June 7, 2002 -- It's never happened before. A drug withdrawn after patient deaths is back on the market.
The drug is Lotronex, originally approved for the treatment of irritable bowel syndrome (IBS). After only eight months on the market, the drug was linked to at least four deaths and nearly 200 serious cases of blocked blood flow or severe constipation. Many of these patients required surgery. Some remain permanently disabled.
The drug now will be approved only for the relatively few IBS patients who have the severe, diarrhea-predominant form of the disease. Even for these patients, there is no guarantee that Lotronex is safe.
"It is still the case that we don't know what the risk factors are to predict which patients will get [severe complications] and which won't," Victor Raczkowski, MD, tells WebMD. "However, all prescription drugs have risks associated. Our goal with this program is to try to put mechanisms in place to assure that only the most severely affected women with IBS diarrhea are affected. These patients might be willing to accept the risks." Raczkowski is deputy chief of gastrointestinal drugs at the FDA.
The risk is not small. Data suggest that 1 in every 350 women who take Lotronex for six months will suffer blocked blood flow to the intestine -- a sometimes-fatal condition called ischemic colitis. The risk for women who take the drug for more than six months is not known.
The FDA's reapproval of the drug comes with unprecedented restrictions:
- The drug can be given only to women with severe IBS and diarrhea so bad it disrupts daily life.
- Patients who agree to take the drug must sign an agreement swearing that their doctor has explained the risks and that they understand them. They must also promise to follow a four-page guide to taking Lotronex.
- Doctors who want to prescribe the drug must sign a contract swearing that they are qualified to treat IBS, that they told their patient of the risks, and that they will report any and all problems to both the FDA and GlaxoSmithKline, the manufacturer of Lotronex.
- Prescriptions for Lotronex must carry a special sticker available only to doctors who have signed up for the program.
- The FDA will closely monitor all reports of adverse events. "If we do see something, we intend to get actively involved," Raczkowski says.
How many people will take the drug? Eric Carter, MD, vice president of gastrointestinal clinical development for GlaxoSmithKline, says he doesn't know.
"Our hope is that there is a significant number of patients who might benefit," Carter tells WebMD.
There may well be quite a few. One in 10 women suffer from IBS diarrhea. Many of these women get little help from available treatments. However, only 1 in 20 people with IBS has severe disease, and not all of these people have diarrhea-predominant IBS.
When the FDA's advisory board met in April 2002 to consider Lotronex reapproval, a parade of patients testified that their lives would not be worth living without Lotronex. Many others, unable to attend because of IBS, submitted moving testimonials in writing.
"After 10 long years of suffering relentlessly, [Lotronex] removed the anxiety, the fear, the shame. ... It was a second chance at life!" writes Liza Kenney, a member of Lotronex Action Group, an IBS patient-advocacy organization. "The day Lotronex returns will indeed be the happiest day of my life and to countless other sufferers as well."
Others wrote to tell of their terrible experiences with the drug. Ann DuPre Royall took part in a clinical trial of Lotronex.
"I developed severe pain from constipation [and] nausea and I was doubled over in pain on the bathroom floor," Royall writes. "I was taken to [the hospital] where I spent two days. It left me so weak that it has taken me two years to feel better. ... Please do not give in to GlaxoSmithKline's request to re-introduce this horrible drug."