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
Aldara Side Effects, and Drug Interactions - Imiquimod
Aldara Side Effects, and Drug Interactions - Imiquimod
SIDE EFFECTS
Healthcare providers and patients may contact 3M or FDA s Medwatch
to report adverse reactions by calling 1-800-814-1795 or 1-800-FDA-1088, or
on the internet at http://www.fda.gov/medwatch.
Dermal safety studies involving induction and challenge phases
produced no evidence that Aldara Cream causes photoallergenicity or contact
sensitization in healthy skin; however, cumulative irritancy testing revealed
the potential for Aldara Cream to cause irritation, and in the clinical studies
application site reactions were reported in a significant percentage of study
patients. Phototoxicity testing was incomplete as wavelengths in the UVB range
were not included and Aldara Cream has peak absorption in the UVB range (320
nm) of the light spectrum.
Actinic Keratosis
The data described below reflect exposure to Aldara Cream or
vehicle in 436 patients enrolled in two double-blind, vehicle-controlled, 2X/week
studies. Patients applied Aldara Cream or vehicle to a 25 cm2 contiguous
treatment area on the face or scalp 2X/week for 16 weeks.
Summary of All Adverse Events Reported by > 1% of Patients
in the Combined 2X/ Week Studies
|
Body System
Preferred Term
|
Imiq 2X/Week
(n= 215)
|
Vehicle 2X/Week
(n= 221)
|
|
APPLICATION SITE DISORDERS
|
|
|
|
APPLICATION SITE REACTION
|
71 ( 33.0%)
|
32 ( 14.5%)
|
|
BODY AS A WHOLE - GENERAL DISORDERS
|
|
|
|
BACK PAIN
|
3 ( 1.4%)
|
2 ( 0.9%)
|
|
FATIGUE
|
3 ( 1.4%)
|
2 ( 0.9%)
|
|
FEVER
|
3 ( 1.4%)
|
0 ( 0.0%)
|
|
HEADACHE
|
11 ( 5.1%)
|
7 ( 3.2%)
|
|
HERNIA NOS
|
4 ( 1.9%)
|
1 ( 0.5%)
|
|
INFLUENZA- LIKE SYMPTOMS
|
4 ( 1.9%)
|
4 ( 1.8%)
|
|
PAIN
|
3 ( 1.4%)
|
3 ( 1.4%)
|
|
RIGORS
|
3 ( 1.4%)
|
0 ( 0.0%)
|
|
CARDIOVASCULAR DISORDERS, GENERAL
|
|
|
|
CHEST PAIN
|
1 ( 0.5%)
|
4 ( 1.8%)
|
|
HYPERTENSION
|
3 ( 1.4%)
|
5 ( 2.3%)
|
|
CENTR & PERIPH NERVOUS SYSTEM DISORDERS
|
|
|
|
DIZZINESS
|
3 ( 1.4%)
|
1 ( 0.5%)
|
|
GASTRO- INTESTINAL SYSTEM DISORDERS
|
|
|
|
DIARRHOEA
|
6 ( 2.8%)
|
2 ( 0.9%)
|
|
DYSPEPSIA
|
6 ( 2.8%)
|
4 ( 1.8%)
|
|
GASTROESOPHAGEAL REFLUX
|
3 ( 1.4%)
|
3 ( 1.4%)
|
|
NAUSEA
|
3 ( 1.4%)
|
3 ( 1.4%)
|
|
VOMITING
|
3 ( 1.4%)
|
1 ( 0.5%)
|
|
HEART RATE AND RHYTHM DISORDERS
|
|
|
|
FIBRILLATION ATRIAL
|
3 ( 1.4%)
