Imiquimod Drug Information

Important Dosage and Administration Instructions Imiquimod Cream is for topical use only. Imiquimod Cream is not for oral, ophthalmic, or intravaginal use. Instruct patients on proper application technique.

Wash hands before and after applying Imiquimod Cream. Wash the treatment area with mild soap and water and allow the area to dry thoroughly (at least 10 minutes) before applying Imiquimod Cream. If an Imiquimod Cream dose is missed, apply the next dose at the regularly scheduled time.

Avoid contact with the eyes, lips, nostrils, or inside the anus and vagina. For patients with AK and sBCC, prescribe no more than 3 boxes (36 packets) of Imiquimod Cream for the entire treatment period. For EGW, one packet of Imiquimod Cream contains sufficient cream to cover a wart area of up to 20 cm 2.

Discard partially used packets and do not reuse.

Dosage and Administration for Actinic Keratosis Apply Imiquimod Cream topically once daily before bedtime 2 times per week for a full 16 weeks to a defined treatment area of AK on the face or scalp (but not both concurrently). Apply Imiquimod Cream to the entire treatment area and rub in until the cream is no longer visible. Apply no more than 1 packet of Imiquimod Cream to the contiguous treatment area at each application.

Leave Imiquimod Cream on the skin for approximately 8 hours and then remove with mild soap and water. For local skin reactions a dosage interruption of several days may be taken if required by the patient's discomfort or severity of the local skin reaction. Do not extend treatment beyond 16 weeks due to missed doses or rest periods.

Assess response to treatment after resolution of local skin reactions.

Dosage and Administration for Superficial Basal Cell Carcinoma Apply Imiquimod Cream topically once daily before bedtime 5 times per week for a full 6 weeks to a biopsy-confirmed sBCC. The target tumor should have a maximum diameter of 2 cm and be located on the trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet). The amount of cream needed to cover the target tumor, including 1 cm of skin surrounding the tumor, is presented in Table 1.

Assess for early clinical clearance after resolution of local skin reactions (e.g., 12 weeks post-treatment). Local skin reactions or other findings (e.g., infection) may require that a patient be seen sooner than the post-treatment assessment for clinical clearance. If there is clinical evidence of persistent tumor at the post-treatment assessment for clinical clearance, consider a biopsy or other alternative intervention.

Instruct patients to contact their healthcare provider if any suspicious lesion arises in the treatment area at any time after a determination of clinical clearance.

Dosage and Administration for External Genital Warts Apply a thin layer of Imiquimod Cream topically once daily before bedtime 3 times per week to EGW until there is total clearance of the genital/perianal warts or for a maximum of 16 weeks. Do not occlude the application site. Leave Imiquimod Cream on the skin for 6 to 10 hours and then remove with mild soap and water.

Treatment may resume once the reaction subsides. Nonocclusive dressings such as cotton gauze or cotton underwear may be used to manage skin reactions. Inform uncircumcised patients treating warts under the foreskin to retract the foreskin and clean the area daily.

Imiquimod Cream may weaken condoms and vaginal diaphragms; therefore, concurrent use is not recommended.

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 436 subjects with AK enrolled in two double-blind, vehicle-controlled trials (Studies AK1 and AK2). The incidence of selected adverse reactions reported by ≥1% of subjects during the trials is presented in Table 2.

Table 3: Application Site Reactions Reported by >1% of Imiquimod-Treated Subjects with AK and at a Greater Frequency than 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. Table 4: Local Skin Reactions in the Treatment Area of Imiquimod-Treated Subjects with AK as Assessed by the Investigator in Studies AK1 and AK2 The adverse reactions that most frequently resulted in clinical intervention (e.g., 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 imiquimod-treated subjects, 32 (91%) resumed therapy after a rest period. Superficial Basal Cell Carcinoma The data described below reflect exposure to imiquimod cream or vehicle in 364 subjects with sBCC enrolled in two double-blind, vehicle-controlled trials (sBCC1 and sBCC2).

