Serious Dermatologic Reactions

Serious skin rash (e.g., Stevens-Johnson syndrome [SJS]) requiring hospitalization and drug discontinuance was reported in adult and pediatric patients receiving modafinil.

Severe rash (e.g., possible SJS, multiorgan hypersensitivity reaction), sometimes associated with fever and other abnormalities (e.g., vomiting, leukopenia), reported in pediatric clinical trials. No serious crashes reported in clinical trials in adults. Serious or life-threatening rash (e.g., SJS, toxic epidermal necrolysis [TEN], drug rash with eosinophilia, and systemic symptoms [DRESS]) are reported rarely during postmarketing experience. Modafinil is not approved for use in pediatric patients for any indication. (See Pediatric Use under Cautions.)

No known risk factors predict the occurrence or severity of the rash. Nearly all cases occurred within 1–5 weeks following initiation of therapy, but cases were also reported after prolonged (e.g., 3 months) treatment.

Benign rashes also occur with modafinil; not possible to predict which rashes will become serious. Therefore, discontinue the drug at the first sign of rash unless clearly not drug-related. (See Advice to Patients.) The rash may become potentially life-threatening or permanently disabling or disfiguring despite drug discontinuance.

Persistent Sleepiness

In patients with abnormal levels of sleepiness, the level of wakefulness may improve with modafinil therapy, but may not return to normal. (See Advice to Patients.)

Frequently reassess the degree of sleepiness, and, if appropriate, advise patients to avoid driving or other potentially dangerous activity. Patients may not acknowledge sleepiness or drowsiness until directly questioned about these symptoms during specific activities. (See Advice to Patients.)

Psychiatric Effects

Adverse psychiatric effects (e.g., mania, delusions, hallucinations, suicidal ideation, aggression), sometimes resulting in hospitalization, were reported in modafinil-treated patients; many, but not all, patients had a psychiatric history.

In controlled clinical trials, psychiatric symptoms that required treatment discontinuance in ≥0.3% of patients and more often for modafinil than for placebo included anxiety, nervousness, insomnia, confusion, agitation, and depression.

Use caution in patients with a history of psychosis, depression, or mania.

Some clinicians recommend careful monitoring of patients receiving modafinil or other CNS stimulants for possible psychiatric effects. If psychiatric symptoms develop, consider drug discontinuance. (See Advice to Patients.)

Sensitivity Reactions

Angioedema and Anaphylactoid Reactions

Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm) were reported with armodafinil. Angioedema was also reported during postmarketing experience with modafinil.

Immediately discontinue therapy if any signs or symptoms of angioedema or anaphylaxis (e.g., swelling of face, eyes, lips, tongue, or larynx; difficulty swallowing or breathing; hoarseness) develop.

Multiorgan Hypersensitivity Reactions

Multiorgan hypersensitivity reactions, including at least 1 fatality, reported with modafinil.

Reactions detected a median of 13 days (range: 4–33 days) after initiation of modafinil. Clinical presentation was variable but typically include fever and rash associated with other organ system involvement (e.g., myocarditis, hepatitis, liver function test abnormalities, hematologic abnormalities [e.g., eosinophilia, leukopenia, thrombocytopenia], pruritus, asthenia).

No risk factors are known to predict occurrence or severity.

If a multi-organ hypersensitivity reaction is suspected, discontinue therapy. Cross-sensitivity with other drugs that produce this syndrome not yet reported but is possible.