ALDARA

Aldara is used to treat external genital warts and perianal warts. It is a patient-applied cream that helps the body fight the virus that causes the warts.

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Brand Name(s): Aldara
Generic Name Imiquimod
Phonetic: (i mi kwi' mod)

Who is this for?
Imiquimod is used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

When should I be careful taking it?
Before using imiquimod,

tell your doctor and pharmacist if you are allergic to imiquimod or any other drugs.
tell your doctor and pharmacist what prescription and nonprescription medications you are taking, including vitamins.
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using imiquimod, call your doctor.
What side effects should I watch for?
Although side effects from imiquimod are not common, they can occur. Tell your doctor if any of these symptoms are severe or do not go away:

redness, itching, or burning of the skin
flaking of the skin
swelling or pain in the area where imiquimod was applied
blisters, scabs, or bumps on the skin
change in skin color
headache
muscle weakness or pain
fever
flu-like symptoms
fungal infection
How should I take it?
Imiquimod comes as a topical cream in unit-of-use packages. It is important to wash your hands before and after applying imiquimod to your skin. One packet of imiquimod is used to apply a thin layer of cream to the wart area three times per week, just before going to sleep. A schedule of Monday, Wednesday, Friday or Tuesday, Thursday, Saturday is suggested. Rub the cream into the skin until no more cream is visible. Do not put any covering on the area. Imiquimod should be left on the skin for 6 to 10 hours. Upon waking, wash the area with mild soap and water to remove excess cream. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use imiquimod exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.

What happens if I miss a dose?
Apply imiquimod just before going to bed on the day that you remember. Apply only the single dose, do not apply a double dose. Resume a Monday, Wednesday, Friday or Tuesday, Thursday, Saturday schedule, depending on what day you resume treatment.

Where should I keep it?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

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For the treatment of anogenital warts

Licensed Indication:

‘Imiquimod cream is indicated for the topical treatment of external genital and perianal warts (condyloma acuminata) in adult patients’.

Background information

Genital warts are the most commonly reported form of sexually transmitted disease. They are caused by the human papillomavirus (HPV). Most HPV infections are asymptomatic, sub-clinical or unrecognised. Patients usually present because they become aware of visible or palpable lesions. Although these lesions may be asymptomatic they can lead to itching, tenderness or bleeding and are associated with significant psychosocial distress.

The most common presentation of warts are of the condylomata acuminata type, which are exophytic, cauliflower-like lesions, most commonly found on moist surfaces. Condyloma acuminata may involve any part of the genitalia. In women, the most common sites involved are the vulva, perianal area and the vagina. In men, the prepuce and glans are usually involved, but lesions can also be found on the urethra, penile shaft, scrotum and perianal area.

In 1997 more than 105,000 cases of genital warts were seen in genitourinary clinics in England. Of these, 85,000 were new cases, with recurrences accounting for 50% of the total.1

Current treatment options

Left untreated, anogenital warts may resolve on their own (in 10-30% of patients), remain unchanged, or increase in size or number; they rarely become malignant.2,3 The primary goal of treatment is to remove warts that cause physical or emotional symptoms. Various treatment options are available for the treatment of anogenital warts. No single treatment appears superior, in terms of clearance or prevention of recurrence, and no single treatment is ideal for all patients or all warts.

Most available treatments are directed at the wart rather than the virus. They include cytotoxic substances such as podophyllum resin, its active constituent podophyllotoxin, and trichloroacetic acid. Physical treatments include cryotherapy, laser therapy and surgical excision. With the exception of podophyllotoxin, these treatments require administration by a physician or trained personnel.

Imiquimod is a new topical treatment licensed for self-administration for the treatment of external genital and perianal warts. It is an immune response modifier and increases the local production of alpha interferon and other cytokines which mediate an immune response to HPV.2,4,5

Dosage and Administration

Imiquimod is available as a 5% cream in single use sachets. The cream should be applied 3 times per week to the cleaned wart area, prior to sleeping and should remain on the skin for 6 to 10 hours. Treatment should continue until there is clearance of visible genital or perianal warts or for a maximum of 16 weeks per episode of warts.4

Uncircumcised males treating warts under the foreskin should retract the foreskin and wash the area daily.

Clinical Efficacy

Imiquimod 5% cream for the treatment of anogenital warts has been evaluated in one phase II and two phase III randomised, double-blind, placebo-controlled trials in a total of 698 immunocompetent adult patients.6-8 Two trials also included an imiquimod 1% cream arm.7,8 All 3 studies are published in full.

