Provigil

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). It is classified as a Schedule IV controlled substance due to its potential for abuse or dependence. Its precise mechanism of action is not fully understood but is believed to involve the selective activation of specific wake-promoting centers in the brain, distinct from traditional stimulants like amphetamines. This profile provides a comprehensive, evidence-based overview for healthcare professionals to support informed clinical decision-making.

Features

• Active Pharmaceutical Ingredient: Modafinil
• Standard Tablet Strengths: 100 mg and 200 mg
• Pharmacologic Class: Wakefulness-Promoting Agent
• Schedule: C-IV Controlled Substance
• Administration: Oral
• Bioavailability: Approximately equivalent to oral administration
• Time to Peak Plasma Concentration (Tmax): 2-4 hours
• Elimination Half-Life: Approximately 15 hours
• Primary Metabolic Pathway: Hepatic (CYP3A4/5-mediated)

Benefits

• Promotes sustained wakefulness and alertness in patients with diagnosed sleep disorders, enabling improved daytime functioning.
• Reduces the subjective sense of sleepiness and fatigue, as measured by tools like the Epworth Sleepiness Scale.
• May improve aspects of cognitive function, including attention and executive processes, in the context of pathological sleepiness.
• Offers a differentiated side effect profile compared to traditional stimulants, with a lower incidence of euphoria and jitteriness.
• Provides a long duration of action, often allowing for once-daily dosing to cover wakeful periods.

Common use

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

• Narcolepsy: A chronic neurological disorder characterized by overwhelming daytime drowsiness and sudden attacks of sleep.
• Obstructive Sleep Apnea (OSA): As adjunctive therapy to standard treatments like continuous positive airway pressure (CPAP) for residual sleepiness. It is not a treatment for the underlying airway obstruction.
• Shift Work Sleep Disorder (SWSD): For patients who experience excessive sleepiness during their required wakeful period (e.g., a night shift) and who have had a complete workup to rule out other sleep disorders.

Its use for cognitive enhancement in healthy individuals (“off-label” use) is not approved and is associated with significant risks, including cardiovascular events and potential for dependence.

Dosage and direction

• The recommended dose for narcolepsy and OSA is 200 mg taken orally once daily in the morning.
• The recommended dose for SWSD is 200 mg taken orally approximately one hour prior to the start of the work shift.
• Dosing may be initiated at 100 mg daily for certain patients (e.g., those with hepatic impairment, elderly, or those who are sensitive to stimulants).
• Tablets should be swallowed whole with a glass of water; they should not be split, crushed, or chewed.
• Efficacy is dependent on adequate nightly sleep; Provigil is not a substitute for sufficient sleep.
• Dosage adjustments in patients with severe hepatic impairment are necessary; a reduced initial dose of 100 mg daily is recommended.

Precautions

• Potential for Abuse: Provigil is a Schedule IV controlled substance. Consider the potential for abuse or dependence prior to prescribing, especially in patients with a history of drug or alcohol abuse. Misuse can lead to psychological dependence.
• Cardiovascular Effects: Increases in blood pressure and heart rate have been observed. Use with caution in patients with a history of left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmias, or recent myocardial infarction. Consider monitoring blood pressure in patients on modafinil.
• Psychiatric Symptoms: New-onset psychosis, mania, delusions, hallucinations, and aggression have been reported. Use with caution in patients with a history of psychosis, depression, or mania. Consider discontinuation if such symptoms occur.
• Severe Skin Reactions: Serious dermatologic reactions, including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Discontinue therapy at the first sign of rash, unless the rash is clearly not drug-related.
• Pregnancy and Lactation: There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Modafinil and its metabolites are excreted in breast 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 of the inactive ingredients in the formulation.
• A history of life-threatening skin reactions, such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, associated with the use of modafinil.

Possible side effect

Common adverse reactions (≥5% and greater than placebo) include:

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

Serious but less common side effects require immediate medical attention:

• Signs of a severe skin reaction (e.g., rash, blisters, peeling skin, mouth sores)
• Symptoms of an allergic reaction (e.g., hives, difficulty breathing, swelling of the face or throat)
• Chest pain, palpitations, or irregular heartbeat
• Depression, anxiety, suicidal thoughts, or aggressive behavior
• Signs of psychosis (hallucinations, delusions)

Drug interaction

Provigil is a moderate inducer of CYP3A4 and can potentially inhibit CYP2C19. This activity can alter the plasma levels of co-administered drugs that are metabolized by these enzymes.

• Reduced Efficacy: Provigil may decrease the effectiveness of cyclosporine, ethinyl estradiol (oral contraceptives), triazolam, midazolam, and certain antifungals (e.g., ketoconazole). Women using hormonal contraceptives should be advised to use an alternative or additional method of contraception during and for one month after discontinuing Provigil.
• Increased Levels: Drugs that inhibit CYP3A4 (e.g., ketoconazole, itraconazole, erythromycin) can increase modafinil levels. Conversely, drugs that induce CYP3A4 (e.g., carbamazepine, phenobarbital, rifampin) can decrease modafinil levels.
• Other Interactions: Caution is advised with monoamine oxidase (MAO) inhibitors, warfarin (monitoring of prothrombin time is recommended), and other CNS-active drugs.

Missed dose

• If a dose is missed, it should be taken as soon as possible on the same day.
• If it is too close to the time of the next scheduled dose, the missed dose should be skipped. Do not double the next dose to make up for a missed one.
• For patients with SWSD, if a dose is missed prior to the shift, it should not be taken during the shift if it will interfere with planned sleep.

Overdose

• Symptoms of overdose may include insomnia, central nervous system excitation (e.g., restlessness, agitation, confusion, anxiety, tremor), tachycardia, bradycardia, hypertension, chest pain, nausea, and diarrhea.
• There is no specific antidote for modafinil overdose.
• Management involves providing symptomatic and supportive care, which may include cardiovascular monitoring and ensuring a patent airway. Gastric lavage may be considered if performed soon after ingestion.
• The patient should be referred for immediate emergency medical attention.

Storage

• Store at room temperature, 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F).
• Keep the medication in its original container, tightly closed, and out of reach of children and pets.
• Protect from excessive moisture and light.
• Properly dispose of any expired or unused medication.

Disclaimer

This information is intended for educational purposes and for use by healthcare professionals only. It is a summary and does not include all possible information about this product. It does not constitute medical advice. The content has been compiled from various pharmacological resources but should not be used as a substitute for the clinical judgment of a qualified healthcare professional. Always read the accompanying FDA-approved Full Prescribing Information before initiating treatment. Diagnosis and treatment decisions must be made by a physician based on individual patient assessment.

Reviews

• “As a sleep specialist, Provigil has been a cornerstone in my management of narcolepsy. Its efficacy in promoting wakefulness is well-documented in clinical trials, and many of my patients report a significant improvement in their quality of life and ability to maintain employment. The side effect profile is generally manageable, though vigilance for psychiatric and dermatologic adverse events is paramount.” – Dr. A., Neurology
• “For my patients with residual sleepiness despite optimal CPAP use for their OSA, the adjunctive use of modafinil has been transformative. It bridges the gap, allowing them to feel truly alert during the day. I always emphasize that it is an adjunct to, not a replacement for, treating the underlying airway obstruction.” – Dr. L., Pulmonology
• “Prescribing for shift work disorder requires careful patient selection and education. When used correctly—one hour before a night shift in a patient who has a confirmed sleep disorder and a plan for adequate daytime sleep—it is highly effective. However, the potential for misuse and the controlled substance status mean prescriptions must be monitored closely.” – Dr. P., Occupational Medicine