Mannitol (Bronchitol) Form

Inhaled dry powder mannitol (Bronchitol®) is a sugar alcohol used as an osmotic agent.
FDA Approved Indication(s) Bronchitol is indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years of age and older with cystic fibrosis (CF). Bronchitol should only be used in adults who have passed the Bronchitol tolerance test (BTT) to identify patients who are suitable candidates for Bronchitol maintenance therapy. 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 Bronchitol 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;
   3. Age ≥ 18 years;
   4. Documentation of inadequate response to hypertonic saline and Pulmozyme®, unless both are contraindicated or clinically significant adverse events are experienced; *Prior authorization may be required for Pulmozyme
2. If request is for the 7-day or 4-week treatment pack, member meets both of the following (a and b): a. Documentation that member has successfully completed the BTT (see Appendix D);
   b. Bronchitol is prescribed concurrently with a short-acting bronchodilator (see Appendix D);

3. Dose does not exceed one of the following (a or b): a. For BTT (both i and ii):
   i. 400 mg once; ii. 10 capsules once; Page 1 of 6

   CLINICAL POLICY Mannitol b. For 7-day or 4-week treatment pack (both i and ii):
   i. 800 mg per day; ii. 20 capsules per day.
   Approval duration:
   BTT: 4 weeks 7-day/4-week treatment pack: 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: CP.CPA.190 for commercial, 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: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
5. 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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Cystic Fibrosis (must meet all):
6. 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);
   2. Member is responding positively to therapy;
   3. If request is for BTT, re-authorization is not permitted;
   4. If this is the first authorization for the 7-day or 4-week treatment pack, member meets both of the following (a and b): a. Documentation that member has successfully completed the BTT (see Appendix D);
      b. Bronchitol is prescribed concurrently with a short-acting bronchodilator (see Appendix D);

7. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 800 mg per day; b. 20 capsules per day.
   Approval duration: 12 months
   Page 2 of 6

   CLINICAL POLICY Mannitol B. Other diagnoses/indications (must meet 1 or 2):

8. 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: CP.CPA.190 for commercial, 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: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

9. 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: CP.CPA.09 for commercial, 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 policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents;
   B. Members < 18 years of age (see Appendix D). IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BTT: Bronchitol tolerance test CF: cystic fibrosis FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Pulmozyme® (dornase alfa) hypertonic saline (HyperSal®, NebuSal®, PulmoSal™) 2.5 mg once daily or 2.5 mg twice daily administration via nebulization 4 mL vial via oral inhalation twice daily through a nebulizer
   Dose Limit/ Maximum Dose 5 mg/day 8 mL/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to mannitol or to any of the capsule components, and failure to pass the BTT Page 3 of 6

   CLINICAL POLICY Mannitol • Boxed warning(s): none reported Appendix D: General Information • Short-acting bronchodilator: albuterol (Accuneb®, Proventil®, Ventolin®, ProAir®, ProAir RespiClick®), levalbuterol (Xopenex®, Xopenex® nebulizer solution), ipratropium bromide/albuterol (Combivent®, Duoneb®). • Prior to a mannitol dose, administer a bronchodilator 5 to 15 minutes before.
   • The three main types of mucus thinners are hypertonic saline, mannitol (Bronchitol), and dornase alfa (Pulmozyme). • BTT is used to identify patients who are suitable candidates for inhaled mannitol use. BTT must be administered under the supervision of healthcare practitioner who can treat severe bronchospasm. If a patient does not experience bronchospasm, a decrease in FEV1, or a decrease in oxygen saturation during BTT, the patient has passed the BTT and is a candidate for Bronchitol therapy.
   • Cystic Fibrosis Foundation guidelines recommend hypertonic saline use in all CF patients regardless of disease severity as maintenance therapy. Dornase alfa is also recommended for all levels of lung disease severity with a strong recommendation in moderate-to- severe lung disease.
   • Bronchitol is not indicated for use in children and adolescents. In clinical trials evaluating the use of Bronchitol in patients with CF 6 years and older, patients treated with mannitol had a higher occurrence of hemoptysis, particularly in pediatric patients. Improvements in FEV1 compared to control in relative change in ppFEV1 were not statistically significant in children and adolescents. V. Dosage and Administration
   Drug Name Mannitol (Bronchitol) Mannitol (Bronchitol Tolerance Test) Dosing Regimen 400 mg (10 capsules) twice a day by oral inhalation, in the morning and evening, with the later dose taken 2-3 hours before bedtime 400 mg (10 capsules) once by oral inhalation under supervision of a healthcare practitioner who is able to manage acute bronchospasm Maximum Dose 800 mg/day 400 mg/day VI. Product Availability
   • 4-week treatment pack (4 x 7-day treatment packs): 4 inhalers, 560 capsules • 7-day treatment pack: 1 inhaler, 140 capsules • Tolerance test: 1 inhaler, 10 capsules VII.