REVISED 1

Supplementary Table 1S. Probable and Possible ischemic colitis events since reintroduction of alosetron (November 20, 2002-June 30, 2008).

Event
(Bowel Segment) / Presenting Symptoms / Age / Dose (mg/day) / Time to onset
(days)/ Duration (days) / Assessments / Sequelae and Outcomes / Concurrent Conditions / Concomitant Medications
Clinical Trial Cases
Ischemic colitis (Splenic flexure; distal transverse and proximal descending colon) / vomiting,
bloody diarrhea abdominal cramping / 62 / 1 / 6/unknown / colonoscopy biopsy / resolved w/out hospitalization / arthritis, hypertension*, diverticulosis, fibromyalgia,
plantar fasciitis, seasonal allergies / lisinopril,
rofecoxib,
glucosamine,
calcium,
fexofenadine
Ischemic colitis
(Distal transverse to proximal sigmoid colon) / abdominal pain
rectal bleeding
nausea
vomiting / 28 / 0.5 / 31/9 / abnormal CT
colonoscopy biopsy / resolved w/out hospitalization / unknown / oral contraceptives
Hemorrhagic colitis (Anal verge to 30 cm. and distal sigmoid) / abdominal pain
blood in stools / 30 / 2 / 3/10 / colonoscopy
Biopsy
/ resolved after hospitalization / unknown / glycopytronium, diphenoxylate/ atropine,
loperamide use prior to study
Segmental colitis (distal ascending colon) / abdominal pain
bloody diarrhea
nausea / 61 / 1.5 / 60/unknown / colonoscopy
biopsy / symptoms resolved / gastritis, diverticulitis / loperamide use prior to study
Ischemic colitis
(descending colon) / abdominal pain
Rectal bleeding
diarrhea / 22 / none (placebo group) / 39/9 / sigmoidoscopy biopsy / resolved w/out hospitalization / unknown / amoxicillin / clavulanate
Postmarketing Cases
Ischemic colitis
(Left colon) / abdominal pain
rectal bleeding / 45 / 2 / 60/3 / sigmoidoscopy / resolved w/out hospitalization / hypothyroid, migraine, diverticulosis / propanolol
Ischemic colitis (Unknown) / abdominal pain
bloody diarrhea
nausea / 61 / 1** / 14/3 / colonoscopy biopsy / resolved
w/ 2 day hospitalization / back pain, cardiac arrhythmia, depression, hysterectomy, ectopic pregnancy, inguinal hernia, oral neoplasm, benign colonic polyposis, migraine / citalopram, diltiazem, alprazolam, ibuprofen, aspirin, acetaminophen/
aspirin/caffeine, sumatriptan
Ischemic colitis
(Descending colon) / bloody diarrhea nausea vomiting abdominal pain / 52 / 1 / 114/na / colonoscopy biopsy / resolved w/out hospitalization / unknown / clonazepam
Ischemic colitis
(Transverse colon adjacent to the splenic flexure) / nausea vomiting
rectal bleeding / 56 / 1** / 29/4 / colonoscopy / resolved
w/ 1 day hospitalization / unknown / conjugated estrogens, hyoscyamine
Ischemic colitis
(Splenic flexure and proximal transverse colon) / abdominal pain nausea
vomiting
diarrhea / 31 / 1 / 21/7 / sigmoidoscopy biopsy / resolved
w/ 1 day hospitalization / drug allergy / esomeprazole, nortriptyline
Ischemic colitis
(Sigmoid colon) / abdominal pain blood in stools constipation / 65 / 1 / 4/30 / colonoscopy biopsy / resolved w/out hospitalization / vasculitis
constipation / conjugated estrogens
Ischemic colitis
(Sigmoid and descending colon) / rectal bleeding abdominal pain / 51 / 2 / 224/unknown / colonoscopy biopsy / resolved
w/4 days hospitalization / hemorrhoids / conjugated estrogens
Ischemic colitis
(Sigmoid and descending colon) / constipation
bloody diarrhea
abdominal pain nausea
vomiting / 81 / 1 / 3/7 / abnormal ct
sigmoidoscopy biopsy / resolved
w/ 6 days hospitalization / cholecystectomy, crest syndrome, hypertension,
constipation,
sjogren's syndrome, osteoporosis / alendronate, telmisartan, metoprolol, amlodipine, cholestyramine, tramadol
Ischemic colitis
(Distal sigmoid colon) / abdominal pain / 56 / 2 / 510/unknown / colonoscopy biopsy / resolved w/out hospitalization / lactose intolerance / ibuprofen
Ischemic colitis
(Descending colon) / abdominal pain nausea
vomiting bloody diarrhea / 52 / 0.5 / 3/2 / abnormal ct
sigmoidoscopy biopsy / resolved
w/2 days hospitalization / diverticulosis, arthritis, hypertension / multivitamins, aspirin,
atenolol, estradiol, ubidecarenone, glucosamine, linseed
Ischemic colitis
(Proximal descending colon) / vomiting bloody diarrhea abdominal pain / 54 / 1 / 510/unknown / colonoscopy biopsy / resolved w/out hospitalization / hemorrhoids, cerebral hemorrhage / amoxicillin, escitalopram, zolpidem, esomeprazole, valdecoxib
Ischemic colitis
(splenic flexure to sigmoid colon) / abdominal pain nausea
bloody diarrhea / 75 / 0.25 / 805/3 / sigmoidoscopy biopsy / improved w/
3 days hospitalization / none / estrogen
Ischemic colitis
(Descending sigmoid colon) / rectal bleeding abdominal pain / 69 / 2 / unknown / abnormal ct
colonoscopy / resolved
w/ 2 days hospitalization / high cholesterol, barretts esophagus, depression,
type 2 diabetes, hypertension, osteoarthritis, iron deficiency anemia / rosuvastatin, duloxetine, valsartan, esomeprazole, thioctic acid
Ischemic colitis
(Unknown) / hematochezia constipation / 74 / 1 / 1095/135 / resolved w/out hospitalization / constipation / cough suppressant
Ischemic colitis
(Unknown) / abdominal pain bloody diarrhea / 44 / 0.5 / 1825/unknown / colonoscopy
biopsy / improved w/out hospitalization / hemorrhoids / none
Ischemic colitis
(Sigmoid and left colon) / rectal bleeding abdominal pain / 62 / 0.5** / 90/3 / biopsy / resolved
w/ 3 days hospitalization / hypertension / esterified estrogens/ methyl-testosterone

