Safinamide (Xadago) Form

Safinamide (Xadago®) is monoamine oxidase type B (MAO-B) inhibitor. FDA Approved Indication(s) Xadago is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing “off” episodes. 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 Xadago is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Parkinson’s Disease (must meet all):

1. Diagnosis of idiopathic PD;
2. Age ≥ 18 years;
3. Member is experiencing “off” time (see Appendix B) on levodopa/carbidopa therapy;
4. Failure of two of the following adjunct drugs prescribed in combination with levodopa/carbidopa, each from different classes, unless clinically significant adverse effects are experienced or all are contraindicated: a. MAO-B inhibitor: rasagiline; b. COMT inhibitor: entacapone (Comtan®/Stalevo®), tolcapone; c. Dopamine agonist: ropinirole/ropinirole ER, pramipexole/pramipexole ER; Prior authorization may be required for the above agents
5. Prescribed in combination with levodopa/carbidopa;

6. Dose does not exceed both of the following (a and b):
   a. 100 mg per day;
   b. 1 tablet per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):

   1. 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 1 of 7

   CLINICAL POLICY
   Safinamide 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

   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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Parkinson’s Disease (must meet all):
   3. 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);
7. Member is responding positively to therapy;

8. If request is for a dose increase, new dose does not exceed both of the following (a and b):
   a. 100 mg per day;
   b. 1 tablet per day. Approval duration:
   HIM/Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

   1. 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
   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 Page 2 of 7

   CLINICAL POLICY
   Safinamide 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 COMT: catechol-O-methyl transferase FDA: Food and Drug Administration MAO-B: monoamine oxidase type B
   PD: Parkinson’s disease 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 Dose Limit/ Maximum Dose COMT Inhibitors carbadopa/levodopa/ entacapone (Stalevo®) PO: Dose should be individualized based on therapeutic response; doses may be adjusted by changing strength or adjusting interval. Fractionated doses are not recommended and only 1 tablet should be given at each dosing interval. PO: 200 mg with each dose of levodopa/carbidopa entacapone (Comtan®) tolcapone (Tasmar®) PO: 100 mg 3 times daily, as adjunct to MAO-B Inhibitors rasagiline (Azilect) Dopamine Agonists pramipexole (Mirapex®) pramipexole ER (Mirapex® ER) levodopa/carbidopa PO: Monotherapy or adjunctive therapy (not including levodopa): 1 mg once daily. Adjunctive therapy with levodopa: Initial: 0.5 mg once daily; may increase to 1 mg once daily based on response and tolerability.
   PO: Initial dose: 0.125 mg 3 times daily, increase gradually every 5 to 7 days; maintenance (usual): 0.5 to 1.5 mg 3 times daily PO: Initial dose: 0.375 mg once daily; increase gradually not more frequently than every 5 to 7 days to 0.75 mg once daily and then, if necessary, by 0.75 mg per dose Page 3 of 7 1,200 mg of levodopa/day (divided doses) 1,600 mg/day (divided doses) 300 mg/day 1 mg/day 4.5 mg/day (divided doses) 4.5 mg/day

   CLINICAL POLICY
   Safinamide Drug Name Dosing Regimen ropinirole ropinirole ER (Requip® ER) PO: Recommended starting dose: 0.25 mg 3 times/day. Based on individual patient response, the dosage should be titrated with weekly increments: Week 1: 0.25 mg 3 times/day; total daily dose: 0.75 mg; week 2: 0.5 mg 3 times/day; total daily dose: 1.5 mg; week 3: 0.75 mg 3 times/day; total daily dose: 2.25 mg; week 4: 1 mg 3 times/day; total daily dose: 3 mg. After week 4, if necessary, daily dosage may be increased by 1.5 mg/day on a weekly basis up to a dose of 9 mg/day, and then by up to 3 mg/day weekly to a total of 24 mg/day.
   PO: Initial dose: 2 mg once daily for 1 to 2 weeks, followed by increases of 2 mg/day at weekly or longer intervals based on therapeutic response and tolerability Dose Limit/ Maximum Dose 24 mg/day (divided doses) 24 mg/day 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. Appendix C: Contraindication/Boxed Warnings • Contraindication(s): o Concomitant use of the following drugs:  Other monoamine oxidase inhibitors or other drugs that are potent inhibitors of monoamine oxidase (e.g., linezolid)
    Opioid drugs (e.g., tramadol, meperidine and related derivatives); serotonin- norepinephrine reuptake inhibitors; tri-or tetra-cyclic or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; St. John’s wort
    Dextromethorphan o A history of a hypersensitivity to safinamide
   o Severe hepatic impairment (Child-Pugh C: 10-15) • Boxed warning(s): none reported Appendix D: General Information • Off time/episodes represent a return of PD symptoms (bradykinesia, rest tremor or rigidity) when the L-dopa treatment effect wears off after each dosing interval.
   • PD symptoms, resulting from too little L-dopa, are in contrast with dyskinesia which typically results from too much L-dopa. The alterations between “on” time (the time when PD symptoms are successfully suppressed by L-dopa) and “off” time is known as “motor fluctuations”. • The addition of carbidopa to levodopa (L-dopa) prevents conversion of L-dopa to dopamine in the systemic circulation and liver. Page 4 of 7

   CLINICAL POLICY
   Safinamide V. Dosage and Administration
   Indication Adjunctive treatment to levodopa/carbidopa in patients with PD experiencing “off” episodes Dosing Regimen 50 mg PO QD; 100 mg PO QD after 2 weeks if needed Maximum Dose 100 mg/day VI. Product Availability
   Tablets: 50 mg, 100 mg VII.