Armodafinil: uses, appearance and warnings

Armodafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD). Limitations of Use In OSA, armodafinil 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 armodafinil tablets for excessive sleepiness. Armodafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD). ( 1 ) Limitations of Use In OSA, armodafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction.

Armodafinil Tablets, 50 mg are white to off-white, round shaped uncoated tablets debossed with ‘K’ on one side and ‘58’ on the other side. Armodafinil Tablets, 150 mg are white to off-white, oval shaped uncoated tablets debossed with ‘K’ on one side and ‘59’ on the other side. Armodafinil Tablets, 200 mg are white to off-white rounded, rectangular uncoated tablets debossed with ‘10’ on one side and ‘N’ on the other side. Armodafinil Tablets, 250 mg are white to off-white, oval shaped uncoated tablets debossed with ‘K’ on one side and ‘60’ on the other side. Tablets: 50 mg, 150 mg, 200 mg, and 250 mg.

16.1 How Supplied Armodafinil Tablets, 50 mg are white to off-white, round shaped uncoated tablets debossed with ‘K’ on one side and ‘58’ on the other side. Bottles of 30 NDC 65862-805-30 Bottles of 60 NDC 65862-805-60 Bottles of 500 NDC 65862-805-05 Armodafinil Tablets, 150 mg are white to off-white, oval shaped uncoated tablets debossed with ‘K’ on one side and ‘59’ on the other side. Bottles of 30 NDC 65862-806-30 Bottles of 60 NDC 65862-806-60 Bottles of 500 NDC 65862-806-05 Armodafinil Tablets, 200 mg are white to off-white rounded, rectangular uncoated tablets debossed with ‘10’ on one side and ‘N’ on the other side. Bottles of 30 NDC 65862-998-30 Armodafinil Tablets, 250 mg are white to off-white, oval shaped uncoated tablets debossed with ‘K’ on one side and ‘60’ on the other side. Bottles of 30 NDC 65862-807-30 Bottles of 60 NDC 65862-807-60 Bottles of 500 NDC 65862-807-05 16.2 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Armodafinil 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) ] . Armodafinil tablets are contraindicated in patients with known hypersensitivity to modafinil or armodafinil.

Serious Rash, including Stevens-Johnson Syndrome: discontinue armodafinil at the first sign of rash, unless the rash is clearly not drug-related. ( 5.1 ) DRESS/Multi-organ Hypersensitivity Reactions: if suspected, discontinue armodafinil. ( 5.2 ) Angioedema and Anaphylaxis Reactions: if suspected, discontinue armodafinil. ( 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 particular caution in treating patients with a history of psychosis, depression, or mania. Consider discontinuing armodafinil if psychiatric symptoms develop. ( 5.5 ) Known Cardiovascular Disease: consider increased monitoring. ( 5.7 ) 5.1 Serious Dermatologic Reactions, including Stevens-Johnson Syndrome and Toxic Epidermal Necrosis Serious rash requiring hospitalization and discontinuation of treatment has been reported in association with the use of armodafinil or modafinil (the racemic mixture of S- and R-enantiomers). Armodafinil has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication. 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/ Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.2) ] . 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. Skin and mouth sores, blistering, and ulceration have been reported with modafinil and armodafinil in the postmarketing setting. Recurrence of signs and symptoms of serious dermatologic reactions following rechallenge has been reported in some cases. Rare cases of serious or life-threatening rash, including SJS and toxic epidermal necrolysis (TEN), have been reported in adults and children in worldwide post-marketing experience with modafinil and armodafinil. There are no factors, including duration of therapy, that are known to predict the risk of occurrence or the severity of rash associated with modafinil or armodafinil. In cases where the time to onset was reported, serious rash occurred 1 day to 2 months after initiation of treatment, but isolated cases of serious dermatologic reactions have been reported with symptoms beginning after prolonged treatment (e.g., 3 months). Although benign rashes also occur with armodafinil, it is not possible to reliably predict which rashes will prove to be serious. Accordingly, armodafinil should be discontinued at the first sign of rash, skin or mouth sores, or blistering or ulceration, 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 Drug Reaction with Eosinophilia and System Symptoms (DRESS)/Multiorgan Hypersensitivity DRESS, also known as multi-organ hypersensitivity, has been reported with armodafinil. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. One fatal case of DRESS that occurred in close temporal association (3 weeks) with the initiation of armodafinil treatment has been reported in the postmarketing setting. In addition, multi-organ hypersensitivity reactions, including at least one fatality in post-marketing experience, have occurred in close temporal association (median time to detection 13 days; range 4 to 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. If a multi-organ hypersensitivity reaction is suspected, armodafinil 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. 5.3 Angioedema and Anaphylaxis Reactions Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm), were observed with armodafinil. 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). 5.4 Persistent Sleepiness Patients with abnormal levels of sleepiness who take armodafinil should be advised that their level of wakefulness may not return to normal. Patients with excessive sleepiness, including those taking armodafinil, 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. …

The following serious adverse reactions are described below and elsewhere in the labeling: Serious Dermatologic Reactions [see Warnings and Precautions (5.1) ] Drug Reaction with Eosinophilia and System Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.2) ] Angioedema and Anaphylaxis 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, dizziness, and insomnia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

Effects of Armodafinil 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 armodafinil 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 armodafinil [see Clinical Pharmacology (12.3) ] . The effectiveness of steroidal contraceptives may be reduced when used with armodafinil 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 armodafinil and for one month after discontinuation of armodafinil treatment. Blood levels of cyclosporine may be reduced when used with armodafinil. …