Lubiprostone (Amitiza®) Vs. Standard Care in Opioid-induced Constipation After Surgery in Inpatient Rehabilitation

The purpose of this study is to assess the efficacy of Lubiprostone (Amitiza) compared to
standard care for the treatment of constipation in orthopedic patients receiving opioids for
pain control during inpatient rehabilitation. Lubiprostone (Amitiza®) is a locally acting
chloride channel activator that increases intestinal fluid, and thus increases intestinal
motility. It has been approved for chronic constipation, but not in the setting of
opioid-induced constipation. Senna is a stimulant laxative that increases propulsive
peristaltic activity of the colon through local effects on the mucosa.

Subjects will be compared using from the Patient Assessment of Constipation (PAC) which has
previously been found to be a valid and reliable way to measure constipation symptoms and
clinical course. (Frank, Kleinman et al. 1999) as well as with other measures of
bowel-related symptoms and functional outcomes.

Inclusion Criteria:

1. Adult, 18 years old or greater.

2. The patient is able to provide informed consent.

3. Anticipated duration of hospitalization of at least 7 days.

4. Woman of childbearing potential must have a negative serum pregnancy test at
enrollment. Exclusions for testing include two years or greater postmenopausal,
hysterectomy or tubal ligation.

5. Use of opioid for post-op analgesia following orthopedic surgical procedures as
defined as IV, IM, transdermal or PO opioid received within the prior 24 hours of
hospitalization for pain control, and expectation that an opioid will be continued
for pain control.

- Medication may be administered on a PRN (as needed) basis or scheduled basis

- One or greater doses has been received within the 24 hours prior to enrollment
as determined by medication administration recorded from the acute care facility
or RIC MAR.

6. At least one associated symptom of constipation at the time of admission, such as,
but not limited to:

- Lumpy or Hard stools

- Feeling of incomplete evacuation of bowels

- Abdominal cramping or pain

- Straining with movement of bowels or painful bowel movement effort

- Need for manual assistance to have a bowel movement

Exclusion Criteria:

1. Known allergy or sensitivity to the study medications

2. Females who are pregnant

3. Diarrhea on the day of admission

4. Diagnosis of Clostridium difficile infection during the current hospitalization

5. Pre-existing medical condition or surgical procedure, which is known to commonly lead
to bowel dysfunction such as, but not limited to:

- Crohn's disease

- Ulcerative colitis

- Multiple sclerosis

- Cerebral palsy

- Spinal Cord Injury

- Colectomy

- Malabsorption Syndrome

- Irritable Bowel Syndrome

- Abdominopelvic neoplasm (gastric, colon cancer)

- Severe liver disease

- Colonic or ileo-colonic resections