Gabapentin ER (Gralise, Horizant) Form

Gabapentin (Gralise®) is an analog of gamma-aminobutyric acid (GABA) that has GABA agonist activity. Gabapentin enacarbil ER (Horizant®) is a prodrug of gabapentin. FDA Approved Indication(s) Gralise and Horizant are indicated for the management of postherpetic neuralgia (PHN).
Horizant is also indicated for the treatment of moderate-to-severe primary restless legs syndrome (RLS) in adults.
Limitation(s) of use:
• Horizant is not recommended for patients who are required to sleep during the daytime and remain awake at night. • Gralise and Horizant are not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. 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 Gralise and Horizant are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Postherpetic Neuralgia (must meet all):

1. Diagnosis of PHN;
   2. Age ≥ 18 years;
   3. Failure of a ≥ 30 day trial of immediate-release gabapentin at ≥ 1,800 mg per day, unless contraindicated to its excipients or clinically significant adverse effects are experienced;
2. Failure of a ≥ 30-day trial of generic pregabalin (immediate-release or controlled- release) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;

3. Failure of a ≥ 30-day trial of a tricyclic antidepressant (TCA) (e.g., amitriptyline, nortriptyline, imipramine) at up to maximally indicated doses, unless clinically Page 1 of 7

   CLINICAL POLICY Gabapentin ER significant adverse effects are experienced, member’s age is ≥ 65, or all are contraindicated;

4. Dose does not exceed (a or b): a. Gralise: 1,800 mg (3 tablets) per day; b. Horizant: 1,200 mg (2 tablets) per day. Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Restless Leg Syndrome (must meet all):
5. Diagnosis of RLS;
   2. Request is for Horizant;
   3. Age ≥ 18 years;
   4. Failure of gabapentin immediate release and generic pregabalin at up to maximally indicated doses, each used for ≥ 30 days, unless both are contraindicated or clinically significant adverse effects are experienced;
   5. Dose does not exceed 600 mg (1 tablet) per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
      C. Other diagnoses/indications (must meet 1 or 2):
6. 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
7. 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):

8. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 2 of 7

   CLINICAL POLICY Gabapentin ER 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 a dose increase, new dose does not exceed (a or b): a. PHN: 1,800 mg (3 tablets) per day (Gralise) or 1,200 mg (2 tablets) per day (Horizant); b. RLS: 600 mg (1 tablet) per day (Horizant). 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):
9. 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

10. 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 GABA: gamma-aminobutyric acid PHN: post herpetic neuralgia RLS: restless legs syndrome TCA: tricyclic antidepressant 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.
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    CLINICAL POLICY Gabapentin ER Drug Name Indication Dosing Regimen gabapentin (Neurontin) PHN RLS RLS PHN PHN PHN PHN pregabalin (Lyrica®)
    pregabalin extended-release (Lyrica CR®) amitriptyline (Elavil®) desipramine (Norpramin®) Dose Limit/ Maximum Dose 3,600 mg/day 3,600 mg/day 450 mg/day 600 mg/day 660 mg/day 150 mg/day 200 mg/day 300 mg PO as a single dose on day 1, then 600 mg/day (300 mg PO BID) on day 2, and 900 mg/day (300 mg PO TID) on day

    3. The dose can then be titrated up as needed for pain relief to a dose of 1,800 mg/day (600 mg PO TID). 300 mg PO daily. The dose can be titrated up by 300 mg every week as needed up to 3,600 mg/day. Doses should be spaced at least 2 hours apart.
       75 mg PO daily. The dose can be titrated up by 75 mg every week as needed up to 450 mg daily.
       2 or 3 divided doses PO per day 165 mg PO QD. Dose may be increased to 330 mg PO QD within 1 week. After 2 to 4 weeks of treatment, dose may be increased to 660 mg PO QD in patients not experiencing adequate pain relief. 25 to 150 mg PO QHS 10 to 25 mg PO QHS and titrate to pain relief as tolerated (in one study, mean dose was 167 mg/day) 75 mg to 150 mg PO daily PHN nortriptyline (Pamelor®) 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. 150 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity (Gralise) • Boxed warning(s): none reported V. Dosage and Administration
       Drug Name gabapentin ER (Gralise) Indication Dosing Regimen PHN Gralise should be initiated and titrated as follows: Day 1: 300 mg PO Day 2: 600 mg PO
       Days 3 to 6: 900 mg PO QD Days 7 to 10: 1,200 mg PO QD Days 11 to 14: 1,500 mg PO QD Days ≥ 15: 1,800 mg PO QD Maximum Dose 1,800 mg/day Page 4 of 7

    CLINICAL POLICY Gabapentin ER Drug Name gabapentin enacarbil ER (Horizant) RLS VI. Product Availability
    Indication Dosing Regimen PHN 600 mg PO QAM for 3 days, then increase to 600 mg PO BID beginning on day 4 600 mg PO QD at about 5 PM Maximum Dose 1,200 mg/day 600 mg/day Drug Name Gabapentin ER (Gralise) Gabapentin enacarbil ER (Horizant) Availability ER tablets: 300 mg, 600 mg
    ER tablets: 300 mg, 600 mg VII.