LYRICA, Pregabalin Form

Pregabalin (Lyrica®, Lyrica® CR), a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is a calcium channel alpha 2-delta ligand with anti- nociceptive and anti-seizure effects. FDA Approved Indication(s) Lyrica is indicated for the treatment of:
• Neuropathic pain associated with diabetic peripheral neuropathy
• Postherpetic neuralgia • Patients 1 month of age and older with partial onset seizures as adjunctive therapy • Fibromyalgia • Neuropathic pain associated with spinal cord injury
Lyrica CR is indicated for the treatment of: • Neuropathic pain associated with diabetic peripheral neuropathy
• Postherpetic neuralgia 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 Lyrica, Lyrica CR, pregabalin, and pregabalin CR are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Neuropathic Pain (must meet all):

1. Diagnosis of neuropathic pain associated with diabetic neuropathy, postherpetic neuralgia, treatment of cancer (immediate-release only), or spinal cord injury;
2. Age ≥ 18 years;
   
   3. Failure of a 30-day trial of gabapentin at ≥ 1,800 mg/day, 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 significant adverse effects are experienced, member’s age is ≥ 65, or all are contraindicated;

4. For all requests except neuropathic pain associated with postherpetic neuralgia, failure of a 30-day trial of a formulary serotonin/norepinephrine reuptake inhibitor Page 1 of 13

   CLINICAL POLICY Pregabalin (SNRI) (e.g., duloxetine, venlafaxine) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;

   6. If request is for controlled-release formulation, member must use immediate-release pregabalin, unless contraindicated or clinically significant adverse effects are experienced;
5. If request is for brand Lyrica, member must use generic pregabalin, unless contraindicated or clinically significant adverse effects are experienced;
6. Dose does not exceed one of the following (a, b, or c): a. Diabetic neuropathy: pregabalin – 300 mg per day; pregabalin CR – 330 mg per day; b. Neuropathic pain associated with treatment of cancer: pregabalin – 300 mg per day; c. Postherpetic neuralgia, neuropathic pain associated with spinal cord injury: pregabalin – 600 mg per day; pregabalin CR – 660 mg per day. Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Partial Onset Seizures (must meet all):
   1. Diagnosis of partial onset seizures;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 1 month;
   4. Request is for immediate-release version;
   5. Member meets one of the following (a or b): a. Request is for the treatment of a member in a State with limitations on step therapy in certain settings (see Appendix E); b. All the following (i, ii, and iii): i. Failure of gabapentin used as adjunctive therapy to other anticonvulsants, unless contraindicated or clinically significant adverse effects are experienced; ii. Failure of TWO anticonvulsants indicated for partial seizures (e.g., carbamazepine, phenytoin, valproic acid, oxcarbazepine, phenobarbital, lamotrigine, levetiracetam, topiramate, zonisamide, tiagabine, felbamate) unless clinically significant adverse effects are experienced or all are contraindicated; iii. If request is for brand Lyrica, member must use generic pregabalin, unless contraindicated or clinically significant adverse effects are experienced;

7. Pregabalin will be used as adjunctive therapy to other anticonvulsants;

   7. Request meets one of the following (a or b): a. For members weighing < 30 kg: Dose does not exceed 420 mg per day; b. For members weighing ≥ 30 kg: Dose does not exceed 600 mg per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less C. Fibromyalgia (must meet all):
   8. Diagnosis of fibromyalgia; Page 2 of 13

   CLINICAL POLICY Pregabalin

8. Age ≥ 18 years;
   
   3. Request is for immediate-release version;
   4. Failure of a 30-day trial of gabapentin at ≥ 1,800 mg/day, unless contraindicated or clinically significant adverse effects are experienced;
9. Failure of a 30-day trial of duloxetine at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
10. Failure of a 30-day trial of cyclobenzaprine or a TCA at up to maximally indicated doses, unless clinically significant adverse effects are experienced, member’s age is ≥ 65, or all are contraindicated;
11. If request is for brand Lyrica, member must use generic pregabalin, unless contraindicated or clinically significant adverse effects are experienced;
12. Dose does not exceed 450 mg per day. Approval duration:
    Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less D. Generalized Anxiety Disorder (off-label) (must meet all):
13. Diagnosis of generalized anxiety disorder;
    2. Age ≥ 18 years;
    3. Request is for immediate-release version;
    4. Failure of TWO of the following alternatives, unless clinically significant adverse effects are experienced or all are contraindicated: escitalopram, paroxetine, venlafaxine ER, duloxetine, buspirone;
14. If request is for brand Lyrica, member must use generic pregabalin, unless contraindicated or clinically significant adverse effects are experienced;
15. Dose does not exceed 600 mg per day. Approval duration:
    Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less E. Other diagnoses/indications (must meet 1 or 2):
16. 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

