Aldara

Imiquimod.

Each sachet contains 12.5 mg of Imiquimod in 250mg cream (5%w/w).
White to faintly yellow cream with a uniform appearance.
Excipients/Inactive Ingredients: Isostearic Acid, Cetyl Alcohol, Stearyl Alcohol, White Soft Paraffin, Polysorbate 60, Sorbitan Stearate, Glycerol, Xanthan Gum, Purified Water, Benzyl Alcohol, Methyl Hydroxybenzoate and Propyl Hydroxybenzoate.

Pharmacology:Pharmacodynamics: Imiquimod is an immune response modifier. It has no direct antiviral activity in cell culture. A mechanism of action study in 22 patients with genital/perianal warts shows that imiquimod induces cytokines including interferon-α at the treatment site. In addition, HPV E7 and L1mRNA as well as HPV DNA are significantly decreased following treatment. However, the clinical relevance of these findings is unknown.
Pharmacokinetics: Percutaneous absorption of [14C] imiquimod was minimal in a study involving 6 healthy subjects treated with a single topical application (5mg) of [¹⁴C] imiquimod cream formulation. No radioactivity was detected in the serum (lower limit of quantitation: 1ng/mL) and <0.9% of the radiolabelled dose was excreted in the urine and faeces following topical application.
Clinical Studies: In a double-blind, placebo-controlled clinical trial, Aldara Cream 5% w/w applied three times a week for treatment of genital and perianal warts had wart clearance rates that were statistically significantly greater than the placebo control. The percentage of patients achieving total clearance was 77% for females and 40% for males. The percentage of patients achieving partial wart area (>50%) reduction was 91% for female and 74% for male. The median baseline wart area was 69mm2 (range 8 to 5525 mm²). Visible wart changes occurred as early as 4 weeks and some patients required 16 weeks. The median time to total wart clearance was 10 weeks. In another study, Aldara Cream 5% w/w applied daily, 59% of the males and 84% of the females achieved total clearance of their genital/perianal warts. A low percentage (6-23%) of the patients who achieved total clearance of their warts experienced a recurrence of their warts during the 12-week follow-up period. In two studies, some patients achieved total clearance or additional reduction in wart area during a 4-week treatment-free observation period following Aldara Cream 5% w/w treatment. Thus, some patients with wart tissue remaining after Aldara Cream 5% w/w treatment may continue to show clearing of their warts.

Aldara Cream 5% w/w is indicated for: Treatment of external genital and perianal warts/condyloma accuminata in adults.
Treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults.
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 efficacy of Aldara Cream 5% w/w have not been established for other types of basal cell carcinomas, including nodular and morpheaform (fibrosing or sclerosing) types.

