What is the recommended dosing for modafinil (provigil)?

Modafinil Dosing Recommendations

The standard starting dose of modafinil is 200 mg once daily in the morning for narcolepsy and obstructive sleep apnea, or 200 mg taken one hour before the work shift for shift work sleep disorder, 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 Goals

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—one open-label study in MS-related fatigue found that most patients (92%) achieved benefit with doses of 100-200 mg daily, with no patient requiring the full 400 mg dose 5

Special Population Dosing

Elderly Patients

• Starting dose: 100 mg once upon awakening 2, 3
• Titration: Increase at weekly intervals as necessary 2
• Rationale: The FDA label recommends considering lower doses in geriatric patients due to age-related changes in elimination 1

Hepatic Impairment

• Severe hepatic impairment: Reduce dose to half the recommended dose 1
• Mechanism: Modafinil is extensively metabolized in the liver, and elimination half-life increases in hepatic impairment 6

Renal Impairment

• While not explicitly addressed in FDA dosing, pharmacokinetic studies show elimination can be slowed in renally compromised patients 6

Pharmacokinetic Considerations for Dosing

Understanding modafinil's pharmacokinetics helps optimize timing and frequency:

• Half-life: Approximately 12-15 hours 3, 6
• Time to peak concentration: 2-4 hours after administration 3, 6
• Steady state: Reached after 2-4 days of dosing 2, 3
• Dose linearity: Pharmacokinetics are dose-independent between 200-600 mg/day 6

This long half-life explains why once-daily dosing is typically sufficient and why the drug does not disturb nighttime sleep patterns 3

Common Pitfalls and Dosing Errors

Avoid These Mistakes:

1. Starting too high in elderly or fatigue patients: Many clinicians default to 200 mg, but 100 mg may be sufficient, particularly for fatigue rather than sleepiness 2, 5
2. Dosing too late in the day: The 15-hour half-life means afternoon doses can cause insomnia 2, 3
3. Rapid dose escalation: Allow at least one week between dose increases to assess response 2
4. Ignoring drug interactions: Modafinil induces CYP3A4 and can reduce oral contraceptive efficacy—counsel patients accordingly 4, 6

Safety Monitoring Requirements

Before initiating and during treatment:

• Screen for cardiovascular contraindications before starting, as modafinil can increase blood pressure and heart rate 4
• Monitor for rash, especially in younger patients, due to rare but serious Stevens-Johnson syndrome risk 2
• Avoid in pregnancy: Higher rates of major congenital anomalies reported in pregnancy registry data 4
• Common adverse effects (≥5%): Headache, nausea, nervousness, insomnia, back pain, anxiety, dizziness, and dyspepsia 3, 7

Clinical Context: Abuse Potential

Unlike traditional stimulants, modafinil has significantly lower abuse potential and is classified as Schedule IV (C-IV) 3. Studies in volunteers demonstrate less abuse liability than dexamphetamine or methylphenidate 8. Importantly, there is no rebound phenomenon or withdrawal symptoms after treatment cessation 8. However, rare cases of dependence have been reported 9, so monitoring remains appropriate.