17. 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 3 of 13

    CLINICAL POLICY Pregabalin 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):

18. 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 a dose increase, new dose does not exceed (a or b): a. Immediate-release pregabalin (i, ii, iii, or iv): i. Diabetic peripheral neuropathy, neuropathic pain associated with treatment of cancer: 300 mg per day; ii. Postherpetic neuralgia, neuropathic pain associated with spinal cord injury, generalized anxiety disorder: 600 mg per day; iii. For partial-onset seizures (a or b): a) For members weighing < 30 kg: dose does not exceed 420 mg per day; b) For members weighing ≥ 30 kg: dose does not exceed 600 mg per day; iv. Fibromyalgia: 450 mg per day; b. Controlled-release pregabalin (i or ii): i. Diabetic peripheral neuropathy: 330 mg per day; ii. Postherpetic neuralgia, neuropathic pain associated with spinal cord injury: 660 mg 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):
19. 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

20. 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 4 of 13

    CLINICAL POLICY Pregabalin 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. Dental pain; B. Essential tremor; C. Social phobia (i.e., social anxiety disorder); D. 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 SNRI: serotonin/norepinephrine reuptake inhibitor
    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.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose TCAs amitriptyline (Elavil®) Fibromyalgia* 10 mg to 50 mg PO QD desipramine (Norpramin®) Neuropathic Pain 25 to 150 mg PO QHS Diabetic Peripheral Neuropathy Initially 25 mg PO QHS, then titrate as tolerated to efficacy (usual range: 75 mg to 150 mg PO QHS) 150 mg/day† 200 mg/day† Postherpetic Neuralgia, Neuropathic Pain associated with Cancer Treatment 10 to 25 mg PO QHS and titrate to pain relief as tolerated (in one study, mean dose was 167 mg/day) Diabetic Peripheral Neuropathy 50 mg to 150 mg PO QHS imipramine (Tofranil®, Tofranil PM®) nortriptyline (Pamelor®) Diabetic Peripheral Neuropathy 50 mg to 75 mg PO daily 150 mg/day 150 mg/day Page 5 of 13

    CLINICAL POLICY Pregabalin Drug Name Dosing Regimen Dose Limit/ Maximum Dose Postherpetic Neuralgia 75 mg to 150 mg PO daily 120 mg/day 225 mg/day Immediate release: 3,600 mg/day† Gralise: 1,800 mg/day† Horizant: 1,200 mg/day† Neuropathic Pain associated with Cancer Treatment 50 to 150 mg PO QHS Serotonin/Norepinephrine Reuptake Inhibitors duloxetine (Cymbalta®) Fibromyalgia 30 to 60 mg PO QD
    venlafaxine extended- release (Effexor XR®) Miscellaneous gabapentin (immediate- release: Neurontin®; extended-release: Horizant®, Gralise®) Neuropathic pain 60 to 120 mg PO QD Fibromyalgia 37.5 to 225 mg PO QD
    Neuropathic pain 75 mg to 225 mg PO QD Diabetic Peripheral Neuropathy, Neuropathic Pain associated with Cancer Treatment Immediate-release: 300 mg PO TID titrated based on clinical response Fibromyalgia 300 mg PO QHS then increased to target dosage of 2,400 mg/day Postherpetic Neuralgia Immediate-release: 300 mg PO QD on day 1, 300 mg PO BID on day 2, 300 mg PO TID on day 3, then titrate as needed to 1800 mg/day Extended-release (Gralise): 300 mg PO on day 1, 600 mg on day 2, 900 mg on days 3- 6, 1200 mg on days 7-10, 1500 mg on days 11-14, and 1800 mg on day 15 and thereafter Extended-release (Horizant): 600 mg/day PO for 3 days, 600 mg PO BID on day 4 and thereafter Partial Seizures Immediate-release: Page 6 of 13

