What is the recommended dosing for modafinil (provigil)?

Modafinil Dosing

The standard recommended dose of modafinil is 200 mg once daily in the morning for narcolepsy and obstructive sleep apnea, with a maximum daily dose of 400 mg. 1

Standard Dosing by Indication

FDA-Approved Indications

• Narcolepsy or Obstructive Sleep Apnea (OSA): 200 mg once daily in the morning 1
• Shift Work Sleep Disorder (SWD): 200 mg once daily, taken approximately one hour prior to the start of the work shift 1
• Maximum daily dose: 400 mg per day, administered as either a single morning dose or divided into two doses (morning and midday) 2, 3

Dose Optimization Based on Clinical Target

The National Comprehensive Cancer Network provides guidance on tailoring doses to specific symptoms:

• For excessive sleepiness: Higher doses of 200-400 mg/day are more effective 2, 4
• For concentration problems and fatigue: Lower doses of 50-200 mg/day may be more appropriate 2, 4

This distinction is clinically important—a patient with primarily fatigue and cognitive complaints may respond better to 100-200 mg daily, while those with severe daytime sleepiness often require 200-400 mg daily 2.

Special Population Dosing

Elderly Patients

• Starting dose: 100 mg once upon awakening 2, 3
• Titration: Increase at weekly intervals as necessary 2
• The lower starting dose accounts for age-related reductions in drug elimination 3

Severe Hepatic Impairment

• Reduce dose to half the recommended dose 1
• Hepatic impairment increases both maximum plasma concentration and elimination half-life 5

Renal Impairment

• While not explicitly stated in FDA labeling, elimination processes are slowed in renally compromised patients 6
• Consider dose reduction based on clinical response and tolerability

Practical Dosing Strategy

Initial Titration Approach

Based on the multiple sclerosis fatigue literature, which demonstrated excellent efficacy with lower doses:

1. Start with 100 mg once daily in the morning 7
2. Assess response after 1-2 weeks 8
3. If inadequate response, increase by 100 mg increments up to maximum 400 mg daily 7
4. Most patients respond to 100-200 mg daily (92% of MS patients in one study required ≤200 mg/day) 7

This graduated approach minimizes side effects while identifying the minimum effective dose for each patient.

Pharmacokinetic Considerations

Timing and Steady State

• Peak plasma concentrations: Reached 2-4 hours after administration 3, 6
• Half-life: Approximately 12-15 hours 3, 6
• Steady state: Achieved within 2-4 days of dosing 2, 3
• Pharmacokinetics are dose-independent between 200-600 mg/day 6

Dosing Schedule Options

• Single morning dose: Most common approach for narcolepsy/OSA 1
• Divided dosing (morning and midday): May be used for sustained wakefulness throughout the day 5
• Pre-shift dosing: Specifically for shift work sleep disorder, taken 1 hour before work 1

Safety Monitoring and Common Pitfalls

Most Common Adverse Effects (≥5%)

• Headache (most frequent, reported in 52% at 200 mg and 51% at 400 mg vs 36% with placebo) 5
• Nausea, nervousness, rhinitis, diarrhea 3
• Back pain, anxiety, insomnia, dizziness, dyspepsia 2, 3

Critical Safety Considerations

• Stevens-Johnson syndrome: Rare but life-threatening; monitor for rash, especially in pediatric patients 9
• Cardiovascular effects: Can increase blood pressure and heart rate; screen for cardiovascular contraindications before initiating 4
• Oral contraceptive interaction: May reduce effectiveness of low-dose oral contraceptives via CYP3A4 induction 4, 5
• Pregnancy: May cause fetal harm; avoid during pregnancy and breastfeeding 4

Abuse Potential

• Schedule IV controlled substance with lower abuse potential than traditional stimulants like amphetamines 3, 5
• No significant withdrawal phenomena reported after treatment cessation 5, 10
• Limited physical and psychological dependence risk 9

Long-Term Use

• Efficacy maintained for at least 40 weeks without evidence of tolerance development 10
• Disease severity remained "much improved" or "very much improved" in 58% of narcolepsy patients at 40 weeks 10
• No dose escalation typically required over time, unlike traditional stimulants 10

Age Restrictions

• Not FDA-approved for patients under 17 years of age 9
• Use in pediatric populations should be approached with extreme caution due to Stevens-Johnson syndrome risk 9