PROVIGIL

Modafinil is a 1:1 racemic compound, whose enantiomers have different pharmacokinetics (e.g., the half-life of R-modafinil is approximately three times that of S-modafinil in adult humans). The enantiomers do not interconvert. At steady state, total exposure to R-modafinil is approximately three times that for S-modafinil. The trough concentration (C min,ss ) of circulating modafinil after once daily dosing consists of 90% of R-modafinil and 10% of S-modafinil. The effective elimination half-lif...

14.1 Narcolepsy The effectiveness of PROVIGIL in improving wakefulness in adult patients with excessive sleepiness associated with narcolepsy was established in two US 9‑week, multi-center, placebo‑controlled, parallel-group, double‑blind studies of outpatients who met the criteria for narcolepsy. A total of 558 patients were randomized to receive PROVIGIL 200 or 400 mg/day, or placebo. The criteria for narcolepsy include either: 1) recurrent daytime naps or lapses into sleep that occur almost daily for at least three months, plus sudden bilateral loss of postural muscle tone in association wi...

The following serious adverse reactions are described elsewhere in the labeling: Serious Rash, including Stevens-Johnson Syndrome [see Warnings and Precautions ( 5.1 )] Angioedema and Anaphylaxis Reactions [see Warnings and Precautions ( 5.2 )] Multi-organ Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Persistent Sleepiness [see Warnings and Precautions ( 5.4 )] Psychiatric Symptoms [see Warnings and Precautions ( 5.5 )] Effects on Ability to Drive and Use Machinery [see Warni...

PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil or armodafinil. ( 4 )

Serious Rash, including Stevens-Johnson Syndrome: Discontinue PROVIGIL at the first sign of rash, unless the rash is clearly not drug-related. ( 5.1 ) Angioedema and Anaphylaxis Reactions: If suspected, discontinue PROVIGIL. ( 5.2 ) Multi-organ Hypersensitivity Reactions: If suspected, discontinue PROVIGIL. ( 5.3 ) Persistent Sleepiness: Assess patients frequently for degree of sleepiness and, if appropriate, advise patients to avoid driving or engaging in any other potentially dangerous activit...

7 DRUG INTERACTIONS 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 PR...