A Review of Lubiprostone (AMITIZA) for Irritable Bowel Syndrome with Constipation

The following article is an update about a new indication and new side effects for a drug we first reviewed in April 2007. Currently, there is no evidence that lubiprostone (AMITIZA) is safer or more effective than other available treatments for irritable bowel syndrome with constipation.

What is lubiprostone?

Lubiprostone (AMITIZA) was first approved by the Food and Drug Administration (FDA) in January 2006 for the treatment of chronic constipation from unknown causes in adults. The drug was approved for irritable bowel syndrome with constipation as the predominant symptom (IBS-C) in women 18 years of age or older in April 2008. The drug has not been approved for any other purposes.

Lubiprostone is the first in a new class of constipation drugs called "chloride channel activators." Although the drug is intended to work in the intestine, chloride channels are present in many rat tissues including skeletal muscle, heart, brain, lung, kidney, and liver. This may explain some of the observed adverse reactions. For example, a serious side effect of lubiprostone is dyspnea (difficulty breathing) which may be due to activation of chloride channels in the lungs, causing secretion of liquid which would interfere with breathing.

What is chronic constipation?

Chronic constipation is defined by the FDA as fewer than three spontaneous bowel movements per week. The constipation has to be present for at least 12 weeks, not necessarily consecutively, in the preceding 12 months.

What is irritable bowel syndrome?

The FDA defines persons with IBS-C as those having two or more of the following symptoms:

1. Fewer than three spontaneous bowel movements per week at least 25 percent of the time;

2. At least 25 percent of spontaneous bowel movements associated with moderate straining;

3. At least 25 percent of spontaneous bowel movements associated with hard stools.

What can cause constipation?

Constipation can be caused by factors such as inadequate fiber in the diet, inadequate intake of liquids, lack of exercise, and problems with the colon, rectum or intestinal function. Constipation can also be a side effect of some drugs, particularly painkillers, antidepressants, antacids, antispasmodics and blood pressure-lowering drugs.

What do we know about the safety and side effects of lubiprostone?

The long-term safety of lubiprostone is unknown.

A total of 1,154 patients took lubiprostone and 256 received an inactive sugar pill (placebo) for 12 weeks in two trials. In these controlled studies, there were significantly higher rates of nausea, diarrhea and abdominal pain in patients using lubiprostone than in those receiving a placebo. In addition, since approval in 2006, the FDA has received reports of side effects such as dyspnea (difficulty breathing), fainting, allergic reactions (rash, swelling, throat tightness), muscle cramps or spasms, and loss of strength.

Although it is not listed in the label, abortion is another possible serious side effect of lubiprostone. Lubiprostone is in the same drug class as the ulcer drug misoprostol (CYTOTEC), a drug widely used in medical abortions because it causes the uterus to contract after pregnancy termination with RU-486 (a "medical abortion"). It is not known if lubiprostone has caused abortions in humans, but it does cause abortions in guinea pigs, the human model for this type of drug. This occurs at doses which are the same as those used for treating chronic constipation.

Public Citizen submitted a petition to the FDA on May 6, 2009, asking that they add a black box warning, as is the case in the misoprostol label. This warning would require women of child-bearing potential to have adequate information about the risks of pregnancy such as an abortion induced by lubiprostone.

What evidence did the FDA use to approve lubiprostone?

The FDA approved lubiprostone primarily on the basis of the two clinical trials described above. The patients answered a single question every week: "How would you rate your relief of IBS symptoms over the past week compared to how you felt before you entered the study?" By the end of the study, patients had to remember how they felt three months previously.

The primary measure of lubiprostone’s effectiveness was a comparison of the proportion between lubiprostone and placebo groups as to whether they were an "overall responder," (increased bowel frequency) for two of three months.

Only six percent more women taking lubiprostone experienced increased bowel movement frequency than those taking the placebo. In fact, the response was so small that the FDA has asked the maker of lubiprostone to do another study using a higher dose. Unfortunately, as the dose increases, so do the side effects.

Is lubiprostone better than older treatments already on the market?

By law, new drugs do not have to be safer or more effective than drugs already on the market to be approved by the FDA.

Are other treatments available to treat IBS-C?

Yes. There are both over-the-counter and prescription drugs that are approved by the FDA to treat constipation; these are listed in the table below.

What is the cost of a one-month supply?

Over-the-counter drugs approved by the FDA to treat constipation are much less expensive than lubiprostone. The cost of a one-month supply of lubiprostone in a dosage of eight micrograms taken twice daily, or 60 capsules, is $215 at an Internet pharmacy.

What You Can Do

Do not use lubiprostone. There are safer and equally or more effective treatments for both chronic constipation and for the constipation variety of irritable bowel syndrome.

Table. Currently Approved Products to Treat Constipation