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Inhaled Antibiotics Duplicate Therapy Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1047
This program applies to Blue Partner, Commercial, GenPlus, and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
04-01-2024 |
04-01-2012 |
FDA APPROVED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Bethkis® (tobramycin inhalation solution)* Oral inhalation |
Management of cystic fibrosis patients with Pseudomonas aeruginosa Safety and efficacy have not been demonstrated in patients under the age of six years, patients with a forced expiratory volume in one second (FEV1) less than 40% or greater than 80% predicted, or patients colonized with Burkholderia cepacia |
* - generic available
|
1 |
Cayston® (aztreonam inhalation solution) Oral inhalation |
To improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with FEV1 less than 25% or greater than 75% predicted, or patients colonized with Burkholderia cepacia |
|
5 |
Kitabis® Pak, Tobramycin Inhalation Solution Pak Oral inhalation |
Management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa Safety and efficacy and have been demonstrated in patients under the age of 6 years, patients with FEV1 less than 25% or greater than 75% predicted, or patients colonized with Burkholderia cepacia |
|
3 |
TOBI® Podhaler® (tobramycin inhalation powder) Oral inhalation |
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 less than 25% or greater than 80%, or patients colonized with Burkholderia cepacia |
|
2 |
TOBI® (tobramycin inhalation solution)* Oral inhalation |
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 forced expiratory volume in 1 second (FEV1) less than 25% or greater than 75% predicted, or patients colonized with Burkholderia cepacia |
* - generic available |
4 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Cystic Fibrosis |
Cystic fibrosis (CF) is a multi-system disorder caused by mutations in the gene for the CF transmembrane conductance regulator (CFTR), which encodes an ion channel protein in epithelial cells on the airway surface.(6) Defects in the ion channel protein cause abnormal ion transport which alters antimicrobial airway defenses. This impaired host defense results in chronic lower airway bacterial infections, the most common of which are Pseudomonas aeruginosa and Staphylococcus aureus. P. aeruginosa, in particular, is linked to greater airway inflammation and overall decline in health.(9,10) Pulmonary disease remains the leading cause of morbidity and mortality in patients with CF.(6,9) The approach to treating infection in CF lung disease is multifaceted, involving antibiotics, chest physiotherapy, inhaled medications to promote secretion clearance, and anti-inflammatory agents.(6) It is hypothesized that P. aeruginosa infections initially occur transiently before progressing to chronic infection. Over time, P. aeruginosa adapts to the airway by developing a “mucoid” phenotype that exists within a biofilm, which contributes to the development of chronic, difficult-to-eradicate infection. However, there is evidence that early antibiotic therapy has the potential to clear or “eradicate” initial P. aeruginosa infection and to postpone chronic infection with this organism.(10) Specifically, both inhaled tobramycin and aztreonam are highly effective at eradicating first or very early infection with P. aeruginosa. Success rates are greater than 75%, and this is seen as important progress in treating CF.(6,9,10) The prevalence of chronic P. aeruginosa infection in the United States CF population has steadily decreased over the last several years, with the greatest reductions observed in younger populations where successful eradication strategies may have played a pivotal role.(9) Undoubtedly, improved use of antibiotics is responsible for a substantial portion of the increased survival that has occurred in patients with CF.(6,9) Prophylactic use of antibiotics to prevent P. aeruginosa acquisition is not recommended, as clinical trials of this approach did not show benefit.(6,7,10) Once P. aeruginosa becomes established in the CF airway, the organisms are difficult to eliminate. Chronic infection is associated with poor growth, more rapid decline in lung function, increased need for antibiotic treatment and hospitalization, and earlier death.(6,10) Eradication remains an important goal, but patients unable to clear P. aeruginosa infection can often be adequately treated for many years with cycled or continuous alternating use of existing antibiotic options.(6,8,9) Chronic treatment with inhaled antibiotics helps to reduce the Pseudomonas bacterial burden and thus lessen its impact. Because most classes of antibiotics that show in vitro activity against P. aeruginosa are ineffective when administered orally, delivery by inhalation presents an attractive alternative since relatively high drug concentrations can be delivered to the site of lung infection with minimal systemic absorption.(6,8) Guidelines for treatment of CF P. aeruginosa infection recommend the use of inhaled tobramycin and inhaled aztreonam.(6,7,9) Tobramycin is recommended as first-line because of the extensive information supporting its safety and efficacy.(6,7,9,10) Trials have demonstrated that chronic treatment with inhaled tobramycin improves lung function, reduces acute pulmonary exacerbations, and improves quality-of-life outcomes.(1-4,6,9,10) Treatment is routinely administered for 28 days on therapy alternating with 28 days off. Inhaled aztreonam can be used as an alternative to inhaled tobramycin in select patients.(6,7,9,10) Trials have demonstrated that chronic treatment with inhaled aztreonam improves lung function, reduces pulmonary exacerbations, and improves quality-of-life outcomes.(5,6,7,10) Candidates for aztreonam include patients who cannot tolerate tobramycin, patients whose pulmonary status is deteriorating despite tobramycin use, patients who are or are planning to become pregnant, or patients who prefer the use of aztreonam to tobramycin.