Imiquimod 12.5 mg/.25g Cream, 12 packets
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Antivirals class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Imiquimod cream is used to treat certain types of actinic keratoses (flat, scaly growths on the skin caused by too much sun exposure), superficial basal cell carcinoma (a type of skin cancer), and warts on the skin of the genital and anal areas. Imiquimod is in a class of medications called immune response modifiers. It may work by increasing the activity of the body's immune system. Imiquimod cream does not cure warts, and new warts may appear during treatment. It is not known whether imiquimod cream prevents the spread of warts to other people.
Read the full MedlinePlus article ↗- Yes — and that's actually expected. Redness, flaking, and even some crusting or sores at the treatment site are a normal sign that the cream is doing its job. For actinic keratoses...
- How long does it take for imiquimod to work, and will the treated area look worse before it gets better?
- It's important to stick to the schedule your doctor prescribed — not more often. Using it more frequently than directed can make skin reactions much more severe without making trea...
- Can I use imiquimod every day to speed things up?
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Supplement & herbal interactions
Some supplements/herbs that may interact with Imiquimod — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
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Cetyl alcohol is a waxy, fatty substance derived from plant or animal sources. It acts as an emulsifier and thickener in medicines, helping blend oil and water components and giving products a smooth, creamy texture.
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Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
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Methylparaben is a preservative derived from benzoic acid that prevents growth of bacteria, fungi, and mold in medicines. It extends the product's shelf life and maintains safety during storage.
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Oleic acid is a naturally occurring fatty acid derived from plant or animal oils. It functions as an emulsifier and solvent in medicines, helping blend water and oil-based ingredients together and dissolving other components.
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A fatty alcohol derived from animal or plant oils. It acts as an emollient and helps stabilize emulsions, allowing oil and water to mix evenly in the medication.
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Petrolatum is a purified mineral oil-based jelly derived from petroleum. In medicines, it acts as an emollient, lubricant, and moisture barrier to soften skin, reduce friction, and help prevent water loss from formulations.
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A synthetic emulsifier derived from sorbitol and fatty acids. It helps mix oil and water-based ingredients together and improves the texture and stability of the medicine.
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Propylparaben is a chemical preservative used to prevent bacterial and fungal growth in medicines and personal care products. It helps extend shelf life and maintain product safety during storage.
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A waxy substance made from sorbitol and stearic acid. It acts as an emulsifier and stabilizer, helping keep oil and water mixed together and preventing separation in the medicine.
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UNII 2KR89I4H1Y
Stearyl alcohol is a waxy, fatty substance derived from natural oils or made synthetically. It acts as an emulsifier and thickener in medicines, helping mix ingredients together and give the product the right texture.
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Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
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Xanthan gum is a thickening and stabilizing ingredient made from fermented corn or other sugars. It's added to medicines to improve texture, prevent separation of liquids and solids, and help the product stay consistent.
13 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $12.145 | $145.74 / 12 packets |
| Medicaid paysCMS SDUD · 12 mo | $9.05 | $108.59 / 12 packets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Imiquimod 50 mg/g 51672-4145-06 | Sun | 24 packets | $0.645 | AB | Availability likely | save 95% |
| Imiquimod 50 mg/g 68462-0536-70 | Glenmark | 24 packets | $0.645 | AB | Availability likely | save 95% |
| Imiquimod 12.5 mg/.25gthis 45802-0368-53 | Padagis | 12 packets | $12.145 | AB | Availability likely | — |
| Imiquimod 12.5 mg/.25g 71335-2725-01 | Bryant | 24 packets | — | AB | FDA listed | — |
| Imiquimod 12.5 mg/.25g 71335-3000-01 | Bryant | 24 packets | — | AB | FDA listed | — |
| Imiquimod 12.5 mg/.25g 72162-2332-02 | Bryant | 24 packets | — | AB | FDA listed | — |
| Imiquimod 12.5 mg/.25g 72189-0084-24 | DIRECT | 25 g | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 45802-0368-53 You're viewing this | 12 PACKET in 1 CARTON (45802-368-53) / .25 g in 1 PACKET | $12.14 / ea | $145.74 | 2012-07-12 | Active |
| 45802-0368-62 | 24 PACKET in 1 CARTON (45802-368-62) / .25 g in 1 PACKET | $0.6445 / ea | $15.47 | 2010-11-09 | Active |
Per ea, this pack runs about 1784% above the cheapest pack (NDC 45802-0368-62, $0.6445 vs $12.14 NADAC).
