Pharmacy Prior Authorization Criteria

Provigil (modafinil), Nuvigil (armodafinil)

Indications for Prior Authorization

Provigil (modafinil)

• For diagnosis of Narcolepsy
  Indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy. [1]

• For diagnosis of Obstructive sleep apnea (OSA)
  Indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA).

  Limitations of Use: Provigil is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating and during treatment with Provigil for excessive sleepiness. [1]

• For diagnosis of Shift work disorder (SWD)
  Indicated to improve wakefulness in adult patients with excessive sleepiness associated with shift work disorder. [1]

• For diagnosis of Fatigue due to multiple sclerosis (MS)
  In a double-blind, placebo-controlled study, treatment with modafinil significantly improved fatigue symptoms compared with placebo in patients with multiple sclerosis (MS) [2,3]

• For diagnosis of Adjunctive therapy for the treatment of major depressive disorder (MDD) or bipolar disorder
  In a meta-analysis of 4 MDD RCTs and 2 bipolar depression RCTs, adjunctive treatment with modafinil improved overall depression scores, remission rates, and fatigue symptoms. [2,4]

Nuvigil (armodafinil)

• For diagnosis of Narcolepsy
  Indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy. [5]

• For diagnosis of Obstructive sleep apnea (OSA)
  Indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA).

  Limitations of Use: Nuvigil is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating Nuvigil for excessive sleepiness. [5]

• For diagnosis of Shift work disorder (SWD)
  Indicated to improve wakefulness in adult patients with excessive sleepiness associated with shift work disorder. [5]

Criteria

Generic armodafinil, Generic modafinil, Brand Nuvigil, or Brand Provigil

Prior Authorization (Initial Authorization)

Length of Approval: 6 Months [A,1,5]
For diagnosis of Obstructive Sleep Apnea (OSA)

• Diagnosis of obstructive sleep apnea defined by one of the following: [6]
• 15 or more obstructive respiratory events per hour of sleep confirmed by a sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible) [6,7,B,C]
OR
• Both of the following: [6,7,B,C]
• 5 or more obstructive respiratory events per hour of sleep confirmed by a sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible)
AND
• One of the following symptoms:
• Unintentional sleep episodes during wakefulness
• Daytime sleepiness
• Unrefreshing sleep
• Fatigue
• Insomnia
• Waking up breath holding, gasping, or choking
• Loud snoring
• Breathing interruptions during sleep
AND
• Both of the following:
• Standard treatments for the underlying obstruction (e.g., continuous positive airway pressure [CPAP], bi-level positive airway pressure [BPAP], etc.) have been used for 3 months or longer [2]
AND
• Patient is fully compliant with standard treatment(s) for the underlying obstruction.
AND
• Trial and failure or intolerance to modafinil (applies to Provigil only)
AND
• Trial and failure or intolerance to armodafinil (applies to Nuvigil only)

Generic armodafinil, Generic modafinil, Brand Nuvigil, or Brand Provigil

Prior Authorization (Reauthorization)

Length of Approval: 6 Months [A,1,5]
For diagnosis of Obstructive Sleep Apnea (OSA)

• Patient continues to be fully compliant on concurrent standard treatment(s) for the underlying obstruction (e.g., CPAP, BPAP, etc.)
AND
• Patient is experiencing relief of symptomatic hypersomnolence with use

Generic modafinil, Brand Provigil

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Fatigue due to MS (off-label) [2,3,8,D]

• Diagnosis of multiple sclerosis (MS)
AND
• Patient is experiencing fatigue
AND
• Used in combination with standard educational therapies (e.g., psychoeducation, behavioral programs, scheduled naps, additional non-pharmacological therapies, etc.)
AND
• Trial and failure or intolerance to modafinil (applies to Provigil only)

Generic modafinil, Brand Provigil

Prior Authorization (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Fatigue due to MS (off-label) [2,3,8,D]

• Patient is experiencing relief of fatigue with therapy
AND
• Used in combination with standard educational therapies (e.g., psychoeducation, behavioral programs, scheduled naps, additional non-pharmacological therapies, etc.)

