Aldara cream, 5%

Aldara ™ is the brand name for imiquimod which is an immune response modifier. Each gram of the 5% cream contains 50 mg of imiquimod in an off-white oil-in-water vanishing cream base consisting of isostearic acid, cetyl alcohol, stearyl alcohol, white petrolatum, polysorbate 60, sorbitan monostearate, glycerin, xanthan gum, purified water, benzyl alcohol, methylparaben, and propylparaben.

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:

Systemic absorption of imiquimod was observed across the affected skin of 12 patients 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 study. 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.

Systemic absorption of imiquimod across the affected skin of 58 patients 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 single-use packet), scalp (25 mg, 2 packets) and hands/arms (75 mg, 6 packets), respectively.

The application surface area was not controlled when more than one 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.

Aldara Cream is indicated for the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults.

Aldara 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. The histological diagnosis of superficial basal cell carcinoma should be established prior to treatment, since safety and effectiveness of Aldara Cream have not been established for other types of basal cell carcinomas, including nodular, morpheaform (fibrosing or sclerosing) types.

Aldara Cream is indicated for the treatment of external genital and perianal warts/condyloma acuminata in individuals 12 years old and above.

This drug is contraindicated in individuals with a history of sensitivity reactions to any of its components. It should be discontinued if hypersensitivity to any of its ingredients is noted.

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, 2 × /week studies. Patients applied Aldara Cream or vehicle to a 25 cm 2 contiguous treatment area on the face or scalp 2 × /week for 16 weeks.

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.

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, 5 × /week studies. Patients applied Aldara Cream or vehicle 5 × /week for 6 weeks. The incidence of adverse events reported by > 1% of subjects during the 6 week treatment period is summarized below.

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.

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.

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 3 × /week application. These reactions were more frequent and more intense with daily application than with 3 × /week application. Some patients also reported systemic reactions. Overall, in the 3 × /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.

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.

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.

Aldara (imiquimod) Cream, 5%, is supplied in single-use packets which contain 250 mg of the cream. Available as: box of 12 packets NDC 0089-0610-12.

Store below 25°C (77°F).

Avoid freezing.

Keep out of reach of children.

Rx only

Manufactured by

3M Health Care Limited

Loughborough LE11 1EP England

Distributed by

3M Pharmaceuticals

Northridge, CA 91324

July 2004

662600

3M and Aldara are trademarks

of the 3M Company

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