Yet Another Medication Carries SJS Risk

Washington, DCA new medication designed to improve wakefulness that was introduced to the US market last month already has a bolded warning for SJS, among other potentially serious SJS side effects. Stevens Johnson Syndrome is a rare, but potentially dangerous condition characterized by skin lesions akin to serious burns.

It can, and has proved fatal.

The onset of SJS as an adverse reaction to medication is not uncommon--and there are various drugs that list SJS as a potential side effect. One of the latest is NUVIGIL (armodafinil), a drug manufactured by Cephalon Inc. for the indication of improved wakefulness in patients with excessive sleepiness.

The latter can be caused by a number of factors. NUVIGIL armodafinil--the longer-lasting cousin to modafinil--is indicated for the treatment of excessive sleepiness associated with treated obstructive sleep apnea, shift work sleep disorder and narcolepsy.

On June 30th of this year it was announced that Cephalon had filed a supplemental New Drug Application (sNDA) with the US Food and Drug Administration (FDA) for approval to include an indication for the relief of excessive sleepiness due to jet lag syndrome.

"This supplemental New Drug Application for a new use of NUVIGIL is another important milestone for Cephalon," said Dr. Lesley Russell, Chief Medical Officer and Executive Vice President at Cephalon, in a release to PRNewswire "We hope that this will be the first of many new indications for NUVIGIL over the next five years."

The proposed NUVIGIL sNDA for the indication of jet lag disorder is based on data from a Phase 3 study recently presented at SLEEP 2009, part of the 23rd Annual Meeting of the Associated Professional Sleep Societies in Seattle, Washington. The data from the novel placebo-controlled pivotal study involved overseas air travel and included an evaluation of the efficacy and safety of NUVIGIL (50 or 150 mg/day) in 427 healthy men and women all of whom had experienced jet lag symptoms at least once during the previous five years. Clinical efficacy was evaluated using two primary endpoints: an objective assessment -- the Multiple Sleep Latency Test (MSLT), and a subjective assessment -- the Patient Global Impression of Severity (PGI-S). Patients taking NUVIGIL (150 mg/day) showed a statistically significant improvement over placebo. The most common adverse events associated with NUVIGIL treatment (five percent or greater) were headache, nausea, diarrhea, and palpitations.

Even so, the NUVIGIL labeling information includes bolded warnings for serious or life-threatening rash, including Stevens Johnson Syndrome, as indicated below…

"Serious Rash, including Stevens-Johnson Syndrome. Serious rash requiring hospitalization and discontinuation of treatment has been reported in adults and children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil)." (source: nuvigil.com)

The manufacturer goes on to say while there were no serous skin rashes associated with either modafinil or armodafinil in adults participating in the clinical trials for both medications, "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 post-marketing experience.

"No serious skin rashes have been reported in adult clinical trials (0 per 1,595) of armodafinil," the manufacturer continues in its warning to patients in the labeling information. "However, because armodafinil is the R isomer of racemic modafinil, a similar risk of serious rash with armodafinil cannot be ruled out."

Given the potential, however small for SJS, patients suffering from severe sleepiness should be aware of the potential SJS side effects--among others--with regard to NUVIGIL. Excessive sleepiness can be debilitating. However, some patients having reactions to other medications have acquired Stevens Johnson Syndrome and have not survived.