MYRBETRIQ, Mirabegron VESICARE, Solifenacin Succinate TOVIAZ, Fesoterodine Fumarate ENABLEX, Darifenacin Hydrobromide Form

The following are overactive bladder agents requiring prior authorization: mirabegron (Myrbetriq®, Myrbetriq® Granules), fesoterodine (Toviaz®), solifenacin (Vesicare®, Vesicare LS™), darifenacin (Enablex®), and vibegron (Gemtesa®).
FDA Approved Indication(s) Gemtesa, Myrbetriq, Toviaz, Vesicare, and Enablex are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Gemtesa, Myrbetriq, Toviaz, and Vesicare are specifically indicated for adults. Myrbetriq, Myrbetriq Granules, Toviaz and Vesicare LS are indicated for the treatment of neurogenic detrusor overactivity in pediatric patients: • Aged 3 years and older and weighing 35 kg or more (Myrbetriq); • Aged 3 years and older (Myrbetriq Granules); • Aged 6 years and older and weighing greater than 25 kg (Toviaz); • Aged 2 years and older (Vesicare LS). 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 overactive bladder agents are medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Overactive Bladder (must meet all):

1. Diagnosis of overactive bladder, including neurogenic detrusor overactivity;

   2. Member meets one of the following (a or b): a. Age ≥ 18 years; b. Member has neurogenic detrusor overactivity, and request is for one of the following (i, ii, iii, or iv): i. Vesicare LS, and age is between 2 to 17 years; ii. Myrbetriq Granules, and age is between 3 to 17 years; iii. Myrbetriq, age is between 3 to 17 years, and member weighs at least 35 kg; iv. Toviaz, age is between 6 to 17 years, and member weights at least 25 kg; Page 1 of 8

   CLINICAL POLICY Overactive Bladder Agents

2. Failure of 2 formulary generic overactive bladder agents (e.g., tolterodine, oxybutynin, trospium) for 30 days, unless clinically significant adverse effects are experienced or all are contraindicated;
3. If request is for brand Vesicare or Enablex: Member must use the generic version of the requested product, unless contraindicated or clinically significant adverse effects are experienced;
4. If request is for Vesicare LS and age ≥ 18 years: Member must use generic solifenacin tablet, unless contraindicated or clinically significant adverse effects are experienced;
5. If request is for Toviaz, member must use generic fesoterodine, unless contraindicated or clinically significant adverse effects are experienced;
6. Dose does not exceed the FDA-approved maximum recommended dose or health plan approved quantity limit for the relevant drug.
   Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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. Overactive Bladder (must meet all):

9. 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 brand Vesicare or Enablex: Member must use the generic version of the requested product, unless contraindicated or clinically significant adverse effects are experienced; Page 2 of 8

   CLINICAL POLICY Overactive Bladder Agents

10. If request is for Vesicare LS and age ≥ 18 years: Member must use generic solifenacin tablet, unless contraindicated or clinically significant adverse effects are experienced;
11. If request is for Toviaz, member must use generic fesoterodine, unless contraindicated or clinically significant adverse effects are experienced;
    6. If request is for a dose increase, new dose does not exceed the FDA-approved maximum recommended dose or health plan approved quantity limit for the relevant drug. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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 policy – CP.CPA.09 for commercial, 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 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 and may require prior authorization.
    Drug Name Dosing Regimen oxybutynin (Ditropan XL®) oxybutynin (Ditropan®) 5 to 10 mg PO QD 5 mg PO BID or TID Page 3 of 8 Dose Limit/ Maximum Dose 30 mg/day 20 mg/day

    CLINICAL POLICY Overactive Bladder Agents Drug Name Dosing Regimen tolterodine IR (Detrol®) trospium (Sanctura®) trospium ER (Sanctura® XR) 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. 2 mg PO BID 20 mg PO BID 60 mg PO QD Dose Limit/ Maximum Dose 4 mg/day 60 mg/day 60 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Gemtesa, Myrbetriq, Myrbetriq Granules, Toviaz, Vesicare, Vesicare LS: Hypersensitivity to any component in the requested product o Enablex, Toviaz, and Vesicare, Vesicare LS are also contraindicated in patients with, or at risk for, the following conditions:  Urinary retention (except Vesicare LS)  Gastric retention  Uncontrolled narrow-angle glaucoma • Boxed warning(s): none reported V. Dosage and Administration
    Drug Name Fesoterodine (Toviaz) Pediatric patients:
    Dosing Regimen

    25 kg to ≤ 35 kg: Recommended dose is 4 mg PO QD. If needed, dosage may be increased to 8 mg PO QD. 35 kg: Recommended starting dose is 4 mg PO QD. After one week, increase to 8 mg PO QD. Adults: 4 mg PO QD 25 mg PO QD; can be given alone for either indication or in combination with solifenacin succinate 5 mg PO QD for OAB Pediatric patients:
    11 to < 22 kg: 3 mL (24 mg) PO QD 22 to < 35 kg: 4 mL (32 mg) PO QD ≥ 35 kg: 6 mL (48 mg) PO QD Mirabegron (Myrbetriq) Mirabegron (Myrbetriq Granules) Adults: A recommended dosage for Myrbetriq Granules for adults has not been determined. Solifenacin (Vesicare) 5 mg PO QD Solifenacin (Vesicare LS) 9-15 kg: 2 mL PO QD 15-30 kg: 3 mL PO QD 30-45 kg: 3 mL PO QD 45-60 kg: 4 mL PO QD Page 4 of 8 Maximum Dose 8 mg/day 50 mg/day 11 to < 22 kg: 6 mL (48 mg)/day 22 to < 35 kg: 8 mL (64 mg)/day
    ≥ 35 kg: 10 mL (80 mg)/day 10 mg/day 9-15 kg: 4 mL
    15-30 kg: 5 mL 30-45 kg: 6 mL 45-60 kg: 8 mL

    CLINICAL POLICY Overactive Bladder Agents Drug Name Dosing Regimen

    60 kg: 5 mL PO QD Maximum Dose 60 kg: 10 mL After administration of the recommended starting dose, the dose may be increased to the lowest effective dose but should not exceed the maximum recommended dose Darifenacin (Enablex) 7.5 mg PO QD 75 mg PO QD Vibegron (Gemtesa) *Myrbetriq and Myrbetriq Granules are two different products, and they are not substitutable on a milligram- per-milligram basis. Do not combine Myrbetriq and Myrbetriq Granules to achieve the total dose. 15 mg/day 75 mg/day VI. Product Availability
    Drug Name Fesoterodine (Toviaz) Mirabegron (Myrbetriq) Mirabegron (Myrbetriq Granules) Solifenacin (Vesicare) Solifenacin (Vesicare LS) Oral suspension: 5 mg/5 mL (1 mg/mL) Extended-release tablets: 7.5 mg, 15 mg Darifenacin (Enablex) Tablets: 75 mg Vibegron (Gemtesa) Availability Extended-release tablets: 4 mg, 8 mg Extended-release tablets: 25 mg, 50 mg Granules for extended-release oral suspension: 8 mg/mL after reconstitution Tablets: 5 mg, 10 mg VII.