Drug Therapy Guidelines Lyrica CR® (pregabalin ER)

Applicable Medical Benefit Effective: 1/1/21 Pharmacy- Formulary 1 x Next Review: 9/21 Pharmacy- Formulary 2 x Date of Origin: 6/18 Pharmacy- Formulary 3/Exclusive x Review Dates: 3/18, 6/18, 9/18, 9/19, 9/20 Pharmacy- Formulary 4/AON x

I. Medication Description

Pregabalin is a structural analogue of gamma-aminobutyric acid (GABA) and has anxiolytic, analgesic, and antiepileptic properties. Pregabalin does not show direct GABA-mimetic effects, but increases neuronal GABA levels as well as produces a dose-dependent increase in glutamic acid decarboxylase activity. Pregabalin reduces neuronal calcium currents by binding to the alpha-2-delta subunit of calcium channels, and this particular mechanism may be responsible for effects in seizure control, neuropathic pain, anxiety, and other pain syndromes. Pregabalin may also interact with descending noradrenergic and serotonergic pathways in the brainstem that modulate pain transmission in the spinal cord.

II. Position Statement

Coverage is determined through a prior authorization process with supporting clinical documentation for every request.

III. Policy

Formulary 1: See Sections A, B, C, and E Formulary 2: See Sections A, B, C, and E Formulary 3: See Sections A, B, D, and E Formulary 4/AON: See Sections A, B, C, and E

Coverage of Lyrica CR is available for the following conditions when the listed criteria are met:

Neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults: A. The member has a documented diagnosis of DPN B. When requesting coverage of a brand medication for which an A/B rated generic is available, coverage will be provided when there is sufficient evidence that the use of the A/B rated generic equivalent has resulted in inadequate results C. Coverage will be provided when the member has experienced intolerance or therapeutic failure with TWO of the plan-preferred medications first (pregabalin AND one of the following: gabapentin, duloxetine, amitriptyline, or venlafaxine) D. Coverage will be provided when the member has experienced intolerance or therapeutic failure with TWO of the plan-preferred medications first (gabapentin, duloxetine, amitriptyline, and venlafaxine) E. When at least ONE of the following criteria have been met: Page 1 of 4

Drug Therapy Guidelines Lyrica CR® (pregabalin ER) Last Review Date: 9/2020

• The plan-preferred medications are contraindicated or will likely cause an adverse reaction by or physical or mental harm to the member. • The plan-preferred medications are expected to be ineffective based on the known clinical history and conditions of the member and the member’s prescription drug regimen. • The member has tried the plan-preferred medications or another prescription drug in the same pharmacologic class or with the same mechanism of action and such prescription drug was discontinued due to lack of efficacy of effectiveness, diminished effect, or an adverse event. • The member is stable on the medication selected by their healthcare professional for the medical condition under consideration (where “stable” is defined as receiving the medication for an adequate period of time, have achieved optimal response, and continued favorable outcomes are expected UNLESS the medication was initially selected solely due to the availability of a drug sample or a coupon card and the member does not otherwise meet the definition of “stable)”. • The plan-preferred medication is not in the best interest of the member because it will likely cause a significant barrier to the member’s adherence or to compliance with the member’s plan of care, will likely worsen a comorbid condition of the member, or will likely decrease the member’s ability to achieve or maintain reasonable functional ability in performing daily activities.

