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The US Food and Drug Administration (FDA) has approved the use of 3.75% imiquimod cream (Zyclara Cream) for the treatment of external anogenital warts in people aged 12 years and older, according to an announcement released by Graceway Pharmaceuticals, which manufactures the cream.

The new preparation works in about half the time of older imiquimod preparations, which should enhance patient compliance, the company stated in a press release.

In an intent-to-treat analysis of all patients participating in 2 large, phase 3, double-blind, placebo-controlled trials, application of imiquimod once a day for up to 8 weeks was associated with complete clearance of the warts in 28.3% of patients compared with 9.4% of the patients using the placebo cream. The investigators defined complete clearance as clearance of baseline and emergent warts. Among the patients who experienced complete wart clearance, only 15% experienced a recurrence within 12 weeks.

The cream was more effective in women, 37% of whom saw complete clearance compared with 19% of men.

This preparation "showed promising results in preventing wart recurrences for 12 weeks in the majority of patients who cleared during the clinical study," said Anita Nelson, MD, from the Department of Obstetrics and Gynecology at Harbor University of California–Los Angeles Medical Center, in the press release.

Imiquimod is an immunomodulator that triggers cytokine production by the immune cells. It has been prescribed in a 5% concentration for treating actinic keratoses and superficial basal cell carcinoma, as well as external anogenital and perianal warts. In a typical treatment regimen for eliminating the warts, patients would apply 5% imiquimod cream to the area 3 days a week and leave it on for 6 to 10 hours, for up to 16 weeks. Avoidance of sexual activity is recommended while the cream is on the skin.

Specific administration instructions for external genital/perianal warts are to apply a thin layer of imiquimod cream once daily until total clearance or for up to 8 weeks, using up to 1 packet at each application (28 packets of 3.75% cream supplied per box). It should be applied before sleep and left on the skin for approximately 8 hours, then washed off with mild soap and water. Patients should wash their hands before and after applying imiquimod cream. Up to 2 boxes (56 packets) should be prescribed for the treatment course, and partially used packets should be discarded and not reused.

Adverse Effects, Precautions

Adverse effects of imiquimod cream include skin inflammation and irritation, pruritus, fatigue, flu-like symptoms, headache, diarrhea, and pain at the application site. In the two phase 3 trials, the most common adverse effects included skin weeping, redness, swelling, and blisters or sores. Less than 1% of patients discontinued the medication as a result of these effects, the company said.

Local skin reactions are common and may require a rest period of several days until the reaction subsides, as well as use of nonocclusive dressings such as cotton gauze or cotton underwear.

Intense local skin reactions, such as skin weeping or erosion, may develop after a few applications of imiquimod cream and may require treatment interruption of dosing.

Imiquimod cream may exacerbate inflammatory skin conditions, such as chronic graft versus host disease, and use of imiquimod cream is not recommended until the skin is healed from any previous drug or surgical treatment. Patients should avoid concomitant use of Zyclara cream and any other imiquimod products in the same treatment area, which may increase the risk for and severity of local skin reactions.

Dosing interruption should be considered, and the patient should be evaluated, for flu-like signs and symptoms such as fatigue, nausea, fever, myalgias, arthralgias, malaise, and chills. These may accompany, or even precede, local skin reactions.

During use of imiquimod cream, patients should avoid or minimize exposure to sunlight and sunlamps, and patients with sunburn should not use imiquimod cream until they are fully recovered. Because imiquimod activates immune cells, it should be used with caution in patients with preexisting autoimmune conditions.

More information on imiquimod is available on the FDA Web site.

Laurie Barclay, MD, contributed to this news article.

Clinical Implications

• The FDA has approved 3.75% imiquimod cream for the treatment of external anogenital warts in people 12 years and older. It should be used once daily until total clearance or for up to 8 weeks. Up to 2 boxes (56 packets) should be prescribed for the treatment course.
• The most common adverse effects of imiquimod cream reported in clinical trials include skin weeping, redness, swelling, and blisters or sores, but less than 1% of patients discontinued treatment because of these effects. Other adverse effects may include fatigue, flu-like symptoms, headache, and diarrhea.
• Imiquimod cream may exacerbate inflammatory skin conditions and should not be used until the skin is healed from sunburn or from any previous drug or surgical treatment. Concomitant use of other imiquimod products in the same treatment area should be avoided. Dosing interruption should be considered, and the patient should be evaluated, for flu-like signs and symptoms. Imiquimod should be used with caution in patients with preexisting autoimmune conditions.

CME

Which of the following statements concerning dosing and administration of imiquimod cream for the treatment of external anogenital warts is not correct?

1. Up to 1 packet 3.75% cream should be applied once daily to the affected area
2. It may be used in people 10 years and older
3. Sexual activity should be avoided while the cream is on the skin
4. The cream should be left on the skin for approximately 8 hours during sleep, then washed off with mild soap and water

Your patient is a 37-year-old woman with external anogenital warts. Which of the following would you mostlikely tell her regarding the risk for adverse effects of imiquimod cream?

1. Risk of her having to discontinue treatment because of adverse events is approximately 10%
2. Local skin reactions are common
3. She should continue treatment without interruption if skin weeping or erosion occurs
4. Flu-like reactions have not been reported in patients who have not had skin reactions first

Which of the following statements concerning precautions regarding use of imiquimod cream for the treatment of external anogenital warts is not correct?

1. Imiquimod cream may exacerbate chronic graft versus host disease
2. Use of imiquimod cream is not recommended until the skin is healed from any previous drug or surgical treatment
3. Other imiquimod products may be used in the same treatment area as Zyclara cream
4. Imiquimod should be used with caution in patients with preexisting autoimmune conditions

解答：

1. Which of the following statements concerning dosing and administration of imiquimod cream for the treatment of external anogenital warts is not correct?

Answer: It may be used in people 10 years and older 
The FDA has approved the use of 3.75% imiquimod cream for the treatment of external anogenital warts in people 12 years and older.

2. Your patient is a 37-year-old woman with external anogenital warts. Which of the following would you mostlikely tell her regarding the risk for adverse effects of imiquimod cream?

Answer: Local skin reactions are common 
In clinical trials, less than 1% of patients discontinued imiquimod cream because of adverse effects. Skin weeping or erosion may develop after a few applications of imiquimod cream and may require treatment interruption. Flu-like signs and symptoms such as fatigue, nausea, fever, myalgias, arthralgias, malaise, and chills may accompany, or even precede, local skin reactions.

3. Which of the following statements concerning precautions regarding use of imiquimod cream for the treatment of external anogenital warts is not correct?

Answer: Other imiquimod products may be used in the same treatment area as Zyclara cream 
Concomitant use of Zyclara cream and any other imiquimod products in the same treatment area may increase the risk for, and severity of, local skin reactions and should be avoided.