This pack accounts for about 4.8% of this product's recent Medicaid fills; most go to a different pack size. See all packs ↓
Pack size FAQ
What quantity is in NDC 45802-0368-53?
What is the difference between NDC 45802-0368-53 and NDC 45802-0368-62?
What NDC number is used to bill for this package of Imiquimod 12.5 mg/.25g Cream?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Imiquimod Cream is indicated for the topical treatment of: • Clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses (AK) on the face or scalp in immunocompetent adults. ( 1.1 ) • Biopsy-confirmed, primary superficial basal cell carcinoma (sBCC) in immunocompetent adults with a maximum tumor diameter of 2.0 cm on trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet), only when surgical methods are medically less appropriate and patient follow-up can be reasonably assured.
( 1.2 ) • External genital and perianal warts (EGW) in immunocompetent patients 12 years of age and older. ( 1.3 )
1.1Actinic Keratosis Imiquimod Cream is indicated for the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses (AK) on the face or scalp in immunocompetent adults.
1.2Superficial Basal Cell Carcinoma Imiquimod Cream is indicated for the topical treatment of biopsy-confirmed, primary superficial basal cell carcinoma (sBCC) in immunocompetent adults, with a maximum tumor diameter of 2.0 cm, located on the trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet), only when surgical methods are medically less appropriate and patient follow-up can be reasonably assured. Establish the histological diagnosis of superficial basal cell carcinoma prior to treatment.
The safety and effectiveness of Imiquimod Cream have not been established for other types of basal cell carcinomas (BCC), including nodular and morpheaform (fibrosing or sclerosing) types.
1.3External Genital Warts Imiquimod Cream is indicated for the topical treatment of external genital and perianal warts (EGW) in immunocompetent patients 12 years of age and older.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • For topical use only; not for oral, ophthalmic, intra-anal or intravaginal use. ( 2.1 ) • AK: Apply once daily before bedtime 2 times per week for a full 16 weeks to a contiguous area of approximately 25 cm 2 on the face or scalp. Apply no more than 1 packet at each application.
( 2.2 ) • sBCC: Apply once daily before bedtime 5 times per week for a full 6 weeks to a target tumor with 2 cm maximum diameter on the trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet). Amount of Imiquimod Cream used based on target tumor diameter. ( 2.3 ) • EGW: Apply thin layer once daily before bedtime 3 times per week until total clearance or for a maximum of 16 weeks.
( 2.4 )
2.1Important 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.
2.2Dosage 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). A treatment area is defined as one contiguous area of approximately 25 cm 2 (e.g., 5 cm × 5 cm) on the face (e.g., forehead or one cheek) or on the scalp. 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 [see Warnings and Precautions ( 5.1 )] .
Do not extend treatment beyond 16 weeks due to missed doses or rest periods. Assess response to treatment after resolution of local skin reactions.
2.3Dosage 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.
Rub Imiquimod Cream into the treatment area until the cream is no longer visible. Leave Imiquimod Cream on the skin for approximately 8 hours and then remove with mild soap and water. Table 1: Amount of Imiquimod Cream to Use for sBCC Target Tumor Diameter Size of Cream Droplet to be Used (Diameter) Approximate Amount of Imiquimod Cream to be Used 0.5 to <1.0 cm 4 mm 10 mg ≥1.0 to <1.5 cm 5 mm 25 mg ≥1.5 to 2.0 cm 7 mm 40 mg 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 [see Warnings and Precautions ( 5.1 )] .
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 clin…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Cream, 5%: a white to off-white cream in unit-dose packets, with each packet containing 250 mg of cream, equivalent to 12.5 mg of imiquimod. • Cream: 5% in unit-dose packets. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Local Skin Reactions: Intense local inflammatory reactions can occur (e.g., skin weeping, erosion) Dosage interruption may be required. Severe vulvar swelling may occur and lead to urinary retention; interrupt dosing or discontinue for severe vulvar swelling. ( 5.1 ) • Local Hypopigmentation Reactions: Localized complete depigmentation has occurred and persisted.
Discontinue if hypopigmentation develops. ( 5.2 ) • Systemic Reactions: Flu-like systemic signs and symptoms have occurred. Consider dosage interruption for systemic reactions.