|
2 ( 0.9%)
|
|
METABOLIC AND NUTRITIONAL DISORDERS
|
|
|
|
HYPERCHOLESTEROLAEMIA
|
4 ( 1.9%)
|
0 ( 0.0%)
|
|
MUSCULO- SKELETAL SYSTEM DISORDERS
|
|
|
|
ARTHRALGIA
|
2 ( 0.9%)
|
4 ( 1.8%)
|
|
ARTHRITIS
|
2 ( 0.9%)
|
3 ( 1.4%)
|
|
MYALGIA
|
3 ( 1.4%)
|
3 ( 1.4%)
|
|
SKELETAL PAIN
|
1 ( 0.5%)
|
3 ( 1.4%)
|
|
NEOPLASM
|
|
|
|
BASAL CELL CARCINOMA
|
5 ( 2.3%)
|
5 ( 2.3%)
|
|
CARCINOMA SQUAMOUS
|
8 ( 3.7%)
|
5 ( 2.3%)
|
|
RESISTANCE MECHANISM DISORDERS
|
9 ( 4.2%)
|
11 ( 5.0%)
|
|
HERPES SIMPLEX
|
4 ( 1.9%)
|
4 ( 1.8%)
|
|
INFECTION VIRAL
|
3 ( 1.4%)
|
2 ( 0.9%)
|
|
RESPIRATORY SYSTEM DISORDERS
|
|
|
|
BRONCHITIS
|
2 ( 0.9%)
|
3 ( 1.4%)
|
|
COUGHING
|
6 ( 2.8%)
|
10 ( 4.5%)
|
|
PHARYNGITIS
|
4 ( 1.9%)
|
4 ( 1.8%)
|
|
PULMONARY CONGESTION
|
1 ( 0.5%)
|
3 ( 1.4%)
|
|
RHINITIS
|
7 ( 3.3%)
|
8 ( 3.6%)
|
|
SINUSITIS
|
16 ( 7.4%)
|
14 ( 6.3%)
|
|
UPPER RESP TRACT INFECTION
|
33 ( 15.3%)
|
27 ( 12.2%)
|
|
SECONDARY TERMS
|
|
|
|
ABRASION NOS
|
7 ( 3.3%)
|
5 ( 2.3%)
|
|
CYST NOS
|
0 ( 0.0%)
|
4 ( 1.8%)
|
|
INFLICTED INJURY
|
19 ( 8.8%)
|
21 ( 9.5%)
|
|
POST- OPERATIVE PAIN
|
3 ( 1.4%)
|
4 ( 1.8%)
|
|
SKIN AND APPENDAGES DISORDERS
|
47 ( 21.9%)
|
42 ( 19.0%)
|
|
ALOPECIA
|
3 ( 1.4%)
|
0 ( 0.0%)
|
|
DERMATITIS
|
3 ( 1.4%)
|
7 ( 3.2%)
|
|
ECZEMA
|
4 ( 1.9%)
|
3 ( 1.4%)
|
|
HYPERKERATOSIS
|
19 ( 8.8%)
|
12 ( 5.4%)
|
|
PHOTOSENSITIVITY REACTION
|
2 ( 0.9%)
|
4 ( 1.8%)
|
|
PRURITUS
|
2 ( 0.9%)
|
3 ( 1.4%)
|
|
RASH
|
5 ( 2.3%)
|
5 ( 2.3%)
|
|
SKIN DISORDER
|
6 ( 2.8%)
|
7 ( 3.2%)
|
|
VERRUCA
|
1 ( 0.5%)
|
3 ( 1.4%)
|
|
URINARY SYSTEM DISORDERS
|
8 ( 3.7%)
|
10 ( 4.5%)
|
|
URINARY TRACT INFECTION
|
3 ( 1.4%)
|
1 ( 0.5%)
|
|
VISION DISORDERS
|
|
|
|
CONJUNCTIVITIS
|
1 ( 0.5%)
|
3 ( 1.4%)
|
|
EYE ABNORMALITY
|
4 ( 1.9%)
|
1 ( 0.5%)
|
|
EYE INFECTION
|
0 ( 0.0%)
|
3 ( 1.4%)
|
Summary of All Application Site Reactions Reported by
> 1% of Patients in the Combined 2X/ Week Studies
| Included Term |
Imiq 2X/Week
(n= 215)
|
Vehicle 2X/Week
(n= 221)
|
|
BLEEDING AT TARGET SITE
|
7 ( 3.3%)
|
1 ( 0.5%)
|
|
BURNING AT REMOTE SITE
|
4 ( 1.9%)
|
0 ( 0.0%)
|
|
BURNING AT TARGET SITE
|
12 ( 5.6%)
|
4 ( 1.8%)
|
|
INDURATION AT REMOTE SITE
|
3 ( 1.4%)
|
0 ( 0.0%)
|
|
INDURATION AT TARGET SITE
|
5 ( 2.3%)
|
3 ( 1.4%)
|
|
IRRITATION AT REMOTE SITE
|
3 ( 1.4%)
|
0 ( 0.0%)
|
|
ITCHING AT REMOTE SITE
|
7 ( 3.3%)
|
3 ( 1.4%)
|
|
ITCHING AT TARGET SITE
|
