LIORESAL INTRATHECAL, Baclofen GABLOFEN, Baclofen OZOBAX, Baclofen Form

Baclofen (Fleqsuvy™, Gablofen®, Lioresal® Intrathecal, Lyvispah™, Ozobax™) is a muscle relaxant and antispastic. Baclofen's pharmacological class is a gamma-aminobutyric acid (GABA)-ergic agonist. FDA Approved Indication(s) Gablofen and Lioresal Intrathecal are indicated for use in the management of severe spasticity of cerebral or spinal cord origin. • Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. • For spasticity of spinal cord origin, chronic infusion of Gablofen/Lioresal Intrathecal via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable central nervous system side effects at effective doses. • Patients with spasticity due to traumatic brain injury (TBI) should wait at least one year after the injury before consideration of long-term intrathecal baclofen therapy. Gablofen and Lioresal Intrathecal are intended for use by the intrathecal route as follows: • • For chronic use, only in implantable pumps approved by the FDA specifically for the In single bolus test doses (via spinal catheter or lumbar puncture); administration of Gablofen/Lioresal Intrathecal into the intrathecal space, including the Medtronic SynchroMed® II Programmable Pump‡. Fleqsuvy, Lvyispah and Ozobax are indicated for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. Fleqsuvy, Lyvispah and Ozobax may also be of some value in patient with spinal cord injuries and other spinal cord diseases. Limitation(s) of use: Fleqsuvy, Lyvispah and Ozobax are not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders. ____ Gablofen is indicated in adults and pediatric patients age 4 years and above; safety and effectiveness of Lioresal Intrathecal in pediatric patients below the age of 4 have not been established. Safety and effectiveness of Fleqsuvy, Lyvispah and Ozobax in pediatric patients below the age of 12 have not been established. Lioresal Intrathecal therapy may be considered an alternative to destructive neurosurgical procedures. ‡See Medtronic SynchroMed® II Programmable Pump information at http://professional.medtronic.com/pt/neuro/itb/prod/index.htm#.WAUxFuArKhc. Page 1 of 9 CLINICAL POLICY
Baclofen 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 Fleqsuvy, Gablofen, Lioresal, Lyvispah, and Ozobax are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Requests for Gablofen or Lioresal (must meet all):

1. Diagnosis of severe spasticity of cerebral or spinal cord origin (e.g., due to spinal cord injury, multiple sclerosis, hypoxic-ischemic encephalopathy, cerebral palsy, TBI);
2. Prescribed by or in consultation with a neurologist, orthopedist, physiatrist, or physical medicine and rehabilitation specialist;
3. Age ≥ 4 years;
   4. If the spasticity is due to TBI, > 1 year has passed since the injury;
   5. Documentation supports inability to use oral baclofen therapy;
   6. Failure of one of the following conventional therapies (a, b, or c), unless clinically significant adverse effects are experienced or all are contraindicated: a. A benzodiazepine (e.g., diazepam, clonazepam); b. Dantrolene; c. Tizanidine;
4. Baclofen will be used in one of the following ways (a or b): a. Screening trial (i and ii): i. Prescribed formulation is one of the following (1 or 2): 1) Gablofen: 50 mcg/mL (1 mL syringe); 2) Lioresal Intrathecal: 50 mcg/mL (1 mL ampule); ii. Dose does not exceed 100 mcg; b. Maintenance therapy (i and ii): i. Prescribed formulation is one of the following (1 or 2): 1) Any Gablofen vial/syringe except the 1 mL syringe; 2) Any Lioresal Intrathecal ampule except the 1 mL ampule; ii. Member responded positively to an intrathecal baclofen screening dose (bolus of ≤ 100 mcg) as evidenced by decrease in muscle tone/frequency or spasm severity. Approval duration:
   Screening – 14 days (up to 3 screening trials) Maintenance – 3 months
   B. Requests for Fleqsuvy, Lyvispah or Ozobax (must meet all):
5. Diagnosis of severe spasticity of multiple sclerosis or due to spinal cord injury or spinal cord diseases;
6. Prescribed by or in consultation with a neurologist, orthopedist, physiatrist, or physical medicine and rehabilitation specialist;

7. Age ≥ 12 years; Page 2 of 9

   CLINICAL POLICY
   Baclofen

8. Member must use compounded baclofen oral solution (using crushed tablets) or baclofen crushed or split tablets administered with food (e.g., applesauce), unless contraindicated or clinically significant adverse effects are experienced;
9. Failure of one of the following conventional therapies (a, b, or c), unless clinically significant adverse effects are experienced or all are contraindicated: a. A benzodiazepine (e.g., diazepam, clonazepam); b. Dantrolene; c. Tizanidine;
10. Dose does not exceed 80 mg per day. Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):
11. 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
12. 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. All Indications in Section I (must meet all):
13. 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. Gablofen and Lioresal requests only: Member meets all of the following (a, b, and c): a. Documented adherence with scheduled refill visits;
       b. Baclofen is requested for continuance of maintenance therapy; c. Prescribed formulation is one of the following (i or ii): i. Any Gablofen vial/syringe except the 1 mL syringe; ii. Any Lioresal Intrathecal ampule except the 1 mL ampule;

14. Fleqsuvy, Lyvispah and Ozobax requests only: If request is for a dose increase, new dose does not exceed 80 mg per day. Page 3 of 9

