What is Glaxo Wellcome's position regarding lotronex?
The manufacturer of Lotronex (alosetron) tablets -- a drug used to
treat irritable bowel syndrome in women -- has voluntarily decided to
withdraw Lotronex from the market after discussions with the Food and Drug
Administration (FDA) on how to best manage risk.
This drug has been associated with reports of serious side effects such
as intestinal damage as a result of reduced blood flow to the intestine (ischemic
colitis), severely obstructed or ruptured bowels (complications of severe
constipation), and death.
What is Lotronex (alosetron hydrochloride)?
Lotronex is a prescription medicine used to treat women with irritable
bowel syndrome (IBS) who have diarrhea as their main symptom
(diarrhea-predominant IBS). Lotronex has not been shown to help men with
What is IBS?
IBS is also called irritable colon and spastic colon.
IBS causes lower abdominal pain and discomfort, urgency (a sudden need to
have a bowel movement), and irregular bowel habits, such as diarrhea or
constipation. In some people IBS causes mostly constipation; in others,
mostly diarrhea; some people have alternating periods of diarrhea and
constipation. Lotronex was approved only for women with
diarrhea-predominant IBS. Lotronex should not have been used by women who
have constipation as their main IBS symptom. IBS is a symptomatic disease
that can cause significant discomfort but which does not result in
complications that need bowel surgery (an operation).
What previous actions have FDA and the manufacturer
FDA has worked with the manufacturer of Lotronex to:
- Develop a Medication Guide that
communicates to patients the risk of rare but serious side effects
while taking Lotronex and which tells patients how they can recognize
those risks and take early action to prevent serious harm.
- Revise the professional labeling to
inform health care providers about these possible serious side effects
of Lotronex, to describe the types of patients that should not receive
Lotronex, to explain when Lotronex therapy should be interrupted or
stopped permanently, and to describe the types of patients that are
most likely to benefit from Lotronex.
- Distribute a "Dear
Health Care Practitioner" and a "Dear
Pharmacist" letter, which the manufacturer of Lotronex has
sent to health care providers to convey new information on safety.
What were some of the options FDA proposed to the manufacturer to
There are no current methods to anticipate which patients may suffer an
adverse reaction. It is for this reason, the FDA discussed with the
company other risk management options, including
restricted distribution or marketing withdrawal.
Because the FDA believes that IBS can be debilitating for some women,
we discussed the option of a restricted drug distribution program with the
company. The goals of a restricted use program would include:
- safer use of Lotronex in appropriately informed patients
- continued access to Lotronex by severely debilitated IBS patients
under closely monitored conditions
- continued clinical studies into the benefits and risks and safe use
Why did FDA approve Lotronex in the first place?
FDA based its approval on the results of two 12-week double-blinded,
placebo-controlled clinical trials. A total of 1273 non-constipated women,
who met specific pain and stool consistency criteria, were enrolled.
In each study, Lotronex was significantly more effective than placebo
in providing relief from IBS pain and discomfort and in reducing the
percentage of days with urgency.
Treatment with Lotronex also resulted in firmer stools and a
significant decrease in stool frequency.
Prior to approval, four cases of ischemic
colitis were observed in clinical studies and were discussed in November
1999 meeting of FDA’s Gastrointestinal Drugs Advisory Committee. At that
adverse events were transient, mild-to-moderate in nature and reversible
upon discontinuation of the drug.
FDA has been closely monitoring Lotronex since cases of intestinal
damage as a result of reduce blood flow to the intestine (ischemic
colitis) and severely obstructed or ruptured bowels (complications of
severe constipation) were first reported to FDA following approval of the
drug on February 9, 2000.
The FDA convened a second public advisory committee meeting on June 27,
2000 where risk management options in response to the serious adverse
event reports were discussed.
The consensus of the advisory committee members was that both doctors
and patients must be informed of the potentially serious adverse events
associated with Lotronex.
As of November 10, 2000, FDA has reviewed a total of 70 cases of
serious post-marketing adverse events, including 49 cases of ischemic
colitis and 21 cases of severe constipation. Of these 70 cases, 34
resulted in hospitalizations without surgery, 10 resulted in surgical
procedures and three resulted in death.
What should I do if I am currently taking Lotronex?
We encourage those people who have taken Lotronex to contact their
doctor and discuss the appropriate follow-up, and alternative treatments.
Any decision about which drug product to take to treat your symptoms
should be made in consultation with your doctor based on an assessment of
your specific treatment needs, specific risk profile, and other factors.
FDA does not regulate the practice of medicine and cannot comment on,
or recommend, a course of treatment for any individual.
Will Lotronex be recalled from the pharmacy?
The FDA did not request a recall of Lotronex. However, the company has
indicated that they are planning to recall the product from pharmacies.
Can my pharmacist continue to fill my prescription for Lotronex?
At this time, Lotronex will remain in pharmacies until supplies are
returned to the manufacturer or exhausted. Many pharmacies may choose to
no longer fill prescriptions for Lotronex. Contact your pharmacist
directly for more information.
Is Lotronex approved in other countries?
At this time Lotronex is also approved but not yet marketed in Mexico,
Argentina, Brazil, and South Korea.
How can I report a serious side effect with Lotronex to FDA?
FDA encourages anyone aware of a serious adverse reaction, including
consumers, to make a MedWatch report.
You can report an adverse event in two ways:
Who manufactures Lotronex?
Research Triangle Park, NC 27709
Where can I get more information relating to the withdrawal of
To find out more about Lotronex from FDA:
Visit the FDA Drug Information web page at: www.fda.gov/cder
Call Drug Information at: 888-INFO-FDA (888-463-6332)