44 ( 20.5%)
|
15 ( 6.8%)
|
|
PAIN AT TARGET SITE
|
5 ( 2.3%)
|
2 ( 0.9%)
|
|
STINGING AT TARGET SITE
|
6 ( 2.8%)
|
2 ( 0.9%)
|
|
TENDERNESS AT TARGET SITE
|
4 ( 1.9%)
|
3 ( 1.4%)
|
Local skin reactions were collected independently of the adverse
event "application site reaction" in an effort to provide a better picture of
the specific types of local reactions that might be seen. The most frequently
reported local skin reactions were erythema, flaking/scaling/dryness, and scabbing/crusting.
The prevalence and severity of local skin reactions that occurred during controlled
studies are shown in the following table.
|
Local Skin Reactions in the Treatment Area as Assessed
by the Investigator (Percentage of Patients) 2X/Week Application
|
| |
Mild/Moderate/Severe
|
Severe
|
| |
Aldara
|
|
Aldara
|
|
| |
Cream
|
Vehicle
|
Cream
|
Vehicle
|
| |
n=215
|
n=220
|
n=215
|
n=220
|
|
Erythema
|
209(97%)
|
206 (93%)
|
38(18%)
|
5 (2%)
|
|
Edema
|
106(49%)
|
22 (10%)
|
0 (0%)
|
0 (0%)
|
|
Weeping/Exudate
|
45 (22%)
|
3 (1%)
|
0 (0%)
|
0 (0%)
|
|
Vesicles
|
19 (9%)
|
2 (1%)
|
0 (0%)
|
0 (0%)
|
|
Erosion/Ulceration
|
103(48%)
|
20 (9%)
|
5 (2%)
|
0 (0%)
|
|
Flaking/Scaling/Dryness
|
199(93%)
|
199 (91%)
|
16 (7%)
|
7 (3%)
|
|
Scabbing/Crusting
|
169(79%)
|
92 (42%)
|
18 (8%)
|
4 (2%)
|
The adverse reactions that most frequently resulted in clinical
intervention (e.g., rest periods, withdrawal from study) were local skin and
application site reactions. Overall, in the clinical studies, 2% (5/215) of
patients discontinued for local skin/application site reactions. Of the 215
patients treated, 35 patients (16%) on Aldara Cream and 3 of 220 patients (1%)
on vehicle cream had at least one rest period. Of these Aldara Cream patients,
32 (91%) resumed therapy after a rest period.
In the AK studies, 22 of 678 imiquimod treated patients developed
treatment site infections that required a rest period off Aldara Cream and were
treated with antibiotics (19 with oral and 3 with topical).
Superficial Basal Cell Carcinoma
The data described below reflect exposure to Aldara Cream or
vehicle in 364 patients enrolled in two double-blind, vehicle-controlled, 5X/week
studies. Patients applied Aldara Cream or vehicle 5X/week for 6 weeks. The incidence
of adverse events reported by > 1% of subjects during the 6 week treatment
period is summarized below.
