Drug Criteria & Outcomes

New FDA Approvals

The FDA has approved Entereg® (alvimopan) to accelerate the restoration of normal bowel function in patients 18 years and older who have undergone partial large or small bowel resection surgery. Alvimopan will be used in hospitalized patients who can receive no more than 15 doses.

"Patients who have undergone abdominal surgery and are on pain medications often experience problems eliminating waste," said Joyce Korvick, MD, deputy director, Division of Gastroenterology Products. "Entereg will help accelerate their recovery, improve bowel function, and get these patients back on a normal diet. As with all FDA-approved products, the agency will monitor Entereg throughout its life cycle."

FDA is approving alvimopan with a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the drug outweigh the risks. The REMS will include limits on dispensing of the drug.

In approving alvimopan, FDA determined that a REMS is necessary to ensure that the benefits of alvimopan outweigh its risks. The REMS will include restricting alvimopan to inpatient use only, requiring that hospitals be specially certified, distribution of educational materials to health care professionals, and regular assessments of the effectiveness of the REMS.

Following major abdominal surgery, some patients develop a condition known as postoperative ileus (POI). POI is a disorder that causes temporary impairment of the gastrointestinal (GI) tract's motility, or the ability of the intestines to push out waste products (not a complete blockage of the GI tract), following surgery. POI can be a by product of a patient taking opioid pain relievers, like morphine, prescribed after surgery which can slow or inhibit normal motility. Alvimopan works by blocking opioid effects in the bowel.

The recommended dose for alvimopan is one 12 mg capsule given just prior to surgery and then another 12 mg dose administered twice daily for up to 7 days or not to exceed 15 doses. The product will only be available to hospitals and will come in blister packs that are marked "HOSPITAL USE ONLY." Alvimopan is not approved for use in pediatric populations.

The safety and efficacy of alvimopan in postoperative patients were demonstrated in five studies that included 2,177 patients, of whom 1,096 received alvimopan and 1,081 received placebo. Bowel recovery times ranged from 10 to 26 hours shorter for alvimopan-treated patients compared to placebo-treated patients in the five studies. The most common side effects reported were low blood calcium levels, anemia, and gastrointestinal problems, including constipation, dyspepsia (heartburn), and flatulence (excess bowel gas).

FDA has reviewed a 12-month study of alvimopan in patients treated with opioid medications for chronic pain. In this study, there were more reports of myocardial infarctions in patients treated with a 0.5 mg dose of alvimopan twice daily, compared with placebo-treated patients. This imbalance has not been observed in other studies of alvimopan, including studies in patients undergoing bowel resection surgery who took 12 mg of alvimopan, twice daily for up to 7 days. A causal relationship with alvimopan and myocardial infarction has not been established.

Consumers and health care professionals are encouraged to report adverse events to FDA's MedWatch program at (800) FDA-1088 or on-line at: www.fda.gov/medwatch/how.htm.

The FDA has approved Amitiza® (lubiprostone) for the treatment of irritable bowel syndrome with constipation (IBS-C) in adult women aged 18 and older. There is currently no prescription drug therapy for IBS-C. With this approval, lubiprostone becomes the only FDA-approved medical treatment for IBS-C available in the United States.

Irritable bowel syndrome is a disorder characterized by cramping, abdominal pain, bloating, constipation, and diarrhea. IBS causes a great deal of discomfort and distress to its sufferers. It affects at least twice as many women as men.

"For some people IBS can be quite disabling, making it difficult for them to fully participate in everyday activities," said Julie Beitz, MD, director of the Office of Drug Evaluation III, Center for Drug Evaluation and Research, FDA. "This drug represents an important step in helping to provide medical relief from their symptoms."

The safety and efficacy of lubiprostone was established in two major studies involving 1,154 patients diagnosed with IBS-C. The majority of the patients studied were women (approximately 8% were men). Patients enrolled in the studies were experiencing at least mild abdominal discomfort or pain that was associated with at least two of the following additional symptoms: 1) fewer than three spontaneous bowel movements per week (that did not result from laxative use); 2) hard stools; or 3) moderate or severe straining with bowel movements. In the studies some patients received lubiprostone and others were given a placebo. More patients treated with lubiprostone reported that their IBS symptoms were moderately or significantly relieved over a 12-week treatment period than patients who received placebo. The safety of long-term treatment was assessed in a study in which all patients were treated with lubiprostone for a duration that ranged 9-13 months. The efficacy of lubiprostone in men was not conclusively demonstrated for IBS-C.

Lubiprostone, like most prescription medications, is accompanied by some side effects. Common side effects of lubiprostone include nausea, diarrhea, and abdominal pain. Other rare side effects include urinary tract infections, dry mouth, syncope (fainting), peripheral edema (swelling of the extremities), dyspnea (difficulty breathing), and heart palpitations.

Lubiprostone should be taken twice daily in 8 mg doses with food and water. Patients and their health care professionals should periodically assess the need for continued therapy.

Lubiprostone is not approved for use in children and men. It is not to be administered to patients suffering from severe diarrhea or patients with known or suspected bowel obstructions. Its safety and efficacy has not been established in patients with renal or hepatic impairment, or in pregnant or nursing mothers.

Lubiprostone is also approved for the treatment of chronic idiopathic constipation (CIC), but the dose for that indication is higher, 24 mg twice a day.

As with all FDA-approved products, the agency will monitor lubiprostone throughout its life cycle. Consumers and health care professionals are encouraged to report adverse events to the FDA's MedWatch program at (800) FDA-1088 or on-line at: www.fda.gov/medwatch/how.htm.