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Amantadine Extended Release Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1090

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

POLICY REVIEW CYCLE                                                                                                                                                                           

Effective Date

Date of Origin 

4/1/2023

4/1/2018

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Gocovri®

(amantadine ER)

Extended-release capsule

Treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications

 

Adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes

1

Osmolex ER®

(amantadine ER)

Extended-release tablet

Treatment of:

  • Parkinson’s disease
  • Drug-induced extrapyramidal reactions in adult patients

3

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

CLINICAL RATIONALE

Parkinson's Disease

Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disorder resulting from the loss of dopamine-producing cells of the substantia nigra.(5) The four primary symptoms of PD are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination.(2,5) Other symptoms may include depression and other emotional changes; difficulty swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions.(2,5) There are currently no blood or laboratory tests that have been proven to help in diagnosing PD. Therefore, diagnosis is based on medical history and neurological examinations. The disease is difficult to accurately diagnose, thus doctors may request (and sometimes repeat) brain scans or laboratory tests in order to rule out other diseases.(7) However, noninvasive diagnostic imaging, such as positron emission tomography (PET) can support a doctor's diagnosis. Conventional methods for diagnosis include the following:(11)

  • The presence of two of the three primary symptoms
  • The absence of other neurological signs upon examination
  • No history of other possible causes of parkinsonism, such as the use of tranquilizer medications, head trauma or stroke
  • Responsiveness to Parkinson's medications, such as levodopa

Management of PD requires consideration of patient’s symptoms, age, stage of disease, degree of functional disability, and level of physical activity and production. A comprehensive care plan should be in place, as agreed to by the person, their family members, and specialist and secondary healthcare providers.(5) Treatment of early stage PD typically includes levodopa, dopamine agonists (e.g., bromocriptine, pramipexole, ropinirole, rotigotine), and monoamine oxidase B inhibitors (MAO-B; e.g., rasagiline, selegiline). Treatment as PD advances includes additional agents such as anticholinergic agents, catechol-O-methyltransferase (COMT) inhibitors, and amantadine.(2,4,5)

Levodopa is converted into dopamine by the body, and therefore helps to replace the dopamine that is lost as part of PD. It is currently the first choice (and thus the most commonly prescribed) treatment for the motor symptoms of PD.(4,5) Dopamine agonists mimic the role of dopamine in the brain but aren’t as effective as levodopa, thus typically reserved for those whose motor symptoms do not impact quality of life. Dopamine agonists may be employed as either monotherapy in early PD or in combination with other antiparkinsonian drugs for the treatment of more advanced disease.(4,5) MAO-B inhibitors block an enzyme that metabolizes dopamine, thereby increasing the amount of dopamine available in the brain. MAO-B inhibitors are typically added as adjunct to levodopa if motor fluctuations develop despite optimal levodopa therapy, and/or if dyskinesia has developed.(5,7)

Although initially effective, dopaminergic therapies are eventually complicated by the development of motor complications such as motor fluctuations and dyskinesia. Motor fluctuations include “on” and “off” states, where patients experience periods of when the medication wears off and the PD symptoms reappear. “Wearing off”, characterized by reemergence of symptoms near the end of the dose interval, is the first and most commonly encountered motor fluctuation in patients with PD. Dyskinesia is defined as drug-induced involuntary movements including chorea and dystonia. Motor complications are usually addressed with levodopa adjustments and the addition of adjunctive medications. Motor fluctuations and dyskinesia can be resistant to medical therapy.(8)

Amantadine increases dopamine release and inhibits dopamine uptake. Amantadine may be considered for patients with dyskinesias not adequately managed by modifying existing therapy.(5) Amantadine also has shown additional benefit in reducing “off” time.(8,9) Until there is a comparison between ER formulations of amantadine and generic amantadine, it is uncertain whether the potential benefits justify the cost.(10)

