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Prior Authorization Protocol
PROVIGILR (modafinil), NUVIGILR (armodafinil)


NATL
Coverage of drugs is first determined by the memberís pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • To improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work disorder
  2. Health Net Approved Indications and Usage Guidelines:
    Narcolepsy:
    • Confirmed diagnosis of narcolepsy (chart note documentation of the following is required):
      • The sleep disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or another general medical condition
    AND
    • The presence of either:
      • 1. Cataplexy, accompanied by irresistible attacks of refreshing sleep that occur daily over at least 3 months

    OR

      • 2. Polysomnogram indicating or suggesting narcolepsy, including at least one of the following:
        • Sleep latency < 10 minutes
        • REM sleep latency < 20 minutes (presence of a sleep-onset REM period)
        • A Multiple Sleep Latency Test (MSLT) demonstrates a mean sleep latency of < 5 minutes PLUS two or more sleep-onset REM periods

    OR

    Obstructive Sleep Apnea (OSA):
    • Presence of residual excessive sleepiness (ES) defined as an Epworth Sleepiness Scale score > 10

    AND

    • Documentation that the patient has been using Continuous Positive Airway Pressure for at least 2 months and is using it on average > 4 hours per night
    OR

    Shift Work Disorder (SWD):
    • Confirmed diagnosis of SWD (chart note documentation including ALL of the following is required):
      • Patient has a primary complaint of insomnia or excessive sleepiness
      • Primary complaint is temporally associated with a work period (usually night work) that occurs during the habitual sleep phase
      • Sleep disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning
      • Sleep disturbance does not occur exclusively during the course of another sleep disorder or other mental disorder
      • Sleep disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition
      • Patient is symptomatic for at least 3 months
    OR

    Multiple Sclerosis-related Fatigue:
    • Diagnosis of multiple sclerosis

    AND

    • Mild fatigue: failure or clinically significant adverse effects to amantadine

    OR

    • Moderate to severe fatigue

    AND

    • The fatigue is not due to the direct physiological effects of a substance (e.g., a benzodiazepine, sedating antidepressant, or sleep agent - see General Information section for examples)
  3. Coverage is Not Authorized For:
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature
  4. General Information:
    • Nuvigil is the R-enantiomer of Provigil. The apparent terminal half-life of Nuvigil is approximately 15 hours. For comparison, the effective elimination half-life of Provigil after multiple doses is also 15 hours
    • Excessive Daytime Sleepiness (EDS) associated with Parkinson's disease (PD): The literature supporting the use of Provigil for this indication consists of 2 randomized trials and one open-label study, all with small sample sizes and improvement in mostly subjective scales of sleepiness. One additional randomized trial found that Provigil did not significantly improve EDS compared to placebo. Based on the available data, the routine use of Provigil for the treatment of EDS associated with PD is not supportable at this time
    • The Multiple Sleep Latency Test (MSLT) is a series of recordings to monitor sleep patterns designed to assess the degree of sleepiness
    • Continuous Positive Airway Pressure (CPAP) is considered the most effective nonsurgical treatment for the alleviation of snoring and/or OSA
    • For multiple sclerosis-related fatigue: examples of potentially sedating antidepressants include, but are not limited to: paroxetine (PaxilR, Paxil CRR), fluvoxamine (LuvoxR), mirtazapine (RemeronR), trazodone, and nefazodone
    • Cephalon filed an sNDA for modafinil for the treatment of ADHD under the brand name of SparloR. The FDA deemed the medication non-approvable for the treatment of ADHD in children and adolescents up to 17 years of age due to safety concerns over high rates of serious adverse dermatological reactions
    • Overall results of studies evaluating the use of Provigil for ADHD support the efficacy of Provigil for this indication, especially in pediatric patients. However, due to the potential for serious rash, and especially in light of the FDA's no-approval of Sparlon citing this as one of the reasons, the routine use of Provigil for ADHD cannot be endorsed at this time.
    • For depression: The lack of data supporting the use of Provigil for depression is consistent with findings from two evidence-based review articles, both of which state that there are "mixed findings". The author of one review assigns Provigil a "C" level of evidence with a caveat for level "B" evidence for SSRI non-responders with fatigue and/or hypersomnolence.
    • Provigil's warning section contains a bolded warning that reads in part, "Modafinil is not approved for use in pediatric patients for any indication." Pediatric is later defined as less than 17 years of age
    • Nuvigil's warning section states, "Armodafinil has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication." Pediatric is later defined as less than 17 years of age
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    Amphetamine salts (AdderallR)

    Narcolepsy
    5-60 mg PO QD

    60 mg

    methylphenidate (RitalinR, Ritalin SRR, MethylinR)

    Narcolepsy
    10-60 mg PO QD

    60 mg

    dextroamphetamine (DexedrineR, DextrostatR, Dexedrine SpansuleR)

    Narcolepsy
    5-60 mg PO QD

    60 mg

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Provigil

    Narcolepsy
    200 mg PO QD
    Obstructive Sleep Apnea
    200 mg PO QD
    Shift Work Disorder
    200 mg PO QD
    Multiple Sclerosis
    100-200 mg PO QD
    Narcolepsy
    Length of benefit
    Obstructive Sleep Apnea
    Initial authorization of 12 months.
    Reauthorization for additional 12 months if patient continues CPAP on average > 4 hours/night while on Provigil.
    Shift Work Disorder
    Initial authorization of 12 months.
    Reauthorization for additional 12 months with chart note documentation of continuous therapeutic response.
    Multiple Sclerosis
    Initial authorization of 12 months.
    Reauthorization for additional 12 months with chart note documentation of continuous therapeutic response.

