Aldara

Aldara (imiquimod 5%) Cream 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 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)-1H-imidazo[4,5-c]quinolin-4-amine. Imiquimod has a molecular formula of C14H16N4 and a molecular weight of 240.3. Its structural formula is:

Dosage Forms And Strengths

Aldara (imiquimod) Cream, 5%, is supplied in single-use packets each of which contains 250 mg of the cream, equivalent to 12.5 mg of imiquimod. Aldara Cream is supplied in boxes of 12 packets each.

Storage And Handling

Aldara (imiquimod) Cream, 5%, is supplied in single-use packets which contain 250 mg of the cream. Available as: box of 12 packets NDC 99207-260-12. Store at 4°–25°C (39°–77°F).

Avoid freezing.

Keep out of reach of children.

Manufactured by: 3M Health Care Limited, Loughborough LE11 1EP United Kingdom, Made in UK. Revised: Aug 2014

Included as part of the "PRECAUTIONS" Section

• Medicis Pharmaceutical Corp.

To make sure you can safely take imiquimod topical, tell your doctor if you have any of these other conditions:

• sunburn or other skin problems;

• a weak immune system or autoimmune disorder;

• graft-versus-host disease;

• if you have recently been treated for actinic keratosis or genital warts with surgery or other medications; or

• if you have recently received a bone marrow transplant or cord blood transplant.

FDA pregnancy category C. It is not known whether imiquimod topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

If you are treating the genital or rectal area with imiquimod topical, avoid sexual activity while the medicine is on your skin. Imiquimod topical can weaken the rubber that condoms or diaphragms are made out of. If you use a condom or diaphragm, these items could break if the rubber weakens, and an unplanned pregnancy could result.

It is not known whether imiquimod topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not use this medicine on a child younger than 12 years old. Imiquimod topical is for use in treating genital warts in patients who are at least 12 years old. All other uses of this medication are for adults over 18 only.

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Using too much of this medicine, or using it for too long can increase your risk of severe skin reactions.

Before applying imiquimod topical, wash your hands and wash the skin area to be treated. Allow the skin to dry for at least 10 minutes before applying the medicine. Always wash your hands after applying the medicine also.

Do not use imiquimod topical on areas of broken, wounded, or burned skin. Wait until these conditions have healed before using imiquimod topical.

Imiquimod topical is normally used 2 to 5 times per week for up to 16 weeks. How you use this medication will depend on the condition you are treating. Follow your doctor's instructions.

Actinic keratosis:

Aldara is usually applied 2 times per week (such as Monday and Thursday, or Tuesday and Friday) for a full 16 weeks. Zyclara is applied once daily for 2 weeks followed by 2 weeks without treatment. Apply the cream to the treatment area in a thin layer, and rub in the cream until it disappears. Use the medicine before going to bed and leave it on for 8 hours. In the morning, wash off the medicine with water and a mild soap.

Superficial basal cell carcinoma:

Usually applied 5 times per week (such as Monday through Friday) for a full 6 weeks. Apply the cream from one imiquimod topical packet to the treatment area and the border of skin around it, and rub in the cream until it disappears. Use the medicine before going to bed and leave it on for 8 hours. In the morning, wash off the medicine with water and a mild soap.

Genital warts:

Usually applied 3 times per week (such as Monday, Wednesday, and Friday) for no longer than 16 weeks. Apply the cream from one imiquimod topical packet to the treatment area, and rub in the cream until it disappears. Do not cover the treated skin areas with any type of plastic bandaging, and avoid nylon underwear. You may wear cotton gauze or underwear over the treated area. Use the medicine before going to bed and leave it on for 6 to 10 hours. Then wash off the medicine with water and a mild soap.

When treating genital warts under the foreskin of an uncircumcised penis, pull back the foreskin and wash it with mild soap and water before applying imiquimod topical. Clean this area daily during treatment.

When treating genital warts around the vagina, avoid getting the cream on the more sensitive inner layers of vaginal tissue. This could result in vaginal swelling or irritation and painful urination.

Imiquimod topical is not a cure for genital warts and it may not keep you from spreading this condition to others through vaginal, anal, or oral sex. You may develop new lesions during treatment with imiquimod topical. For best results, keep using the medicine for the entire length of time prescribed by your doctor.

All conditions:

Your doctor will need to check your skin on a regular basis, especially if you have a more severe skin reaction to the medication. Do not miss any scheduled appointments.

Call your doctor if your skin condition does not improve or if it gets worse during treatment.

Do not use imiquimod topical to treat any skin condition that has not been checked by a doctor. Do not share this medication with anyone else, even if they have the same symptoms you have.

Each packet of imiquimod topical is for a single application only. Throw away the packet after one use, even if there is medicine left in it. If you treat more than one skin area at a time, ask your doctor how many packets to use.

Store at room temperature away from moisture and heat. Do not freeze. Keep each packet unopened until you are ready to use it.

Skip the missed dose and wait until the next time you are getting ready for bed to use the medicine. Do not use extra medicine to make up the missed dose.

