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Lyrica and Savella Step Therapy with Quantity Limit Program Summary

Policy Number: PH-91055

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.            

POLICY REVIEW CYCLE                                                                                                                                                                           

Effective Date

Date of Origin 

07-01-2025            

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

LYRICA®

(pregabalin)*

Capsule

Oral solution

Neuropathic pain associated with diabetic peripheral neuropathy (DPN)

Postherpetic neuralgia (PHN)

Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older

Fibromyalgia

Neuropathic pain associated with spinal cord injury

*generic available

1

LYRICA® CR

(pregabalin ER)*

Tablet

The management of:

  • neuropathic pain associated with diabetic peripheral neuropathy (DPN)
  • postherpetic neuralgia (PHN)

Efficacy of LYRICA CR has not been established for the management of fibromyalgia or as adjunctive therapy for adult patients with partial onset seizures. 

*generic available

9

Savella®

(milnacipran)

Tablet

Titration pack

Management of fibromyalgia

Savella is not approved for use in pediatric patients.

2

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Fibromyalgia

Fibromyalgia is a chronic condition with unknown etiology and is characterized by generalized body pain, fatigue, sleep disturbance, impaired cognition, and anxiety. Diagnosis is often made by exclusion of other conditions such as neurological syndromes and depression. There is no clear specific pathophysiological therapeutic target. Various guidelines for treatment exist and they are not in agreement. There has been an increased focus on non-pharmacologic therapies discussed in the guidelines, however, pharmacology remains the mainstay of therapy. Pharmacologic therapy varies, including classical analgesics, antidepressants, and anticonvulsants. Commonly used agents include tricyclic antidepressants (TCAs), pregabalin, gabapentin, serotonin and norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), tramadol, and cyclobenzaprine.(3)

Neuropathic Pain

Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM), impacting up to 50% of patients.(12) Early prevention of neuropathy and appropriate management of diabetic patients are important since there is no specific treatment to reverse the underlying nerve damage. Focus should be on prevention of disease progression and symptom management. Prevention includes glucose control, modifiable risk factors (e.g., lipids and blood pressure), and lifestyle modifications (e.g., dietary modifications and exercise). For patients with diabetic neuropathy, foot care is important to prevent ulceration and amputation.(4,5) Currently, pregabalin (LYRICA), duloxetine (Cymbalta), tapentadol (NUCYNTA ER), and capsaicin patch (Qutenza) are FDA-labeled therapies for DPN. Many treatments have also been successful off-label for the treatment of DPN.(5) Alternatives treatments include topical agents such as capsaicin 8% patch and 0.075% cream, lidocaine 5% patch, and alpha-lipoic acid and are considered second-line.(4)

American Diabetes Association (ADA) and the American Academy of Neurology (AAN) recommends gabapentiniods (gabapentin, pregabalin), SNRIs (duloxetine, venlafaxine, desvenlafaxine), TCAs (amitriptyline), and sodium channel blockers (lamotrigine, lacosamide, carbamazepine, oxcarbazepine, valproic acid) as first-line treatments for DPN.(4,12) 

American Academy of Family Physicians (AAFP) recommends pregabalin, gabapentin, amitriptyline, and duloxetine as first-line agents. Carbamazepine and oxcarbazepine are alternatives to first-line options due to tolerability, adverse effects, and monitoring demands. Other antidepressants such as bupropion, imipramine, nortriptyline, and venlafaxine, should be reserved as alternatives to first-line treatments due to lower quality trials showing benefit and adverse effects.(5)

The Center for Disease Control (CDC), AAN, and AAFP no longer recommend the use of opioids, including tramadol and tapentadol, for painful diabetic neuropathy.(4)

Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. PHN is defined as pain in the dermatomal distribution that is sustained for at least 90 days after the rash. PHN is caused by nerve damage secondary to an inflammatory response induced by viral replication within a nerve. Pain management strategies should focus on symptom control. Some patients have complete resolution of symptoms at several years while others continue medications indefinitely.(6)

The anticonvulsants gabapentin and pregabalin are FDA labeled for treatment of PHN.(11) TCAs used off-label are also effective in treating PHN, but up to one-fourth of patients discontinue treatment due to adverse reactions.(6,10) Both gabapentinoids and TCAs are unanimously recognized as first-line drugs.(10) Both topical (capsaicin and lidocaine) and systemic treatments can be effective in the management of PHN but various guidelines do not agree on efficacy in treatment of PHN.(6,10) Opioids are considered third-line treatment with two systematic reviews finding tramadol provided significant pain relief in patients with PHN.(6,11) Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be ineffective for neuropathic pain.(11)

Neuropathic Pain due to Spinal Cord Injury

Spinal cord injury (SCI) is an injury to the spinal cord that leads to varying degrees of motor and/or sensory deficits and paralysis. Chronic neuropathic pain is common and contributes to reduced quality of life. First-line drugs commonly used are amitriptyline, gabapentin, and pregabalin. Alternative agents are tramadol and duloxetine.(7)

