A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Carac Side Effects, and Drug Interactions - Fluorouracil
Carac Side Effects, and Drug Interactions - Fluorouracil
SIDE EFFECTS
The following were adverse events considered to be drug-related
and occurring with a frequency of ³1% with Carac:
application site reaction (94.6%), and eye irritation (5.4%). The signs and
symptoms of facial irritation (application site reaction) are presented below.
|
Summary of Facial Irritation Signs and Symptoms - Pooled
Phase 3 Studies
|
|
Clinical Sign or Symptom
|
Active One Week
|
Active Two Week
|
Active Four Week
|
ALL Active Treatments
|
Vehicle Treatments
|
| |
N=85
|
N=87
|
N=85
|
N=257
|
N=127
|
| |
n
|
(%)
|
n
|
(%)
|
n
|
(%)
|
n
|
(%)
|
n
|
(%)
|
| |
|
|
|
|
|
|
|
|
|
|
|
Erythema
|
76
|
(89.4)
|
82
|
(94.3)
|
82
|
(96.5)
|
240
|
(93.4)
|
76
|
(59.8)
|
|
Dryness
|
59
|
(69.4)
|
76
|
(87.4)
|
79
|
(92.9)
|
214
|
(83.3)
|
60
|
(47.2)
|
|
Burning
|
51
|
(60.0)
|
70
|
(80.5)
|
71
|
(83.5)
|
192
|
(74.7)
|
28
|
(22.0)
|
|
Erosion
|
21
|
(24.7)
|
38
|
(43.7)
|
54
|
(63.5)
|
113
|
(44.0)
|
17
|
(13.4)
|
|
Pain
|
26
|
(30.6)
|
34
|
(39.1)
|
52
|
(61.2)
|
112
|
(43.6)
|
7
|
(5.5)
|
|
Edema
|
12
|
(14.1)
|
28
|
(32.2)
|
51
|
(60.0)
|
91
|
(35.4)
|
6
|
(4.7)
|
During clinical trials, irritation generally began on day 4
and persisted for the remainder of treatment. Severity of facial irritation
at the last treatment visit was slightly below baseline for the vehicle group,
mild to moderate for the 1 week active treatment group, and moderate for the
2 and 4 week active treatment groups. Mean severity declined rapidly for each
active group after completion of treatment and was below baseline for each group
at the week 2 post-treatment follow-up visit.
Thirty-one patients (12% of those treated with Carac in the
Phase 3 clinical studies) discontinued study treatment early due to facial irritation.
Except for three patients, discontinuation of treatment occurred on or after
day 11 of treatment.
Eye irritation adverse events, described as mild to moderate
in intensity, were characterized as burning, watering, sensitivity, stinging
and itching. These adverse events occurred across all treatment arms in one
of the two Phase 3 studies.
Summary of All Adverse Events Reported in ³
1% of Patients in the Combined Active
|
Treatment and Vehicle Groups – Pooled Phase 3 Studies
|
| |
9721 and 9722 Combined
|
|
Adverse Event
|
Active One Week
|
Active Two Week
|
Active Four Week
|
ALL Active Treatments
|
Vehicle Treatments
|
| |
N= 85
|
N= 87
|
N= 85
|
N=257
|
N=127
|
| |
n
|
(%)
|
n
|
(%)
|
n
|
(%)
|
n
|
(%)
|
n
|
(%)
|
|
BODY AS A WHOLE
|
7
|
(8.2)
|
6
|
(6.9)
|
12
|
(14.1)
|
25
|
(9.7)
|
15
|
(11.8)
|
|
Headache
|
3
|
(3.5)
|
2
|
(2.3)
|
3
|
(3.5)
|
8
|
(3.1)
|
3
|
(2.4)
|
|
Common Cold
|
4
|
(4.7)
|
|
0
|
2
|
(2.4)
|
6
|
(2.3)
|
3
|
(2.4)
|
|
Allergy
|
|
0
|
2
|
(2.3)
|
1
|
(1.2)
|
3
|
(1.2)
|
2
|
(1.6)
|
|
Infection Upper
|
|
0
|
|
0
|
|
0
|
|
0
|
2
|
(1.6)
|
|
Respiratory
|
|
MUSCULOSKELETAL
|
1
|
(1.2)
|
1
|
(1.1)
|
1
|
(1.2)
|
3
|
(1.2)
|
5
|
(3.9)
|
|
Muscle Soreness
|
|
0
|
|
0
|
|
0
|
|
0
|
2
|
(1.6)
|
|
RESPIRATORY
|
5
|
(5.9)
|
|
0
|
1
|
(1.2)
|
6
|
(2.3)
|
6
|
(4.7)
|
|
Sinusitis
|
4
|
(4.7)
|
|
0
|
|
0
|
4
|
(1.6)
|
2
|
(1.6)
|
|
SKIN & APPENDAGES
|
78
|
(91.8)
|
83
|
(95.4)
|
82
|
(96.5)
|
243
|
(94.6)
|
85
|
(66.9)
|
|
Application Site
|
78
|
(91.8)
|
83
|
(95.4)
|
82
|
(96.5)
|
243
|
(94.6)
|
83
|
(65.4)
|
|
Reaction
|
|
Irritation Skin
|
1
|
(1.2)
|
|
0
|
2
|
(2.4)
|
3
|
(1.2)
|
|
0
|
|
SPECIAL SENSES
|
6
|
(7.1)
|
4
|
(4.6)
|
6
|
(7.1)
|
16
|
(6.2)
|
6
|
(4.7)
|
|
Eye Irritation
|
5
|
(5.9)
|
3
|
(3.4)
|
6
|
(7.1)
|
14
|
(5.4)
|
3
|
(2.4)
|
Adverse Experiences Reported by Body System:
In the Phase 3 studies, no serious adverse event was considered
related to study drug. A total of five patients, three in the active treatment
groups and two in the vehicle group, experienced at least one serious adverse
event. Three patients died as a result of adverse event(s) considered unrelated
to study drug (stomach cancer, myocardial infarction and cardiac failure).
Post-treatment clinical laboratory
tests other than pregnancy tests were not performed during the Phase 3
clinical studies. Clinical laboratory tests were performed during conduct of a Phase 2
study of 104 patients and 21 patients in a Phase 1 study. No abnormal serum
chemistry, hematology, or urinalysis results in these studies were considered
clinically significant.
DRUG INTERACTIONS
No information available.
top