It is not likely that other drugs you take orally or inject will have an effect on topically applied imiquimod topical. But many drugs can interact with each other. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Actinic Keratosis

Topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratosis on the face or scalp in immunocompetent adults.1 34 35 36

Basal Cell Carcinoma

Topical treatment of biopsy-confirmed, primary superficial basal cell carcinoma in immunocompetent adults.1 Safety and efficacy not established for other types of basal cell carcinoma, including nodular and morpheaform (fibrosing or sclerosing) types.1

Use only when superficial basal cell carcinoma tumor diameter is ≤2 cm and is located on the trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet).1

Use only when surgical methods are medically less appropriate and patient follow-up can be reasonably assured.1

Human Papillomavirus (HPV) Infections

Treatment of external genital and perianal exophytic warts (condylomata acuminata) caused by HPV in adults and adolescents ≥12 years of age.1 5 6 15 20 22 23 25 26

CDC and others recommend that external HPV warts be treated with a self-administered topical therapy (imiquimod, podofilox), a topical therapy administered by a health-care provider (podophyllum resin, trichloroacetic acid [TCA], bichloroacetic acid [BCA]), or a surgical technique (cryotherapy, electrosurgery, surgical excision).2 3 5 6 15 20 22 Alternative therapies include intralesional interferon alfa or laser surgery.22

A preferred treatment regimen for external genital HPV warts in HIV-infected† adults and adolescents;39 data are limited regarding the response rate in HIV-infected patients compared with those without HIV infection.39 An alternative treatment regimen for external HPV warts in HIV-infected children†; topical therapies often are ineffective in such children and a surgical technique (cryotherapy, electrosurgery) usually is preferred.40

Primary goal is destruction or clearance of visible, symptomatic warts.2 4 5 22 27 No regimen has been shown to eradicate HPV or affect natural history of HPV infection;2 3 4 22 27 effect on transmission of HPV unknown.1 22

Should not be used to treat subclinical genital HPV infection (without exophytic warts).22

Safety and efficacy for treatment of urethral, intravaginal, cervical, rectal, or anal HPV warts not established.1 22 Some clinicians suggest use of topical imiquimod for treatment of distal meatal HPV warts†, but data are limited.22

Molluscum Contagiosum

Has been effective in a limited number of children, adolescents, and adults for the treatment of molluscum contagiosum†,31 32 33 but safety and efficacy not established.1

Clinical studies in children 2–12 years of age with molluscum contagiosum indicate imiquimod is no more effective than placebo.1

• Importance of reading manufacturer’s patient information.1

• Importance of not using the drug for any disorder other than that for which it was prescribed.1 12

• Importance of applying to affected areas as directed and not administering orally, intravaginally, or intra-anally.1 12 Importance of avoiding contact with eyes, lips, and nostrils.1 Advise patients to immediately rinse with water if the cream gets into the mouth or eyes.1

• Advise patients to apply the cream at bedtime, leave the cream on the skin for the prescribed period of time, and not bathe or get treatment area wet until the following morning (6–10 hours after application).12

• Importance of not using occlusive dressings.1 Advise patients that cotton gauze dressing can be used, if needed; cotton underwear can be worn if the genital and perianal area is being treated.12

• Advise patients that if a dose is missed, the dose should be applied as soon as it is remembered and the regular treatment schedule continued.1

• Advise patients that they may experience local skin reactions during treatment (e.g., edema, erosion/ulceration, erythema, flaking/scaling/dryness, scabbing/crusting, vesicles, weeping/exudate) or application site reactions (e.g., burning, pruritus) that are mild to severe in intensity and may extend beyond the application site onto surrounding skin.1

• Advise patients to contact their clinician if they experience any sign or symptom at the application site that restricts or prohibits their daily activity or makes continued application of the cream difficult.1

• Advise patients that local skin reactions may be severe enough to require temporary discontinuance of the drug.1 Treatment can be resumed as directed by the clinician after the skin reaction has subsided.1

• If doses are missed or treatment is temporarily discontinued because of local skin reactions, the total duration of treatment should not be extended beyond the maximum recommended duration (i.e., 16 weeks for treatment of actinic keratosis, 6 weeks for treatment of superficial basal cell carcinoma, 16 weeks for treatment of genital and perianal HPV warts).1

• Importance of using sunscreen and avoiding or minimizing exposure to natural or artificial sunlight (e.g., tanning bed) during imiquimod treatment.1

• Advise patients that localized hypopigmentation or hyperpigmentation has been reported and that these skin color changes may be permanent in some patients.1

• Advise patients being treated for superficial basal cell carcinoma to contact their clinician if any suspicious lesion arises in the treatment area at any time after initial clinical clearance of superficial basal cell carcinoma.1

• Advise patients being treated for genital HPV warts that imiquimod is not a cure for HPV infection and that the drug’s effect on transmission of HPV is unknown.1 22 New HPV warts may develop during or after treatment.1 22 Importance of patient watching for recurrences of HPV warts, particularly during the first 3 months.22

