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IMPORTANT SAFETY INFORMATION
Serious adverse events that may be associated with the use of NUVIGIL® (armodafinil) Tablets [C-IV] include: serious rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment; angioedema and hypersensitivity, including fatal multi-organ hypersensitivity reactions; psychiatric adverse experiences; persistent sleepiness; and cardiovascular adverse events.
Read more Important Safety Information

About NUVIGIL

If your patients are suffering from excessive sleepiness (ES) associated with shift work disorder (SWD), obstructive sleep apnea (OSA), or narcolepsy, NUVIGIL may help.1

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Once-daily dosing

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Once-daily dosing

In patients with SWD, OSA, or narcolepsy, NUVIGIL improves wakefulness with once-daily dosing.1

NUVIGIL is available in 4 strengths1

There is no generic equivalent for NUVIGIL available

  • NUVIGIL can be taken with or without food, but food may delay absorption by ≥2 hours1
  • The effectiveness of steroidal contraceptives may be reduced when used with NUVIGIL and for one month after discontinuation of therapy1
  • Dose-related adverse events include: headache, rash, depression, dry mouth, insomnia, and nausea.
  • NUVIGIL is a Schedule IV controlled substance because it has the potential to be abused or lead to dependence. Physicians should follow patients closely, especially those with a history of drug and/or stimulant abuse.
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Improved wakefulness for patients with ES associated with SWD

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Improved wakefulness for patients with ES associated with SWD

In pivotal trials, patients taking NUVIGIL for ES associated with SWD experienced improved wakefulness and an improvement in overall clinical condition.1,2

Pivotal Trial: NUVIGIL improved wakefulness throughout the shift (2 AM to 8 AM) in patients with ES associated with SWD1,2

  • Data from a 12-week, multicenter, double-blind, placebo-controlled study in patients with ES associated with SWD1
  • The Multiple Sleep Latency Test (MSLT) is used to measure wakefulness1
*The MSLT is an objective test that measures the time required to fall asleep in a 20-minute period, using polysomnography.1
  • Coprimary endpoint was the average of 4 evaluations from 2 AM to 8 AM at final visit2
  • Study drug was administered at approximately 10 PM on study nights2
  • Serious rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment has been reported in association with the use of NUVIGIL or modafinil. NUVIGIL should be discontinued at the first sign of rash unless the rash is clearly not drug-related.
  • NUVIGIL is not approved for use in pediatric patients for any indication.
  • Other serious adverse events associated with the use of NUVIGIL or modafinil include angioedema and hypersensitivity, including fatal multi-organ hypersensitivity reactions, psychiatric adverse experiences (including suicidal ideation), persistent sleepiness, and cardiovascular adverse events. If hypersensitivity reaction is suspected, NUVIGIL should be discontinued. Consider discontinuing NUVIGIL if psychiatric symptoms develop. Use with caution in patients with known cardiovascular disease.

Pivotal Trial: NUVIGIL improved patients' overall clinical condition as related to sleepiness during night shifts, including the commute to and from work1,2

  • A significantly greater percentage of patients taking NUVIGIL (79%) experienced at least minimal improvement in overall clinical condition compared with patients taking placebo (59%) at final visit (P<0.05)1
  • A significantly greater percentage of patients taking NUVIGIL (79%) experienced at least minimal improvement in overall clinical condition compared with patients taking placebo (59%) at final visit (P<0.05)1
Improvement in Clinical Global Impression of Change (CGI-C)
Score at Final Visit1

  • Physicians in the study rated change in sleepiness, as measured by a modified CGI-C, as a coprimary endpoint1,3
    • Physicians were asked: "Compared to the patient's condition at baseline, how much has the patient changed with regard to the severity of sleepiness during night shifts (including the commute to and from work)?"
  • Improvement was defined as a rating of Minimally, Much, or Very Much Improved on a 7-point scale3
  • Although NUVIGIL has not been shown to produce functional impairment, any drug affecting the CNS may alter judgment, thinking or motor skills. Patients should be frequently reassessed for their degree of sleepiness and functional impairment and, if appropriate, advised to avoid driving or any other potentially dangerous activity.
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Improved wakefulness for patients with ES associated with OSA

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Improved wakefulness for patients with ES associated with OSA