Generic armodafinil, Generic modafinil, Brand Nuvigil, or Brand Provigil

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Narcolepsy

• Diagnosis of narcolepsy as confirmed by sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible) [6,9-11,E-G]
AND
• Trial and failure or intolerance to modafinil (applies to Provigil only)
AND
• Trial and failure or intolerance to armodafinil (applies to Nuvigil only)

Generic armodafinil, Generic modafinil, Brand Nuvigil, or Brand Provigil

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Narcolepsy

• Patient demonstrates positive clinical response to therapy

Generic armodafinil, Generic modafinil, Brand Nuvigil, or Brand Provigil

Prior Authorization (Initial Authorization)

Length of Approval: 6 Months [A,1,5]
For diagnosis of Shift Work Disorder (SWD)

• Diagnosis of Shift Work Disorder confirmed by one of the following: [6,12]
• Symptoms of excessive sleepiness or insomnia, for at least 3 months, which is temporally associated with a work period (usually night work) that occurs during the habitual sleep phase
OR
• Sleep study demonstrating loss of a normal sleep wake pattern (i.e., disturbed chronobiologic rhythmicity)
AND
• Confirmation that no other medical conditions or medications are causing the symptoms of excessive sleepiness or insomnia [6,12]
AND
• Trial and failure or intolerance to modafinil (applies to Provigil only)
AND
• Trial and failure or intolerance to armodafinil (applies to Nuvigil only)

Generic armodafinil, Generic modafinil, Brand Nuvigil, or Brand Provigil

Prior Authorization (Reauthorization)

Length of Approval: 6 Months [A,1,5]
For diagnosis of Shift Work Disorder (SWD)

• Patient demonstrates positive clinical response to therapy

Generic modafinil, Brand Provigil

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Adjunctive therapy for the treatment of major depressive disorder or bipolar depression (off-label) [2,4]

• Treatment-resistant depression, defined as both of the following:
• Diagnosis of one of the following [4]:
• Major depressive disorder (MDD)
• Bipolar depression
AND
• History of failure, contraindication, or intolerance to at least two antidepressants from different classes (e.g., SSRIs, SNRIs, bupropion)
AND
• Used as adjunctive therapy
AND
• Trial and failure or intolerance to modafinil (applies to Provigil only)

Generic modafinil, Brand Provigil

Prior Authorization (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Adjunctive therapy for the treatment of major depressive disorder or bipolar depression (off-label) [2,4]

• Patient demonstrates positive clinical response to therapy
AND
• Used as adjunctive therapy

Generic armodafinil 50 mg, Generic modafinil 100 mg, Brand Nuvigil 50 mg, or Brand Provigil 100 mg

Authorization will be issued for the length of therapy based on indication, except for titration purposes (Narcolepsy: 12 months, All other indications: 6 months). Not to exceed maximum FDA-approved dose.

Quantity Limit

• One of the following:
• Quantity limit override requests must involve an FDA-approved indication.
OR
• Quantity limit override requests involving off-label indications must meet off-label guideline requirements.
AND
• One of the following:
• For titration purposes (one time authorization)
OR
• Requested strength/dose is commercially unavailable
OR
• Patient is on a dose alternating schedule

Generic modafinil 200 mg, Brand Provigil 200 mg

Authorization will be issued for the length of therapy based on indication (Narcolepsy: 12 months, All other indications: 6 months). **NOTE: Published biomedical literature may be used as evidence to support safety and additional efficacy at higher than maximum doses for the diagnosis provided.

Quantity Limit

• One of the following:
• Quantity limit override requests must involve an FDA-approved indication.
OR
• Quantity limit override requests involving off-label indications must meet off-label guideline requirements.
AND
• History of inadequate response to Provigil 200 mg/day
AND
• One of the following:**
• Higher dose or quantity is supported in the dosage and administration section of the manufacturer's prescribing information
OR
• Higher dose or quantity is supported by one of following compendia:
• American Hospital Formulary Service Drug Information
• Micromedex DRUGDEX System

Generic armodafinil 150 mg, Brand Nuvigil 150 mg, Generic armodafinil 200 mg, Brand Nuvigil 200 mg, Generic armodafinil 250 mg, or Brand Nuvigil 250 mg

Authorization will be issued for the length of therapy based on indication, except for titration purposes (Narcolepsy: 12 months, All other indications: 6 months). Not to exceed maximum FDA-approved dose. NOTE: Published biomedical literature may be used as evidence to support safety and additional efficacy at higher than maximum doses for the diagnosis provided.

Quantity Limit

• One of the following:
• Quantity limit override requests must involve an FDA-approved indication.
OR
• Quantity limit override requests involving off-label indications must meet off-label guideline requirements.
AND
• One of the following**
• Higher dose or quantity is supported in the dosage and administration section of the manufacturer's prescribing information
OR
• Higher dose or quantity is supported by one of following compendia
• American Hospital Formulary Service Drug Information
• Micromedex DRUGDEX System

Brand Provigil 200mg, Generic modafinil 200mg

**Requests for greater than twice-daily dosing must be reviewed using the Quantity Limit General Administrative Guideline.

