Comparison of Armodafinil and Modafinil

What is Modafinil?

Provigil (modafinil) is a stimulant medication that activates the nervous system. Provigil was approved by the U.S. Food and Drug Administration (FDA) in 1998. The drug is approved to promote wakefulness in adults with the following sleep disorders:

• Narcolepsy or excessive daytime sleepiness;
• Sleep apnea, a condition that frequently interrupts breathing during sleep;
• Shift work sleep disorder, a sleep disorder that can affect individuals working night or rotating shifts, impacting their sleep-wake schedule.

Modafinil is available in tablet form, with two strengths: 100 milligrams and 200 mg. The recommended dose and frequency depend on the reason for use as follows:

• Typical dosing for narcolepsy and sleep apnea: 200 mg once daily in the morning;
• Typical dosing for shift work sleep disorder: 200 mg one hour before the start of the work shift.
• For elderly individuals or those with liver problems, a lower dose of 100 mg is recommended.

What is Armodafinil?

Nuvigil (armodafinil) is very similar to modafinil. The FDA approved Nuvigil in 2007 to prevent excessive sleepiness in adults with the following sleep-related disorders:

• Narcolepsy
• Sleep apnea
• Shift work disorder

The drug is available in tablet form, with four different strengths: 50 mg, 150 mg, 200 mg, and 250 mg. The recommended dosage depends on the condition:

• Typical dosing for narcolepsy and sleep apnea: 150 mg to 250 mg once daily in the morning.
• Typical dosing for shift work sleep disorder: 150 mg one hour before the start of the work shift.
• Like modafinil, lower doses (50 mg to 150 mg) are typically recommended for individuals with liver problems or the elderly.

Armodafinil is used for many of the same purposes as modafinil.

How Do Armodafinil and Modafinil Differ?

Armodafinil and modafinil are very similar drugs. Armodafinil was developed by making minor changes to the composition of modafinil. As a result, the primary differences relate to their recommended doses, relative potency, and duration of effect. On a per-milligram basis, modafinil’s stimulating effect wears off more quickly than armodafinil’s. Although armodafinil and modafinil have similar half-lives of approximately 15 hours, blood levels of armodafinil remain higher for a longer period when both drugs are taken in the same amount. This is a critical point for cases of shift work sleep disorder. When taken an hour before a night shift, modafinil’s wakefulness-promoting effect may fade during the final third of the shift. This means the drug’s effectiveness in maintaining wakefulness decreases as the night shift approaches morning, increasing the risk of accidents if a person becomes excessively sleepy.

In one study comparing the two drugs for shift work sleep disorder, researchers found that taking 150 mg of armodafinil provided the same safe and effective reduction in sleepiness as 200 mg of modafinil.

Is Armodafinil or Modafinil Safer?

For most people, armodafinil and modafinil are safe options for reducing excessive sleepiness due to narcolepsy, sleep apnea, or shift work sleep disorder.

Given their similarities, both drugs are associated with the same side effects, which are discussed below.

A review of multiple studies found no significant differences in safety or side effects between the two drugs.

Side Effects

Armodafinil and modafinil may cause similar side effects. Mild side effects typically include the following:

• Headache
• Nausea
• Nervousness
• Nasal congestion or runny nose
• Diarrhea
• Anxiety
• Insomnia
• Dizziness
• Upset stomach

These side effects may occur more frequently at higher doses but may diminish or disappear as your body adjusts.

Less commonly, armodafinil or modafinil may cause serious side effects, such as:

• Severe skin reactions. Symptoms may include rash, itching, blistering, or peeling.
• Severe allergic reactions. Symptoms may include hives, difficulty breathing, or swelling of the tongue, throat, or lips.
• Worsening heart problems. Symptoms may include chest pain, rapid heartbeat, or shortness of breath.
• Psychiatric or mental changes. Symptoms may include increased aggression, delusions, or hallucinations.

If side effects from either drug persist, consult a doctor for advice.

Who Should Avoid Armodafinil or Modafinil? Who Should Use Armodafinil or Modafinil with Caution?

• Individuals with a history of allergic reactions to armodafinil or modafinil
• Individuals with a history of psychosis, depression, or mania
• Individuals with persistent excessive sleepiness despite using armodafinil or modafinil
• Individuals with a history of heart problems

Summary

Nuvigil (armodafinil) and Provigil (modafinil) are similar stimulant medications used to reduce excessive sleepiness from the following:

• Narcolepsy
• Sleep apnea
• Shift work sleep disorder

The two drugs share many similarities, including how they work, potential side effects, precautions, and interactions.

Key Differences:

• Dosage
• Relative potency (strength required for the drugs to produce an effect)
• Duration of their effect compared on a per-milligram basis

Sources

Peñalosa RA, Sarkar U, Claman DM, et al. Trends in on-label and off-label modafinil use in a nationally representative sample. JAMA Intern Med. 2013;173(8):704–706. doi:10.1001/jamainternmed.2013.2807

U.S. Food and Drug Administration. Nuvigil (armodafinil) label.

Robalino S, Anderson R, Harrod C. Off-label use of modafinil (ProvigilTM) and armodafinil (NuvigilTM). Evidence-Based Policy Center, Oregon Health & Science University. 2019.

Darwish M, Kirby M, Hellriegel ET, et al. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009;29(9):613-23. doi:10.2165/11315280

Tembe DV, Dhavale A, Desai H, et al. Armodafinil versus modafinil in patients with excessive sleepiness associated with shift work sleep disorder: a randomized double-blind multicenter clinical trial. Neurol Res Int. 2011, 514351. doi:10.1155/2011/514351.

Chapman JL, Vakulin A, Hedner J, et al. Modafinil/armodafinil in obstructive sleep apnea: a systematic review and meta-analysis. Eur Respir J. 2016;47(5):1420-8. doi:10.1183/13993003.01509-2015.

Author: Patricia Weiser, PharmD, is a licensed pharmacist and freelance medical writer with over 14 years of professional experience.