( 5.3 ) • Ultraviolet Light Exposure Risks: Avoid or minimize exposure to sunlight and sunlamps. Wear sunscreen and protective clothing. ( 5.4 )
5.1Local Skin Reactions Local skin reactions including skin weeping or erosion have been reported with Imiquimod Cream and can occur after a few applications [see Adverse Reactions ( 6.1 )] . Concomitant use of Imiquimod Cream and any other imiquimod products, in the same treatment area, may increase the risk for and severity of local skin reactions. Imiquimod Cream has the potential to exacerbate inflammatory conditions of the skin, including chronic graft versus host disease.
Severe local inflammatory reactions of the female external genitalia can lead to severe vulvar swelling and urinary retention. Avoid sexual (genital, anal, oral) contact while Imiquimod Cream is on the skin. To reduce the risk of local skin reactions and manage local skin reactions that occur with Imiquimod Cream treatment: • Avoid concomitant use of Imiquimod Cream with any other imiquimod product in the same treatment area. • Avoid application of Imiquimod Cream to skin that is not intact (i.e., any area with an abrasion, cut, burn, rash, infection, or other condition that has altered skin integrity). • An interruption of dosing may be required for local skin reactions [see Dosage and Administration ( 2.2 , 2.3 , 2.4 )] .
Interrupt dosing or discontinue Imiquimod Cream for severe vulvar swelling [see Dosage and Administration ( 2.4 )] . • If severe local skin reactions occur, instruct patients to remove Imiquimod Cream by washing the treatment area with mild soap and water.
5.2Local Hypopigmentation Reactions Cases of hypopigmentation, including complete depigmentation, were reported during postmarketing use of Imiquimod Cream. In some cases, hypopigmentation and complete depigmentation did not improve or resolve with treatment and persisted for up to 60 months at the time of reporting. Discontinue Imiquimod Cream if hypopigmentation develops.
5.3Systemic Reactions Flu-like signs and symptoms have been reported with use of Imiquimod Cream and may accompany, or even precede, local inflammatory reactions [see Adverse Reactions ( 6.1 )] . Signs and symptoms may include malaise, fever, nausea, myalgias, and rigors. Concomitant use of Imiquimod Cream and any other imiquimod products may increase the risk for and severity of systemic reactions.
Consider an interruption of dosing if systemic reactions occur.
5.4Ultraviolet Light Exposure Risks Imiquimod Cream may cause heightened sunburn susceptibility. Avoid or minimize exposure to sunlight (including sunlamps) during use of Imiquimod Cream. Instruct patients to use sunscreen and wear protective clothing (e.g., a hat). Advise patients not to use Imiquimod Cream until fully recovered from a sunburn.
🤒 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 )] • Local Hypopigmentation Reactions [see Warnings and Precautions ( 5.2 )] • Systemic Reactions [see Warnings and Precautions ( 5.3 )] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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) [see Clinical Studies (14.1)] . 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.
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 Imiquimod Cream (n= 215) Vehicle (n= 220) All Grades* Severe All Grades* Severe Erythema 209 (97%) 38 (18%) 206 (93%) 5 (2%) Flaking/Scaling/Dryness 199 (93%) 16 (7%) 199 (91%) 7 (3%) Scabbing/Crusting 169 (79%) 18 (8%) 92 (42%) 4 (2%) Edema 106 (49%) 0 (0%) 22 (10%) 0 (0%) Erosion/Ulceration 103 (48%) 5 (2%) 20 (9%) 0 (0%) Weeping/Exudate 45 (22%) 0 (0%) 3 (1%) 0 (0%) Vesicles 19 (9%) 0 (0%) 2 (1%) 0 (0%) *Mild, Moderate, or Severe 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 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.
In the AK…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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 2 to 4% and 15 to 20%, 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.
No treatment-related effects on embryofetal toxicity or malformation were noted at 2 mg/kg/day (1.5 times the MRHD based on BSA comparison), the highest dose evaluated in this study, or 1 mg/kg/day (407 times the MRHD based on AUC comparison). A combined fertility and peri- and postnatal development study was conducted in rats. Oral doses of 1, 1.5, 3, and 6 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).
8.2Lactation Risk Summary There is no information available on the presence of imiquimod in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production after topical application of Imiquimod Cream to women who are breastfeeding. Systemic concentration following topical administration of imiquimod cream is low; therefore, transfer of Imiquimod Cream into breastmilk is likely to be low [see Clinical Pharmacology (12.3)] . The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Imiquimod Cream and any potential adverse effects on the breastfed infant from Imiquimod Cream or from the underlying maternal condition.
