Modafinil Dosage Recommendations
The standard recommended dose of modafinil is 200 mg taken orally once daily in the morning for narcolepsy and obstructive sleep apnea, with a maximum daily dose of 400 mg. 1
Standard Dosing by Indication
Narcolepsy and Obstructive Sleep Apnea
- Start with 200 mg once daily in the morning as the FDA-approved standard dose 1
- Doses up to 400 mg/day as a single dose have been well tolerated, though there is no consistent evidence that 400 mg provides additional benefit beyond 200 mg 1
- Higher doses (200-400 mg/day) are more effective for treating sleepiness, while lower doses (50-200 mg/day) may be more appropriate for concentration problems and fatigue 2
Shift Work Sleep Disorder
- 200 mg taken once daily approximately 1 hour prior to the start of the work shift 1
Maximum Dose
- The absolute maximum total daily dose is 400 mg per day, which can be administered as a single morning dose or divided into two doses 2, 3
Special Population Dosing
Elderly Patients
- Start with 100 mg once upon awakening 2
- The dose can be increased at weekly intervals as necessary 2
- Consider using lower doses and close monitoring in geriatric patients 1
Severe Hepatic Impairment
- Reduce the dose to one-half of the standard recommended dose (i.e., 100 mg instead of 200 mg) 1
Renal Impairment
- While not explicitly addressed in FDA labeling for dose adjustment, both maximum plasma concentration and elimination half-life are increased in patients with renal impairment 4
Pharmacokinetic Considerations
- Modafinil has a half-life of approximately 15 hours 2, 3
- Steady state is typically reached after 2-4 days of dosing 2, 3
- Peak plasma concentrations occur approximately 2-4 hours after oral administration 4
- The pharmacokinetics are linear and dose-dependent over the 200-600 mg range 4
Common Pitfalls and Safety Considerations
Serious Adverse Events to Monitor
- Discontinue modafinil immediately at the first sign of rash, as serious rashes including Stevens-Johnson Syndrome can occur, particularly within 1-5 weeks of treatment initiation 1, 2
- Modafinil is not FDA-approved for patients under 17 years of age due to increased risk of serious skin reactions 2
Common Side Effects (≥5%)
- Headache, nausea, nervousness, rhinitis, and diarrhea are the most frequent adverse events 3, 1
- Back pain, anxiety, insomnia, dizziness, and dyspepsia also occur commonly 2, 3
- Most adverse events are mild to moderate and not dose-related 4
Drug Interactions
- Modafinil reduces the efficacy of steroidal contraceptives (e.g., ethinyl estradiol); use alternative or concomitant contraception methods during treatment and for one month after discontinuation 1
- May reduce blood concentrations of cyclosporine 1
- May increase exposure of CYP2C19 substrates such as omeprazole, phenytoin, and diazepam 1
Long-Term Efficacy and Tolerability
- Modafinil maintains efficacy for at least 40 weeks without evidence of tolerance developing 5
- Disease severity remained "much improved" or "very much improved" in approximately 58% of patients at 40 weeks 5
- Unlike traditional stimulants, modafinil has lower abuse potential and is not associated with significant withdrawal phenomena after treatment cessation 2, 3, 4
- The drug is classified as a federally controlled substance (C-IV) due to potential for abuse, though this risk is substantially lower than with amphetamines 3