Amantadine ER (Gocovri, Osmolex ER) Form

Amantadine extended-release (Gocovri®, Osmolex ER®) is a weak uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor.
FDA Approved Indication(s) Gocovri is indicated: • For the treatment of dyskinesia in patients with Parkinson’s disease (PD) receiving levodopa- based therapy, with or without concomitant dopaminergic medications; • As adjunctive treatment to levodopa/carbidopa in patients with PD experiencing “off” episodes.
Osmolex ER is indicated for the treatment of PD and for the treatment of drug-induced extrapyramidal reactions in adult patients. 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 Gocovri and Osmolex ER are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Dyskinesia in Patients with Parkinson’s Disease (must meet all):

1. Diagnosis of dyskinesia in patients with PD;
   2. Age ≥ 18 years;
   3. Member is receiving levodopa-based therapy;
   4. Member must use immediate-release amantadine, unless contraindicated or clinically significant adverse effects are experienced;

2. Dose does not exceed one of the following (a or b):
   a. Gocovri, both of the following (i and ii):
   i. 274 mg per day;
   ii. 2 capsules per day;
   b. Osmolex ER, both of the following (i and ii) i. 322 mg per day;
   ii. 2 tablets per day. Approval duration:
   Medicaid/HIM – 12 months Page 1 of 8

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   Commercial – 12 months or duration of request, whichever is less B. Parkinson’s Disease With “Off” Episodes (must meet all):

3. Diagnosis of PD;
   2. Request is for Gocovri;
   3. Age ≥ 18 years;
   4. Member is experiencing “off” time (see Appendix D) on levodopa/carbidopa therapy;
   5. 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
4. Member must use immediate-release amantadine, unless contraindicated or clinically significant adverse effects are experienced;
5. Prescribed in combination with levodopa/carbidopa;
   8. Dose does not exceed both of the following (a and b):
      a. 274 mg per day;
      b. 2 capsules per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
      C. Drug Induced Extrapyramidal Reactions (must meet all):
   9. Diagnosis of a drug induced extrapyramidal reaction;
   10. Request is for Osmolex ER;
   11. Age ≥ 18 years;
   12. Member must use immediate-release amantadine, unless contraindicated or clinically significant adverse effects are experienced;
6. Dose does not exceed both of the following (a and b):
   a. 322 mg per day;
   b. 2 tablets per day. Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
   D. 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 Page 2 of 8

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   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. All Indications in Section I (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);
10. Member is responding positively to therapy (e.g., reductions in OFF time, improvement in dyskinesia symptoms);
11. If request is for a dose increase, new dose does not exceed one of the following (a or b):
    a. Gocovri, both of the following (i and ii):
    i. 274 mg per day;
    ii. 2 capsules per day;
    b. Osmolex ER, both of the following (i and ii):
    i. 322 mg per day;
    ii. 2 tablets per day.
    Approval duration:
    Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less 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 Page 3 of 8

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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 COMT: catechol-O-methyl transferase FDA: Food and Drug Administration MAO-B: monoamine oxidase type B
    NMDA: N-methyl-D-aspartate 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.
    Drugs Dosing Regimen Dose Limit/ Maximum Dos 400 mg/day 1,200 mg levodopa/day (divided doses) 1,600 mg/day (divided doses) 300 mg/day 1 mg/day Titrated up to 100 mg PO QID amantadine immediate-release 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®) 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.
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    Drugs Dosing Regimen Dopamine Agonists pramipexole (Mirapex®) pramipexole ER (Mirapex® ER) ropinirole ropinirole ER (Requip® XL) 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 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 Dos 4.5 mg/day (divided doses) 4.5 mg/day 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: Contraindications/Boxed Warnings • Contraindication(s): end-stage renal disease • 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.
    • Parkinson’s disease symptoms, resulting from too little levodopa (L-dopa), are in contrast with dyskinesia which typically results from too much L-dopa. The alterations between “on” time (the time when Parkinson’s disease symptoms are successfully suppressed by L-dopa) and “off” time is known as “motor fluctuations”. • The addition of carbidopa to L-dopa prevents conversion of L-dopa to dopamine in the systemic circulation and liver. Page 5 of 8

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    V. Dosage and Administration
    Indication Drug Name Dosing Regimen Amantadine ER (Gocovri) Dyskinesia or “off” episodes in PD
    Amantadine ER (Osmolex ER) Dyskinesia in PD; drug induced extrapyramidal reaction VI. Product Availability
    137 mg PO QHS for 1 week. After 1 week, increase to 274 mg (two 137 mg capsules) PO QHS 129 mg PO QAM, increase dose in weekly intervals Maximum Dose 274 mg/day 322 mg/day Drug Name Amantadine ER (Gocovri) Amantadine ER (Osmolex ER) Availability Extended-release capsules: 68.5 mg, 137 mg Extended-release tablets: 129 mg, 193 mg, 258 mg VII.