Postherpetic neuralgia (PHN) in adults: A. The member has a documented diagnosis of PHN B. When requesting coverage of a brand medication for which an A/B rated generic is available, coverage will be provided when there is sufficient evidence that the use of the A/B rated generic equivalent has resulted in inadequate results C. Coverage will be provided when the member has experienced intolerance or therapeutic failure with TWO of the plan-preferred medications first (pregabalin AND one of the following: gabapentin, topical lidocaine, amitriptyline, or nortriptyline) D. Coverage will be provided when the member has experienced intolerance or therapeutic failure with TWO of the plan-preferred medications first (gabapentin, topical lidocaine, amitriptyline, and nortriptyline) E. When at least ONE of the following criteria have been met: • The plan-preferred medications are contraindicated or will likely cause an adverse reaction by or physical or mental harm to the member. • The plan-preferred medications are expected to be ineffective based on the known clinical history and conditions of the member and the member’s prescription drug regimen. • The member has tried the plan-preferred medications or another prescription drug in the same pharmacologic class or with the same mechanism of action and such prescription drug was discontinued due to lack of efficacy of effectiveness, diminished effect, or an adverse event. • The member is stable on the medication selected by their healthcare professional for the medical condition under consideration (where “stable” is defined as receiving the medication for an adequate period of time, have achieved optimal response, and continued favorable outcomes are expected UNLESS the medication was initially selected solely due to the availability of a drug sample or a coupon card and the member does not otherwise meet the definition of “stable)”. • The plan-preferred medication is not in the best interest of the member because it will likely cause a significant barrier to the member’s adherence or to compliance with the member’s plan of care,

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Drug Therapy Guidelines Lyrica CR® (pregabalin ER) Last Review Date: 9/2020

will likely worsen a comorbid condition of the member, or will likely decrease the member’s ability to achieve or maintain reasonable functional ability in performing daily activities.

IV. Quantity Limitations

Coverage is available for up to 30 tablets per month.

Coverage for increased quantities is determined through the prior authorization process using the following criteria: • Member meets coverage criteria for Lyrica CR as outlined in Section III AND • Member is switching from immediate-release Lyrica/ pregabalin to Lyrica CR and requires a dose of Lyrica CR that will require multiple ER tablets per day as recommended by the FDA approved prescribing information (see Table 1 below)

Table 1: Conversion from Lyrica / pregabalin Capsules or Oral Solution to Lyrica CR Lyrica / pregabalin Total Daily Dose Lyrica CR Dose 75mg daily 82.5mg daily 150mg daily 165mg daily 225mg daily 247.5mg daily 300mg daily 330mg daily 450mg daily 495mg daily 600mg daily 660mg daily

V. Coverage Duration

Coverage is available for 12 months and may be renewed.

VI. Coverage Renewal Criteria

Coverage can be renewed based upon the following criteria: • Clinical response or remission of disease is maintained with continued use AND • Absence of unacceptable toxicity from the drug

VII. Billing/Coding Information

Lyrica CR is available as 82.5mg, 165mg, and 330mg extended-release tablets.

VIII. Summary of Policy Changes

• 6/1/18: new policy • 8/15/18: added diagnosis-specific preferred medication trials to coverage criteria, added quantity limits • 11/1/18: no policy changes • 11/15/19: no policy changes Page 3 of 4

Drug Therapy Guidelines Lyrica CR® (pregabalin ER) Last Review Date: 9/2020

• 1/1/21: no policy changes

IX. References

1. Lyrica CR® (package insert). Pfizer distributed by Parke-Davis, a Division of Pfizer, New York NY; 6/2020. 2. Pregabalin. In: IBM Micromedex® DRUGDEX® (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/. Accessed 7/2019. 3. Pregabalin. Clinical Pharmacology, accessed online 8/2020. www.clinicalpharmacology.com. Elsevier/Gold Standard. 4. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011; 76:1758. 5. Feldman E, McCulloch D. Treatment of diabetic neuropathy. In: UpToDate, Shefner, Jeremy (Ed), UpToDate, Waltham, MA, April 2018. 6. Bajwa Z, Ortega E. Postherpetic neuralgia. In: UpToDate, Shefner, Jeremy (Ed), UpToDate, Waltham, MA, April 2018. 7. Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010; 17:1113.

The Plan fully expects that only appropriate and medically necessary services will be rendered. The Plan reserves the right to conduct pre-payment and post-payment reviews to assess the medical appropriateness of the above-referenced therapies.

The preceding policy applies only to members for whom the above named pharmacy benefit medications are included on their covered formulary. Members with closed formulary benefits are subject to trying all appropriate formulary alternatives before a coverage exception for a non-formulary medication will be considered.

The preceding policy is a guideline to allow for coverage of the pertinent medication/product, and is not meant to serve as a clinical practice guideline.

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