Modafinil (Provigil)

Modafinil (Trade name: Provigil) is a/an wakefulness-promoting agent and CNS stimulant. It is commonly used in the treatment of sleep disorders such as narcolepsy and daytime fatigue in obstructive sleep apnea.

Pharmacokinetics of Modafinil

Modafinil: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 3A4
Induces 3A4, 2B6, 1A2
Inhibits 2C19

Dosing for Modafinil

Starting 100mg PO BID (at 0800 and 1200)
Titration Increase by 100 mg
Maximum 200 mg PO BID (maximum total dose 400 mg PO daily)
Taper No tapering required
  • Although studies have shown that patients may need and tolerate daily doses of up to 500mg, limited data from trials in healthy controls suggest that the number and type of side effects increase significantly after single doses of 300 mg.[1]
  • Modafinil comes in oral formulation.
  • In 2019, Health Canada issued a contraindication to modafinil for women who are pregnant or may become pregnant due to increased signal for congenital malformations.[2]
    • The frequency of major congenital anomalies was cited as 17.3% and cardiac anomalies as 4%, above the frequency observed in the general population of 3% and 1% respectively.
  • More recent studies have suggested no increased risk for major congenital anomalies, though did find reduced birthweight and smaller head circumference.[3]
  • Co-administration of modafinil with drugs such as diazepam, phenytoin and propranolol (which are largely eliminated via CYP2C19 pathway), may increase the circulating levels of these drugs.
  • Similarly, modafinil can reduced the efficacy of steroidal contraceptives due to induction of CYP3A4/5, and can reduce the efficacy of combined oral contraceptives, transdermal patches, and progesterone contraceptives.
  • Thus, women of child-bearing age are advised to not use oral steroidal contraceptives and instead use alternative contraceptive methods including copper intrauterine devices, levonorgestrel releasing intrauterine systems, and depot medroxyprogesterone acetate (DMPA).
    • These methods of birth control are not affected and should be recommended for all women of child-bearing age.
  • There is a risk for Stevens-Johnson Syndrome and patients should be counselled on this potential risk.[4]
  • There is an increased risk for major congenital malformations when used during pregnancy.[5]