What is the recommended dose of Modafinil (Provigil) for adults with conditions such as narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea?

Modafinil Dosing for Narcolepsy, Obstructive Sleep Apnea, and Shift Work Sleep Disorder

The recommended dose of modafinil for adults with narcolepsy or obstructive sleep apnea is 200 mg taken orally once daily in the morning, while for shift work sleep disorder the dose is 200 mg taken approximately 1 hour before the start of the work shift. 1

Standard Dosing by Indication

Narcolepsy and Obstructive Sleep Apnea

• Start with 200 mg once daily in the morning as a single dose 1
• Doses up to 400 mg/day as a single dose have been well tolerated, but there is no consistent evidence that 400 mg provides additional benefit beyond 200 mg/day 1
• For patients experiencing late-afternoon or evening sleepiness despite morning dosing, a split-dose regimen (200 mg in morning, 200 mg at midday) may be superior to once-daily 400 mg dosing for sustaining wakefulness throughout the entire day 2

Shift Work Sleep Disorder

• Administer 200 mg orally once daily approximately 1 hour prior to the start of the work shift 1

Special Population Adjustments

Elderly Patients

• Start with 100 mg once upon awakening in the morning 3
• Increase at weekly intervals as necessary based on response and tolerability 3
• Typical effective doses range from 200 to 400 mg per day 3
• Lower doses and close monitoring are recommended due to age-related pharmacokinetic changes 1

Severe Hepatic Impairment

• Reduce the dose to one-half of the standard recommended dose (i.e., 100 mg instead of 200 mg) 1
• This adjustment is necessary because both maximum plasma concentration and elimination half-life are increased in hepatic impairment 4

Dose Titration Strategy

• Begin with the standard 200 mg dose for most adult patients 1
• If inadequate response after 1 week, consider increasing to 400 mg once daily 3
• For persistent late-day sleepiness, split the 400 mg dose (morning and midday) rather than giving once daily 2
• Weekly dose adjustments allow adequate time to assess efficacy while monitoring for adverse effects 3

Common Adverse Effects to Monitor

The most common adverse reactions include:

• Headache (occurs in 34% vs 23% with placebo) 5
• Nausea (11% vs 3% with placebo) 5
• Nervousness 3, 5
• Dyspepsia, pain, and vomiting (each occurring in approximately 6% of patients) 2

Critical Safety Monitoring

Cardiovascular Monitoring

• Monitor blood pressure at baseline and during treatment, particularly when initiating or adjusting stimulant doses 3
• Watch for hypertension, palpitations, or arrhythmias 3
• Clinically significant increases in blood pressure are infrequent (diastolic BP increase in <1% of patients) 5

Behavioral and Psychiatric Effects

• Assess for irritability or behavioral manifestations such as psychosis 3
• Question patients about excessive stimulatory effects or nocturnal sleep disturbances 3

Serious Dermatologic Reactions

• Be vigilant for serious rash, including Stevens-Johnson Syndrome, particularly in younger patients 6, 1
• Rare cases of life-threatening rash including Toxic Epidermal Necrolysis and DRESS have been reported 1
• Discontinue immediately if rash develops 1

Efficacy Assessment and Follow-Up

• Use the Epworth Sleepiness Scale (ESS) at each visit to monitor subjective sleepiness and treatment response 3
• More frequent follow-up is necessary when starting medication or adjusting doses 3
• Modafinil improves but does not eliminate sleepiness, so ongoing assessment of functional impairment due to residual sleepiness is necessary 3
• Long-term management is typically required as narcolepsy and related disorders are lifelong conditions 3

Important Clinical Considerations

What Modafinil Does NOT Treat

• Modafinil does not suppress cataplexy 4
• For obstructive sleep apnea, modafinil treats excessive sleepiness but not the underlying airway obstruction 1
• Maximal effort to treat OSA with CPAP should be made before and during modafinil therapy 1

Advantages Over Traditional Stimulants

• Modafinil has no rebound phenomena after treatment withdrawal 4
• Low abuse potential compared to amphetamines and methylphenidate 4
• Does not affect nocturnal sleep architecture or parameters 5, 4
• Patients maintain ability to nap when necessary 4

Drug Interactions

• May reduce efficacy of low-dose oral contraceptives via enzymatic induction 4
• Consider alternative or additional contraceptive methods in women of childbearing potential

When to Refer to Sleep Specialist

Refer when:

• Narcolepsy or idiopathic hypersomnia is suspected but diagnosis uncertain 3
• Patient is unresponsive to initial or subsequent therapy 3
• Complex patients requiring specialized management 3