The application frequency for Aldara Cream 5% w/w is different for each indication.
External Genital/Perianal Warts: Aldara Cream 5% w/w is to be applied three times per week, prior to normal sleeping hours, and left on the skin for 6-10 hours. A thin layer is to be applied to the wart area and rubbed in until the cream is no longer visible.
Aldara Cream 5% w/w is supplied in single-use sachets which contain sufficient cream to cover a wart area of up to 20cm², use of excessive amounts of cream should be avoided. Handwashing before and after cream application is recommended. The application site is not to be occluded. During the 6-10 hours treatment period, showering or bathing should be avoided. Following the treatment period, Aldara Cream 5% w/w should be removed by washing the treated area with mild soap and water. Examples of 3 times per week application schedules are Monday, Wednesday, Friday; or Tuesday, Thursday, Saturday application prior to sleeping hours. Aldara Cream 5% w/w treatment should continue until there is total clearance of the genital/perianal warts or for maximum of 16 weeks.
Local skin reactions (erythema) at the treatment site are common. A rest period of several days may be taken if required by the patient's discomfort or severity of the local skin reaction. Treatment may resume once the reaction subsides. Non-occlusive dressings such as cotton gauze or cotton underwear may be used in the management of skin reactions.
Actinic Keratosis: Aldara Cream 5% w/w should be applied 2 times per week for a full 16 weeks to a defined treatment area on the face or scalp (but not both concurrently). The treatment area is defined as one contiguous area of approximately 25cm² (e.g. 5 cm x 5 cm) on the face (e.g.forehead or one cheek) or on the scalp. Examples of 2 times per week application schedules are Monday and Thursday, or Tuesday and Friday. Aldara Cream 5% w/w should be applied to the entire treatment area and rubbed in until the cream is no longer visible. No more than one sachet or one pump of Aldara Cream 5% w/w should be applied to the contiguous treatment area at each application. Aldara Cream 5% w/w should be applied prior to normal sleeping hours and left on the skin for approximately 8hours, after which time the cream should be removed by washing the area with mild soap and water. The prescriber should demonstrate the proper application technique to maximize the benefit of Aldara Cream 5% w/w therapy.
It is recommended that patients wash their hands before and after applying Aldara Cream 5% w/w. Before applying the cream, the patient should wash the treatment area with mild soap and water and allow the area to dry thoroughly (at least 10 minutes).
Contact with the eyes, lips and nostrils should be avoided.
Local skin reactions in the treatment area are common. [see Adverse Reactions] A rest period of several days may be taken if required by the patient's discomfort or severity of the local skin reaction. However, the treatment period should not be extended beyond 16weeks due to missed doses or rest periods. Response to treatment cannot be adequately assessed until resolution of local skin reactions. Lesions that do not respond to treatment should be carefully re-evaluated and management reconsidered.
Aldara Cream 5% w/w is supplied in following package system: 12 sachets supplied per box.
Patients should be prescribed no more than 3 boxes (36 sachets) for the 16-week treatment period. Unused sachets should be discarded. Partially used sachets should be discarded and not reused.
Superficial Basal Cell Carcinoma: Aldara Cream 5% w/w should be applied 5 times per week for a full 6 weeks to a biopsy confirmed superficial basal cell carcinoma. An example of a 5 times per week application schedule is to apply Aldara Cream 5% w/w, once per day, Monday through Friday. Aldara Cream 5% w/w should be applied prior to normal sleeping hours and left on the skin for approximately 8 hours, after which time the cream should be removed by washing the area with mild soap and water. The prescriber should demonstrate the proper application technique to maximize the benefit of Aldara Cream 5% w/w therapy.
It is recommended that patients wash their hands before and after applying Aldara Cream 5% w/w. The patient should wash the treatment area with mild soap and water before applying the cream, and allow the area to dry thoroughly.
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 treatment area should include a 1 cm margin of skin around the tumor. Sufficient cream should be applied to cover the treatment area, including 1 centimeter of skin surrounding the tumor. Aldara Cream 5% w/w should be rubbed into the treatment area until the cream is no longer visible. (See table.)

Click on icon to see table/diagram/image

Contact with the eyes, lips and nostrils should be avoided.
Local skin reactions in the treatment area are common. [see Adverse Reactions] A rest period of several days may be taken if required by the patient's discomfort or severity of the local skin reaction.
Early clinical clearance cannot be adequately assessed until 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, a biopsy or other alternative intervention should be considered. Lesions that do not respond to therapy should be carefully reevaluated and management reconsidered; the safety and efficacy of a repeat course of Aldara Cream 5% w/w treatment have not been established. If any suspicious lesion arises in the treatment area at any time after a determination of clinical clearance, the patient should seek a medical evaluation.
Aldara Cream 5% w/w is supplied in following package system: 12 sachets supplied per box.
Patients should be prescribed no more than 3 boxes (36 sachets) for the 16-week treatment period. Unused sachets should be discarded. Partially used sachets should be discarded and not reused.

Overdosage of Aldara Cream 5% w/w in humans is unlikely due to minimal percutaneous absorption. Animal studies reveal a dermal lethal dose of greater than 5000mg/kg. Persistent topical overdosing of Aldara Cream 5% w/w could result in severe local skin reactions. These usually subside within 2 weeks of Aldara Cream 5% w/w discontinuation.
Following accidental ingestion of a single 200mg imiquimod (corresponds to the content of approximately 16 sachets), nausea, emesis, headache and fever can occur. The most clinically serious adverse event reported following multiple oral imiquimod doses of >200mg was hypotension which resolved following oral or intravenous fluid administration.

Hypersensitivity to imiquimod or to any of the excipients.

