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
Clinical Trial Cases
vomiting,
Ischemic colitis
(Splenic flexure; bloody diarrhea
distal transverse abdominal
cramping
and proximal
descending
colon)
Age
Dose
(mg/day)
Time to onset
(days)/
Duration (days)
Assessments
Sequelae and
Outcomes
Concurrent
Conditions
Concomitant
Medications
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
unknown
amoxicillin /
clavulanate
sigmoidoscopy
biopsy
resolved w/out
hospitalization
REVISED
2
Postmarketing Cases
abdominal pain
Ischemic colitis
rectal bleeding
(Left colon)
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
REVISED
3
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)
Ischemic colitis
(Sigmoid and
descending
colon)
rectal bleeding
abdominal pain
51
2
224/unknown
colonoscopy
biopsy
resolved
w/4 days
hospitalization
hemorrhoids
conjugated
estrogens
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
REVISED
4
Ischemic colitis
(splenic flexure
to sigmoid colon)
abdominal pain
nausea
bloody diarrhea
75
0.25
805/3
Ischemic colitis
(Descending
sigmoid colon)
rectal bleeding
abdominal pain
69
2
unknown
Ischemic colitis
(Unknown)
hematochezia
constipation
74
1
1095/135
Ischemic colitis
(Unknown)
abdominal pain
bloody diarrhea
44
0.5
1825/unknown
Ischemic colitis
(Sigmoid and left
colon)
rectal bleeding
abdominal pain
62
0.5**
90/3
sigmoidoscopy
biopsy
improved w/
3 days
hospitalization
none
estrogen
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
resolved
w/out
hospitalization
improved
w/out
hospitalization
constipation
cough
suppressant
hemorrhoids
none
resolved
w/ 3 days
hospitalization
hypertension
esterified
estrogens/
methyltestosterone
colonoscopy
biopsy
biopsy
*Conditions and medications possibly associated with IC are indicated by italics.
** indicates prior alosetron use
REVISED
5
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
Concurren
Conditions
abdominal pain
distention
nausea
vomiting
61
0.5
10/4
abnormal ct
barium enema
resolved
w/ 4 days
hospitalization
cholecystitis,
peptic ulcer,
abdominal ven
hernia
constipation
nausea
distension
cramping
50
2
25/1
resolved
w/ 1 day
hospitalization
diabetes mellit
asthma,
manic depressi
illness,
gastroesophage
reflux disease,
hypothyroidism
obesity,
allergies
abdominal pain
bloating
59
1**
5/3
barium enema
abnormal xray
resolved
w/ 3 days
hospitalization
hypothyroidism
vaginal
hysterectomy,
appendectomy
hypokalemia
Ileus (small intestine)
nausea vomiting
constipation
82
1**
26/
unknown
unknown
resolved
w/
hospitalization
breast cancer,
chronic
lymphocytic
leukemia
Obstruction***
(left colon)
abdominal pain
37
2
87/
unknown
abnormal ct
colonoscopy
resolved
w/
hospitalization
unknown
Obstruction
unknown
na
unknown
3/0.25
unknown
resolved
w/out
hospitalization
Clinical Study Cases
Obstruction
(descending colon)
Impaction
Postmarketing Cases
Obstruction
(small intestine)
psychiatric
problems
REVISED
Impaction
(Ascending colon)
Obstruction
(Small intestine)
6
diarrhea
abdominal pain
nausea
49
4
84/
unknown
abnormal ct
resolved
w/o
hospitalization
asthma,
depression,
hypertension,
migraines
constipation
41
unknown
unknown
unknown
unknown
unknown w/
hospitalization
myotonic
dystrophy,
multiple surger
(unspecified)
* Italics indicate conditions associated with constipation.
** Indicates prior alosetron use.
*** This patient had secondary IC-see results for further information