# Presentation: 015741

## Lotronex ® 

**Presentation to**
**GI Advisory Committee**
**June 27, 2000**

**Hugo E. Gallo-Torres MD, PHD**
**Medical Team Leader**
**DGICDP**
**CDER, FDA**

## Lotronex®-Associated SAEs of the GI Tract

## Summary 

## Summary of Lotronex®-Associated SAEs of the GI Tract

## Hepatotoxicity SAEs

## Hepatotoxicity

## Hepatotoxicity

## Colonopathies 

## Ischemic Colitis

**Female 53y   -   Diarrhea type IBS    A0120828A**
**History: Diverticular disease (Sigmoidoscopy one week prior)**
**Meds: Ciprofloxacin (for suspected diverticulitis)**
**Treatment : Alosetron 1 mg BID for 2 days**
**Hospitalized 2-3 days: ****Rectal bleeding**** **
**Abdominal CT: ****Thickening splenic flexure **
**                            ****(colitis or ischemic colitis)**
**Histopathology: ****Ischemic colitis**

**Colonoscopy: ****Confirmed Ischemic colitis**

## Lotronex® and Ischemic Colitis

**Presentation and diagnostic criteria :**
**Rectal bleeding       **
**Abdominal pain       **
**Bloody diarrhea**
**Duration of Treatment at Onset: 2 to 54 Days **
**Abdominal CT Scan:**** **
**     ****Mural thickening of varying degrees of severity in small and large bowel**

## 
Colonoscopy-patchy, friable, ischemic or hyperemic, 		edematous mucosa with erosions that later 
		become necrotic, ulcerated and hemorrhagic  
		with mucosal sloughing 

Histopathology: Mild edema of lamina propria, 		focal coagulation necrosis of superficial crypts
		Normal architecture and spacing of deeper crypts 

**Colonoscopy-****patchy, friable, ischemic or hyperemic, ****	****	****edematous mucosa with erosions that later **
**	****	****become necrotic, ulcerated and hemorrhagic  **
**	****	****with mucosal sloughing **
**Histopathology: ****Mild edema of lamina propria, ****	****	****focal coagulation necrosis of superficial crypts**
**	****	****Normal architecture and spacing of deeper crypts**** **

**Lotronex® and Ischemic Colitis**
**(cont.)**

## Colonopathies 

## Surgical Complications of Constipation

## Surgical Complications of Constipation

## Surgical Complications of Constipation

**Surgical Complications of Constipation**

## Lotronex® and Constipation Fecal Impaction [n=7]

**Fecal Impaction**
**Not requiring hospitalization: [n=1]**
** ****Abdominal pain, Constipation**

**Lotronex® and Constipation ****Fecal Impaction [n=7]**

## Lotronex® and Constipation

**Fecal Impaction**** **
**	**** ****Hospitalized without Surgery:[n=3]**
** ****Abdominal pain, Constipation**
** ****Abdominal pain, Small bowel obstruction**
** ****Abdominal pain, Bowel obstruction,**
**Distal transverse colon ulcer,**
**Ischemic ulceration **

**Lotronex® and Constipation**
**Fecal Impaction [n=7]**

## Lotronex® and Constipation Fecal Impaction [n=7]

**Fecal Impaction, hospitalized and required surgery: [n=3]  **
** ****Small bowel obstruction **
**Required temporary decompression colostomy**
** ****Perforation sigmoid colon with Abscess **
**Required surgical repair of perforation**
** ****Toxic megacolon, Gangrenous colitis **
**Required total colectomy with Ileostomy**

## Lotronex® Treatment for IBS

**Palliative (not curative)**
**Symptomatic**
**Not shown to prevent **
**progression of symptoms**

## Irritable Bowel Syndrome 

**Life threatening sequelae**
**Progression to colonic organic disease**

**Irritable Bowel Syndrome**
-  **Functional Gastrointestinal Disorder**

**  ****Ischemic colitis**

**  ****Constipation that may require surgery**