Summary of All Adverse Events Reported by > 1% of Patients
in the Combined 5X/ Week Studies
Body System
Preferred Term |
Imiquimod 5x/Week (n= 185) N %
|
Vehicle 5x/Week (n= 179) N %
|
| APPLICATION SITE DISORDERS |
|
|
| APPLICATION SITE REACTION |
52 (28.1%)
|
5 ( 2.8%)
|
|
BODY AS A WHOLE - GENERAL DISORDERS
|
|
ALLERGY AGGRAVATED
|
2 ( 1.1%)
|
1 ( 0.6%)
|
|
BACK PAIN
|
7 ( 3.8%)
|
1 ( 0.6%)
|
|
CHEST PAIN
|
2 ( 1.1%)
|
0 ( 0.0%)
|
|
FATIGUE
|
4 ( 2.2%)
|
2 ( 1.1%)
|
|
FEVER
|
3 ( 1.6%)
|
0 ( 0.0%)
|
|
PAIN
|
3 ( 1.6%)
|
2 ( 1.1%)
|
|
CARDIOVASCULAR DISORDERS, GENERAL
|
|
HYPERTENSION
|
5 ( 2.7%)
|
1 ( 0.6%)
|
|
CENTR & PERIPH NERVOUS SYSTEM DISORDERS
|
|
DIZZINESS
|
2 ( 1.1%)
|
1 ( 0.6%)
|
|
HEADACHE
|
14 ( 7.6%)
|
4 ( 2.2%)
|
|
GASTRO- INTESTINAL SYSTEM DISORDERS
|
|
ABDOMINAL PAIN
|
1 ( 0.5%)
|
2 ( 1.1%)
|
|
DIARRHOEA
|
1 ( 0.5%)
|
2 ( 1.1%)
|
|
DYSPEPSIA
|
3 ( 1.6%)
|
2 ( 1.1%)
|
|
GASTRO- INTESTINAL DISORDER NOS
|
1 ( 0.5%)
|
2 ( 1.1%)
|
|
NAUSEA
|
2 ( 1.1%)
|
0 ( 0.0%)
|
|
TOOTH DISORDER
|
0 ( 0.0%)
|
2 ( 1.1%)
|
|
METABOLIC AND NUTRITIONAL DISORDERS
|
|
GOUT
|
2 ( 1.1%)
|
0 ( 0.0%)
|
|
MUSCULO-SKELETAL SYSTEM DISORDERS
|
|
SKELETAL PAIN
|
3 ( 1.6%)
|
2 ( 1.1%)
|
|
PSYCHIATRIC DISORDERS
|
|
ANXIETY
|
2 ( 1.1%)
|
1 ( 0.6%)
|
|
RESISTANCE MECHANISM DISORDERS
|
|
INFECTION
|
1 ( 0.5%)
|
3 ( 1.7%)
|
|
INFECTION FUNGAL
|
2 ( 1.1%)
|
2 ( 1.1%)
|
|
RESPIRATORY SYSTEM DISORDERS
|
|
COUGHING
|
3 ( 1.6%)
|
1 ( 0.6%)
|
|
PHARYNGITIS
|
2 ( 1.1%)
|
1 ( 0.6%)
|
|
RHINITIS
|
5 ( 2.7%)
|
1 ( 0.6%)
|
|
SINUSITIS
|
4 ( 2.2%)
|
1 ( 0.6%)
|
|
UPPER RESP TRACT INFECTION
|
6 ( 3.2%)
|
2 ( 1.1%)
|
|
SECONDARY TERMS
|
|
INFLICTED INJURY
|
3 ( 1.6%)
|
3 ( 1.7%)
|
|
PROCEDURAL SITE REACTION
|
2 ( 1.1%)
|
3 ( 1.7%)
|
|
SKIN AND APPENDAGES DISORDERS
|
|
HYPERKERATOSIS
|
3 ( 1.6%)
|
2 ( 1.1%)
|
|
RASH
|
3 ( 1.6%)
|
1 ( 0.6%)
|
|
SKIN DISORDER
|
1 ( 0.5%)
|
3 ( 1.7%)
|
|
WHITE CELL AND RES DISORDERS
|
|
LYMPHADENOPATHY
|
5 ( 2.7%)
|
1 ( 0.6%)
|
In controlled clinical studies, the most frequently reported
adverse reactions were local skin and application site reactions including erythema,
edema, induration, erosion, flaking/scaling, scabbing/crusting, itching and
burning at the application site. The incidence of the application site reactions
reported by > 1% of the subjects during the 6 week treatment period is summarized
in the table below.
