Recommended Dose of Modafinil for Adults
The standard recommended dose of modafinil for adults 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 Disorder (SWD): 200 mg once daily, taken approximately one hour prior to the start of the work shift 1
- Maximum total daily dose: 400 mg per day, administered either as a single morning dose or divided into morning and midday doses 2, 1
Dosing Flexibility Based on Clinical Response
Higher doses (200-400 mg/day) are more effective for treating excessive sleepiness, while lower doses (50-200 mg/day) may be more appropriate for concentration problems and fatigue. 2 The National Comprehensive Cancer Network supports this dose-response relationship, particularly in cancer-related fatigue management 2.
- The last dose should be taken no later than 2:00 PM to avoid insomnia 2
- Doses can be given as a single morning dose or split into morning and midday administration 2
Special Population Adjustments
Elderly Patients
- Start with 100 mg once upon awakening 2
- Increase dose at weekly intervals as necessary 2
- Consider using lower doses overall due to age-related changes in drug elimination 1
Hepatic Impairment
- Severe hepatic impairment: Reduce dose to half the recommended dose (i.e., 100 mg daily) 1
- Modafinil elimination is slowed in hepatically compromised patients 3
Renal Impairment
- Exercise caution in severe renal insufficiency due to substantial increases in modafinil acid metabolite levels 4
Pharmacokinetic Rationale
- Half-life: Approximately 12-15 hours 3
- Time to peak concentration: 2-4 hours after administration 3
- Steady state: Reached within 2-4 days of dosing 2, 3
- Pharmacokinetics are dose-independent between 200-600 mg/day 3
Common Adverse Effects to Monitor
The most frequently reported adverse events (≥5%) include 1:
- Headache (most common, occurring in >50% at therapeutic doses) 5
- Nausea 1, 4
- Nervousness 2, 1, 4
- Insomnia 2, 1, 4
- Back pain 2, 1
- Dyspepsia 2, 1
Critical Safety Considerations
Life-Threatening Reactions
- Discontinue immediately at the first sign of rash unless clearly not drug-related, due to risk of Stevens-Johnson syndrome 2, 1
- Monitor for angioedema and anaphylaxis reactions 1
- Watch for multi-organ hypersensitivity reactions 1
Cardiovascular Monitoring
- Modafinil can increase blood pressure and heart rate 6
- Consider increased monitoring in patients with known cardiovascular disease 1
Drug Interactions
- Reduces effectiveness of oral contraceptives: Use alternative or concomitant contraception during treatment and for one month after discontinuation 2, 1
- May reduce cyclosporine blood concentrations 1
- May increase exposure of CYP2C19 substrates (omeprazole, phenytoin, diazepam) 1
Pregnancy and Lactation
- Contraindicated in pregnancy: May cause fetal harm based on animal data and increased rates of major congenital anomalies in pregnancy registry reports 6
- Avoid during breastfeeding 6
Clinical Efficacy Timeline
- Initial response: Significant improvement in daytime sleepiness typically seen within 2 weeks 7
- Long-term efficacy: Maintained for at least 40 weeks without evidence of tolerance development 7
- Disease severity rated as "much improved" or "very much improved" in approximately 58-59% of patients by 24-40 weeks 7
Abuse Potential
Modafinil has substantially lower abuse potential compared to traditional stimulants like amphetamines or methylphenidate. 2, 5, 4 There is no evidence of rebound phenomena after treatment withdrawal 5, and limited physical and psychological dependence risk has been documented 2.