(6) Treatment is routinely administered for 28 days on therapy alternating with 28 days off.(6) For patients with deteriorating pulmonary status and/or recurrent pulmonary exacerbations despite cycling between 28 days on and 28 days off of a single inhaled antibiotic, it has become common practice for clinicians to prescribe continuous treatment by alternating between two different antibiotics (e.g., tobramycin and aztreonam), each for a 28-day period. This approach was evaluated in a randomized clinical trial in patients with a wide range of pulmonary function (FEV1 25 to 75 percent predicted), in which 28 days of inhaled aztreonam or placebo alternated with 28-day cycles of inhaled tobramycin. The study was terminated early because of inability to meet recruitment targets, in part because many clinicians and patients had already adopted continuously alternating therapy into their treatment regimen. Due to early termination of the study, statistical significance was not reached; however, the study showed 25% reduction in pulmonary exacerbation, 36% reduction in hospitalization for a respiratory event, and median time to first exacerbation was increased. Nonetheless, due to the early termination of the study and lack of statistical significance, there is insufficient evidence for guidelines to support the practice of alternating inhaled antibiotics for all patients with chronic P. aeruginosa infection. Despite this, many experts feel that it is reasonable practice for patients with advanced lung disease or those with frequent pulmonary exacerbations or accelerated decline in pulmonary status.(6,8,9) For individuals with advanced cystic fibrosis lung disease, the Cystic Fibrosis Foundation Consensus Guidelines for the Care of Individuals with Advanced Cystic Fibrosis Lung Disease (2020), recommends a trial of continuous alternating inhaled antibiotics as dictated by bacterial pathogens identified in respiratory cultures.(11) |
REFERENCES
Number |
Reference |
1 |
Bethkis prescribing information. Chiesi USA, Inc. February 2023. |
2 |
TOBI Podhaler prescribing information. Mylan Pharmaceuticals Inc. February 2023. |
3 |
Kitabis Pak prescribing information. Pari Respiratory Equipment, Inc. August 2023. |
4 |
TOBI prescribing information. Mylan Specialty LP. February 2023. |
5 |
Cayston prescribing information. Gilead Sciences, Inc. November 2019. |
6 |
Simon RH, et al. Cystic Fibrosis: Antibiotic Therapy for Chronic Pulmonary Infection. UpToDate. Last updated September 2023. Literature review current through September 2023. |
7 |
Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic Fibrosis Pulmonary Guidelines. Chronic Medications for Maintenance of Lung Health. Am J Respir Crit Care Med. 2013;187(7):680-689. |
8 |
Flume PA, Clancy JP, Retsch-Bogart GZ, et al. Continuous Alternating Inhaled Antibiotics for Chronic Pseudomonal Infection in Cystic Fibrosis. J Cyst Fibros. 2016;15(6):809-815. |
9 |
Nichols DP, Durmowicz AG, Field A, et al. Developing Inhaled Antibiotics in Cystic Fibrosis: Current Challenges and Opportunities. Ann Am Thorac Soc. 2019;16(5):534-539. |
10 |
Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic Fibrosis Foundation Pulmonary Guideline: Pharmacologic Approaches to Prevention and Eradication of Initial Pseudomonas aeruginosa Infection. Ann Am Thorac Soc. 2014;11(10):1640-1650. |
11 |
Cystic Fibrosis Foundation Consensus Guidelines for the Care of Individuals with Advanced Cystic Fibrosis Lung Disease. J Cystic Fibrosis. 2020;19(3):344-354. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Cayston |
aztreonam lysine for inhal soln |
75 MG |
M ; N ; O ; Y |
N |
|
|
Tobi podhaler |
tobramycin inhal cap |
28 MG |
M ; N ; O ; Y |
N |
|
|
Bethkis |
Tobramycin Nebu Soln 300 MG/4ML |
300 MG/4ML |
M ; N ; O ; Y |
O ; Y |
|
|
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
M |
M ; O ; Y |
|
|
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
M ; N ; O ; Y |
M ; O ; Y |
|
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Day Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
|
|||||||||
Bethkis |
Tobramycin Nebu Soln 300 MG/4ML |
300 MG/4ML |
56 |
Ampules |
56 |
DAYS |
|
|
|
Cayston |
aztreonam lysine for inhal soln |
75 MG |
84 |
Vials |
56 |
|
|
|
|
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
56 |
Ampules |
56 |
DAYS |
|
|
|
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
56 |
Ampules |
56 |
DAYS |
|
|
|
Tobi podhaler |
tobramycin inhal cap |
28 MG |
28 |
Blisters |
56 |
DAYS |
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Bethkis |
Tobramycin Nebu Soln 300 MG/4ML |
300 MG/4ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Cayston |
aztreonam lysine for inhal soln |
75 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Tobi podhaler |
tobramycin inhal cap |
28 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Bethkis |
Tobramycin Nebu Soln 300 MG/4ML |
300 MG/4ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Cayston |
aztreonam lysine for inhal soln |
75 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Kitabis pak ; Tobi |
Tobramycin Nebu Soln 300 MG/5ML |
300 MG/5ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
Tobi podhaler |
tobramycin inhal cap |
28 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||
|
TARGET AGENT(S) Preferred Inhaled Antibiotic Agent(s):
Non-Preferred Inhaled Antibiotic Agent(s): Standalone Inhaled Antibiotic Agent(s): Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. *Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required. |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: 12 months |
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
ALBP _ Commercial _ CSReg _ Inhaled_Antibiotics_Duplicate_Therapy_PAQL _ProgSum_ 04-01-2024 _© Copyright Prime Therapeutics LLC. January 2024 All Rights Reserved