In October 2007, the Food and Drug Administration (FDA) issued warnings about modafinil (Provigil), a drug that is commonly used in people with MS.  These warnings are about possible severe rashes, allergic reactions, and psychiatric side effects that may occur with the use of the medication.

Provigil was approved for use by the FDA in 1998.  It is currently approved for treating various sleep disorders, including narcolepsy, which is sometimes referred to as sleeping sickness.  In addition, over the past several years, Provigil has been prescribed by physicians to attempt to treat fatigue in people with MS—this use of the drug is supported by some studies that show fatigue-relieving effects of Provigil in MS. 

Of note, the use of Provigil for MS fatigue is an off-label use of the drug—that is, it is prescribed by some physicians for MS fatigue, but it is not officially approved by the FDA for this specific purpose.

Rashes
In the notice issued by FDA, it states that various severe skin rashes may rarely occur with Provigil.  These rashes may disfigure the skin, be associated with other symptoms (such as fever and vomiting), and be life-threatening.  The medical terms for these rashes are Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). 

Mild and benign rashes may also occur with Provigil.  At this time, it is not known if these mild rashes will develop into severe rashes.  As a result, if a person develops even a mild rash while taking Provigil, the current FDA recommendation is to discontinue Provigil, unless the rash is clearly not drug-related.

Allergic Reactions
It is thought that various severe allergic reactions may occur with Provigil.  One of these reactions, known as anaphylaxis, may cause difficulty with breathing and swallowing.  Another severe allergy, angioedema, causes swelling of the face, eyes, lips, or tongue.  Multi-organ hypersensitivity reaction, a serious allergic response that affects different organs in the body, may also occur with Provigil use.

Psychiatric Symptoms
The FDA warning also indicates that psychiatric symptoms may develop in those taking Provigil.  Specifically, Provigil use has been associated with hallucinations, anxiety, severe agitation (mania), and depression.  The drug should be used with caution in those with a history of depression, mania, or psychosis.

How Concerned Should You Be?
The FDA statement does not report how common these reactions are.  These side effects were identified through post-marketing reports, which are reports of side effects that are collected after drugs have been approved.  Through this reporting system, it is difficult to determine the exact risk for various side effects.  For Provigil, it appears that some of the severe side effects appear to be more common in the general population—however, some of these conditions are extremely rare in the general population. 

For example, in the general population, TEN and SJS, the severe skin reactions that may occur with Provigil, occur in only one or two people for every million years that people are monitored.  Hopefully, these extremely rare conditions are only slightly more common in those taking Provigil.  However, with the limited information that is currently available, it is not possible to determine exactly how common these side effects are with Provigil use.

For more information or to report a problem:

  • More information may be obtained from:www.fda.gov/medwatch/safety/2007/safety07.htm#Provigil. 
  • If you suspect that you have a Provigil-related side effect, you should discuss this with your physician.  Provigil side effects may be reported to: FDA’s MedWatch program:  800-332-1088, www.fda.gov/medwatch
  • The Medical Department at Cephalon, the manufacturer of Provigil:  800-896-5855 


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