*Conditions and medications possibly associated with IC are indicated by italics.

** indicates prior alosetron use

REVISED 1

Supplementary Table 2S. Probable complications of constipation events since reintroduction of alosetron (November 20, 2002-June 30, 2008).

Event (Bowel Segment) / Presenting GI symptoms / Age / Dose
mg/day / Time to onset (days)/
Duration
( days) / Assessments / Sequelae and Outcomes / Concurrent Conditions* / Concomitant Medications*
Clinical Study Cases
Obstruction
(descending colon) / abdominal pain distention nausea
vomiting / 61 / 0.5 / 10/4 / abnormal ct
barium enema / resolved
w/ 4 days
hospitalization / cholecystitis, peptic ulcer, abdominal ventral hernia / unknown
Impaction / constipation
nausea distension cramping / 50 / 2 / 25/1 / resolved
w/ 1 day
hospitalization / diabetes mellitus*
asthma,
manic depressive illness, gastroesophageal reflux disease, hypothyroidism, obesity,
allergies / fluticasone / salmeterol, valsartan, doxepin,
lithium, pantoprazole, thyroxine, bupropion
thiothixene
Postmarketing Cases
Obstruction
(small intestine) / abdominal pain bloating / 59 / 1** / 5/3 / barium enema
abnormal x-ray / resolved
w/ 3 days hospitalization / hypothyroidism, vaginal hysterectomy, appendectomy, hypokalemia / omeprazole, thyroxine, venlafaxin, aspirin,
lysine,
vitamins a & d
Ileus (small intestine) / nausea vomiting
constipation / 82 / 1** / 26/
unknown / unknown / resolved
w/ hospitalization / breast cancer, chronic lymphocytic leukemia / chlordiazepoxide/clidinium, doxepin, loratadine, alprazolam
Obstruction***
(left colon) / abdominal pain / 37 / 2 / 87/
unknown / abnormal ct
colonoscopy / resolved
w/ hospitalization / unknown / loperamide
Obstruction / unknown / na / unknown / 3/0.25 / unknown / resolved
w/out hospitalization / psychiatric problems / unknown
Impaction
(Ascending colon) / diarrhea
abdominal pain nausea / 49 / 4 / 84/
unknown / abnormal ct / resolved
w/o hospitalization / asthma, depression, hypertension, migraines / cholestyramine, loperamide, promethazine, salbutamol, verapamil, diazepam, potassium, diphenoxylate/ atropine, hyoscyamine
Obstruction
(Small intestine) / constipation / 41 / unknown / unknown
unknown / unknown / unknown w/
hospitalization / myotonic dystrophy, multiple surgeries (unspecified) / desogestril/ ethinyl estradiol, modafinil

* Italics indicate conditions associated with constipation.

** Indicates prior alosetron use.

*** This patient had secondary IC-see results for further information