A Review of Lubiprostone (AMITIZA) For Chronic Constipation

The following article is meant to help introduce Worst Pills readers to a new drug that will probably receive a substantial amount of public attention. Public Citizen does not think that there is currently enough evidence that lubiprostone (AMITIZA) is safer or more effective than other treatments currently available for chronic constipation. This article compiles the most important information, alternative treatments for the drug’s indication and our recommendation for use of this drug in an easy-to-read format. This guide will help answer questions about lubiprostone, allowing you to make better choices when faced with new drug decisions in the future.

What is Lubiprostone?
Lubiprostone was approved by the Food and Drug Administration (FDA) in January 2006 only for the treatment of chronic constipation from unknown causes in adults. The drug has not been shown to be safe and effective for any other purposes. The drug has not been studied in pediatric patients.

Lubiprostone is the first in a new of drugs for constipation called chloride channel activators.

What is Chronic Constipation?
For the purpose of the FDA approving lubiprostone, chronic constipation was defined as less than three spontaneous bowel movements per week. The constipation had to be present for at least 12 weeks, which did not have to be consecutive, in the preceding 12 months.

What is Known About the Safety of Lubiprostone?
The long-term safety of lubiprostone is unknown. A total of 878 patients have taken lubiprostone for up to 48 weeks in studies submitted to the FDA.  

Because lubiprostone is the first in a new of drugs that works in a new way, it is possible that unknown and unpredictable side effects may occur after the drug is used in large numbers of patients.

In the controlled studies, there were significantly higher rates of nausea, diarrhea, headache and abdominal pain in patients using lubriprostone than in those receiving a placebo.

What Factors Contribute to the Development of Constipation?
Factors contributing to the development of constipation include inadequate fiber in the diet, lack of exercise, neurological and systemic disorders and problems with the colon, rectum or intestinal function. The side effects of some drugs may contribute to constipation, particularly painkillers, antidepressants, antacids, antispasmodics and blood pressure-lowering drugs.

What Evidence Did FDA Use to Approve Lubiprostone?
The FDA approved lubiprostone primarily on the basis of two clinical trials that compared the active drug to an inactive placebo given over a period of four weeks.  

How Was the Efficacy or Effectiveness of Lubiprostone Measured?
The primary measure of lubiprostone’s effectiveness was the frequency of spontaneous bowel movements during one week.

What Was the Difference in Bowel Movement Frequency Between Lubiprostone and Placebo During One Week?
At the beginning, in the main studies submitted to the FDA, patients had on average one spontaneous bowel movement every four to five days. After beginning treatment with lubiprostone, this number increased to one spontaneous bowel movement every one to two days.  

Is Lubiprostone Better Than Older Treatments Already on the Market?
The answer to this question is unknown. By law, new drugs do not have to be safer or more effective than drugs already on market to be approved by the FDA.

It is a violation of the advertising provisions of the Food, Drug and Cosmetic Act for a drug manufacturer to make claims of therapeutic superiority without scientific evidence reviewed and approved by the FDA. The manufacturer of lubiprostone can not legally claim that lubiprostone is a better treatment for constipation than drugs that are already on the market.

Are There Other Treatments Available to Treat Chronic Constipation?
Yes. There are both over-the-counter and prescription drugs that are approved by the FDA to treat constipation.

Currently Approved Over-the-Counter Products

1. Bulk-forming laxatives are generally considered the safest and most mild treatments, but they are not always effective in relieving constipation and can interfere with the absorption of some drugs. These laxatives are also known as fiber supplements. These products usually contain bran or psyllium.
2. Stimulants cause rhythmic muscle contractions in the intestines. Brand names include CORRECTOL, DULCOLAX, PURGE and SENOKOT. Studies suggest that phenolphthalein, an ingredient in some stimulant laxatives, may increase the risk of cancer. The FDA has proposed a ban on all over-the-counter products containing phenolphthalein. (We recommend against using these drugs because they can lead to dependance.)
3. Stool softeners provide moisture to the stool. Products include COLACE and SURFAK. (We recommend against using these drugs.)
4. Lubricants grease the stool enabling it to move through the intestine more easily. Mineral oil and glycerin suppositories are the most common examples.
5. Saline laxatives act like a sponge to draw water into the colon for easier passage of stool. Laxatives in this group include MILK of MAGNESIA, CITRATE of MAGNESIA and HALEY’S M-O.
6. Osmotic agents draw water into the bowel and increase the overall volume of the stool. These agents are made from certain types of salts or sugars. Agents in this group include magnesium citrate and sodium citrate.
7. Enemas empty the colon or rectum of retained stool through mechanical expansion of the bowel. Tap water or other osmotic, stimulant or irritative substances can be used. (We recommend against using these drugs in an enema.)

Currently Approved Prescription Products

1. Polyethylene glycol (MIRALAX) acts as an osmotic agent that causes water to be retained within the stool. It may require two to four days of treatment to produce a bowel movement. Prolonged use of this product may cause an imbalance of minerals in the blood and dependence. The most common adverse effects are nausea, abdominal bloating, cramping and gas. High doses may cause diarrhea.
2. Tegaserod (ZELNORM) was approved by the FDA in July 2002. This drug is approved for the treatment of patients less than 65 years of age with chronic constipation of unknown cause. Diarrhea is a common side effect and the label carries a warning about a decrease in blood volume (hypovolemia), low blood pressure (hypotension), fainting spells (syncope), and a potentially life-threatening loss of blood flow to the intestine known as ischemic colitis. (We recommend against using this drug.)

What is the Cost of a One-Month Supply of Lubiprostone?
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 24 micrograms taken twice daily, or 60 capsules, is $173.98 at a popular Internet pharmacy.

What You Can Do
Do not use lubiprostone until 2014 – seven years after the date of FDA approval. You should wait at least seven years from the date of FDA approval to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs. This is because new drugs are tested in a relatively small number of people before being released, and serious side effects or life-threatening drug interactions may not be detected until the new drug has been taken by hundreds of thousands of people. A number of new drugs have been withdrawn within the first seven years of release. Also, warnings about serious new side effects have been added to the labeling of a number of drugs, or new drug interactions have been detected, usually within the first seven years of a drug’s release.

The information in this article is based on publicly-available documents prepared by Food and Drug Administration (FDA) scientific and medical staff that is available at: http://www.fda.gov/cder/foi/nda/2006/021908s000_Amitiza_MEDR.pdf. These FDA documents are the most complete and objective information available at the time a new drug is approved.