    CLINICAL POLICY Pregabalin Drug Name Dosing Regimen Dose Limit/ Maximum Dose Adults: initially 300 mg PO TID; effective range 900-1,800 mg/day but up to 2400 mg/day has been used long term Children 3-12 years: 10-15 mg/kg/day PO in 3 divided doses; effective dose 25-35 mg/kg/day if > 5 years and 40 mg/kg/day if 3-4 years Fibromyalgia 10 mg to 20 mg PO QHS 20 mg/day Refer to prescribing information Refer to prescribing information cyclobenzaprine (Flexeril®) Anticonvulsants carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®, Tegretol XR®) felbamate (Felbatol®) lamotrigine (Lamictal®, Lamictal CD®, Lamictal ODT®, Lamictal XR®) levetiracetam (Elepsia XR®, Keppra®, Keppra XR®, Roweepra®, Spritam®) oxcarbazepine (Oxtellar XR®, Trileptal®) phenobarbital (Luminal®) phenytoin (Dilantin®, Phenytek®) tiagabine (Gabitril®) topiramate (Qudexy XR®, Topamax®, Topamax Sprinkle®, Topiragen®, Trokendi XR®) valproic acid (divalproex sodium, Depakote Sprinkle®, Depakote ER®, Depakote®, Depakene®) zonisamide (Zonegran®) 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. *Agents not included in this list may not have evidence supporting their use in the indications covered by this policy Off-label use Page 7 of 13

    CLINICAL POLICY Pregabalin †Maximum dose for drug, not necessarily indication Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to pregabalin or any of its components • Boxed warning(s): none reported Appendix D: General Information
    • Class IIb recommendation in Micromedex for Generalized Anxiety Disorder is supported by 5 randomized, double blind, placebo-controlled studies. It is also considered a second- line agent by the Canadian Psychiatric Association. Appendix E: States with Limitations against Redirections in Certain Settings State Step Therapy Notes Prohibited? No NV Applies to Medicaid requests only Partial onset seizures: Failure of ONE of the following, unless clinically significant adverse effects are experienced or all are contraindicated: generic pregabalin, gabapentin (used as adjunctive therapy to other anticonvulsants), alternative anticonvulsants indicated for partial seizures (e.g., carbamazepine, phenytoin, valproic acid, oxcarbazepine, phenobarbital, lamotrigine, levetiracetam, topiramate, zonisamide, tiagabine, felbamate). V. Dosage and Administration
    Drug Name Indication Pregabalin (Lyrica)* Dosing Regimen 3 divided doses PO per day 2 or 3 divided doses PO per day Diabetic peripheral neuropathy Neuropathic pain associated with treatment of cancer Postherpetic neuralgia Partial onset seizures Adults: 2 or 3 divided doses PO per day 2 or 3 divided doses PO per day Maximum Dose 300 mg/day 300 mg/day 600 mg/day Adults: 600 mg/day Pediatric patients weighing > 30 kg: 2.5 mg/kg/day in 2 or 3 divided doses Pediatrics < 30 kg: 14 mg/kg/day
    Pediatric patients weighing < 30 kg: 3.5 mg/kg/day • 1 month to < 4 years old: 3 divided doses • ≥ 4 years old: 2 or 3 divided doses Page 8 of 13

    CLINICAL POLICY Pregabalin Drug Name Indication Fibromyalgia Neuropathic pain associated with spinal cord injury
    Generalized anxiety disorder Pregabalin extended- release (Lyrica CR) Diabetic peripheral neuropathy Postherpetic neuralgia Dosing Regimen 2 divided doses PO per day 2 divided doses PO per day Maximum Dose 450 mg/day 600 mg/day 600 mg/day 330 mg/day
    660 mg/day Initially, 75 mg PO BID. If tolerated after 1 week, the dose may be increased to 150 mg PO BID. Thereafter, the dose may be adjusted according to response and tolerability. Data from clinical trials indicate an effective dose range is 150 to 225 mg PO BID. 165 mg PO QD. Dose may be increased to 330 mg PO QD within 1 week. 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.

    • Lyrica should be administered orally starting at 150 mg/day. It should be titrated up to 300 mg/day within 1 week for all indications except partial onset seizures. VI. Product Availability
      Drug Name Pregabalin (Lyrica) Availability Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg Oral solution: 20 mg/mL Pregabalin extended-release (Lyrica CR) Tablets: 82.5 mg, 165 mg, 330 mg VII.