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 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. Overall, in the clinical trials, 2% (4/185) of imiquimod-treated subjects discontinued for local skin/application site reactions. In the sBCC trials, 17 of 1266 (1.3%) imiquimod-treated subjects developed treatment site infections that required a rest period and treatment with antibiotics.

External Genital Warts In controlled clinical trials for EGW, including a double-blind, vehicle-controlled clinical trial in 209 adult subjects with EGW (Study EGW1), 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 The most frequently reported adverse reactions were local skin and application site reactions.

Overall, 1.2% (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 Remote site skin reactions were also reported.

Other adverse reactions reported by more than 1% of imiquimod-treated subjects included: Application Site Disorders: hypopigmentation, irritation, rash, sensitivity, stinging, tenderness Body as a Whole: fatigue, fever Gastrointestinal System Disorders: diarrhea Remote Site Reactions: bleeding, burning, itching, pain, tenderness, tinea cruris

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

Pregnancy Risk Summary Available data from case reports and case series of use with imiquimod during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are no controlled or large-scale epidemiologic studies and no exposure registries with imiquimod use in pregnant women. In animal reproduction studies, there were no adverse developmental effects observed after oral administration of imiquimod in pregnant rats and intravenous administration of imiquimod in pregnant rabbits during organogenesis at doses up to 98 times and 407 times, respectively, the maximum recommended human dose (MRHD) (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data The MRHD was set at 2 packets per treatment of Imiquimod Cream (25 mg imiquimod) for the animal multiples of human exposure presented in this label. Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 1, 5, and 20 mg/kg/day imiquimod were administered during the period of organogenesis to pregnant female rats.

In the presence of maternal toxicity, fetal effects noted at 20 mg/kg/day (577 times the MRHD based on AUC comparison) included increased resorptions, decreased fetal body weights, delays in skeletal ossification, bent limb bones, and two fetuses in one litter (2 of 1567 fetuses) demonstrated exencephaly, protruding tongues and low-set ears. No treatment-related effects on embryofetal toxicity or malformation were noted at 5 mg/kg/day (98 times the MRHD based on AUC comparison). Intravenous doses of 0.5, 1, and 2 mg/kg/day imiquimod were administered during the period of organogenesis to pregnant female rabbits.

A combined fertility and peri- and postnatal development study was conducted in rats. Oral doses of mg/kg/day imiquimod were administered to male rats from 70 days prior to mating through the mating period and to female rats from 14 days prior to mating through parturition and lactation. No effects on growth, fertility, reproduction, or postnatal development were noted at doses up to 6 mg/kg/day (87 times the MRHD based on AUC comparison), the highest dose evaluated in this study.

In the absence of maternal toxicity, bent limb bones were noted in the F1 fetuses at a dose of 6 mg/kg/day (87 times the MRHD based on AUC comparison). This fetal effect was also noted in the oral rat embryofetal development study conducted with imiquimod. No treatment-related malformations were noted at 3 mg/kg/day (41 times the MRHD based on AUC comparison).

Pediatric Use Actinic Keratosis and Superficial Basal Cell Carcinoma The safety and effectiveness of Imiquimod Cream for the treatment of AK or sBCC in pediatric patients have not been established. External Genital Warts The safety and effectiveness of Imiquimod Cream for the treatment of EGW in pediatric patients 12 years of age and older have been established. Use of Imiquimod Cream for this indication is supported by evidence from adequate and well controlled trials in adults.

The safety and effectiveness of Imiquimod Cream for the treatment of EGW in pediatric patients less than 12 years of age have not been established. Molluscum Contagiosum The safety and effectiveness of Imiquimod Cream for the treatment of molluscum contagiosum (MC) in pediatric patients have not been established.

Topical overdosing of Imiquimod Cream could result in an increased incidence of severe local skin reactions and may increase the risk for systemic reactions. The most clinically serious adverse reaction reported following multiple oral imiquimod doses of >200 mg (equivalent to imiquimod content of >16 packets of Imiquimod Cream) was hypotension, which resolved following oral or intravenous fluid administration. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.