Quantity Limit

Length of Approval: 12 Month(s)
For diagnosis of Narcolepsy: Twice-daily (BID) Therapy**

• Diagnosis of narcolepsy as confirmed by sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible) [3,6,9-11,E-G]
AND
• One of the following
• Clinical research in two articles from major peer reviewed medical journals that present data supporting requested dose as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer-reviewed medical journal
• Trial and inadequate response to once daily treatment
OR
• A once daily treatment is not appropriate to treat the patient’s condition
AND
• Requested dose does not exceed maximum dose range found in labeling or supported by one of the following off label compendia for the requested product:
• American Hospital Formulary Service Drug Information
• Micromedex Drug System
• Clinical research in two articles from major peer reviewed medical journals that present data supporting requested dose as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer-reviewed medical journal

P & T Revisions

2024-11-01, 2023-10-03, 2023-08-23, 2022-12-15, 2022-10-09, 2021-10-21, 2021-09-28, 2021-05-25, 2020-12-03, 2020-11-04, 2020-09-02, 2020-03-30, 2019-10-29, 2019-08-19

References

1. Provigil Prescribing Information. Teva Pharmaceuticals USA, Inc. North Wales, PA. July 2019.
2. Drugdex Evaluations: Modafinil. Thomson MICROMEDEX Web site. http://www.thomsonhc.com. Accessed October 11, 2024.
3. Lange R, Volkmer M, Heesen C, et al. Modafinil effects in multiple sclerosis patients with fatigue. J Neurol 2009 Apr;256(4):645-650.
4. Goss AJ, Kaser M, Costafreda SG, et al. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry 2013 Nov;74(11):1101-7.
5. Nuvigil Prescribing Information. Teva Pharmaceuticals USA, Inc. North Wales, PA. July 2019.
6. Sateia MJ. International classification of sleep disorders - third edition: highlights and modifications. CHEST. 2014 Nov;146(5):1387-94.
7. Epstein LJ, Kristo D, Strollo PJ, et al. Clinical Guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009 Jun 15;5(3):263-76.
8. Per clinical consult with multiple sclerosis specialist, April 24, 2013.
9. Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. Journal of Clinical Sleep Medicine. 2021 Sep;17(9):1881-93.
10. Morgranthaler TI, Kapur VK, Brown T, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin: An American Academy of Sleep Medicine report. Sleep. 2007 Dec;30(12)1705-11.
11. UpToDate. Clinical features and diagnosis of narcolepsy. Available by subscription at: https://www.uptodate.com. Accessed October 12, 2024.
12. UpToDate. Sleep-wake disturbances in shift workers. Available by subscription at: https://www.uptodate.com. Accessed October 12, 2024.
13. Cleveland Clinic. Sleep Glossary. Available at: http://my.clevelandclinic.org/disorders/sleep_disorders/hic_sleep_glossary.aspx. Accessed September 5, 2019.
14. Strohl, K. Obstructive Sleep Apnea. Available at https://www.msdmanuals.com/professional/pulmonary-disorders/sleep-apnea/obstructive-sleep-apnea. Accessed October 21, 2021.
15. Pavwoski, P., Shelgikar, V. Treatment Options for Obstructive Sleep Apnea. Neurol Clin Pract 2017 Feb; 7(1): 77-85. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964869/ . Accessed October 21, 2021.
16. Pacheco, D. Diagnosing Shift Work Disorder. Available at https://www.sleepfoundation.org/shift-work-disorder/diagnosis. Accessed October 21, 2021.
17. Suni, E. Narcolepsy. Available at https://www.sleepfoundation.org/narcolepsy. Accessed October 21, 2021.
18. Owens, A. Treatment-Resistant Depression: Why Depression Meds Don't Always Work. Available at https://www.psycom.net/treatment-resistant-depression. Accessed October 21, 2021.
19. DiSciullo, A., English, C. et al. Modafinil Induced Psychosis in a Patient with Bipolar 1 Depression. 2018 Oct. Available at https://doi.org/10.1155/2018/3732958. Accessed October 21, 2021
20. Carter, J. Fatigue in Patients With Multiple Sclerosis. 2018 July/Aug. Available at https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis. Accessed October 21, 2021
21. Provigil (Modafinil) for Fatigue in Multiple Sclerosis. Available at https://multiplesclerosisnewstoday.com/provigil-modafinil-fatigue-ms/. Accessed October 21, 2021.