In pivotal trials, patients taking NUVIGIL for ES associated with OSA experienced improved wakefulness and an improvement in overall clinical condition.1,3

Pivotal Trials: Patients with OSA taking NUVIGIL as adjunctive therapy for OSA experienced significant improvement in wakefulness throughout the day1

OSA Trial I
OSA Trial II
Wakefulness Throughout the Day
(9 AM to 3 PM)1,3,4*
Primary Endpoint
*
The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient’s ability to remain awake. Each test session was terminated after 30 minutes if no sleep occurred or immediately after sleep onset.1

Average of 4 evaluations from 9 AM to 3 PM. In patients with OSA, there is no consistent evidence that doses up to 250 mg/day taken orally as a single dose confer additional benefit beyond that of the 150 mg/day dose.1

P<0.05 vs placebo.1
Wakefulness Throughout the Day
(9 AM to 3 PM)1,3,5*
Primary Endpoint
*
The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient’s ability to remain awake. Each test session was terminated after 30 minutes if no sleep occurred or immediately after sleep onset.1

Average of 4 evaluations from 9 AM to 3 PM. In patients with OSA, there is no consistent evidence that doses up to 250 mg/day taken orally as a single dose confer additional benefit beyond that of the 150 mg/day dose.1

P<0.05 vs placebo.1
  • Study drug was taken at approximately 7 AM on clinic visit days4,5
  • Patients should be advised that their level of wakefulness may not return to normal. Patients should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity.

Pivotal Trials: NUVIGIL demonstrated improvement in overall clinical condition as measured by the Clinical Global Impression of Change (CGI-C)1,3

OSA Trial I
OSA Trial II
Improvement in CGI-C Score at Final Visit1,3
§P<0.05 vs placebo.
Improvement in CGI-C Score at Final Visit1,3
§P<0.05 vs placebo.1
  • Although NUVIGIL has not been shown to produce functional impairment, any drug affecting the CNS may alter judgment, thinking or motor skills. Patients should be frequently reassessed for their degree of sleepiness and functional impairment and, if appropriate, advised to avoid driving or any other potentially dangerous activity.
  • Improvement was defined as a rating of Minimally, Much, or Very Much Improved on a 7-point scale1
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Improved wakefulness for patients with ES associated with narcolepsy

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Improved wakefulness for patients with ES associated with narcolepsy

In a pivotal trial, patients taking NUVIGIL for ES associated with narcolepsy experienced improved wakefulness and an improvement in overall clinical condition.1,6

Pivotal Trial: Patients with ES associated with narcolepsy taking NUVIGIL experienced significant improvement in wakefulness throughout the day1

  • Primary efficacy measure was the Maintenance of Wakefulness Test (MWT)1
Wakefulness Throughout the Day
(9 AM to 3 PM)1,6*
Primary Endpoint
*
The MWT is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Longer latencies indicate a greater ability to remain awake. Each test session was terminated after 20 minutes if no sleep occurred or immediately after sleep onset.6

Average of 4 evaluations from 9 AM to 3 PM. N values shown represent the number of patients included in the efficacy analysis.3,6

P<0.05 vs placebo.1
  • Patients should be advised that their level of wakefulness may not return to normal. Patients should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity.

Pivotal Trial: NUVIGIL demonstrated improvement in overall condition as measured by the Clinical Global Impression of Change (CGI-C) (primary endpoint)1,6

  • 73% of patients taking NUVIGIL 250 mg (n=60) and 69% of patients taking NUVIGIL 150 mg (n=58) improved at final visit compared to 33% of patients taking placebo (n=58) — a significantly greater improvement (P<0.05)1,3
  • Physicians in the study rated change in sleepiness, as measured by a modified CGI-C, as a coprimary endpoint1,3
    • Physicians were asked: "Compared to the patient's condition at baseline, how much has the patient changed with regard to the severity of sleepiness during night shifts (including the commute to and from work)?"3
  • Improvement was defined as a rating of Minimally, Much, or Very Much Improved on a 7-point scale3

Pivotal Trial: Patients with narcolepsy taking NUVIGIL showed improvements as measured by the Epworth Sleepiness Scale3

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The science of NUVIGIL

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The science of NUVIGIL

NUVIGIL contains a nonamphetamine wake-promoting agent.1

The half-life of R-modafinil is longer than that of S-modafinil (10 to 15 hours vs 3 to 4 hours)7

  • The chemical structure of NUVIGIL is different from traditional stimulants like amphetamines and methylphenidate1
  • NUVIGIL contains R-modafinil, the longer-lasting isomer of modafinil1
  • NUVIGIL is a Schedule IV (C-IV) controlled substance because it has the potential to be abused or lead to dependence1

The effect of half-life on clinical efficacy has not been established.

