and mixed results when combined with antimicrobials. Antitoxins may be considered when antimicrobials are not appropriate or resistance is suspected. When systemic anthrax is suspected, treatment should include urgent IV antimicrobial combination therapy, antitoxin, drainage of effusions, and supportive care per clinical guidance.

Antitoxins are generally given in combination with appropriate antibacterial drugs.
Animal studies: antitoxin monotherapy improved survival vs placebo; combination therapy did not consistently show added benefit over antimicrobials alone.
Clinical management of systemic anthrax should prioritize prompt IV antimicrobial therapy with consideration of antitoxin adjunctive therapy.

inv-28: Pre-exposure vaccination (AVA) — vaccine series schedule: 2 IM doses then 3 SC doses with annual booster

Primary series schedule2 intramuscular (IM) doses given 4 weeks apart, followed by 3 subcutaneous (SC) doses at 6, 12, and 18 months.

Route detailsInitial two doses by intramuscular injection; subsequent three doses by subcutaneous injection as specified in the series.

Booster frequencyAnnual booster injections are recommended after completion of the primary series.

Target populationRecommended for ACIP‑defined high‑risk occupational and laboratory groups where exposure risk cannot be adequately controlled.

Adverse reactionsMild local reactions in about 30% of recipients (tenderness, redness); systemic reactions occur in fewer than 0.2% of recipients.

inv-29: Raxibacumab / Obiltoxaximab / Anthrasil — definitions of antitoxin/immune products and indications

RaxibacumabA monoclonal antibody that neutralizes B. anthracis toxins; FDA approved (Dec 14, 2012) for treatment of inhalational anthrax and for prevention when alternatives are not available or appropriate.

Obiltoxaximab (Anthim)A monoclonal antibody (ETI-204) that neutralizes anthrax toxins; FDA approved (Mar 18, 2016) for treatment of inhalational anthrax in combination with antibacterial drugs and for prevention when alternatives are not available or appropriate; carries a Boxed Warning for allergic reactions including anaphylaxis.

Anthrasil (intravenous human anthrax immune globulin)Human anthrax immune globulin manufactured from plasma of vaccinated donors; FDA approved to treat inhalational anthrax in combination with appropriate antibacterial drugs, with animal studies supporting efficacy and human safety evaluated in 74 volunteers.

Indications/common useThese products are used for treatment of inhalational anthrax and may be used for prevention when alternatives are unavailable or inappropriate; typically given in combination with appropriate antibacterial therapy.

Evidence basisApprovals were supported primarily by Animal Rule efficacy studies demonstrating improved survival in animal models and by human safety data cohorts.