Clinical Considerations Avoid application of Imiquimod Cream to areas with increased r…
🤰 Pregnancy ▾
8.1Pregnancy 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 2 to 4% and 15 to 20%, 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.
No treatment-related effects on embryofetal toxicity or malformation were noted at 2 mg/kg/day (1.5 times the MRHD based on BSA comparison), the highest dose evaluated in this study, or 1 mg/kg/day (407 times the MRHD based on AUC comparison). A combined fertility and peri- and postnatal development study was conducted in rats. Oral doses of 1, 1.5, 3, and 6 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 ▾
8.4Pediatric 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 [see Clinical Studies (14.3)] .
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. Safety and effectiveness of Imiquimod Cream was not demonstrated in two randomized, vehicle-controlled, double-blind trials involving 702 pediatric subjects with MC (470 exposed to Imiquimod Cream; median age 5 years, range 2–12 years).
Adverse reactions reported in pediatric subject with MC (and not previously reported) included otitis media (5% Imiquimod Cream vs. 3% vehicle) and conjunctivitis (3% Imiquimod Cream vs. 2% vehicle).
In a pharmacokinetics trial in subjects aged 2 to 12 years with extensive MC involving at least 10% of total body surface area; among the 20 subjects with evaluable laboratory assessments, the median white blood cell (WBC) count decreased by 1.4 x 10 9 /L and the median absolute neutrophil count decreased by 1.42 x 10 9 /L.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 215 subjects treated with imiquimod cream in the AK clinical trials, 127 subjects (59%) were 65 years of age or older, while 60 subjects (28%) were 75 years of age or older. Of the 185 subjects treated with imiquimod cream in the sBCC clinical trials, 65 subjects (35%) were 65 years of age or older, while 25 subjects (14%) were 75 years of age or older. No overall differences in safety or effectiveness of Imiquimod Cream have been observed between subjects 65 years of age and older and younger adult subjects.
🆘 Overdosage ▾
10 OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of Imiquimod Cream in treating AK, sBCC, and EGW lesions is unknown.
12.2Pharmacodynamics Actinic Keratosis In a trial of 18 subjects with AK comparing imiquimod cream to vehicle, increases from baseline in Week 2 biomarker levels were reported for CD3, CD4, CD8, CD11c, and CD68 for imiquimod-treated subjects; however, the clinical relevance of these findings is unknown. Superficial Basal Cell Carcinoma An open-label trial in 6 subjects with sBCC suggests that treatment with imiquimod cream may increase the infiltration of lymphocytes, dendritic cells, and macrophages into the tumor lesion; however, the clinical significance of these findings is unknown.
External Genital Warts Imiquimod has no direct antiviral activity in cell culture. A trial in 22 subjects with EGW comparing imiquimod cream and vehicle shows that imiquimod cream induces mRNA encoding cytokines including interferon-ɑ at the treatment site. In addition, HPVL1 mRNA and HPV DNA are significantly decreased following treatment.
However, the clinical relevance of these findings is unknown.
12.3Pharmacokinetics Absorption Systemic absorption of imiquimod across the affected skin of 58 subjects with AK was observed with a dosing frequency of 3 applications per week for 16 weeks. Mean peak serum drug concentrations at the end of Week 16 were approximately 0.1, 0.2, and 3.5 ng/mL for the applications to face (12.5 mg imiquimod, 1 unit-dose packet), scalp (25 mg, 2 packets), and hands/arms (75 mg, 6 packets), respectively. Table 10: Mean Serum Imiquimod Concentration in Adults Following Administration of the Last Topical Dose during Week 16 (Actinic Keratosis) Amount of Imiquimod Cream Applied Mean Peak Serum Imiquimod Concentration [C max ] 12.5 mg (1 packet) 0.1 ng/mL 25 mg (2 packets) 0.2 ng/mL 75 mg (6 packets) 3.5 ng/mL The application surface area was not controlled when more than 1 packet was used.
Dose proportionality was not observed. However, it appears that systemic exposure may be more dependent on surface area of application than amount of applied dose. The apparent half-life was approximately 10 times greater with topical dosing than the 2-hour apparent half-life seen following subcutaneous dosing, suggesting prolonged retention of drug in the skin.
Mean urinary recoveries of imiquimod and metabolites combined were 0.08% and 0.15% of the applied dose in the group using 75 mg (6 packets) for males and females, respectively following 3 applications per week for 16 weeks. Systemic absorption of imiquimod was observed across the affected skin of 12 subjects with genital/perianal warts, with an average dose of 4.6 mg. Mean peak drug concentration of approximately 0.4 ng/mL was seen during the trial.