NUVIGIL sustains higher plasma concentrations vs modafinil on a mg/mg basis8

Steady-State Plasma Concentrations of NUVIGIL vs Modafinil Over 24 Hours (Mean ± SEM)8
  • Data from a multicenter, open-label, randomized, crossover study8
  • Systemic exposure was compared in patients receiving NUVIGIL and modafinil for excessive sleepiness associated with obstructive sleep apnea (OSA) (day 10)8|*

The effect of higher plasma concentration on clinical efficacy has not been established.8

*
In OSA, the recommended dose of NUVIGIL is 150 mg to 250 mg taken orally once daily. There is no consistent evidence that doses up to 250 mg/day taken orally as a single dose confer additional benefit beyond that of the 150 mg/day dose.1
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NUVIGIL safety profile

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NUVIGIL safety profile

Most frequently reported adverse events (≥5%)

SWD Clinical Trial3
*Dose-releated adverse events.
  • In clinical trails, patients taking NUVIGIL reported an incidence ≤5% of anxiety, agitation, or nervousness1
    • Anxiety: 4% with NUVIGIL vs 1% with placebo
    • Agitation or nervousness: 1% with NUVIGIL vs 0% with placebo
  • In the SWD clinical trial, 6% of patients taking NUVIGIL and 3% of patients taking placebo discontinued due to adverse events3

NUVIGIL does not typically affect sleep when patients usually sleep1

  • In clinical trials, NUVIGIL did not affect sleep as measured by polysomnography1
  • Daytime polysomnography was conducted over an 8-hour period starting at 10:15 AM2
  • Sleep efficiency measures time asleep as a percentage of total time in bed2
  • In clinical studies, 5% of patients taking NUVIGIL reported insomnia vs 1% taking placebo1
  • In the clinical trials, the most commonly reported adverse events (≥5%) associated with the use of NUVIGIL were headache, nausea, dizziness, and insomnia.
OSA Clinical Trials I and II3
*Dose-releated adverse events.
Narcolepsy Clinical Trials3
*Dose-releated adverse events.
Four Clinical Trials in OSA, SWD and Narcolepsy1†
*Dose-releated adverse events.

Four double-blind, placebo-controlled clinical studies in OSA, SWD, and narcolepsy.
  • Over all clinical trials, 7% of patients taking NUVIGIL discontinued due to adverse events vs 4% of patients taking placebo1
    • The most frequent reason for discontinuation was headache (1%)
  • Serious rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment has been reported in association with the use of NUVIGIL or modafinil. NUVIGIL should be discontinued at the first sign of rash unless the rash is clearly not drug-related. NUVIGIL is not approved for use in pediatric patients for any indication.
  • In controlled trials in adults administered NUVIGIL, psychiatric symptoms resulting in treatment discontinuation were anxiety, agitation, nervousness, irritability, and depression. Caution should be exercised in patients with a history of psychosis, depression, or mania. Consider discontinuing NUVIGIL if psychiatric symptoms develop.
 

IMPORTANT SAFETY INFORMATION

Contraindications: NUVIGIL is contraindicated in patients with a known hypersensitivity to modafinil or armodafinil or its inactive ingredients.

Serious rash: Serious rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment has been reported in association with the use of NUVIGIL or modafinil. There are no factors, including duration of therapy, that are known to predict the risk of occurrence or the severity of rash. Although benign rashes also occur with NUVIGIL, it is not possible to reliably predict which rashes will prove to be serious. NUVIGIL should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.

NUVIGIL has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication.

