Modafinil

PROVIGIL is indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD). Limitations of Use In OSA, PROVIGIL is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating and during treatment with PROVIGIL for excessive sleepiness.

The mechanism(s) through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although the pharmacologic profile is not identical to that of the sympathomimetic amines. Modafinil-induced wakefulness can be attenuated by the α1-adrenergic receptor antagonist, prazosin, however, modafinil is inactive in other in vitro assay systems known to be responsive to α-adrenergic agonists such as the rat vas deferens preparation. Modafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, modafinil binds to the dopamine transporter and inhibits dopamine reuptake. This activity has been associated in vivo with increased extracellular dopamine levels in some brain regions of animals.

The recommended dosage of PROVIGIL for each indication is as follows: Narcolepsy or OSA: 200 mg once a day in the morning. SWD: 200 mg once a day, taken approximately one hour prior to start of the work shift. Severe Hepatic Impairment: reduce dose to half the recommended dose. Geriatric Patients: consider lower dose.

PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients. PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil or armodafinil.

Serious Rash, including Stevens-Johnson Syndrome: Discontinue PROVIGIL at the first sign of rash, unless the rash is clearly not drug-related. Angioedema and Anaphylaxis Reactions: If suspected, discontinue PROVIGIL. Multi-organ Hypersensitivity Reactions: If suspected, discontinue PROVIGIL. 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 caution in patients with a history of psychosis, depression, or mania. Consider discontinuing PROVIGIL if psychiatric symptoms develop. Known Cardiovascular Disease: Consider increased monitoring.

The following serious adverse reactions are described elsewhere in the labeling: Serious Rash, including Stevens-Johnson Syndrome Angioedema and Anaphylaxis Reactions Multi-organ Hypersensitivity Reactions Persistent Sleepiness Psychiatric Symptoms Effects on Ability to Drive and Use Machinery Cardiovascular Events Most common adverse reactions (≥5%): headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. Dosage adjustment of these drugs should be considered when these drugs are used concomitantly with PROVIGIL. The effectiveness of steroidal contraceptives may be reduced when used with PROVIGIL and for one month after discontinuation of therapy. Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with PROVIGIL and for one month after discontinuation of PROVIGIL treatment. Blood levels of cyclosporine may be reduced when used with PROVIGIL.

Storage Store at 20 o C ‑ 25 o C (68 o F ‑ 77 o F).