Provigil Hair and Skin Changes: What Modafinil Users and Clinicians Need to Know

What skin reactions does modafinil's label warn about?

Rare cases of serious or life-threatening rash, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS), have been reported in adults and children in worldwide postmarketing experience with modafinil [1]. The label states that the reporting rate of TEN and SJS with modafinil exceeds the background incidence, which it puts at 1 to 2 cases per million person-years in the general population [1].

The label also says plainly that there are no factors known to predict whether a rash will occur or how severe it will be [1].

Is serious rash a boxed warning on modafinil?

No. The Provigil prescribing information has no boxed warning and places serious skin and hypersensitivity reactions in Warnings and Precautions, with serious rash as section 5.1 [1].

The only contraindication listed for modafinil is known hypersensitivity to modafinil or armodafinil or their inactive ingredients [1].

When do rashes appear?

Nearly all cases of serious rash associated with modafinil occurred within 1 to 5 weeks after treatment began, although isolated cases have been reported after prolonged treatment, for example at about 3 months [1]. The label is explicit that duration of therapy cannot be relied on to predict the risk signalled by the first appearance of a rash [1].

What does the label say about a rash?

The Provigil label recommends discontinuing the drug at the first sign of rash unless the rash is clearly not drug-related, because it is not possible to predict reliably which rashes will turn out to be serious [1]. The label adds that stopping treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring [1].

A separate warning covers angioedema and anaphylaxis, which appeared in armodafinil trials and have been reported in postmarketing use with modafinil [1]. The label says patients should be advised to stop the drug and to report immediately swelling of the face, eyes, lips, tongue or larynx, difficulty swallowing or breathing, or hoarseness [1].

Multi-organ hypersensitivity

The label describes multi-organ hypersensitivity reactions detected at a median of 13 days after starting modafinil, with a range of 4 to 33 days, and at least one death in postmarketing reports [1]. Patients typically, though not exclusively, had fever and rash together with other organ involvement; listed features include myocarditis, hepatitis, liver function test abnormalities, eosinophilia, leukopenia, thrombocytopenia, pruritus and asthenia [1]. The label recommends discontinuing modafinil if the reaction is suspected [1].

What the pediatric data show

Modafinil is not approved for pediatric patients for any indication [1]. In clinical trials, rash leading to discontinuation occurred in about 0.8% of pediatric patients (13 of 1,585) and in none of the 380 children given placebo; the cases included one possible SJS and one apparent multi-organ hypersensitivity reaction, and several involved fever, vomiting or leukopenia [1].

Does modafinil cause hair loss?

Hair loss is not among the adverse reactions that occurred in more than 1% of patients and more often than placebo in Provigil's pooled placebo-controlled trials, which enrolled 934 patients on modafinil and 567 on placebo [1]. Those trials do not establish whether modafinil affects hair shedding either way.

A general review of diet and hair loss says people with hair loss should be screened by medical history, dietary history and physical exam for risk factors for nutrient deficiency, and that documented deficiencies should be corrected [2]. That review does not examine modafinil.

Does modafinil cause acne or seborrheic dermatitis?

The pooled Provigil trial table does not list acne, oiliness or seborrheic dermatitis among the reactions in more than 1% of patients [1]. These trials do not establish whether modafinil affects those conditions [1].