• Advise patients being treated for genital HPV warts that uncircumcised males should clean under the foreskin before treatment and once daily during treatment and that females should avoid intravaginal application and take special care when applying near vaginal opening since local reactions at this site may result in pain or swelling and difficult urination.12

• Advise patients being treated for genital HPV warts to avoid sexual (genital, anal, oral) contact while imiquimod cream is on the skin and that the cream may weaken condoms and vaginal diaphragms.1 12

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 12

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 12

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

• If you have an allergy to imiquimod or any other part of Aldara (imiquimod cream (aldara)).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If your skin has not healed from other care or surgery.
• If you are using another drug that has the same drug in it.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Aldara with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In an oral (gavage) rat carcinogenicity study, imiquimod was administered to Wistar rats on a 2×/week (up to 6 mg/kg/day) or daily (3 mg/kg/day) dosing schedule for 24 months. No treatment related tumors were noted in the oral rat carcinogenicity study up to the highest doses tested in this study of 6 mg/kg administered 2×/week in female rats (87× MRHD based on weekly AUC comparisons), 4 mg/kg administered 2×/week in male rats (75× MRHD based on weekly AUC comparisons) or 3 mg/kg administered 7×/week to male and female rats (153× MRHD based on weekly AUC comparisons).

In a dermal mouse carcinogenicity study, imiquimod cream (up to 5 mg/kg/application imiquimod or 0.3% imiquimod cream) was applied to the backs of mice 3×/week for 24 months. A statistically significant increase in the incidence of liver adenomas and carcinomas was noted in high dose male mice compared to control male mice (251× MRHD based on weekly AUC comparisons). An increased number of skin papillomas was observed in vehicle cream control group animals at the treated site only. The quantitative composition of the vehicle cream used in the dermal mouse carcinogenicity study is the same as the vehicle cream used for Aldara Cream, minus the active moiety (imiquimod).

In a 52-week dermal photoco-carcinogenicity study, the median time to onset of skin tumor formation was decreased in hairless mice following chronic topical dosing (3×/week; 40 weeks of treatment followed by 12 weeks of observation) with concurrent exposure to UV radiation (5 days per week) with the Aldara Cream vehicle alone. No additional effect on tumor development beyond the vehicle effect was noted with the addition of the active ingredient, imiquimod, to the vehicle cream.

Imiquimod revealed no evidence of mutagenic or clastogenic potential based on the results of five in vitro genotoxicity tests (Ames assay, mouse lymphoma L5178Y assay, Chinese hamster ovary cell chromosome aberration assay, human lymphocyte chromosome aberration assay and SHE cell transformation assay) and three in vivo genotoxicity tests (rat and hamster bone marrow cytogenetics assay and a mouse dominant lethal test).

Daily oral administration of imiquimod to rats, throughout mating, gestation, parturition and lactation, demonstrated no effects on growth, fertility or reproduction, at doses up to 87× MRHD based on AUC comparisons.

Applies to imiquimod topical: topical cream, topical kit

Along with its needed effects, imiquimod topical (the active ingredient contained in Aldara) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking imiquimod topical:

• Blisters on the skin
• body aches or pain
• chills
• cough
• difficulty with breathing
• ear congestion
• itching in the genital or other skin areas
• loss of voice
• open sores or scabs on the skin
• pain or tenderness around the eyes and cheekbones
• redness of the skin (severe)
• scaling
• shortness of breath or troubled breathing
• skin rash
• sneezing
• sore throat
• stuffy or runny nose
• tightness of the chest or wheezing
• unusual tiredness or weakness

• Abdominal or stomach pain
• ankle, knee, or great toe joint pain
• bladder pain
• bloody or cloudy urine
• blurred vision
• chest pain
• cold flu-like symptoms
• difficult, burning, or painful urination
• dizziness
• fainting
• fast or irregular heartbeat
• frequent urge to urinate
• hoarseness
• joint stiffness or swelling
• lower back or side pain
• lump in the abdomen or stomach
• nervousness
• persistent non-healing sore
• pink growth on the skin
• pounding in the ears
• reddish patch or irritated area
• severe headache
• shiny bump on the skin
• slow or fast heartbeat
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• white, yellow or waxy scar-like area

• Blue lips and fingernails
• convulsions
• coughing that sometimes produces a pink frothy sputum
• dilated neck veins
• extreme fatigue
• fast, irregular, or pounding heartbeat
• headache
• irregular breathing
• nausea or vomiting
• pain in the shoulders, arms, jaw, or neck
• slurred speech
• sudden and severe inability to speak
• suicide
• sweating
• swelling of the face, fingers, feet, or lower legs
• temporary blindness
• weakness in the arm or leg on one side of the body
• weight gain

Get emergency help immediately if any of the following symptoms of overdose occur while taking imiquimod topical:

• Confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

Some side effects of imiquimod topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning or stinging of the skin (mild)
• flaking of the skin
• mild headache
• pain, soreness, or tenderness of the skin (mild)
• rash
• redness of the skin (mild)
• swelling at place of application

• Back pain
• lightening of the treated skin