Imiquimod
Generic: IMIQUIMOD
Basic Information
Manufacturer
Oceanside Pharmacueticals
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
TOPICAL
FDA Set ID
d86eeb0e-70e0-4c72-aaa3-37daa1d8611e
Indications & Usage
1 INDICATIONS AND USAGE Imiquimod Cream, 3.75% is indicated for the topical treatment of clinically typical, visible, or palpable actinic keratoses (AK) of the face or balding scalp in immunocompetent adults.
( 1.1 ) Imiquimod Cream, 3.75% is indicated for the topical treatment of external genital and perianal warts (EGW) in immunocompetent patients 12 years of age or older.
( 1.2 ) 1.1 Actinic Keratosis Imiquimod Cream, 3.75% is indicated for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the face or balding scalp in immunocompetent adults.
1.2 External Genital Warts Imiquimod Cream, 3.75% is indicated for the topical treatment of external genital and perianal warts (EGW) in immunocompetent patients 12 years of age and older.
( 1.1 ) Imiquimod Cream, 3.75% is indicated for the topical treatment of external genital and perianal warts (EGW) in immunocompetent patients 12 years of age or older.
( 1.2 ) 1.1 Actinic Keratosis Imiquimod Cream, 3.75% is indicated for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the face or balding scalp in immunocompetent adults.
1.2 External Genital Warts Imiquimod Cream, 3.75% is indicated for the topical treatment of external genital and perianal warts (EGW) in immunocompetent patients 12 years of age and older.
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Local Skin Reactions [see Warnings and Precautions ( 5.1 )] Systemic Reactions [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (≥4%) are local skin reactions (erythema, scabbing/crusting, flaking/scaling/dryness, edema, erosion/ulceration, exudate), headache, application site pain, application site irritation, application site pruritus, fatigue, influenza-like illness, and nausea.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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.
Actinic Keratosis The data described below reflect exposure to Imiquimod Cream or vehicle in 479 subjects with AK enrolled in two double-blind, vehicle-controlled trials (Studies AK1 and AK2) [see Clinical Studies ( 14.1 )] .
Subjects applied up to two packets of Imiquimod Cream, 3.75%, Imiquimod Cream, 2.5%, or vehicle once daily, to the skin of the affected area (either entire face or balding scalp) for two 2-week treatment cycles separated by a 2-week no treatment period.
Selected adverse reactions are listed in Table 1.
Table 1: Selected Adverse Reactions Occurring in ≥2% of Imiquimod Cream-Treated Subjects with AK and at a Greater Frequency than Vehicle in Studies AK1 and AK2 Adverse Reaction Imiquimod Cream, 3.75% (N=160) Imiquimod Cream, 2.5% (N=160) Vehicle (N=159) Headache 10 (6%) 3 (2%) 5 (3%) Application site pruritus 7 (4%) 6 (4%) 1 (<1%) Fatigue 7 (4%) 2 (1%) 0 Nausea 6 (4%) 1 (1%) 2 (1%) Application site irritation 5 (3%) 4 (3%) 0 Application site pain 5 (3%) 2 (1%) 0 Pyrexia 5 (3%) 0 0 Anorexia 4 (3%) 0 0 Dizziness 4 (3%) 1 (<1%) 0 Herpes simplex 4 (3%) 0 1 (<1%) Lymphadenopathy 3 (2%) 4 (3%) 0 Diarrhea 3 (2%) 2 (1%) 0 Arthralgia 2 (1%) 4 (3%) 0 Influenza like illness 1 (<1%) 6 (4%) 0 Oral herpes 0 4 (3%) 0 Cheilitis 0 3 (2%) 0 Local skin reactions were recorded as adverse reactions if they extended beyond the treatment area, or required any medical intervention, or resulted in patient discontinuation from the trial.
The incidence and severity of selected local skin reactions are shown in Table 2.
Table 2: Local Skin Reactions in the Treatment Area in Imiquimod Cream-Treated Subjects with AK as Assessed by the Investigator in Studies AK1 and AK2 All Grades* (%) Severe (%) Imiquimod Cream, 3.75% (N=160) Imiquimod Cream, 2.5% (N=160) Vehicle (N=159) *Mild, moderate, or severe Erythema* Severe erythema 96% 25% 96% 14% 78% 0% Scabbing/Crusting* Severe scabbing/crusting 93% 14% 84% 9% 45% 0% Flaking/Scaling/Dryness* Severe flaking/scaling/dryness 91% 8% 88% 4% 77% 1% Edema* Severe edema 75% 6% 63% 4% 19% 0% Erosion/Ulceration* Severe erosion/ulceration 62% 11% 52% 9% 9% 0% Exudate* Severe exudate 51% 6% 39% 1% 4% 0% In the AK trials, 11% (17/160) of subjects in the Imiquimod Cream, 3.75% arm, 7% (11/160) of subjects in the Imiquimod Cream, 2.5% arm, and 0% in the vehicle arm required rest periods due to adverse local skin reactions.
