A Handy Modafinil Dosage Field Guide

The Standard Modafinil Dosage

modafinil pharmacokinetics

A standard modafinil (Provigil) dosage is 200 mg. Note that this differs from the standard armodafinil (Nuvigil) dosage of 150 mg. Less armodafinil is needed to produce the same effects because it’s more potent and selective.

Modafinil tablets come in two flavors: 200 mg and 100 mg. The 200 mg variety is more frequently prescribed.

The official package insert for Provigil (modafinil) states the following:

The recommended dosage of PROVIGIL for each indication is as follows:

  • Narcolepsy or OSA: 200 mg once a day in the morning.
  • SWD: 200 mg once a day, taken approximately one hour prior to start of the work
  • Severe Hepatic Impairment: reduce dose to half the recommended dose.
  • Geriatric Patients: consider lower dose.

Exceptions And Precautions

In pharmacology, there’s heterogeneity when it comes to dose-response. What this means is that an effective dose for one person may be ineffective or unsafe for another person.

Consider the following guidelines.

Low-Dose Responders

Low-dose responders with anxiety may benefit from modafinil doses in the range of 50-100 mg but will find 200 mg overstimulating.

High-Dose Responders

High-dose responders with narcolepsy may need to take as much as 400 mg of modafinil in divided doses. For example, one study concluded “A split-dose 400-mg regimen may be superior to once-daily dosing for sustaining wakefulness throughout the entire waking day” [^1].

Modafinil Interactions Affect Dosage

Modafinil interacts with a number of drugs which can affect its metabolism and impact the appropriate dosage.

Modafinil Non-Responders

A fraction of population are modafinil non-responders. For genetic reasons they don’t fully benefit from modafinil.

One hypothesis is that modafinil’s efficacy in enhancing vigilance is contingent on catechol-O-methyl transferase (COMT) polymorphisms.[^3]

Individuals with the Val/Val genotype may realize greater improvements in their cognitive function. Conversely, people with the Met/Met allele experience neglibile enhancement.

Note that Val/Val increases COMT activity, whereas Met/Met diminishes COMT acitivty. Since COMT metabolizes dopamine – reducing its extracellular concentrations – reduced activity increases synaptic dopamine. Modafinil also increases synaptic dopamine (by weakly inhibiting DAT). Hence it makes sense that individuals with the Met/Met allele wouldn’t respond to modafinil since their baseline dopamine availability is already high.

Further reading:

Notable excerpt[^4]:

“The combined effects on dopamine levels of amphetamine and high working memory load push individuals with the met/met genotype beyond the critical threshold at which compensation can be made,” suggest the researchers. They note evidence from other studies that too much dopamine activity in the prefrontal cortex may disorganize neural networks by activating inhibitory mechanisms.

Modafinil Drug-Drug Interactions

Modafinil is metabolized by the liver and excreted in urine. Less than 1/10th of the drug is excreted unchanged.

Metabolism is mainly via amide hydrolysis; cytochrome P450 (CYP)-mediated oxidative pathways play a lesser role.

In patients with liver or kidney impairment, drug elimination can be slowed. Likewise, elimination in the elderly may be reduced on account of ordinary effects of aging. Modafinil dosages should be adjusted downward based on this information.

Modafinil’s metabolic drug-drug interactions are well-characterized. Modafinil induces CYP3A4, CYP2B6 and CYP1A2 and suppresses the activities of CYP2C9 in primary cultures.

Researchers[^2] examined modafinil’s interactions with:

  • methylphenidate
  • dexamfetamine
  • ethinylestradiol
  • warfarin
  • triazolam.

The only substantial interactions found were with ethinylestradiol and triazolam, apparently through induction of CYP3A4 in the gastrointestinal system.

[^1]: Schwartz JR, Feldman NT, Bogan RK, Nelson MT, Hughes RJ. Dosing regimen effects of modafinil for improving daytime wakefulness in patients with narcolepsy. Clin Neuropharmacol. 2003;26(5):252-7.
[^2]: Robertson P, Hellriegel ET. Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37.
[^3]: Bodenmann S, Xu S, Luhmann UF, et al. Pharmacogenetics of modafinil after sleep loss: catechol-O-methyltransferase genotype modulates waking functions but not recovery sleep. Clin Pharmacol Ther. 2009;85(3):296-304.
[^4]: https://www.nimh.nih.gov/news/science-news/2003/gene-enhances-prefrontal-function-at-a-price.shtml

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