In each trial study medication was rubbed into clean, dry, wart-area skin by the patients, then washed off 8 ± 2 hours7,8 or 24 hours6 after application. The medication was to be applied daily7 or 3 times a week6,8 until all warts had disappeared, or for a maximum of 86 or 167,8 weeks.

In trials up to 16 weeks duration, using intention-to-treat analysis, a significantly higher proportion of patients treated with imiquimod 5% cream (37-52%), achieved complete clearance of baseline warts, compared with imiquimod 1% cream (14-21%) and placebo (0-11%), p<0.001.6-8 Rates of complete clearance with imiquimod 5% cream were higher in female patients compared to male patients, 64-72% vs 33-42% (statistical significance not stated).7,8 This may be attributed to a better absorption of cream by female patients than by male patients, due to the different type of skin on which the warts were located.

Median times to complete clearance with imiquimod 5% cream ranged from 7-9 weeks.6,7 Recurrence rates, within a 12 week follow-up period, occurred in 13-19% of patients who achieved complete clearance of baseline warts.7,8

The proportion of patients demonstrating a partial response (³ 50% reduction in baseline warts), using treatment failure analysis, was significantly higher in patients treated with imiquimod 5% cream (76-93%) compared with imiquimod 1% cream (40-41%) and placebo treated patients (8-31%); imiquimod 5% cream vs placebo, p < 0.001.6-8

Imiquimod has not been directly compared to other currently available treatments.

Adverse Effects

In the clinical trials safety evaluations included investigator and patient assessments of adverse events. The most commonly noted adverse events reported by investigators were local skin reactions. These included erythema, erosion, excoriation, flaking and oedema. Less frequently reported skin reactions included induration, ulceration, scabbing and vesicles. Most skin reactions were mild to moderate in severity and resolved within 2 weeks of treatment discontinuation. A higher incidence of local skin reactions was noted in the daily application trial. The most frequently reported local effects by the patients included itching, burning, tenderness and pain. Systemic adverse events were uncommon and were of a similar incidence to that of placebo.6-8

Imiquimod is not recommended in uncircumcised males for the treatment of foreskin associated warts, due to isolated cases of stricture and phimosis. Further studies in this patient population are being undertaken.

Summary

Placebo-controlled trials in nearly 700 patients have evaluated the efficacy of imiquimod 5% cream for the treatment of anogenital warts. These trials demonstrated that imiquimod 5% cream is an effective treatment in terms of partial and complete clearance of warts, particularly in women. However, its efficacy and safety relative to other patient applied treatments has not been studied.

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Results from a clinical trial show that Aldara(TM) (imiquimod) cream 5% is a safe, effective treatment for genital warts.

The trial results were published in the January edition of the journal Archives of Dermatology.


In a clinical trial with 311 patients, 72 percent of women and 33 percent of men using 5% Aldara cream achieved total wart clearance after a maximum of 16 weeks compared to 11 percent of patients using vehicle cream. In addition, 72 percent of those who cleared using Aldara and 82 percent of the vehicle group remained wart clear after 12 weeks.


"This study highlights that Aldara cream, used three times a week, is a safe and effective patient-applied therapy," said Mary Owens, MD, associate director of clinical research, 3M Pharmaceuticals.


The newest in a class of drugs called immune response modifiers and representing the first new therapeutic approach to genital warts in five years, Aldara was approved by the United States Food and Drug Administration in March, 1997 and has been available to patients since June, 1997.


Genital warts is a sexually transmitted disease (STD) caused by the human papillomavirus (HPV). HPV is one of the most common -- and least talked about -- of all STDs. At least 10 to 20 percent of sexually-active Americans are thought to be infected.


Genital warts is growing at a rate of 750,000 new cases each year, is spread by sexual contact with an infected partner and is highly contagious. This life long virus can cause warts in the genital and perianal areas in females and males. Male sexual partners of infected women often have HPV penile infection.


Genital warts may cause itching, burning, pain and tenderness. Although there is no cure for genital warts, treatment can alleviate physical symptoms and psychological reactions such as problems with sexuality, shame, embarrassment and self-blame.


Until recently, most treatment options for genital warts were tissue destructive involving chemical agents, procedures such as loop electrocautery excision (burning), surgery, cryotherapy (freezing) and tissue destructive drugs such as podofilox and podophyllin.


"Many patients have previously avoided treatment for genital warts because of fear of chemical and surgical procedures," said Karl Beutner, MD, PhD, associate clinical professor, University of California, San Francisco and chief investigator in the clinical trial of Aldara. "Self-administered Aldara cream is an effective, patient-friendly treatment that can be applied in the privacy of home to clear up warts."

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