Other adverse reactions observed in subjects treated with Imiquimod Cream included: application site bleeding, application site swelling, chills, dermatitis, herpes zoster, insomnia, lethargy, myalgia, pancytopenia, pruritus, squamous cell carcinoma, and vomiting.
External Genital Warts In two double-blind, placebo-controlled trials 602 subjects with EGW applied up to one packet of Imiquimod Cream, 3.75% or vehicle to all warts once daily for up to 8 weeks (Studies EGW1 and EGW2) [see Clinical Studies ( 14.2 )] .
The most frequently reported adverse reactions were application site reactions and local skin reactions.
Selected adverse reactions are listed in Table 3.
Table 3: Selected Adverse Reactions Occurring in ≥2% of Imiquimod Cream-Treated Subjects with EGW and at a Greater Frequency than Vehicle in Studies EGW1 and EGW2 Adverse Reaction Imiquimod Cream, 3.75% (N=400) Vehicle (N=202) Application site pain 28 (7%) 1 (<1%) Application site irritation 24 (6%) 2 (1%) Application site pruritus 11 (3%) 2 (1%) Vaginitis bacterial* 6 (3%) 2 (2%) Headache 6 (2%) 1 (<1%) *Percentage based on female population of 6/216 for Imiquimod Cream, 3.75% and 2/106 for vehicle Local skin reactions were recorded as adverse reactions if they extended beyond the treatment area, or required any medical intervention, or resulted in patient discontinuation from the trial.
The incidence and severity of selected local skin reactions are shown in Table 4.
Table 4: Selected Local Skin Reactions in the Treatment Area in Imiquimod Cream-Treated Subjects with EGW Assessed by the Investigator in Studies EGW1 and EGW2 All Grades* (%) Severe (%) Imiquimod Cream, 3.75% (N=400) Vehicle (N=202) *Mild, moderate, or severe Erythema* Severe erythema 70% 9% 27% <1% Edema* Severe edema 41% 2% 8% 0% Erosion/ulceration* Severe erosion/ulceration 36% 11% 4% <1% Exudate* Severe exudate 34% 2% 2% 0% The frequency and severity of local skin reactions were similar in both sexes, with the following exceptions: a) flaking/scaling occurred in 40% of males and in 26% of females and b) scabbing/crusting occurred in 34% of males and in 18% of females.
In Studies EGW1 and EGW2, 32% (126/400) of subjects who used Imiquimod Cream, 3.75% and 2% (4/202) of subjects who used vehicle discontinued treatment temporarily (required rest periods) due to adverse local skin reactions, and 1% (3/400) of subjects who used Imiquimod Cream, 3.75% discontinued treatment permanently due to local skin/application site reactions.
Other adverse reactions reported in subjects treated with Imiquimod Cream, 3.75% included: rash, back pain, application site rash, application site cellulitis, application site excoriation, application site bleeding, scrotal pain, scrotal erythema, scrotal ulcer, scrotal edema, sinusitis, nausea, pyrexia, and influenza-like symptoms.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of imiquimod.
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, supraventricular 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, urinary retention, dysuria Skin and Appendages : exfoliative dermatitis, erythema multiforme, hyperpigmentation, hypertrophic scar, hypopigmentation Vascular : Henoch-Schönlein purpura syndrome
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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.
Actinic Keratosis The data described below reflect exposure to Imiquimod Cream or vehicle in 479 subjects with AK enrolled in two double-blind, vehicle-controlled trials (Studies AK1 and AK2) [see Clinical Studies ( 14.1 )] .
Subjects applied up to two packets of Imiquimod Cream, 3.75%, Imiquimod Cream, 2.5%, or vehicle once daily, to the skin of the affected area (either entire face or balding scalp) for two 2-week treatment cycles separated by a 2-week no treatment period.
Selected adverse reactions are listed in Table 1.
Table 1: Selected Adverse Reactions Occurring in ≥2% of Imiquimod Cream-Treated Subjects with AK and at a Greater Frequency than Vehicle in Studies AK1 and AK2 Adverse Reaction Imiquimod Cream, 3.75% (N=160) Imiquimod Cream, 2.5% (N=160) Vehicle (N=159) Headache 10 (6%) 3 (2%) 5 (3%) Application site pruritus 7 (4%) 6 (4%) 1 (<1%) Fatigue 7 (4%) 2 (1%) 0 Nausea 6 (4%) 1 (1%) 2 (1%) Application site irritation 5 (3%) 4 (3%) 0 Application site pain 5 (3%) 2 (1%) 0 Pyrexia 5 (3%) 0 0 Anorexia 4 (3%) 0 0 Dizziness 4 (3%) 1 (<1%) 0 Herpes simplex 4 (3%) 0 1 (<1%) Lymphadenopathy 3 (2%) 4 (3%) 0 Diarrhea 3 (2%) 2 (1%) 0 Arthralgia 2 (1%) 4 (3%) 0 Influenza like illness 1 (<1%) 6 (4%) 0 Oral herpes 0 4 (3%) 0 Cheilitis 0 3 (2%) 0 Local skin reactions were recorded as adverse reactions if they extended beyond the treatment area, or required any medical intervention, or resulted in patient discontinuation from the trial.
