Inhaled Antibiotics for Cystic Fibrosis

POLICY NUMBER

L.5.01.519

Bethkis (tobramycin inhalation solution)

Cayston (aztreonam lysine inhalation solution)

Kitabis Pak (tobramycin inhalation solution)

TOBI (tobramycin inhalation solution)

TOBI Podhaler (tobramycin inhalation powder)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Cystic fibrosis (CF) is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. In people with CF, a defective gene causes a thick, sticky buildup of mucus in the lungs, pancreas, and other organs. In the lungs, the mucus clogs the airways and traps bacteria leading to infections, extensive lung damage, and eventually, respiratory failure. In the pancreas, the mucus prevents the release of digestive enzymes that allow the body to break down food and absorb vital nutrients.

Pseudomonas aeruginosa strain of bacteria are widely found in the environment. It is the key bacterial agent of CF lung infections, and the most important pathogen in progressive and severe CF lung disease. About half of all people with CF have Pseudomonas and more than 60 percent of adults with CF have Pseudomonas. This opportunistic pathogen can grow and proliferate in patients and exposure can occur in hospitals and other healthcare settings. Once Pseudomonas is established in the airways, it's very difficult to eliminate. However, aggressive treatment with inhaled antibiotics can delay the development of long-term infection.

FDA APPROVED INDICATIONS

Bethkis (tobramycin inhalation solution) is an inhaled aminoglycoside antibacterial indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa. Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with a forced expiratory volume in one second (FEV₁) <40% or > 80% predicted, or patients colonized with Burkholderia cepacia.

Cayston (aztreonam inhalation solution) is a monobactam antibacterial indicated to improve respiratory symptoms in cystic fibrosis patients with Pseudomonas aeruginosa. Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with FEV₁ <25% or >75% predicted, or patients colonized with Burkholderia cepacia.

Kitabis Pak (tobramycin inhalation solution) is an aminoglycoside antibacterial drug indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa. Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with FEV₁ <25% or > 75% predicted, or patients colonized with Burkholderia cepacia.

Tobi (tobramycin inhalation solution) is an aminoglycoside antibacterial indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa. Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with FEV₁ <25% or >75% predicted, or patients colonized with Burkholderia cepacia.

Tobi Podhaler (tobramycin inhalation powder) is an aminoglycoside antibacterial indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa. Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with FEV₁ <25% or >80%, or patients colonized with Burkholderia cepacia.

POLICY

Prior Authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Initial Review

Tobramycin inhalation (Bethkis, Kitabis Pak, TOBI, TOBI Podhaler) or aztreonam inhalation (Cayston) may be considered medically necessary when ALL of the following are met:

1. ONE of the following:

   1. The individual is 6 years of age or older and the request is for tobramycin inhalation; OR

   2. The individual is 7 years of age or older and the request is for aztreonam;

2. The individual has a confirmed diagnosis of cystic fibrosis andPseudomonas aeruginosa;

3. The individual’s FEV1 corresponds with ONE of the following:

   1. Bethkis: FEV₁ must be >40% and % predicted <80%;

   2. Kitabis, TOBI, or Cayston: FEV₁ must be >25% and % predicted <75%; OR

   3. TOBI Podhaler: FEV₁ must be >25% and % predicted <80%;

4. The individual's therapeutic plan does not include being treated with another inhaled antibiotic for cystic fibrosis (or is not alternating with another inhaled antibiotic);

5. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 6 months

Renewal Evaluation

The requested agent may be approved for continuation when ALL of the following criteria are met:

1. The individual has previously been approved for the requested medication through the BCBSMS PA process;

2. The individual has documented clinical improvement as evidenced by improvement in or stabilization of pulmonary function, quality of life, and/or number of hospitalizations;

3. The individual's therapeutic plan does not include being treated with another inhaled antibiotic for cystic fibrosis (or is not alternating with another inhaled antibiotic);

4. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

1. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

2. appropriate with regard to standards of good medical practice; and

3. not solely for the convenience of the Member, his or her Provider; and

4. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors.  In order for equipment, devices, drugs or supplies [ie, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

02/05/2019: New policy added. Reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Effective 01/01/2019.

03/26/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added drug name to the top of the policy. Policy description updated regarding FDA approved indications. Initial prior authorization criteria for tobramycin inhalation and aztreonam (Cayston) revised and updated to state that the patient's therapeutic plan does not include being treated with another inhaled antibiotic for cystic fibrosis (or is not alternating with another inhaled antibiotic). For the initial prior authorization criteria, the length of approval is 6 months. Added renewal prior authorization criteria to policy section. Sources updated.

11/01/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding FDA approved indications, dosing information, and quantity limits. Additional criteria added to medically necessary statements for initial review. Renewal evaluation criteria updated to add statement that the quantity requested does not exceed the FDA-approved dosing limits. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and to define investigative. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

03/20/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated with minor revisions to the medication indications. Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary coverage criteria for aztreonam inhalation (Cayston) combined with first medically necessary policy statement. Initial and renewal criteria updated regarding contraindications. Sources updated.

SOURCE(S)

1. Bethkis prescribing information. Chiesi USA, Inc. February 2023. Last accessed January 2025.

2. Cayston prescribing information. Gilead Sciences Inc. December 2021. Last accessed January 2025.

3. Center for Disease Control www.cdc.gov/nai/organisms

4. Cystic Fibrosis Foundation

   www.cff.org

5. Kitabis Pak prescribing information. Pari Respiratory Equipment, Inc. November 2024. Last accessed January 2025.

6. Simon RH. Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection. UpToDate, Connor RF (Ed), Wolters Kluwer. https://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-chronic-pulmonary-infection . Accessed January 10, 2025.

7. Tobi prescribing information. Mylan Specialty L.P. February 2023.Last accessed January 2025.

8. Tobi Podhaler prescribing information. Mylan Specialty L.P. February 2023. Last accessed January 2025

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CODE REFERENCE

None