Armodafinil - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Serious Rash, including Stevens-Johnson Syndrome: discontinue NUVIGIL at the first sign of rash, unless the rash is clearly not drug-related.

DRESS/Multi-organ Hypersensitivity Reactions: if suspected, discontinue NUVIGIL.

Angioedema and Anaphylaxis Reactions: if suspected, discontinue NUVIGIL.

Persistent Sleepiness: assess patients frequently for degree of sleepiness and, if appropriate, advise patients to avoid driving or engaging in any other potentially dangerous activity.

Psychiatric Symptoms: use particular caution in treating patients with a history of psychosis, depression, or mania.

Consider discontinuing NUVIGIL if psychiatric symptoms develop.

Known Cardiovascular Disease: consider increased monitoring.

5.1 Serious Dermatologic Reactions, including Stevens-Johnson Syndrome and Toxic Epidermal Necrosis Serious rash requiring hospitalization and discontinuation of treatment has been reported in association with the use of NUVIGIL (armodafinil) or modafinil (the racemic mixture of S- and R-enantiomers).

NUVIGIL has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication.

In clinical trials of modafinil, the incidence of rash resulting in discontinuation was approximately 0.8% (13 per 1,585) in pediatric patients (age <17 years); these rashes included 1 case of possible Stevens-Johnson syndrome (SJS) and 1 case of apparent multi-organ hypersensitivity reaction/ Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions ] .

Several of the cases were associated with fever and other abnormalities (e.g., vomiting, leukopenia).

The median time to rash that resulted in discontinuation was 13 days.

No such cases were observed among 380 pediatric patients who received placebo.

Skin and mouth sores, blistering, and ulceration have been reported with modafinil and NUVIGIL in the postmarketing setting.

Recurrence of signs and symptoms of serious dermatologic reactions following rechallenge has been reported in some cases.

Rare cases of serious or life-threatening rash, including SJS and toxic epidermal necrolysis (TEN), have been reported in adults and children in worldwide postmarketing experience with modafinil and NUVIGIL.

There are no factors, including duration of therapy, that are known to predict the risk of occurrence or the severity of rash associated with modafinil or NUVIGIL.

In cases where the time to onset was reported, serious rash occurred 1 day to 2 months after initiation of treatment, but isolated cases of serious dermatologic reactions have been reported with symptoms beginning after prolonged treatment (e.g., 3 months).

Although benign rashes also occur with NUVIGIL, it is not possible to reliably predict which rashes will prove to be serious.

Accordingly, NUVIGIL should be discontinued at the first sign of rash, skin or mouth sores, or blistering or ulceration, unless the rash is clearly not drug-related.

Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.

5.2 Drug Reaction with Eosinophilia and System Symptoms (DRESS)/Multiorgan Hypersensitivity DRESS, also known as multi-organ hypersensitivity, has been reported with NUVIGIL.

DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection.

Eosinophilia is often present.

This disorder is variable in its expression, and other organ systems not noted here may be involved.