Provigil

— THERAPEUTIC CATEGORIES —
  • Sleep-wake disorders
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Provigil Generic Name & Formulations

    Legal Class

    CIV

    General Description

    Modafinil 100mg, 200mg+; tabs; +scored.

    Pharmacological Class

    Wakefulness-promoter.

    How Supplied

    Tabs—30

    How Supplied

    Provigil is available as 30-count bottles in:

    • 100 mg: Each capsule-shaped, white to off white tablet is debossed with “PROVIGIL” on one side and “100 MG” on the other.

    • 200 mg: Each capsule-shaped, white to off white, scored tablet is debossed with "PROVIGIL" on one side and "200 MG" on the other.

    Storage

    • Store at 20° ‑ 25°C (68° ‑ 77°F).

    Manufacturer

    Teva Pharmaceuticals

    Mechanism of Action

    The mechanism(s) through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although the pharmacologic profile is not identical to that of the sympathomimetic amines. Modafinil binds to the dopamine transporter and inhibits dopamine reuptake in vitro.

    Provigil Indications

    Indications

    To improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD).

    Limitations of Use

    In OSA: not for treating underlying obstruction.

    Provigil Dosage and Administration

    Adult

    ≥17yrs: 200mg once daily in the AM; SWD: take dose 1hr before work. Max 400mg/day. Severe hepatic impairment: 100mg once daily in the AM. Elderly, concomitant CYP3A4 substrates or drugs eliminated by CYP2C19: see full labeling.

    Children

    <17yrs: not established.

    Hepatic Impairment

    • Severe hepatic impairment: reduce dose of Provigil to ½ of the recommended dose for patients with normal hepatic function.

    Provigil Contraindications

    Not Applicable

    Provigil Boxed Warnings

    Not Applicable

    Provigil Warnings/Precautions

    Warnings/Precautions

    History of LV hypertrophy or symptomatic mitral valve prolapse (eg, ischemic ECG changes, chest pain, arrhythmias associated with CNS stimulants): not recommended. Discontinue if rash appears (unless clearly not drug-related), or if angioedema, anaphylaxis, or multi-organ hypersensitivity reaction occurs. Recent MI. Unstable angina. Monitor HR and BP. Cardiovascular disease. Psychosis. Depression. Mania. Severe hepatic impairment. Reevaluate periodically. Elderly. Pregnancy (Cat.C). Nursing mothers.

    Warnings/Precautions

    Serious Rash, including Stevens-Johnson Syndrome

    • Rare cases of serious or life-threatening rash, including SJS, Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported.

    • Most cases of serious rash occurred within 1 to 5 weeks after initiating treatment.

    • Discontinue at the first sign of rash unless the rash is clearly not drug-related.

    Angioedema and Anaphylaxis Reactions

    • Discontinue therapy and immediately report any signs or symptoms of angioedema or anaphylaxis to a healthcare provider.

    Multi-organ Hypersensitivity Reactions

    • Multi-organ hypersensitivity reactions, including at least one fatality in postmarketing experience, have occurred in close temporal association (median time to detection 13 days: range 4-33) to the initiation of modafinil. These reactions can result in hospitalization or be life-threatening.

    • Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. 

    • Discontinue Provigil if a multi-organ hypersensitivity reaction is suspected.

    Persistent Sleepiness

    • Frequently reassess patients with excessive sleepiness, including those taking Provigil, for their degree of sleepiness and, if appropriate, advise to avoid driving or any other potentially dangerous activity. 

    • Prescribers should also be aware that patients may not acknowledge sleepiness or drowsiness until directly questioned about drowsiness or sleepiness during specific activities.

    Psychiatric Symptoms

    • Exercise caution in patients with a history of psychosis, depression, or mania. Consider the possible emergence or exacerbation of psychiatric symptoms when using Provigil.

    • Consider discontinuing Provigil if psychiatric symptoms develop in association with Provigil.

