The U.S. Food and Drug Administration (FDA) beefed-up warnings for carbamazepine, a medication used to treat epilepsy, bipolar disorder, and nerve pain. Included among the changes is a new recommendation that patients of Asian descent undergo genetic testing before using the drug.

Carbamazepine is sold as a generic drug under the brand names Carbatrol (Shire PLC), Tegretol (Novartis AG), and Equetro (Validus Pharmaceuticals Inc.). The drugs already carry a warning in the prescribing information of the possibility of rare but severe, and at-times life-threatening, skin reactions for all patients beginning therapy; the difference is that the FDA has now requested that this warning be moved to a more prominent location in an already-existing black box warning on the drug’s label.

Skin reactions include Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), allergic reactions that can cause severe blistering, rashes, and fever, and, under certain circumstances, may be fatal.

According to the FDA, research has indicated a relationship between certain serious skin reactions to the drug and an inherited variant of the gene HLA-B 1502, which is almost exclusively found in individuals of Asian descent. The FDA’s genetic testing recommendation for such individuals will also be added to the drugs’ boxed warning.

Source: Jennifer Corbett Dooren, “Epilepsy Drug to Get Stronger Warning,” Wall Street Journal, December 13, 2007.

On September 21, 2007, Cephalon sent a letter to healthcare professionals, alerting them to life-threatening dangers associated with Cephalon’s drug Provigil. Known generically as modafinil, Provigil is a drug designed to improve wakefulness in patients with sleep-deprivation illnesses. According to the letter, Provigil may cause serious skin and other hypersensitivity reactions, such as Stevens-Johnsons Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).

The letter instructed physicians specifically that:

• They should instruct patients who experience allergic reactions to discontinue use and contact their physician immediately;
• Provigil is not approved for use in pediatric patients; and
• Provigil can cause psychiatric symptoms.

Source: Cephalon letter to physicians, September 21, 2007.

Sabrina Brierton Johnson, a minor child of 7, filed a lawsuit in Los Angeles Superior Court on December 29, 2004, alleging that Children’s Motrin, manufactured by Johnson & Johnson, caused the allergic reaction known as Stevens-Johnson Syndrome. Miss Johnson became blind and photosensitive as a result. Her complaint charges Johnson & Johnson with negligence, breach of express and implied warranties, and deceit by concealment.

Defendants names in Ms. Johnson’s lawsuit include McNeil Consumer & Specialty Pharmaceuticals, McKesson Corporation, SAV-ON Drug Stores, Inc., and Ralphs Grocery Company.

On September 8, 2003, Miss Johnson, then age 6, was given Children’s Motrin after complaining of a fever. After two doses of the drug given at intervals specified on the label, she was rushed to the Pediatric Intensive Care Unit at Cedars-Sinai Medical Center in Los Angeles, CA, with a high fever, a redness of the sclera(white of the eye), a sore throat, and a rash that covered her back, trunk, and other parts of her body.

Within another twenty-four hours her eyes could only be forcibly opened by an ophthalmologist, causing her excruciating pain. By November, Miss Johnson was completely blind. It was discovered that she was suffering the adverse skin reaction known as Stevens-Johnson Syndrome. She continues to suffer ongoing medical problems and has undergone nearly 20 surgeries to attempt to correct her vision.

Miss Johnson alleges that the defendants knew of the high risk to consumers and users of Children’s Motrin after the completion of a clinical trial, used as the basis for the FDA’s approval of the drug, proved that there were cases of Stevens-Johnson syndrome but they were misrepresented.

Source: “Lawsuit: Children’s Motrin Caused Blindness,” Associated Press, December 28, 2003.

Pfizer, the pharmaceutical manufacturer of the COX-2 inhibitor Bextra, updated its warning about its drug’s link to a rare but fatal skin disorder known as Stevens-Johnson syndrome. Pfizer stated that cases of the condition are seen more often with Bextra than other drugs in the same class. An experimental intravenous version of the drug Pfizer is currently working on may never reach the U.S. market in the wake of this news.

Stevens-Johnson syndrome is a form of allergic reaction usually caused by certain types of drugs. Symptoms usually begin as a blistering of the lips and mouth that spreads to the throat, tongue, and other parts of the body. The blisters sometimes become so extensive that they are fatal. Jean Farrell, founder of the non-profit Stevens-Johnson Foundation, said that within weeks of Bextra hitting the market she had an increase in calls about the disease, claiming to have had “six cases of SJS reported to us” within three weeks of the availability of Bextra.

Following the withdrawal of Vioxx, Merck and Co.’s similar anti-inflammatory medication, Pfizer announced the findings of two small clinical trials that showed heart bypass surgery patients taking Bextra also had an increased risk of heart attack and stroke.

Source: Reuters Health , “Another Arthritis Drug Shows Risks,” 11/01/04.

The FDA has updated the warnings section of the labeling for the prescription drug Trileptal (oxcarbazepine), indicated for the treatment of partial seizures in adults and children aged 4-16 years old with epilepsy. (Trileptal (oxcarbazepine) has been associated with incidents of Stevens-Johnson Syndrome and toxic epidermal necrolysis in patients. Trileptal (oxcarbazepine) is marketed by Novartis Pharmaceuticals Corporation.

Stevens-Johnson Syndrome, or SJS, is a serious and sometimes fatal allergic skin reaction to an adverse drug. Victims of SJS develop painfully large blisters on their skin and inside mucous membranes such as the eyes and mouth. SJS may be preceded by an extremely high fever and other flu-like symptoms. As it progresses, SJS can cause swelling, conjunctivitis, skin erosions, and skin loss.

In the last stages of SJS, toxic epidermal necrolysis (TEN) occurs. At this stage of the illness, a person’s skin literally sloughs off their body. The skin is the largest organ of the body; skin death is usually fatal. More information on Stevens-Johnson syndrome and its relation to Trileptal (oxcarbazepine), Bextra, ibuprofen, and other drugs can be found at the Stevens-Johnson Foundation.