|
Summary of All Application Site Reactions Reported by
> 1% of Patients in the Combined 5X/ Week Studies
|
| |
Imiquimod
|
Vehicle
|
| |
5x/ Week
|
5x/ Week
|
| |
(n= 185)
|
(n= 179)
|
|
Included Term
|
N %
|
N %
|
|
ITCHING AT TARGET SITE
|
30 (16.2%)
|
1 ( 0.6%)
|
|
BURNING AT TARGET SITE
|
11 ( 5.9%)
|
2 ( 1.1%)
|
|
PAIN AT TARGET SITE
|
6 ( 3.2%)
|
0 ( 0.0%)
|
|
TENDERNESS AT TARGET SITE
|
2 ( 1.1%)
|
0 ( 0.0%)
|
|
ERYTHEMA AT REMOTE SITE
|
3 ( 1.6%)
|
0 ( 0.0%)
|
|
PAPULE( S) AT TARGET SITE
|
3 ( 1.6%)
|
0 ( 0.0%)
|
|
BLEEDING AT TARGET SITE
|
4 ( 2.2%)
|
0 ( 0.0%)
|
|
TINGLING AT TARGET SITE
|
1 ( 0.5%)
|
2 ( 1.1%)
|
|
INFECTION AT TARGET SITE
|
2 ( 1.1%)
|
0 ( 0.0%)
|
Local skin reactions were collected independently of the adverse
event "application site reaction" in an effort to provide a better picture of
the specific types of local reactions that might be seen. The prevalence and
severity of local skin reactions that occurred during controlled studies are
shown in the following table.
|
Most Intense Local Skin Reactions in the Treatment Area
as Assessed by the Investigator (Percentage of Patients) 5X/Week Application
|
| |
Mild/Moderate
|
Severe
|
| |
Aldara Cream
|
Vehicle
|
Aldara Cream
|
Vehicle
|
| |
n=184
|
n=178
|
n=184
|
n=178
|
|
Edema
|
71%
|
36%
|
7%
|
0%
|
|
Erosion
|
54%
|
14%
|
13%
|
0%
|
|
Erythema
|
69%
|
95%
|
31%
|
2%
|
|
Flaking/Scaling
|
87%
|
76%
|
4%
|
0%
|
|
Induration
|
78%
|
53%
|
6%
|
0%
|
|
Scabbing/Crusting
|
64%
|
34%
|
19%
|
0%
|
|
Ulceration
|
34%
|
3%
|
6%
|
0%
|
|
Vesicles
|
29%
|
2%
|
2%
|
0%
|
The adverse reactions that most frequently resulted in clinical
intervention (e.g., rest periods, withdrawal from study) were local skin and
application site reactions; 10% (19/185) of patients received rest periods.
The average number of doses not received per patient due to rest periods was
7 doses with a range of 2 to 22 doses; 79% of patients (15/19) resumed therapy
after a rest period. Overall, in the clinical studies, 2% (4/185) of patients
discontinued for local skin/application site reactions.
In the sBCC studies, 17 of 1266 (1.3%) imiquimod-treated patients
developed treatment site infections that required a rest period off Aldara Cream
and were treated with antibiotics.
External Genital Warts
In controlled clinical trials for genital warts, the most frequently
reported adverse reactions were local skin and application site reactions.
