3 )] Most common application site or local skin adverse reactions (incidence >28%) are erythema, flaking/scaling/dryness, scabbing/crusting, edema, erosion/ulceration, induration, itching, burning, excoriation, vesicles. Other reported systemic adverse reactions (≥1%): fatigue, fever, and headache.
gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
1)] . Subjects applied Imiquimod Cream, 5% or vehicle topically, to a 25 cm 2 contiguous treatment area on the face or scalp once daily 2 times per week for 16 weeks. The incidence of selected adverse reactions reported by ≥1% of subjects during the trials is presented in Table 2.
Table 2:
Selected Adverse Reactions Occurring in ≥1% of Imiquimod-Treated Subjects with AK and at a Greater Frequency than Vehicle in Studies AK1 and AK2 Imiquimod Cream (n= 215) Vehicle (n= 221) Application Site Reaction 71 (33%) 32 (14%) Upper Respiratory Tract Infection 33 (15%) 27 (12%) Sinusitis 16 (7%) 14 (6%) Headache 11 (5%) 7 (3%) Carcinoma Squamous 8 (4%) 5 (2%) Diarrhea 6 (3%) 2 (1%) Eczema 4 (2%) 3 (1%) Back Pain 3 (1%) 2 (1%) Fatigue 3 (1%) 2 (1%) Fibrillation Atrial 3 (1%) 2 (1%) Infection Viral 3 (1%) 2 (1%) Dizziness 3 (1%) 1 (<1%) Vomiting 3 (1%) 1 (<1%) Urinary Tract Infection 3 (1%) 1 (<1%) Fever 3 (1%) 0 (0%) Rigors 3 (1%) 0 (0%) Alopecia 3 (1%) 0 (0%) The incidence of application site reactions reported by >1% of subjects during the trials is presented in Table 3.
Table 3:
Application Site Reactions Reported by >1% of Imiquimod-Treated Subjects with AK and at a Greater Frequency than Vehicle in Studies AK1 and AK2 Imiquimod Cream (n= 215) Vehicle (n= 221) Itching 44 (20%) 17 (8%) Burning 13 (6%) 4 (2%) Bleeding 7 (3%) 1 (<1%) Stinging 6 (3%) 2 (1%) Pain 6 (3%) 2 (1%) Induration 5 (2%) 3 (1%) Tenderness 4 (2%) 3 (1%) Irritation 4 (2%) 0 (0%) Local skin reactions were collected independently of the adverse reaction "application site reaction".
The incidence and severity of local skin reactions that occurred during controlled trials are shown in Table 4. , rest periods, withdrawal from trial) were local skin and application site reactions. In the trials, 2% (5/215) of subjects discontinued for local skin/application site reactions.
Of the 215 subjects treated, 35 subjects (16%) on imiquimod cream and 3 of 220 subjects (1%) on vehicle had at least one rest period. Of the imiquimod-treated subjects, 32 (91%) resumed therapy after a rest period. 2%) of imiquimod-treated subjects developed treatment site infections that required a rest period off imiquimod cream and were treated with antibiotics (19 with oral and 3 with topical).
9%) had a greater degree of scarring scores at 8 weeks post-treatment than at baseline. 2 )] . Subjects applied imiquimod cream, 5% or vehicle topically 5 times per week for 6 weeks. The incidence of selected adverse reactions reported by ≥1% of subjects during the trials is summarized in Table 5.
Table 5:
Selected Adverse Reactions Reported by ≥1% of Imiquimod-Treated Subjects with sBCC and at a Greater Frequency than Vehicle in Studies sBCC1 and sBCC2 Imiquimod Cream (n= 185) N % Vehicle (n= 179) N % Application Site Reaction 52 (28%) 5 (3%) Headache 14 (8%) 4 (2%) Back Pain 7 (4%) 1 (<1%) Upper Respiratory Tract Infection 6 (3%) 2 (1%) Rhinitis 5 (3%) 1 (<1%) Lymphadenopathy 5 (3%) 1 (<1%) Fatigue 4 (2%) 2 (1%) Sinusitis 4 (2%) 1 (<1%) Dyspepsia 3 (2%) 2 (1%) Coughing 3 (2%) 1 (<1%) Fever 3 (2%) 0 (0%) Dizziness 2 (1%) 1 (<1%) Anxiety 2 (1%) 1 (<1%) Pharyngitis 2 (1%) 1 (<1%) Chest Pain 2 (1%) 0 (0%) Nausea 2 (1%) 0 (0%) The most frequently reported adverse reactions were local skin and application site reactions.
The incidence of application site reactions reported by >1% of the subjects during the 6-week treatment period is summarized in Table 6.
Table 6:
Application Site Reactions Reported by > 1% of Imiquimod-Treated Subjects with sBCC and at a Greater Frequency than Vehicle in Studies sBCC1 and sBCC2 Imiquimod Cream (n= 185) Vehicle (n= 179) Itching 30 (16%) 1 (1%) Burning 11 (6%) 2 (1%) Pain 6 (3%) 0 (0%) Bleeding 4 (2%) 0 (0%) Erythema 3 (2%) 0 (0%) Papule(s) 3 (2%) 0 (0%) Tenderness 2 (1%) 0 (0%) Infection 2 (1%) 0 (0%) Local skin reactions were collected independently of the adverse reaction “application site reaction”.