Mean urinary recoveries of imiquimod and metabolites combined over the whole course of treatment, expressed as percent of the estimated applied dose, were 0.11% and 2.41% in the males and females, respectively.
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action of Imiquimod Cream in treating AK, sBCC, and EGW lesions is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Imiquimod Cream, 5% is supplied in unit-dose packets each of which contains 250 mg of a white to off-white cream. Available as: a box of 12 packets (NDC 45802- 368 -53) and a box of 24 packets (NDC 45802- 368 -62). Store at 4°-25°C (39°-77°F). Avoid freezing.
📋 Description ▾
11 DESCRIPTION Imiquimod Cream, 5% is an immune response modifier for topical administration. Each gram contains 50 mg of imiquimod in an off-white oil-in-water vanishing cream base consisting of benzyl alcohol, cetyl alcohol, glycerin, methylparaben, oleic acid, oleyl alcohol, polysorbate 60, propylparaben, purified water, stearyl alcohol, sorbitan monostearate, white petrolatum, and xanthan gum. Chemically, imiquimod is 1-(2-methylpropyl)-1 H -imidazo[4,5-c]quinolin-4-amine.
Imiquimod has a molecular formula of C 14 H 16 N 4 and a molecular weight of 240.3. Its structural formula is: Image 11
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Important Administration Instructions Inform all patients of the following: [see Dosage and Administration ( 2.1 )] • Imiquimod Cream is for topical use only; avoid contact with the eyes, lips, nostrils, or inside the anus and vagina. Instruct patients to rinse their mouth or eyes with water right away if contact with these areas occur. • Wash hands before and after applying Imiquimod Cream. • If an Imiquimod Cream dose is missed, apply the next dose at the regularly scheduled time. • Discard and do not reuse partially used packets.
Inform patients with EGW of the following [see Dosage and Administration ( 2.4 )]: • Uncircumcised patients treating warts under the foreskin should retract the foreskin and clean the area daily. • Imiquimod Cream may weaken condoms and vaginal diaphragms; therefore, concurrent use is not recommended. • Avoid sexual (genital, anal, oral) contact while Imiquimod Cream is on the skin. • Do not bandage or otherwise occlude the treatment area. Lactation Advise breastfeeding women to avoid application of Imiquimod Cream to areas with increased risk for potential ingestion by or ocular exposure to the breastfeeding child [see Use in Specific Populations ( 8.2 )].
Local Skin Reactions Inform patients of the following [see Dosage and Administration ( 2.2 , 2.3 , 2.4 ) and Warnings and Precautions ( 5.1 )]: • Local skin reactions may occur during treatment with Imiquimod Cream, ranging from mild to severe in intensity and extending beyond the application site onto the surrounding skin, and may require an interruption of dosing. • For female patients being treated for EGW, apply Imiquimod Cream at the opening of the vagina, avoiding intravaginal application because local skin reactions may cause difficulty in passing urine. • If severe local skin reactions occur, remove Imiquimod Cream by washing the treatment area with mild soap and water. • Contact their healthcare provider promptly if they experience any sign or symptom at the application site that restricts or prohibits their daily activity or makes continued application of Imiquimod Cream difficult. • Because of local skin reactions, during treatment and until healed, the treatment area is likely to appear noticeably different from normal skin.
Local Hypopigmentation Reactions Inform patients that cases of hypopigmentation, including complete depigmentation, were reported during postmarketing use of Imiquimod Cream and, in some cases, hypopigmentation and complete depigmentation did not improve or resolve with treatment and persisted for up to 60 months at the time of reporting. Advise patient to inform their healthcare provider if hypopigmentation is observed [see Warnings and Precautions ( 5.2 )]. Systemic Reactions Inform patients that they may experience flu-like systemic signs and symptoms during treatment with Imiquimod Cream and these symptoms may require an interruption of dosing [see Warnings and Precautions ( 5.3 )].
Ultraviolet Light Exposure Risks Instruct patients to avoid or minimize exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using Imiquimod Cream. Instruct patients to use sunscreen and to wear protective clothing, and to not use Imiquimod Cream if sunburned [see Warnings and Precautions ( 5.4 )]. Manufactured by Padagis ® Yeruham, Israel www.padagis.com Rev 01-25 2H100 RC PH8