Efficacy

Amantadine for the treatment of dyskinesia in patients with PD was assessed in two randomized, double-blind, placebo-controlled efficacy trials. In both studies, the primary efficacy endpoint was the change in total score of the Unified Dyskinesia Rating Scale (UDysRS) between baseline and Week 12. In both studies, a significant decrease in mean UDysRS total score (reduction in dyskinesia) was observed at Week 12 compared to placebo.(1) The effect of amantadine IR formulation on dyskinesias has been examined in multiple small studies. In a 6-week, placebo-controlled, double-blind, crossover study, PD patients (n=18) receiving amantadine IR (average dose of 350 mg/day) had around a 60% reduction in dyskinesia compared with placebo.(6) The authors conducted a follow-up study and found that 13 of 17 patients originally treated in the short-term study had a 56% reduction in dyskinesia scores at 1 year.(7)

In a randomized, double-blind, placebo-controlled trial, 126 patients with levodopa-induced dyskinesia were randomly assigned to ER amantadine (274 mg capsule at bedtime) or placebo. At 12 weeks compared with placebo, the active drug reduced the duration, severity, and impact of dyskinesia as measured by the UDysRS. In addition, treatment with the active drug reduced mean "off" time by 0.6 hours, while mean "off" time increased 0.3 hours with placebo. The most common significant adverse effects were mild and reversible visual hallucinations.(8) A subsequent trial with 77 patients reported similar results at 12 weeks, demonstrating reduced severity of dyskinesia and reduced mean "off" time by 0.5 hours, while mean "off" time increased 0.6 hours with placebo.(9)

Safety

Gocovri and Osmolex ER are both contraindicated in patients with end-stage renal disease (i.e., creatinine clearance below 15 mL/min/1.73 m2).(1,3)

REFERENCES                                                                                                                                                                            

Number

Reference

1

Gocovri prescribing information. Adamas Pharma, LLC. January 2021.

2

National Institute of Neurological Disorders and Stroke. Parkinson’s Disease Information Page. Updated April 2020. Available at: www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Information-Page.

3

Osmolex ER prescribing information. Vertical Pharmaceuticals LLC. January 2020.

4

Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and Movement Disorder Society Evidence-Based Medicine Review: Update on Treatments for the Motor Symptoms of Parkinson’s Disease. Mov Disord. 2018 Aug;33(8):1248-1266.

5

National Institute for Health and Care Excellence (NICE). Guideline on Parkinson’s Disease in Adults (NG71). July 2017. Available at: https://www.nice.org.uk/guidance/ng71.

6

Verhagen Metman L, Del Dotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN. Amantadine as Treatment for Dyskinesias and Motor Fluctuations in Parkinson’s Disease. Neurology. 1998;50(5):1323–1326.

7

Verhagen Metman L, Del Dotto P, LePoole K, Konitsiotis S, Fang J, Chase TN. Amantadine for Levodopa-Induced Dyskinesias: A 1-Year Follow-Up Study. Arch Neurol. 1999;56:1383-1386.

8

Pahwa R, Tanner CM, Hauser RA, et al. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE-LID Study). JAMA Neurol. 2017 Aug;74(8):941-949.

9

Oertel W, Eggert K, Pahwa R, et al. Randomized, Placebo-Controlled Trial of ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dysinesia in Parkinson’s Disease (EASE-LID-3). Mov Disord. 2017 Dec;32(12):1701-1709.

10

Shukla AW. Extended-Release Amantadine – A Smart Pill for Treatment of Levodopa-Induced Dyskinesia but Does the Evidence Justify the Cost? JAMA Neurol. 2017;74(8):904-905.

11

American Association of Neurological Surgeons. Parkinson’s Disease. Updated 2022. Available at: https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Parkinsons-Disease.

