Modafinil: uses, appearance and warnings

Modafinil tablets are 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, modafinil tablets are 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 modafinil tablets for excessive sleepiness. Modafinil tablets are 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, modafinil tablets are indicated to treat excessive sleepiness and not astreatment for the underlying obstruction.

Modafinil Tablets, USP 100mg–White to off white capsule shaped uncoated tablets debossed with AC 132 on one side and plain on other side. Modafinil Tablets, USP 200 mg – White to off white round shaped uncoated tablet scored on the one side with AC above and 133 below and plain on other side. Tablets: 100 mg and 200 mg

16.1 How Supplied Modafinil Tablets, USP are available as follows: 100 mg White to off white capsule shaped uncoated tablets debossed with AC 132 on one side and plain on other side. NDC 23155-604-03 - Bottles of 30 NDC 23155-604-09 - Bottles of 90 NDC 23155-604-01 - Bottles of 100 NDC 23155-604-05 - Bottles of 500 200 mg White to off white round shaped uncoated tablet scored on the one side with AC above and 133 below and plain on other side. NDC 23155-862-03 - Bottles of 30 NDC 23155-862-09 - Bottles of 90 NDC 23155-862-01 - Bottles of 100 NDC 23155-862-05 - Bottles of 500 16.2 Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Dispense in a tight container. 16.1 How Supplied Modafinil Tablets, USP are available as follows: 100 mg White to off white capsule shaped uncoated tablets debossed with AC 132 on one side and plain on other side. NDC 23155-604-03 - Bottles of 30 NDC 23155-604-09 - Bottles of 90 NDC 23155-604-01 - Bottles of 100 NDC 23155-604-05 - Bottles of 500 200 mg White to off white round shaped uncoated tablet scored on the one side with AC above and 133 below and plain on other side. NDC 23155-862-03 - Bottles of 30 NDC 23155-862-09 - Bottles of 90 NDC 23155-862-01 - Bottles of 100 NDC 23155-862-05 - Bottles of 500 16.2 Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Dispense in a tight container.

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

Serious Rash, including Stevens - Johnson Syndrome: Discontinue Modafinil tablets at the first sign of rash, unless the rash is clearly not drug-related. (5.1) Angioedema and Anaphylaxis Reactions: If suspected, discontinue modafinil tablets. (5.2) Multi-organ Hypersensitivity Reactions: If suspected, discontinue modafinil tablets. (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 activity. (5.4) Psychiatric Symptoms: Use caution in patients with a history of psychosis, depression, or mania. Consider discontinuing modafinil tablets if psychiatric symptoms develop. (5.5) Known Cardiovascular Disease: Consider increased monitoring. (5.7) 5.1 Serious Rash, including Stevens - Johnson Syndrome Serious rash requiring hospitalization and discontinuation of treatment has been reported in association with the use of modafinil. 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. 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. Modafinil tablets are not approved for use in pediatric patients for any indication [see Use in Specific Populations (8.4) ]. Rare cases of serious or life-threatening rash, including 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. The reporting rate of TEN and SJS associated with modafinil use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate. Estimates of the background incidence rate for these serious skin reactions in the general population range between 1 to 2 cases per million-person years. There are no factors that are known to predict the risk of occurrence or the severity of rash associated with modafinil tablets. Nearly all cases of serious rash associated with modafinil occurred within 1 to 5 weeks after treatment initiation. However, isolated cases have been reported after prolonged treatment (e.g., 3 months). Accordingly, duration of therapy cannot be relied upon as a means to predict the potential risk heralded by the first appearance of a rash. Although benign rashes also occur with modafinil tablets, it is not possible to reliably predict which rashes will prove to be serious. Accordingly, modafinil tablets should be discontinued at the first sign of rash, 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 Angioedema and Anaphylaxis Reactions Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm), were observed in patients treated with armodafinil, the R enantiomer of modafinil (which is the racemic mixture). No such cases were observed in modafinil clinical trials. However, angioedema has been reported in postmarketing experience with modafinil. Patients should be advised to discontinue therapy and immediately report to their physician any signs or symptoms suggesting angioedema or anaphylaxis (e.g., swelling of face, eyes, lips, tongue or larynx; difficulty in swallowing or breathing; hoarseness). 5.3 Multi-organ Hypersensitivity Reactions Multi-organ hypersensitivity reactions, including at least one fatality in postmarketing experience, have occurred in close temporal association (median time to detection 13 days: range 4-33) to the initiation of modafinil. Although there have been a limited number of reports, multi-organ hypersensitivity reactions may result in hospitalization or be life-threatening. There are no factors that are known to predict the risk of occurrence or the severity of multi-organ hypersensitivity reactions. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations included myocarditis, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, leukopenia, thrombocytopenia), pruritus, and asthenia. Because multi-organ hypersensitivity is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If a multi-organ hypersensitivity reaction is suspected, modafinil tablets should be discontinued. Although there are no case reports to indicate cross-sensitivity with other drugs that produce this syndrome, the experience with drugs associated with multi-organ hypersensitivity would indicate this to be a possibility. 5.4 Persistent Sleepiness Patients with abnormal levels of sleepiness who take modafinil tablets should be advised that their level of wakefulness may not return to normal. Patients with excessive sleepiness, including those taking modafinil tablets, should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity. Prescribers should also be aware that patients may not acknowledge sleepiness or drowsiness until directly questioned about drowsiness or sleepiness during specific activities. 5.5 Psychiatric Symptoms Psychiatric adverse reactions have been reported in patients treated with modafinil. …

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 Warnings and Precautions (5.6) ] Cardiovascular Events [see Warnings and Precautions (5.7) ] Most common adverse reactions (≥5%): headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Effects of Modafinil Tablets 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 modafinil tablets 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 modafinil tablets [see Clinical Pharmacology (12.3) ]. The effectiveness of steroidal contraceptives may be reduced when used with modafinil tablets 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 modafinil tablets and for one month after discontinuation of modafinil tablets treatment. …