Seizure Disorders

The occurrence of a single seizure does not always require initiation of antiepileptic drugs (AEDs). In the absence of risk factors, physicians should consider delaying used of AEDs until a second seizure occurs. Treatment should begin with monotherapy.(8) LYRICA has FDA approval for adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older.(1)

Safety

LYRICA and LYRICA CR are contraindicated in patients with a known hypersensitivity to pregabalin or any of its components.(1,9)

Savella has the following contraindications:(2)

  • Do not use MAOIs intended to treat psychiatric disorders with Savella or within 5 days of stopping treatment with Savella
  • Do not use Savella within 14 days of stopping an MAOI intended to treat psychiatric disorders
  • Do not start Savella in a patient who is being treated with linezolid or intravenous methylene blue

Savella carries a boxed warning for suicidality and antidepressant drugs.(2)

  • Increased risk of suicidal ideation, thinking, and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders
  • Savella is not approved for use in pediatric patients

REFERENCES                                                                                                                                                                           

Number

Reference

1

LYRICA prescribing information. Parke-Davis Div of Pfizer Inc. June 2020.

2

Savella prescribing information. Allergan, Inc. May 2024.

3

Kia S, Choy E. Update on Treatment Guideline in Fibromyalgia Syndrome with Focus on Pharmacology. Biomedicines. 2017;5(2):20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489806/ 

4

ElSayed NA, Aleppo G, Bannuru RR, et al. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes - 2024. Diabetes Care. 2023;47(Supplement_1):S231-S243. doi:10.2337/dc24-s012

5

Bragg, Marrison S, Haley. Diabetic Peripheral Neuropathy: Prevention and Treatment. American Family Physician. 2024;109(3):226-232.

6

Saguil AS, Kane S, Mercado M, et al. Herpes Zoster and Postherpetic Neuralgia: Prevention and Management. Am Fam Physician. 2017;96(10):656-663. Available at: https://www.aafp.org/afp/2017/1115/p656.pdf  

7

Hagen EM, Rekand T. Management of Neuropathic Pain Associated with Spinal Cord Injury. Pain Ther 2015;4(1):51-65. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470971/#__ffn_sectitle. 

8

Liu G, Slater N, Perkins A. Epilepsy: Treatment Options. American Family Physician. 2017; 95(2):87-96. https://www.aafp.org/afp/2017/0715/p87.html  

9

LYRICA CR prescribing information. Parke-Davis Div of Pfizer. June 2020.

10

Beben D, Kowalewski J, Recka K, et al. Post-herpetic neuralgia: currently available oral and topical medications in the management of pain - a review. Journal of Pre-Clinical and Clinical Research. Published online June 14, 2024. doi:10.26444/jpccr/189442

11

Johnson RW, Rice ASC. Postherpetic neuralgia. New England Journal of Medicine. 2014;371(16):1526-1533. doi:10.1056/nejmcp1403062

12

Price R, Smith D, Franklin G, et al. Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update summary. Neurology. 2021;98(1):31-43. doi:10.1212/wnl.0000000000013038