The incidence and severity of local skin reactions that occurred during the controlled trials are shown in Table 7. , rest periods, withdrawal from trial) were local skin and application site reactions; 10% (19/185) of imiquimod-treated subjects received rest periods.
The average number of doses not received per imiquimod-treated subject due to rest periods was 7 doses with a range of 2 to 22 doses; 79% of subjects (15/19) resumed therapy after a rest period. Overall, in the clinical trials, 2% (4/185) of imiquimod-treated subjects discontinued for local skin/application site reactions.
3%) imiquimod-treated subjects developed treatment site infections that required a rest period and treatment with antibiotics. 3 )] , imiquimod cream, 5% was applied topically to EGW in 109 subjects. Selected adverse reactions in imiquimod-treated subjects are listed below (see Table 8).
Table 8:
Selected Adverse Reactions in Imiquimod-Treated Subjects with EGW in Vehicle-Controlled Clinical Trials Females Males Imiquimod Cream (n=117) Vehicle (n=103) Imiquimod Cream (n=156) Vehicle (n=158) Wart Site Itching 38 (32%) 21 (20%) 34 (22%) 16 (10%) Burning 30 (26%) 12 (12%) 14 (9%) 8 (5%) Pain 9 (8%) 2 (2%) 3 (2%) 1 (1%) Soreness 3 (3%) 0 (0%) 0 (0%) 1 (1%) Fungal Infection 13 (11%) 3 (3%) 3 (2%) 1 (1%) Systemic Reactions Headache 5 (4%) 3 (3%) 8 (5%) 3 (2%) Influenza-like Symptoms 4 (3%) 2 (2%) 2 (1%) 0 (0%) Myalgia 1 (1%) 0 (0%) 2 (1%) 1 (1%) The most frequently reported adverse reactions were local skin and application site reactions.
2% (4/327) of the subjects discontinued treatment due to local skin/application site reactions. The incidence and severity of local skin reactions during controlled clinical trials are shown in Table 9.
Table 9:
Local Skin Reactions in the Treatment Area of Imiquimod-Treated Subjects with EGW as Assessed by the Investigator in Vehicle-Controlled Clinical Trials Imiquimod Cream Vehicle Females (n=114) Males (n=156) Females (n=99) Males (n=157) All Grades* Severe All Grades* Severe All Grades* Severe All Grades* Severe Erythema 74 (65%) 4 (4%) 90 (58%) 6 (4%) 21 (21%) 0 (0%) 34 (22%) 0 (0%) Erosion 35 (31%) 1 (1%) 47 (30%) 2 (1%) 8 (8%) 0 (0%) 10 (6%) 0 (0%) Excoriation/ Flaking 21 (18%) 0 (0%) 40 (26%) 1 (1%) 8 (8%) 0 (0%) 12 (8%) 0 (0%) Edema 20 (18%) 1 (1%) 19 (12%) 0 (0%) 5 (5%) 0 (0%) 1 (1%) 0 (0%) Scabbing 4 (4%) 0 (0%) 20 (13%) 0 (0%) 0 (0%) 0 (0%) 4 (3%) 0 (0%) Induration 6 (5%) 0 (0%) 11 (7%) 0 (0%) 2 (2%) 0 (0%) 3 (2%) 0 (0%) Ulceration 9 (8%) 3 (3%) 7 (4%) 0 (0%) 1 (1%) 0 (0%) 1 (1%) 0 (0%) Vesicles 3 (3%) 0 (0%) 3 (2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) *Mild, Moderate, or Severe Remote site skin reactions were also reported.
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%). 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of imiquimod cream.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Application Site Disorders: tingling at the application site Body as a Whole: angioedema Cardiovascular: capillary leak syndrome, cardiac failure, cardiomyopathy, pulmonary edema, arrhythmias (tachycardia, atrial fibrillation, palpitations), chest pain, ischemia, myocardial infarction, syncope Endocrine: thyroiditis Gastrointestinal System Disorders: abdominal pain Hematological: decreases in red cell, white cell, and platelet counts (including idiopathic thrombocytopenic purpura), lymphoma Hepatic: abnormal liver function Infections and Infestations: herpes simplex Musculoskeletal System Disorders: arthralgia Neuropsychiatric: agitation, cerebrovascular accident, convulsions (including febrile convulsions), depression, insomnia, multiple sclerosis aggravation, paresis, suicide Respiratory: dyspnea Urinary System Disorders: proteinuria, dysuria, urinary retention Skin and Appendages: exfoliative dermatitis, erythema multiforme, hypertrophic scar, hyperpigmentation, hypopigmentation, including complete depigmentation.
Vascular:
Henoch-Schönlein purpura syndrome