    CLINICAL POLICY
    Baclofen Approval duration: 6 months (Gablofen, Lioresal) or 12 months (Fleqsuvy, Lyvispah, Ozobax) B. Other diagnoses/indications (must meet 1 or 2):

15. 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

16. 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. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration TBI: traumatic brain injury 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.
    Dosing Regimen Drug Name 5 mg PO TID; increase slowly every 3 days by 5 mg PO TID up to 40 to 80 mg/day given in 3 to 4 divided doses Varies Varies Dose Limit/ Maximum Dose 150 mg/day baclofen oral tablets benzodiazepines (e.g., diazepam, clonazepam) dantrolene (Dantrium®) 25 mg PO QD; a gradual dose titration of 25 mg PO QD for 7 days, 25 mg PO TID for 7 days, 50 mg 400 mg/day Page 4 of 9

    CLINICAL POLICY
    Baclofen Drug Name Dosing Regimen Dose Limit/ Maximum Dose Tizanidine (Zanaflex®) PO TID for 7 days, and 100 mg PO TID QD is recommended. 2 mg PO QD; dose can be repeated at 6 to 8 hour intervals as needed to a maximum of 3 doses/24 hrs. Gradually increase the dose by 2 to 4 mg at each dose, with 1-4 days in between dose increases until satisfactory reduction in muscle tone is achieved. 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. 36 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to baclofen o Gablofen and Lioresal only – do not use via intravenous, intramuscular, subcutaneous, or epidural routes of administration • Boxed warning(s):
    o Gablofen and Lioresal only – do not discontinue abruptly  Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death. o Fleqsuvy, Lyvispah and Ozobax – none reported V. Dosage and Administration
    Maximum Dose Not available Drug Name
    Intrathecal baclofen (Gablofen, Lioresal Intrathecal) Dosing Regimen Screening phase: initial: 50 mcg (or 25 mcg for very small patient) intrathecally by barbotage over a period of at least 1 minute, and observed over 4 to 8 hours. If the initial response is less than desired, a second bolus of 75 mcg intrathecally may be given 24 hours after the first dose, and again observe for 4 to 8 hours. If the response is still inadequate, a final bolus of 100 mcg intrathecally may be given 24 hours later. Patients who do not respond to the 100 mcg dose should not be considered candidates for an implanted pump for chronic infusion. Maintenance therapy: Titrate patients individually; lowest dose with an optimal response should be used, generally 300 mcg/day to 800 mcg/day for spasticity of spinal cord origin (for children < 12 years, average dose was 274 mcg/day) and 90 mcg/day to 703 mcg/day for spasticity of cerebral origin (for children < 12 years, average dose was 274 mcg/day). Page 5 of 9

    CLINICAL POLICY
    Baclofen Maximum Dose 80 mg/day 80 mg/day 80 mg/day Drug Name
    Baclofen oral granules (Lyvispah) Baclofen oral solution (Ozobax) Baclofen oral suspension (Fleqsuvy) Dosing Regimen Initiate Lyvispah with a low dosage, preferably in divided doses, administered orally. The following gradually increasing dosage regimen is suggested, but should be adjusted based on clinical response and tolerability:
    • 5 mg three times a day for three days • 10 mg three times a day for three days • 15 mg three times a day for three days • 20 mg three times a day for three days Additional increases may be necessary up to the maximum recommended dosage of 80 mg daily (20 mg four times a day).
    Initiate Ozobax with a low dosage, preferably in divided doses, administered orally. The following gradually increasing dosage regimen is suggested, but should be adjusted based on clinical response and tolerability: • 5 mL (5 mg) three times a day for three days • 10 mL (10 mg) three times a day for three days • 15 mL (15 mg) three times a day for three days • 20 mL (20 mg) three times a day for three days Additional increases may be necessary up to the maximum recommended dosage of 80 mg daily (20 mg four times a day). Initiate Fleqsuvy with a low dosage, preferably in divided doses, administered orally. The following gradually increasing dosage regimen is suggested, but should be adjusted based on clinical response and tolerability: • 1 mL (5 mg) three times a day for three days • 2 mL (10 mg) three times a day for three days • 3 mL (15 mg) three times a day for three days • 4 mL (20 mg) three times a day for three days Additional increases may be necessary up to the maximum recommended dosage of 80 mg daily [4 mL (20 mg) four times a day]. VI. Product Availability Drug Baclofen intrathecal injection (Gablofen) Availability
    Injection: 50 mcg/1 mL, 10,000 mcg/20 mL (500 mcg/mL), 20,000 mcg/20 mL (1,000 mcg/mL) , 40,000 mcg/20 mL (2,000 mcg/mL) Page 6 of 9

    CLINICAL POLICY
    Baclofen Drug Baclofen intrathecal injection (Lioresal Intrathecal) Baclofen oral granules (Lyvispah) Baclofen oral solution (Ozobax) Baclofen oral suspension (Fleqsuvy) Availability
    Injection ampules: 0.05 mg/mL (50 mcg/mL), 10 mg/20 mL (500 mcg/mL), 10 mg/5 mL (2,000 mcg/mL), 40 mg/20 mL (2,000 mcg/mL) Oral granules packets: 5 mg, 10 mg, 20 mg Oral solution: 5 mg/5 mL (1 mg/mL) Oral suspension: 25 mg/5 mL (5 mg/mL) VII.