    Effects on Ability to Drive and Use Machinery

    • Exercise caution when operating an automobile or other hazardous machinery until it is reasonably certain that Provigil will not affect their ability.

    Cardiovascular Events

    • Provigil 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.

    • Consider cardiac evaluation if new onset of cardiovascular adverse reactions occur. Consider increased monitoring in patients with a recent history of MI or unstable angina.

    • Use caution when prescribing Provigil to patients with known cardiovascular disease.

    Pregnancy Considerations

    Pregnancy Category C

    • No adequate and well-controlled studies of modafinil in pregnant women.

    • Intrauterine growth restriction and spontaneous abortion have been reported in association with modafinil (a mixture of R- and S-modafinil) and armodafinil (the R-enantiomer of modafinil). 

    • Use Provigil during pregnancy only if the potential benefit justifies the potential risk to the fetus.

    Pregnancy Registry

    • A pregnancy registry has been established to collect information on the pregnancy outcomes of women exposed to Provigil. Healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-866-404-4106 (toll free).

    Nursing Mother Considerations

    • It is not known whether modafinil or its metabolites are excreted in human milk.

    • Exercise caution in nursing women because many drugs are excreted in human milk.

    Pediatric Considerations

    • Safety and effectiveness in pediatric patients have not been established.

    Geriatric Considerations

    • Consider using lower doses in elderly patients and monitor closely in this population.

    Hepatic Impairment Considerations

    • Severe hepatic impairment: reduce dose of Provigil to ½ of the recommended dose for patients with normal hepatic function.

    Provigil Pharmacokinetics

    Absorption

    • Peak plasma concentrations occur at 2 to 4 hours after administration.

    • Time to reach peak plasma concentration (tmax) may be delayed by approximately 1 hour if taken with food.

    Distribution

    • Apparent volume of distribution: approximately 0.9 L/kg.

    • Approximately 60% plasma protein bound, mainly to albumin.

    Metabolism

    • Approximately 90% is metabolized primarily by the liver.

    • Hydrolytic deamidation, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation.

    Elimination

    • Renal (80%), fecal (1%).

    • Half-life: ~15 hours.

    Provigil Interactions

    Interactions

    May antagonize hormonal contraceptives (eg, ethinyl estradiol); use alternative or additional contraceptive method during and for one month after treatment. Avoid alcohol. Caution with MAOIs. Modafinil levels may be decreased by CYP3A4 inducers (eg, carbamazepine, phenobarbital, rifampin) and increased by CYP3A4 inhibitors (eg, ketoconazole, erythromycin). May decrease levels of drugs metabolized by CYP3A4/5 (eg, cyclosporine, midazolam, triazolam), CYP1A2 or CYP2B6. May increase levels of drugs metabolized by CYP2C9 (eg, warfarin) or CYP2C19 (eg, phenytoin, diazepam, propranolol, omeprazole, clomipramine), and levels of tricyclics and SSRIs in patients deficient in CYP2D6 (consider dose reduction). Monitor warfarin, phenytoin.

    Provigil Adverse Reactions

    Adverse Reactions

    Headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, dyspepsia; rash (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis).

    Provigil Clinical Trials

    Clinical Trials

    Narcolepsy

    • Two US 9‑week, multicenter, placebo‑controlled, parallel-group, double‑blind studies evaluated the efficacy of Provigil for improving wakefulness in 558 adult outpatients with excessive sleepiness associated with narcolepsy. Patients were randomly assigned to receive Provigil 200 or 400 mg/day, or placebo.

    • All eligible patients were required to have objectively documented excessive daytime sleepiness, via a Multiple Sleep Latency Test (MSLT) with 2 or more sleep onset REM periods and the absence of any other clinically significant active medical or psychiatric disorder. 

    • In both studies, the primary measures of effectiveness were: 1) sleep latency, as assessed by the Maintenance of Wakefulness Test (MWT); and 2) the change in the patient’s overall disease status, as measured by the Clinical Global Impression of Change (CGI-C). For a successful trial, both measures had to show statistically significant improvement.