 

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)

Target Generic Agent(s)

Strength

Targeted MSC

Available MSC

Preferred Status

Effective Date

Gocovri

amantadine hcl cap er

137 MG ; 68.5 MG

M ; N ; O ; Y

N

Osmolex er

amantadine hcl tab er

129 MG ; 193 MG ; 258 MG

M ; N ; O ; Y

N

Osmolex er

amantadine hcl tab er

129 MG

M ; N ; O ; Y

N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

QL Amount

Dose Form

Days Supply

Duration

Addtl QL Info

Allowed Exceptions

Targeted NDCs When Exclusions Exist

Effective Date

Gocovri

Amantadine HCl Cap ER 24HR 137 MG (Base Equivalent)

137 MG

60.0

CAPS

30

Days

Gocovri

Amantadine HCl Cap ER 24HR 68.5 MG (Base Equivalent)

68.5 MG

30.0

CAPS

30

Days

Osmolex er

Amantadine HCl Tab ER 24HR 129 MG (Base Equivalent)

129 MG

30.0

TABS

30

Days

Osmolex er

Amantadine HCl Tab ER 24HR 193 MG (Base Equivalent)

193 MG

30.0

TABS

30

Days

Osmolex er

Amantadine HCl Tab ER 24HR 258 MG (Base Equivalent)

258 MG

30.0

TABS

30

Days

Osmolex er

Amantadine HCl Tab ER 24HR Pak 129 MG & 193 MG (322 MG Dose)

129 MG

1.0

BOX

30

Days

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Gocovri

amantadine hcl cap er

137 MG ; 68.5 MG

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

Osmolex er

amantadine hcl tab er

129 MG ; 193 MG ; 258 MG

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

Osmolex er

amantadine hcl tab er

129 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

Gocovri

Amantadine HCl Cap ER 24HR 137 MG (Base Equivalent)

137 MG

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

Gocovri

Amantadine HCl Cap ER 24HR 68.5 MG (Base Equivalent)

68.5 MG

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

Osmolex er

Amantadine HCl Tab ER 24HR 129 MG (Base Equivalent)

129 MG

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

Osmolex er

Amantadine HCl Tab ER 24HR 193 MG (Base Equivalent)

193 MG

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

Osmolex er

Amantadine HCl Tab ER 24HR 258 MG (Base Equivalent)

258 MG

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

Osmolex er

Amantadine HCl Tab ER 24HR Pak 129 MG & 193 MG (322 MG Dose)

129 MG

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

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. ONE of the following:
    1. The requested agent is Gocovri AND ALL of the following:
      1. The patient has a diagnosis of Parkinson’s disease AND
      2. ONE of the following:
        1. The requested agent will be used for the treatment of dyskinesia OR
        2. The requested agent will be used for the adjunctive treatment in patients experiencing “off” episodes AND
      3. BOTH of the following:
        1. The patient is currently treated with levodopa-based therapy AND
        2. The patient will continue levodopa-based therapy in combination with the requested agent OR
    2. The requested agent is Osmolex ER AND ONE of the following:
      1. The patient has a diagnosis of Parkinson’s disease OR
      2. The patient has a diagnosis of drug-induced extrapyramidal reactions AND the prescriber has assessed and adjusted, if applicable, any medications known to cause extrapyramidal symptoms OR
    3. The patient has another FDA approved indication for the requested agent AND
  2. ONE of the following:
    1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
    2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND
  3. ONE of the following:
    1. The patient has tried and had an inadequate response to immediate release amantadine OR
    2. The patient has an intolerance or hypersensitivity to immediate release amantadine that is not expected to occur with the requested agent OR
    3. The patient has an FDA labeled contraindication to immediate release amantadine that is not expected to occur with the requested agent AND
  4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

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

 

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND
  2. If the requested agent is Gocovri, the patient will be using levodopa-based therapy in combination with the requested agent AND
  3. The patient has had clinical benefit with the requested agent AND
  4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  5. The patient does NOT have any FDA labeled contraindications to the requested agent

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

QL with PA

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. ALL of the following:
    1. The requested quantity (dose) is greater than the program quantity limit AND
    2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
    3. 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. ALL of the following:
    1. The requested quantity (dose) is greater than the program quantity limit AND
    2. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication AND
    3. The prescriber has provided information in support of therapy with a higher dose for the requested indication

Length of Approval: 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 _ Amantadine Extended Release Prior Authorization with Quantity Limit _ProgSum_ 4/1/2023