CAYSTON, Aztreonam Lysine Form

Aztreonam (Cayston®) is a monobactam antibacterial. FDA Approved Indication(s) Cayston is indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa.
Limitation(s) of use:
• Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with forced expiratory volume in one second (FEV1) < 25% or > 75% predicted, or patients colonized with Burkholderia cepacia. • To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cayston and other antibacterial drugs, Cayston should be used only to treat patients with CF known to have Pseudomonas aeruginosa in the lungs. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Cayston is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Cystic Fibrosis (must meet all):

1. Diagnosis of CF;
   2. Prescribed by or in consultation with a pulmonologist or infection disease specialist;
   3. Age ≥ 6 years;
   4. Pseudomonas aeruginosa is present in at least one airway culture;
   5. Member meets one of the following (a or b): a. Failure of inhaled tobramycin (TOBI® and TOBI® Podhaler™ are preferred) unless contraindicated or clinically significant adverse effects are experienced;
      *Prior authorization may be required for inhaled tobramycin
      b. Antibiotic susceptibility testing indicates that aztreonam would be more effective than tobramycin;

2. If Cayston is prescribed concurrently (or for alternating use) with inhaled tobramycin (Bethkis®, Kitabis Pak®, TOBI, TOBI Podhaler), documentation supports inadequate Page 1 of 6

   CLINICAL POLICY Aztreonam response to either agent alone (e.g., deteriorating pulmonary status, recurrent pulmonary exacerbations);

3. Dose does not exceed 225 mg per day administered on a 28 days on/28 days off cycle. Approval duration: 6 months
   B. Other diagnoses/indications (must meet 1 or 2):
4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Cystic Fibrosis (must meet all):
5. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
6. Member is responding positively to therapy as evidenced by reduction in respiratory symptoms (e.g., cough, wheezing, sputum production, or pulmonary exacerbations due to Pseudomonas aeruginosa);
7. If Cayston is prescribed concurrently (or for alternating use) with inhaled tobramycin (Bethkis, Kitabis Pak, TOBI, TOBI Podhaler), documentation supports inadequate response to either agent alone (e.g., deteriorating pulmonary status, recurrent pulmonary exacerbations);
8. If request is for a dose increase, new dose does not exceed 225 mg per day administered on a 28 days on/28 days off cycle.
   Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): Page 2 of 6

   CLINICAL POLICY Aztreonam a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      III. Diagnoses/Indications for which coverage is NOT authorized:
      A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents.
      IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CF: cystic fibrosis FDA: Food and Drug Administration FEV1: forced expiratory volume in one second Appendix B: Therapeutic Alternatives Drug Name Dosing Regimen inhaled tobramycin (Bethkis, Kitabis Pak, TOBI, TOBI Podhaler) Inhalation solution (Bethkis, Kitabis Pak, TOBI): 300 mg inhaled BID for 28 days (followed by 28 days off tobramycin therapy) Inhalation powder (TOBI Podhaler): 112 mg (4 capsules) inhaled BID for 28 days (followed by 28 days off tobramycin therapy) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Dose Limit/ Maximum Dose Solution: 600 mg/day Powder: 224 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known allergy • Boxed warning(s): none reported Appendix D: General Information • Aztreonam is recommended for chronic use in both mild and moderate-to-severe disease per the American Thoracic Society 2013 CF guidelines. Severity of lung disease is defined by FEV1 predicted as follows: normal, > 90% predicted; mildly impaired, 70- Page 3 of 6

   CLINICAL POLICY Aztreonam 89% predicted; moderately impaired, 40-69% predicted; and severely impaired, < 40% predicted. • The use of continuous alternating therapy (i.e., alternating different inhaled antibiotics in order to provide continuous therapy) lacks sufficient evidence. The efficacy of this practice was evaluated in a randomized, double-blind, phase 3 trial. 90 patients received 28-days inhaled tobramycin alternating with either 28-days inhaled aztreonam or placebo. Although the study found reduced exacerbation and respiratory hospitalization rates with the alternating tobramycin/aztreonam regimen compared to tobramycin/placebo, it was underpowered, and these results were not statistically significant. V. Dosage and Administration
   Indication CF Dosing Regimen One dose (one single use vial and ampule of diluent) inhaled TID for 28 days (followed by 28 days off Cayston therapy)
   Maximum Dose 225 mg/day VI. Product Availability
   Vial: 75 mg VII.