These reactions were usually mild to moderate in intensity;
however, severe reactions were reported with 3X/week application. These reactions
were more frequent and more intense with daily application than with 3X/week
application. Some patients also reported systemic reactions. Overall, in
the 3X/week application clinical studies, 1.2% (4/327) of the patients discontinued
due to local skin/application site reactions. The incidence and severity of
local skin reactions during controlled clinical trials are shown in the following
table.
|
Wart Site Reaction as Assessed by Investigator (Percentage
of Patients) 3X/Week Application
|
| |
Mild/Moderate/Severe
|
|
Severe
|
|
| |
Females
|
Males
|
Females
|
Males
|
| |
Aldara
|
|
Aldara
|
|
Aldara
|
|
Aldara
|
|
| |
Cream
|
Vehicle
|
Cream
|
Vehicle
|
Cream
|
Vehicle
|
Cream
|
Vehicle
|
| |
n=114
|
n=99
|
n=156
|
n=157
|
n=114
|
n=99
|
n=156
|
n=157
|
|
Erythema
|
74(65%)
|
21(21%)
|
90(58%)
|
34 (22%)
|
4 (4%)
|
0 (0%)
|
6 (4%)
|
0 (0%)
|
|
Erosion
|
35(31%)
|
8 (8%)
|
47(30%)
|
10 (6%)
|
1 (1%)
|
0 (0%)
|
2 (1%)
|
0 (0%)
|
|
Excoriation/Flaking
|
21(18%)
|
8 (8%)
|
40(26%)
|
12 (8%)
|
0 (0%)
|
0 (0%)
|
1 (1%)
|
0 (0%)
|
|
Edema
|
20(18%)
|
5 (5%)
|
19(12%)
|
1 (1%)
|
1 (1%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
|
Induration
|
6 (5%)
|
2 (2%)
|
11 (7%)
|
3 (2%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
|
Ulceration
|
9 (8%)
|
1 (1%)
|
7 (4%)
|
1 (1%)
|
3 (3%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
|
Scabbing
|
4 (4%)
|
0 (0%)
|
20(13%)
|
4 (3%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
|
Vesicles
|
3 (3%)
|
0 (0%)
|
3 (2%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
Remote site skin reactions were also reported in female and
male patients treated 3X/week with Aldara Cream. The severe remote site skin
reactions reported for females were erythema (3%), ulceration (2%), and edema
(1%); and for males, erosion (2%), and erythema, edema, induration, and excoriation/flaking
(each 1%).
Adverse events judged to be probably or possibly related to
Aldara Cream reported by more than 5% of patients are listed below; also included
are soreness, influenza-like symptoms and myalgia.
|
3X/Week Application
|
| |
Females
|
Males
|
|
| |
Aldara Cream
|
Vehicle
|
Aldara Cream
|
Vehicle
|
| |
n=117
|
n=103
|
n=156
|
n=158
|
|
Application Site Disorders:
|
|
|
|
|
|
Application Site Reactions
|
|
|
|
|
|
Wart Site:
|
|
|
|
|
|
Itching
|
32%
|
20%
|
22%
|
10%
|
|
Burning
|
26%
|
12%
|
9%
|
5%
|
|
Pain
|
8%
|
2%
|
2%
|
1%
|
|
Soreness
|
3%
|
0%
|
0%
|
1%
|
|
Fungal Infection*
|
11%
|
3%
|
2%
|
1%
|
|
Systemic Reactions:
|
|
|
|
|
|
Headache
|
4%
|
3%
|
5%
|
2%
|
|
Influenza-like symptoms
|
3%
|
2%
|
1%
|
0%
|
|
Myalgia
|
1%
|
0%
|
1%
|
1%
|
|
* Incidences reported without regard to causality with
Aldara Cream.
|
Adverse events judged to be possibly or probably related to
Aldara Cream and reported by more than 1% of patients included: Application
Site Disorders: Wart Site Reactions (burning, hypopigmentation, irritation,
itching, pain, rash, sensitivity, soreness, stinging, tenderness); Remote
Site Reactions (bleeding, burning, itching, pain, tenderness, tinea cruris);
Body as a Whole: fatigue, fever, influenza-like symptoms; Central
and Peripheral Nervous System Disorders: headache; Gastro-Intestinal
System Disorders: diarrhea; Musculo-Skeletal System Disorders: myalgia.
DRUG INTERACTIONS
No information available.
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