    • Results from both studies showed that treatment with Provigil 200 mg and 400 mg achieved improvement in objective and subjective measures of excessive daytime sleepiness compared with placebo. 

    • Provigil 200 mg and 400 mg doses achieved a statistically significantly enhanced ability to remain awake on the MWT at each dose compared to placebo at final visit. Each dose of Provigil also had a statistically significantly greater number of patients with improvement in overall clinical condition as rated by the Clinical Global Impression of Change (CGI-C) scale at final visit.

     

    Obstructive Sleep Apnea (OSA)

    Two multicenter, placebo-controlled clinical studies evaluated the efficacy and safety of Provigil for improving wakefulness in adults with excessive sleepiness associated with OSA. 

    Study 1

    • 327 patients with OSA were randomly assigned to receive Provigil 200 mg/day, 400 mg/day, or placebo for 12 weeks. The primary measures of effectiveness were 1) sleep latency, as assessed by the MWT and 2) the change in the patient’s overall disease status, as measured by the CGI-C at the final visit. 

    • Treatment with Provigil achieved a statistically significant improvement in the ability to remain awake compared with placebo, as measured by the MWT at final visit. There was also a greater number of patients treated with Provigil who achieved statistically significant improvement in overall clinical condition as rated by the CGI-C scale at final visit.

    Study 2

    • 157 patients with OSA were randomly assigned to Provigil 400 mg/day or placebo for 4 weeks. The primary measure of effectiveness was the change from baseline on the ESS at final visit. 

    • At week4, treatment with Provigil reduced the ESS score by 4.6 compared with a reduction of 2.0 in the placebo group.

     

    Shift Work Disorder (SWD)

    • A 12-week placebo-controlled clinical trial evaluated the efficacy of Provigil in improving wakefulness in 209 patients with excessive sleepiness associated with SWD. Patients were randomly assigned to receive Provigil 200 mg/day or placebo.

    • Enrolled patients were also required to work a minimum of 5 night shifts per month, have excessive sleepiness at the time of their night shifts (MSLT score < 6 minutes), and have daytime insomnia documented by a daytime polysomnogram.

    • The primary measures of effectiveness were 1) sleep latency, as assessed by the MSLT performed during a simulated night shift at the final visit and 2) the change in the patient’s overall disease status, as measured by the CGI-C at the final visit.

    • Results showed that treatment with Provigil achieved a statistically significant prolongation in the time to sleep onset compared to placebo-treated patients, as measured by the nighttime MSLT at final visit. Treatment with Provigil also had a statistically significant greater number of patients who improved in overall clinical condition as rated by the CGI-C scale at final visit.

    Provigil Note

    Not Applicable

    Provigil Patient Counseling

    Patient Counseling

    Allergic Reactions

    • Advise patients to discontinue therapy and immediately report any signs or symptoms of angioedema or anaphylaxis to a healthcare provider.

    Driving and Dangerous Activities

    • Exercise caution when operating an automobile or other hazardous machinery until it is reasonably certain that Provigil will not affect their ability.

    Continuing Previously Prescribed Treatments

    • Inform patients that it may be critical that they continue to take their previously prescribed treatments (eg, patients with OSA receiving CPAP should continue to do so).

    Discontinuing Drug Due to Adverse Reactions

    • Stop taking the medication and contact their physician immediately if chest pain, rash, depression, anxiety, or signs of psychosis or mania occur. 

    Pregnancy

    • Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy. Caution patients regarding the potential increased risk of pregnancy when using steroidal contraceptives (including depot or implantable contraceptives) with Provigil and for 1 month after discontinuation of therapy.

    Nursing

    • Notify your physician if you are breastfeeding an infant.

    Alcohol

    • Provigil has not been studied  in combination with alcohol. Advise patients to avoid alcohol during treatment.

    • Latest News Your top articles for Thursday

    • Haymarket Medical NetworkTop Picks

    • Loading...

      Continuing Medical Education (CME/CE) Courses

      Show More