POLICY AGENT SUMMARY STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

pregabalin tab er

165 MG ; 330 MG ; 82.5 MG

Y

O ; Y

Lyrica

100 MG ; 150 MG ; 20 MG/ML ; 200 MG ; 225 MG ; 25 MG ; 300 MG ; 50 MG ; 75 MG

M ; N ; O

O ; Y

Lyrica cr

165 MG ; 330 MG ; 82.5 MG

M ; N ; O

O ; Y

Savella ; Savella titration pack

100 MG ; 12.5 & 25 & 50 MG ; 12.5 MG ; 25 MG ; 50 MG

M ; N ; O

N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

QL Amount

Dose Form

Day Supply

Duration

Addtl QL Info

Allowed Exceptions

Targeted NDCs When Exclusions Exist

Lyrica

Pregabalin Cap 100 MG

100 MG

180

Capsules

30

DAYS

Lyrica

Pregabalin Cap 150 MG

150 MG

90

Capsules

30

DAYS

Lyrica

Pregabalin Cap 200 MG

200 MG

90

Capsules

30

DAYS

Lyrica

Pregabalin Cap 225 MG

225 MG

60

Capsules

30

DAYS

Lyrica

Pregabalin Cap 25 MG

25 MG

360

Capsules

30

DAYS

Lyrica

Pregabalin Cap 300 MG

300 MG

60

Capsules

30

DAYS

Lyrica

Pregabalin Cap 50 MG

50 MG

270

Capsules

30

DAYS

Lyrica

Pregabalin Cap 75 MG

75 MG

180

Capsules

30

DAYS

Lyrica

Pregabalin Soln 20 MG/ML

20 MG/ML

900

mLs

30

DAYS

Lyrica cr

Pregabalin Tab ER 24HR 165 MG

165 MG

30

Tablets

30

DAYS

Lyrica cr

Pregabalin Tab ER 24HR 330 MG

330 MG

60

Tablets

30

DAYS

Lyrica cr

Pregabalin Tab ER 24HR 82.5 MG

82.5 MG

30

Tablets

30

DAYS

Savella

milnacipran hcl tab

100 MG ; 12.5 MG ; 25 MG ; 50 MG

60

Tablets

30

DAYS

Savella titration pack

Milnacipran HCl Tab 12.5 MG (5) & 25 MG (8) & 50 MG (42) Pak

12.5 & 25 & 50 MG

1

Pack

180

DAYS

CLIENT SUMMARY – STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

pregabalin tab er

165 MG ; 330 MG ; 82.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

100 MG ; 150 MG ; 20 MG/ML ; 200 MG ; 225 MG ; 25 MG ; 300 MG ; 50 MG ; 75 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica cr

165 MG ; 330 MG ; 82.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Savella ; Savella titration pack

100 MG ; 12.5 & 25 & 50 MG ; 12.5 MG ; 25 MG ; 50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Lyrica

Pregabalin Cap 100 MG

100 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 150 MG

150 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 200 MG

200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 225 MG

225 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 25 MG

25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 300 MG

300 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 50 MG

50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Cap 75 MG

75 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica

Pregabalin Soln 20 MG/ML

20 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica cr

Pregabalin Tab ER 24HR 165 MG

165 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica cr

Pregabalin Tab ER 24HR 330 MG

330 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Lyrica cr

Pregabalin Tab ER 24HR 82.5 MG

82.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Savella

milnacipran hcl tab

100 MG ; 12.5 MG ; 25 MG ; 50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Savella titration pack

Milnacipran HCl Tab 12.5 MG (5) & 25 MG (8) & 50 MG (42) Pak

12.5 & 25 & 50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

STEP THERAPY CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Lyrica

TARGET AGENT(S)

PREREQUISITE AGENT(S)

LYRICA*

immediate release pregabalin

* - generic available 

Target Agent(s) will be approved when ONE of the following is met:

  1. The requested agent is eligible for continuation of therapy AND ONE of the following:

Agents Eligible for Continuation of Therapy

All target agents are eligible for continuation of therapy
    1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
    2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
  2. ONE of the following:
    1. The patient has ONE of the following:
      1. Has a medication history of use in the past 90 days to ONE prerequisite agent OR
      2. Has an intolerance or hypersensitivity to ONE prerequisite agent that is NOT expected to occur with the requested agent OR
    2. The patient has an FDA labeled contraindication to ALL prerequisite agent(s) that is NOT expected to occur with the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Lyrica CR

TARGET AGENT(S)

PREREQUISITE AGENT(S)

extended release pregabalin 

immediate release pregabalin

LYRICA CR*

immediate release pregabalin

AND

extended release pregabalin

* - generic available 

Target Agent(s) will be approved when ONE of the following is met:

  1. The requested agent is eligible for continuation of therapy AND ONE of the following:

Agents Eligible for Continuation of Therapy

All target agents are eligible for continuation of therapy
    1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
    2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
  2. If the requested agent is generic extended release pregabalin, then ONE of the following: 
    1. The patient has ONE of the following:
      1. Has a medication history of use in the past 90 days to ONE prerequisite agent OR
      2. Has an intolerance or hypersensitivity to ONE prerequisite agent OR
    2. The patient has an FDA labeled contraindication to ALL prerequisite agent(s) OR
  3. If the requested agent is brand LYRICA CR, then ONE of the following:
    1. The patient has ONE of the following:
      1. Has a medication history of use in the past 180 days to TWO prerequisite agents OR
      2. Has a medication history of use in the past 180 days to ONE prerequisite agent and an intolerance or hypersensitivity to ONE prerequisite agent OR
      3. Has an intolerance or hypersensitivity to TWO prerequisite agents OR
    2. The patient has an FDA labeled contraindication to ALL prerequisite agent(s)

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Savella

 

TARGET AGENT(S)

PREREQUISITE AGENT(S)

Savella (milnacipran)

duloxetine
amitriptyline
nortriptyline
imipramine
desipramine
cyclobenzaprine
venlafaxine
immediate release gabapentin
immediate release pregabalin
tramadol

Target Agent(s) will be approved when ONE of the following is met:

  1. The requested agent is eligible for continuation of therapy AND ONE of the following:

Agents Eligible for Continuation of Therapy

All target agents are eligible for continuation of therapy
    1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
    2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
  2. ONE of the following:
    1. The patient has ONE of the following:
      1. Has a medication history of use in the past 90 days to ONE prerequisite agent OR
      2. Has an intolerance or hypersensitivity to ONE prerequisite agent OR
    2. The patient has an FDA labeled contraindication to ALL prerequisite agent(s)

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

  1. The requested quantity (dose) does NOT exceed the program quantity limit OR
  2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
    1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
    2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
    3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

 

 

 

Commercial _ PS _ Lyrica_and_Savella_STQL _ProgSum_ 07-01-2025