Provigil (modafinil) is a prescription-only wakefulness-promoting agent indicated for the improvement of wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), and shift work sleep disorder (SWSD). Its unique mechanism of action, distinct from traditional stimulants, targets specific neural pathways to promote alertness without the typical pattern of widespread CNS excitation. This profile provides a comprehensive overview of its pharmacological properties, clinical applications, and essential safety information for healthcare professionals and informed patients.

Features

• Active Ingredient: Modafinil
• Pharmacologic Class: Wakefulness-Promoting Agent
• Dosage Forms: Oral tablets (100 mg, 200 mg)
• Mechanism of Action: Exact mechanism unknown; believed to work through selective activation of wake-promoting centers (e.g., hypothalamus) via interaction with dopamine, norepinephrine, orexin, and histamine systems, notably by inhibiting dopamine reuptake.
• Bioavailability: Well absorbed, with or without food; peak plasma concentrations reached in approximately 2-4 hours.
• Half-Life: 15 hours (allowing for once-daily dosing).
• Metabolism: Primarily hepatic, via CYP3A4/5 and other enzymatic pathways.
• Excretion: Primarily renal (as metabolites).

Benefits

• Promotes sustained wakefulness and alertness in patients with diagnosed sleep disorders, enabling full daytime function.
• Improves ability to maintain attention and reduces the frequency of lapses into sleep during required wakeful periods.
• Supports cognitive functions such as memory, executive function, and mental processing in states of sleep deprivation.
• Offers a favorable side effect profile compared to traditional stimulants like amphetamines, with a lower potential for euphoria and abuse (though still present).
• Once-daily dosing regimen enhances patient compliance and convenience.
• Does not generally interfere with normal sleep architecture when taken as prescribed in the morning.

Common use

Provigil is FDA-approved for the treatment of excessive sleepiness associated with:

• Narcolepsy: A chronic neurological disorder characterized by the brain’s inability to regulate sleep-wake cycles normally.
• Obstructive Sleep Apnea (OSA): As adjunctive therapy to standard treatments like continuous positive airway pressure (CPAP) for residual daytime sleepiness. It is not a treatment for the underlying airway obstruction.
• Shift Work Sleep Disorder (SWSD): For patients who experience excessive sleepiness during their scheduled work shifts, which occur during habitual sleep hours.

Its use for cognitive enhancement in healthy individuals (“off-label” use) is not approved by the FDA and is associated with significant risks, including serious dermatological and psychiatric reactions.

Dosage and direction

• The recommended dose for narcolepsy or OSA is 200 mg taken orally once daily in the morning.
• For SWSD, the recommended dose is 200 mg taken orally approximately one hour prior to the start of the work shift.
• Doses of 400 mg daily have been well-tolerated but show no consistent additional benefit.
• Dosage adjustment should be considered in severe hepatic impairment, with a recommended dose of 100 mg daily.
• The tablet should be swallowed whole with a glass of water. It may be taken with or without food.
• Administration later in the day may increase the risk of insomnia.

Precautions

• Serious Rash: Discontinue Provigil at the first sign of rash, unless the rash is clearly not drug-related. Serious dermatological reactions, including Stevens-Johnson Syndrome (SJS) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported.
• Psychiatric Symptoms: Anxiety, nervousness, insomnia, aggression, agitation, depression, suicidal ideation, and psychosis have been reported. Use with caution in patients with a history of psychosis, depression, or mania.
• Cardiovascular Effects: Increases in blood pressure and heart rate have been observed. Caution is advised in patients with a history of left ventricular hypertrophy, ischemic heart disease, mitral valve prolapse, or other cardiovascular conditions. Consider monitoring blood pressure in patients on modafinil.
• Abuse Potential: Provigil is a Schedule IV controlled substance. The potential for abuse, though lower than Schedule II stimulants, exists. Evaluate patients for a history of drug abuse and observe them for signs of misuse or abuse.
• Pregnancy and Lactation: Provigil may cause fetal harm based on animal data. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if modafinil is excreted in human milk; a decision should be made to discontinue nursing or discontinue the drug.

Contraindications

Provigil is contraindicated in patients with:

• Known hypersensitivity to modafinil, armodafinil, or any inactive ingredient in the formulation.
• A history of serious dermatologic reaction (e.g., SJS, Toxic Epidermal Necrolysis) to modafinil.

Possible side effect

Common side effects (≥1%) include:

• Headache
• Nausea
• Nervousness
• Anxiety
• Insomnia
• Dizziness
• Diarrhea
• Rhinitis
• Back pain

Serious but less common side effects require immediate medical attention:

• Serious skin rashes or blistering (SJS, TEN, DRESS)
• Symptoms of psychosis (e.g., hallucinations, delusions)
• Symptoms of mania or depression
• Chest pain, palpitations, or irregular heartbeat
• Signs of an allergic reaction (e.g., hives, difficulty breathing, swelling of the face or throat)

Drug interaction

Provigil is a moderate inducer of CYP3A4 and an inhibitor of CYP2C19. This can affect the plasma levels of concomitant medications.

• Decreased Efficacy: Provigil may reduce the effectiveness of drugs metabolized by CYP3A4 (e.g., cyclosporine, ethinyl estradiol, triazolam, midazolam, certain statins).
• Increased Exposure: Provigil may increase levels of drugs metabolized by CYP2C19 (e.g., diazepam, phenytoin, propranolol, omeprazole, certain tricyclic antidepressants).
• Monoamine Oxidase Inhibitors (MAOIs): Use with MAOIs is not recommended due to theoretical concerns.
• Warfarin: A dose adjustment of warfarin may be necessary; monitor prothrombin time/INR.

Missed dose

If a dose is missed, it should be taken as soon as possible. However, if it is close to the time of the next scheduled dose, the missed dose should be skipped. Do not double the dose to make up for a missed one, as this increases the risk of side effects and insomnia.

Overdose

• Symptoms: Reported symptoms of overdose include insomnia, central nervous system excitation (e.g., restlessness, agitation, confusion, anxiety, tremor), tachycardia, bradycardia, hypertension, chest pain, nausea, and diarrhea.
• Management: There is no specific antidote for modafinil overdose. Management involves providing symptomatic and supportive care, including cardiovascular monitoring. The patient should be assessed for the possible ingestion of multiple substances.

Storage

• Store Provigil tablets at room temperature, between 20°C to 25°C (68°F to 77°F).
• Keep in the original container, tightly closed, and out of reach of children and pets.
• Protect from excessive moisture and light.
• Properly dispose of any unused or expired medication.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

• “As a sleep specialist, I find Provigil to be a valuable tool in my arsenal for treating residual sleepiness in compliant CPAP users. Its targeted mechanism offers effective wakefulness with a generally manageable side effect profile, though vigilance for dermatologic and psychiatric events is paramount.” – Dr. A., Neurologist
• “After being diagnosed with narcolepsy, Provigil gave me my life back. I can now stay awake through my workday and engage with my family in the evenings. The difference is night and day, though I did experience some initial headaches that subsided.” – Patient J.S.
• “The abuse potential, while categorized as Schedule IV, is a significant clinical consideration, particularly in populations with a history of substance use disorder. It should be prescribed judiciously and with clear patient education on its proper use.” – Clinical Pharmacist, M.H.