Aldara Cream 5% w/w has not been evaluated for the treatment of internal genital warts and should not be used to treat urethral, intra-vaginal, cervical, rectal, or intra-anal warts due to unknown local tolerance and potential systemic absorption. Aldara Cream 5% w/w has not been evaluated for the treatment of warts in these locations.
Local skin reactions such as erythema, erosion, excoriation/flaking and oedema are common. Most skin reactions are mild to moderate. These reactions may be due to the pharmacological response of the body's immune system to Aldara Cream 5% w/w. Should severe local skin reaction occur, the cream should be removed by washing the treatment area with mild soap and water.
Treatment with Aldara Cream 5% w/w can be resumed after the skin reaction has subsided. The use of an occlusive dressing is not recommended with Aldara Cream 5% w/w. Higher than recommended doses may lead to increased local skin reactions. Uncircumcised males treating warts under the foreskin should retract the foreskin and clean the area daily.
There is no clinical experience with Aldara Cream 5% w/w therapy immediately following the treatment of genital/perianal warts with other cutaneously applied drugs; therefore, Aldara Cream 5% w/w administration is not recommended until genital/perianal tissue is healed from any previous drug. Aldara Cream 5% w/w has been applied to traumatized genital skin following wart ablation by electrocautery or cryotherapy in two pilot studies and Aldara Cream 5% w/w did not prolong wound healing in these patients.
Aldara Cream 5% w/w, as an immune response modifier, has been shown to induce mRNA for IL-8 and has the potential to exacerbate inflammatory conditions of the skin.
The effect of Aldara Cream 5% w/w on the transmission of genital/perianal warts is unknown. Sexual (genital, anal, oral) contact should be avoided while the cream is on the skin. Aldara Cream 5% w/w may weaken condoms and vaginal diaphragms. Therefore, concurrent use is not recommended.
Carcinogenicity, Mutagenesis, and Impairment of Fertility: Imiquimod was without effect in a series of eight different mutagenicity assays including Ames, mouse lymphoma, CHO chromosome aberration, human lymphocyte chromosome aberration, SHE cell transformation, rat and hamster bone marrow cytogenetics, and mouse dominant lethal test. Orally administered imiquimod is neither mutagenic nor teratogenic in rats and rabbits. Imiquimod applied dermally was not carcinogenic in mice. Daily oral administration of imiquimod to rats, at doses up to 8 times the recommended human dose on a mg/m² basis throughout mating, gestation, parturition and lactation, demonstrated noimpairment of reproduction.
Use in children: Safety and efficacy in patients below the age of 18 years have not been established.

Use in Pregnancy (Category B): There are no adequate and well-controlled studies in pregnant women. Imiquimod was not found to be teratogenic in rat or rabbit teratology studies. In rats at high maternally toxic dose (28 times human dose on a mg/mm2 basis), reduced pup weights and delayed ossification were observed. In developmental studies with offspring of pregnant rats treated with imiquimod (8 times human dose), no adverse effects were demonstrated.
Use in Lactation: It is not known whether topically applied imiquimod is excreted in breast milk.

In controlled clinical trials, the most frequently reported adverse reactions were those of local skin and application site reactions; some patients also reported systemic reactions. These reactions were usually mild to moderate in intensity; however, severe reactions were reported with three times a week application. These reactions were more frequent and more intense with daily application than with three times a week application. Overall, in clinical studies applying Aldara Cream 5% w/w three times a week, 1.2% (4/327) of the patients discontinued due to local skin/application site reactions.
Reported adverse events in 273 patients treated with Aldara Cream 5% w/w applied three times a week are presented at frequencies of: Very common ≥ 1/10 (10%); Common ≥ 1/100 (1%) and < 1/10 (10%).
Application Site: Wart Site: very common: erythema, erosion, excoriation/flaking, oedema, itching, burning; common: induration, ulceration, scabbing, vesicle, pain, soreness, burning, irritation, pain, hypopigmentation, itching, rash, sensitivity, soreness, stinging, tenderness.
Remote site: common: bleeding, burning, itching, pain, tenderness, tinea cruris.
Body as a whole: Common: influenza symptoms, fatigue, fever, fungal infection.
Central and Peripheral Nervous System: Common: headache.
Digestive System: Common: diarrhoea.
Musculo-Skeletal System: Common: myalgia.

None known.
The efficacy of Aldara Cream 5% w/w in patients with HIV has not been studied adequately, Limited information suggest that efficacy may be reduced in these patients. The implications for patients with impairment of the immune system for other reasons are not known.
Treatment beyond 16 weeks and repeat treatment with Aldara Cream 5% w/w after initial successful therapy have not been adequately studied.

Store below 30°C. Avoid freezing.

Topical Antivirals

D06BB10 - imiquimod ; Belongs to the class of topical antivirals used in the treatment of dermatological diseases.

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