The incidence and severity of selected local skin reactions are shown in Table 2.
Table 2: Local Skin Reactions in the Treatment Area in Imiquimod Cream-Treated Subjects with AK as Assessed by the Investigator in Studies AK1 and AK2 All Grades* (%) Severe (%) Imiquimod Cream, 3.75% (N=160) Imiquimod Cream, 2.5% (N=160) Vehicle (N=159) *Mild, moderate, or severe Erythema* Severe erythema 96% 25% 96% 14% 78% 0% Scabbing/Crusting* Severe scabbing/crusting 93% 14% 84% 9% 45% 0% Flaking/Scaling/Dryness* Severe flaking/scaling/dryness 91% 8% 88% 4% 77% 1% Edema* Severe edema 75% 6% 63% 4% 19% 0% Erosion/Ulceration* Severe erosion/ulceration 62% 11% 52% 9% 9% 0% Exudate* Severe exudate 51% 6% 39% 1% 4% 0% In the AK trials, 11% (17/160) of subjects in the Imiquimod Cream, 3.75% arm, 7% (11/160) of subjects in the Imiquimod Cream, 2.5% arm, and 0% in the vehicle arm required rest periods due to adverse local skin reactions.
Other adverse reactions observed in subjects treated with Imiquimod Cream included: application site bleeding, application site swelling, chills, dermatitis, herpes zoster, insomnia, lethargy, myalgia, pancytopenia, pruritus, squamous cell carcinoma, and vomiting.
External Genital Warts In two double-blind, placebo-controlled trials 602 subjects with EGW applied up to one packet of Imiquimod Cream, 3.75% or vehicle to all warts once daily for up to 8 weeks (Studies EGW1 and EGW2) [see Clinical Studies ( 14.2 )] .
The most frequently reported adverse reactions were application site reactions and local skin reactions.
Selected adverse reactions are listed in Table 3.
Table 3: Selected Adverse Reactions Occurring in ≥2% of Imiquimod Cream-Treated Subjects with EGW and at a Greater Frequency than Vehicle in Studies EGW1 and EGW2 Adverse Reaction Imiquimod Cream, 3.75% (N=400) Vehicle (N=202) Application site pain 28 (7%) 1 (<1%) Application site irritation 24 (6%) 2 (1%) Application site pruritus 11 (3%) 2 (1%) Vaginitis bacterial* 6 (3%) 2 (2%) Headache 6 (2%) 1 (<1%) *Percentage based on female population of 6/216 for Imiquimod Cream, 3.75% and 2/106 for vehicle Local skin reactions were recorded as adverse reactions if they extended beyond the treatment area, or required any medical intervention, or resulted in patient discontinuation from the trial.
The incidence and severity of selected local skin reactions are shown in Table 4.
Table 4: Selected Local Skin Reactions in the Treatment Area in Imiquimod Cream-Treated Subjects with EGW Assessed by the Investigator in Studies EGW1 and EGW2 All Grades* (%) Severe (%) Imiquimod Cream, 3.75% (N=400) Vehicle (N=202) *Mild, moderate, or severe Erythema* Severe erythema 70% 9% 27% <1% Edema* Severe edema 41% 2% 8% 0% Erosion/ulceration* Severe erosion/ulceration 36% 11% 4% <1% Exudate* Severe exudate 34% 2% 2% 0% The frequency and severity of local skin reactions were similar in both sexes, with the following exceptions: a) flaking/scaling occurred in 40% of males and in 26% of females and b) scabbing/crusting occurred in 34% of males and in 18% of females.
In Studies EGW1 and EGW2, 32% (126/400) of subjects who used Imiquimod Cream, 3.75% and 2% (4/202) of subjects who used vehicle discontinued treatment temporarily (required rest periods) due to adverse local skin reactions, and 1% (3/400) of subjects who used Imiquimod Cream, 3.75% discontinued treatment permanently due to local skin/application site reactions.
Other adverse reactions reported in subjects treated with Imiquimod Cream, 3.75% included: rash, back pain, application site rash, application site cellulitis, application site excoriation, application site bleeding, scrotal pain, scrotal erythema, scrotal ulcer, scrotal edema, sinusitis, nausea, pyrexia, and influenza-like symptoms.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of imiquimod.
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, supraventricular 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, urinary retention, dysuria Skin and Appendages : exfoliative dermatitis, erythema multiforme, hyperpigmentation, hypertrophic scar, hypopigmentation Vascular : Henoch-Schönlein purpura syndrome