Angioedema and hypersensitivity reactions: Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm) were observed in patients with NUVIGIL. Multi-organ hypersensitivity reactions, including at least one fatality in post-marketing experience, have occurred in close temporal association to the initiation of modafinil. Patients should be advised to discontinue NUVIGIL and immediately report to their physician any signs or symptoms suggesting angioedema or anaphylaxis, or multi-organ hypersensitivity.

Psychiatric symptoms: Psychiatric adverse experiences have been reported in patients treated with NUVIGIL and modafinil. In controlled trials in adults treated with NUVIGIL, psychiatric symptoms resulting in treatment discontinuation included anxiety, agitation, nervousness, irritability, and depression. Postmarketing adverse reactions associated with the use of modafinil have included mania, delusions, hallucinations, suicidal ideation, and aggression, some resulting in hospitalization. Caution should be exercised when NUVIGIL is given to patients with a history of psychosis, depression, or mania. Consider discontinuing NUVIGIL if psychiatric symptoms develop.

Persistent sleepiness and CNS effects: Patients should be advised that their level of wakefulness may not return to normal. Although NUVIGIL has not been shown to produce functional impairment, any drug affecting the CNS may alter judgment, thinking or motor skills. Patients should be frequently reassessed for their degree of sleepiness and functional impairment and, if appropriate, advised to avoid driving or any other potentially dangerous activity.

Cardiovascular events: Cardiovascular adverse reactions have been reported in patients treated with modafinil in association with mitral valve prolapse or left ventricular hypertrophy. NUVIGIL is not recommended in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced mitral valve prolapse syndrome when previously receiving CNS stimulants. If findings of mitral valve prolapse syndrome occur, consider cardiac evaluation. In clinical studies, a greater proportion of patients on NUVIGIL required new or increased use of antihypertensive medications compared to patients on placebo. Increased monitoring of heart rate and blood pressure may be appropriate in patients on NUVIGIL. Caution should be exercised when prescribing NUVIGIL to patients with known cardiovascular disease.

Drug interactions: NUVIGIL may interact with drugs that are substrates for CYP3A4/5 or CYP2C19. Dose adjustment of these drugs may be required. The effectiveness of steroidal contraceptives may be reduced when used with NUVIGIL and for one month after discontinuation of therapy.

Common adverse reactions: In clinical trials, the most commonly reported adverse reactions (≥5%) associated with the use of NUVIGIL were headache, nausea, dizziness, and insomnia.

NUVIGIL is a Schedule IV controlled substance because it has the potential to be abused or lead to dependence. Physicians should follow patients closely, especially those with a history of drug and/or stimulant abuse.

Physicians should be aware and inform their patients of the availability of the Medication Guide for NUVIGIL.

Please see Full Prescribing Information for NUVIGIL.

References:
  1. NUVIGIL [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc; 2015.
  2. Czeisler CA, Walsh JK, Wesnes KA, Arora S, Roth T. Armodafinil for treatment of excessive sleepiness associated with shift work disorder: a randomized controlled study. Mayo Clin Proc. 2009;84(11):958-972.
  3. Data on file. Teva Pharmaceuticals USA, Inc.
  4. Roth T, White D, Schmidt-Nowara W, 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. 2006;28(5):689-706.
  5. Hirshkowitz M, Black JE, Wesnes K, Niebler G, Arora S, Roth T. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respir Med. 2007;101(3):616-627.
  6. Harsh JR, Hayduk R, Rosenberg R, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006;22(4):761-774.
  7. Nishino S, Okuro M. Armodafinil for excessive daytime sleepiness. Drugs Today (Barc). 2008;44(6):395-414.
  8. Darwish M, Kirby M, DʼAndrea DM, Yang R, Hellriegel ET, Robertson P Jr. Pharmacokinetics of armodafinil and modafinil after single and multiple doses in patients with excessive sleepiness associated with treated obstructive sleep apnea: a randomized, open-label, crossover study. Clin Ther. 2010;32(12):2074-2087.
IMPORTANT SAFETY INFORMATION
Serious adverse events that may be associated with the use of NUVIGIL® (armodafinil) Tablets [C-IV] include: serious rash, including Stevens-Johnson Syndrome, requiring hospitalization and discontinuation of treatment; angioedema and hypersensitivity, including fatal multi-organ hypersensitivity reactions; psychiatric adverse experiences; persistent sleepiness; and cardiovascular adverse events. Read more Important Safety Information