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End Notes

1. The effectiveness of modafinil (greater than 12 weeks for obstructive sleep apnea or SWD) and the effectiveness of armodafinil in long-term use (greater than 12 weeks) have not been systematically evaluated in placebo-controlled trials. [1,5]
2. International Classification of Sleep Disorders (ICSD-3) diagnostic criteria for obstructive sleep apnea-hypopnea syndrome (OSAHS) include: One of the following: 1. Polysomnography (PSG) shows greater than or equal to 5 obstructive respiratory events per hour of sleep in a patient with one or more of the following: a. sleepiness, nonrestorative sleep, fatigue or insomnia symptoms b. waking up with breath holding, gasping or choking c. habitual snoring, breathing interruptions, or both noted by a bed partner or other observer d. hypertension, mood disorder, cognitive dysfunction, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, or type 2 diabetes mellitus 2. Greater than or equal to 15 obstructive respiratory events per hour of sleep, regardless of the presence of associated symptoms or comorbidities. In addition, the disorder is not explained by another current sleep disorder, medical or neurological disorder, medication use, or substance use disorder [6].
3. Examples of obstructive respiratory events include: obstructive and mixed apneas, hypopneas, or respiratory effort related arousals (RERA) [6].
4. Despite lack of consistent clinical evidence or statement/guideline from a United States professional society, use of modafinil for fatigue is considered the standard practice in MS patients [8]. The 2022 National Institute for Health and Care Excellence guidance on MS lists modafinil as an option for managing fatigue in adults with MS [3].
5. The American Academy of Sleep Medicine (AASM) guidelines list modafinil as a "standard" patient care strategy (generally accepted patient-care strategy that reflects a high degree of clinical certainty). [10] The use of modafinil for the treatment of narcolepsy is a strong recommendation. [9]
6. ICSD-3 diagnostic criteria for narcolepsy with cataplexy (narcolepsy type 1) include: 1. Daily periods of irrepressible need for sleep or daytime lapses into sleep (i.e., excessive daytime sleepiness) for at least 3 months. 2. One or both of the following: cataplexy and a mean sleep latency of less than or equal to 8 minutes and 2 or more sleep onset REM periods (SOREMPs) on a multiple sleep latency test (MSLT) performed using standard techniques (a SOREMP within 15 minutes of sleep onset on the preceding nocturnal polysomnogram may replace 1 of the SOREMPs on the MSLT); or cerebrospinal fluid (CSF) hypocretin-1 concentration is low (less than 110 pg/mL or one-third of the normative values with the same standardized assay). 3. Exclusion of alternative causes of chronic daytime sleepiness by history, physical exam, and polysomnography. Other conditions that cause chronic daytime sleepiness include insufficient sleep, untreated sleep apnea, periodic limb movements of sleep, and idiopathic hypersomnia (chronic sleepiness but without SOREMPs or other evidence of abnormal REM sleep). In addition, the effects of sedating medications should be excluded. [6,11]
7. ICSD-3 diagnostic criteria for narcolepsy without cataplexy (narcolepsy type 2) include: 1. Daily periods of irrepressible need for sleep or daytime lapses into sleep (i.e., excessive daytime sleepiness) for at least 3 months. 2. Cataplexy is absent 3. CSF hypocretin-1 levels, if measured, must not meet the narcolepsy type 1 criterion. 4. A mean sleep latency of less than or equal to 8 minutes and 2 or more SOREMPs on a MSLT performed using standard techniques (a SOREMP within 15 minutes of sleep onset on the preceding nocturnal polysomnogram may replace 1 of the SOREMPs on the MSLT). 5. Exclusion of alternative causes of chronic daytime sleepiness by history, physical exam, and polysomnography. Other conditions that cause chronic daytime sleepiness include insufficient sleep, untreated sleep apnea, periodic limb movements of sleep, and idiopathic hypersomnia (chronic sleepiness but without SOREMPs or other evidence of abnormal REM sleep). In addition, the effects of sedating medications should be excluded. [6,11]

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Revision History

• 2024-11-01: 2024 Annual Review - no criteria changes
• 2023-10-03: 2023 Annual Review
• 2023-08-23: update guideline
• 2022-12-15: Removed note from quantity limit section referencing "titration" and "not to exceed maximum FDA-approved dose" per PA team feedback.
• 2022-10-09: 2022 Annual Review.
• 2021-10-21: 2021 Annual Review
• 2021-09-28: Addition of EHB formulary. No changes to criteria
• 2021-05-25: Addition of EHB formulary. No changes to criteria
• 2020-12-03: 2020 Annual Review: no changes. effective date changed 1/1/2021
• 2020-11-04: 2020 Annual Review: no changes
• 2020-09-02: Updated guideline to include new QL override section for Provigil 200mg/modafinil 200mg
• 2020-03-30: update criteria for Brand Nuvigil
• 2019-10-29: Annual Review- SWSD criteria updated.
• 2019-08-19: Updated SWSD initial authorization and reauthorization criteria.

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