    Nuvigil

    Narcolepsy
    150-250 mg PO QD
    Obstructive Sleep Apnea
    150-250 mg PO QD
    Shift Work Disorder
    150 mg PO QD
    Multiple Sclerosis
    150-250 PO QD
    Narcolepsy
    Length of benefit
    Obstructive Sleep Apnea
    Initial authorization of 12 months.
    Reauthorization for additional 12 months if patient continues CPAP on average > 4 hours/night while on Nuvigil.
    Shift Work Disorder
    Initial authorization of 12 months.
    Reauthorization for additional 12 months with chart note documentation of continuous therapeutic response.
    Multiple Sclerosis
    Initial authorization of 12 months.
    Reauthorization for additional 12 months with chart note documentation of continuous therapeutic response.
  7. Product Availability:

    Provigil: 100 mg, 200 mg tablets
    Nuvigil: 50 mg, 150 mg, 200 mg, 250 mg tablets

  8. References:
    1. Provigil [Prescribing Information] North Wales, PA: Cephalon, Inc.: January 2015.
    2. Nuvigil [Prescribing Information] North Wales, PA: Cephalon, Inc.; April 2015.
    3. Practice parameters for the treatment of narcolepsy: an update for 2000. Sleep. 2001;24 (4):451-466.
    4. US Modafinil in Narcolepsy Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology. 2000;54(5):1166-1175.
    5. Pack AI, Black JE, Schwartz RL, Matheson JK. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med. 2001;164:1675-1681.
    6. Kingshott RN, Vennelle M, Coleman EL, et al. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep/apnea/hypopnea syndrome. Am J Resp Crit Care Med. 2001;163:918-923.
    7. Rammohan KW, et al. Efficacy and safety of modafinil (ProvigilR) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. J Neurol Neurosurg Psychiatry. 2002;72:179-183.
    8. Adler CH, et al. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinsons disease. Movement Disorders. 2003;18(3):287-293.
    9. Hogl B, et al. Modafinil for the treatment of daytime sleepiness in Parkinsons disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial. Sleep. 2002;25(8):62-66.
    10. Nieves AV, Lang AE. Treatment of excessive daytime sleepiness in patients with Parkinsons disease with modafinil. Clinical Neuropharmacology. 2002;25(2):111-114.
    11. Ondo WG, et al. Modafinil for daytime somnolence in Parkinsons disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry 2005:76:1636-1639.
    12. Stankoff B, Waubant E, Confavreux C, et al. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology. 2005;64(7):1139-1143.
    13. Roth T, et al. Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: A 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults. Clin Ther. 2005;28(5):689-706.
    14. Harsh JR, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006 Apr;22(4):761-774.
    15. Hirshkowitz M, et al. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respir Med. 2007 Mar;101(3):616-627.
    16. Roth T, et al. Randomized, double-blind placebo-controlled study of armodafinil for the treatment of excessive sleepiness associated with chronic shift work sleep disorder [Poster Presentation] Presented at the 44th Annual Meeting of the American College of Neuropsychopharmacology, Waikaloa, HI, December 11-15, 2005.
    17. Rugino TA et al. Modafinil in children with Attention Deficit Hyperactivity Disorder. Ped Neuro 2003; 29(2):136-42.
    18. Biederman J, et al. A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study. J Clin Psychiatry. 2006;67:727-35.
    19. Boellner SW, et al. Modafinil in children and adolescents with attention-deficit/hyperactivity disorder: a preliminary 8-week, open-label study. Curr Med Res Opinion. 2006;22(12):2457-65.
    20. Biederman J, et al. Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, flexible-dose study. Pediatrics. 2005;116:777-84.
    21. Greenhill LL, et al. A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2006;45(5):503-11.
    22. Swanson JM, et al. Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation. J Clin Psychiatry. 2006;67:137-47.
    23. Thase ME. Therapeutic alternatives for difficult-to-treat depression: a narrative review of the state of the evidence. CNS Spectrums. 2004;9(11):808-821.
    24. Lam JY, et al. Modafinil augmentation for residual symptoms of fatigue in patients with a partial response to antidepressants. Ann Pharmacother. 2007;41:1005-12.
    25. DRUGDEXR System [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 2, 2015.
    26. Provigil. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 2, 2015.
    27. Nuvigil. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 2, 2015.
    28. Clinical Pharmacology Website. Available at: http://www.clinicalpharmacology-ip.com/Default.aspx. Accessed July 2, 2015.
    29. Health Net Clinical Pharmacy Advisory Committee Provigil Position Statement, April 2013.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.