Aldara® [Imiquimod]

Pharmacological properties

imiquimod is an immune response modifier. A study of saturated binding suggests the presence of protein receptors that respond to imiquimod on the membranes of immunocytes. imiquimod does not have direct antiviral activity. in experimental animal models, imiquimod showed antiviral activity and acted as an antitumor agent, mainly inducing the synthesis of α-interferon and other cytokines. the induction of the synthesis of α-interferon and other cytokines after applying Aldar cream to tissues affected by genital warts was also detected during clinical studies.

An increase in the systemic level of α-interferon and other cytokines after topical application of the drug Aldara was determined in pharmacokinetic studies.

Pharmacokinetics When applied topically, 0.9% of a dose of labeled imiquimod penetrated the skin. A small amount of cream that was absorbed into the circulatory system was rapidly excreted through the urinary system and intestines in an average ratio of 3: 1.

The systemic effect (penetration through the skin) was determined from the calculation of carbon-14 reduction [¹⁴C] imiquimod in urine and feces.

C_max the active substance in blood plasma at the end of the 16th week was achieved in the range of 9 and 12 hours and was 0.1; 0.2 and 1.6 ng / ml when applied to the skin of the face (12.5 mg, 1 sachet for single use), head (25 mg, 2 sachets) and hands (75 mg, 6 sachets), respectively. The area of ​​the application areas was not taken into account. T_½ after sc administration - 2 hours. When applied to skin T_½ 10 times more, which suggests that the drug stays on the skin for a long time. Urinary excretion in patients - 0.6% of the applied dose, applied for 16 weeks.

Indications

Aldar cream is used for local treatment:

• external genital and perianal warts (genital warts);
• small superficial basal cell carcinomas;
• clinically typical, non-hyperkeratic, non-hypertrophic actinic keratosis on the skin of the face or head in patients with a normally functioning immune system, when the size or amount of the lesion limits the effectiveness and / or appropriateness of cryotherapy, and other local methods of treatment are contraindicated or less appropriate.

Application

The frequency and duration of use is determined by the doctor individually for each patient.

External genital warts in adults. Cream with imiquimod must be applied 3 times a week (for example, Monday, Wednesday and Friday or Tuesday, Thursday and Saturday) before bedtime and left on the skin for 6-10 hours. Treatment with cream with imiquimod should be continued until the disappearance of genital and perianal condylomas or no more 16 weeks with each appearance of genital warts.

The cream is applied in a thin layer and rubbed into a clean surface of the areas affected by condylomas until completely absorbed. It should be applied only to the affected areas. Within 6-10 hours after applying the cream on the skin should not take a shower or bath. After that, it must be washed off with warm water and soap. Applying an excessive amount of cream or prolonged contact with the skin may cause a reaction at the site of application. A cream of 1 sachet is enough to apply on a skin area of ​​20 cm². Reusing cream from a previously opened sachet is prohibited. Before and after applying the cream, wash your hands with warm water and soap.

Men who have not been circumcised during treatment with genital warts under the foreskin should move the foreskin and wash the area under it daily.

Superficial basal cell carcinoma in adults. Apply imiquimod cream 5 days a week for 6 weeks (for example, from Monday to Friday) before bedtime and leave on the skin for about 8 hours.

Before applying the cream with imiquimod, it is necessary to wash the affected areas with soap and allow them to dry.A sufficient amount of cream is applied to the entire affected surface, including healthy skin, 1 cm from the edge of the tumor. The cream should be rubbed into the affected area until it is completely absorbed. The cream must be applied before bedtime, it must remain on the skin for 8 hours. At this time, you should avoid taking a shower or bath. After this, the cream must be washed off with warm water and soap.

Reusing cream from a previously opened sachet is prohibited. Before and after applying the cream, wash your hands with warm water and soap.

The response of the treated tumor to the cream must be assessed 12 weeks after the end of treatment. If there is no response to the therapy used, another treatment should be prescribed.

If the local skin reaction to the cream causes increased discomfort or if infection of the treated surface has occurred, treatment should be interrupted for several days.

Actinic keratosis in adults. Treatment is prescribed and monitored by a doctor. Cream with imiquimod should be applied 3 times a week (for example, Monday, Wednesday and Friday or Tuesday, Thursday and Saturday) before bedtime for 4 weeks and leave on the skin for 8 hours. A sufficient amount of cream must be applied to the entire affected surface. 4 weeks after discontinuation of treatment, the presence of actinic keratosis should be assessed. If residual manifestations of the disease are present, treatment must be continued for another 4 weeks.

The maximum single dose is 1 sachet. The maximum duration of treatment is 8 weeks.

If a local acute reaction of inflammation or infection of the treated surface is noted, treatment should be discontinued. In the latter case, appropriate measures must be taken. Each treatment period should not exceed 4 weeks, including missed days.

If skin lesions do not fully respond to the prescribed therapy, then after 4-8 weeks of the second treatment period, a new therapy should be prescribed.

Before applying the cream, wash the affected areas with soap and allow them to dry. Apply a sufficient amount of cream to the entire affected surface. The cream must be rubbed into the affected area until it is completely absorbed. The cream is applied before bedtime, it should remain on the skin for 8 hours. At this time, you should avoid taking a shower or bath. After the specified time, the cream must be washed off with warm water and soap.

Reusing cream from a previously opened sachet is prohibited. Before and after applying the cream, wash your hands with warm water and soap.

If the dose is missed, the patient should apply the cream as soon as he remembers, and then continue treatment according to the usual schedule. However, it should be remembered that the cream can be applied no more than 1 time per day.

Contraindications

Hypersensitivity to the active substance or other components of the drug.

Side effects

The frequency of adverse reactions is defined as very often (≥1 / 10), often (from ≥1 / 100, 1/10) and infrequently (from ≥1 / 1000, 1/100).

External genital warts. When using the cream 3 times a week, the most frequent undesirable effects were reactions at the cream application site: erythema, erosion, peeling, and edema. Some systemic adverse reactions were also noted, namely: headache, flu-like symptoms, muscle pain.

Delayed skin reactions, mainly erythema, were also observed in unaffected areas that could come in contact with Aldar cream. Most of these reactions disappeared within 2 weeks after the end of treatment. However, in some cases, these reactions were severe and caused dysuria in women.

Infections and infestations: often - a tendency to bacterial infections; infrequently - herpes simplex, genital candidiasis, vaginitis, bacterial infection, mycosis, upper respiratory tract infections, vulvitis.

From the blood system and lymphatic system: infrequently - lymphadenopathy.

From the side of metabolism: infrequently - anorexia.

From the psyche: infrequently - insomnia, depression.

From the nervous system: often - headache; infrequently - paresthesia, dizziness, hemicrania, drowsiness.

From the side of the organ of hearing and balance: infrequently - tinnitus.

From the side of the vessels: infrequently - hyperemia.

From the respiratory system: infrequently - pharyngitis, rhinitis.

From the digestive tract: often - nausea; infrequently - vomiting, abdominal pain, diarrhea, painful urge to defecate, impaired rectal area.

From the skin and subcutaneous tissue: infrequently - itching, dermatitis, folliculitis, erythematous rash, eczema, increased sweating, urticaria.

From the side of musculoskeletal and connective tissue: often - muscle pain; infrequently - pain in the joints, back.

From the kidneys and urinary system: infrequently - dysuria.

From the reproductive system: infrequently - pain on the genital area in men, penile disorders, dyspareunia, erectile dysfunction, prolapse of the uterus and vagina, vaginal pain, atrophic vaginitis, vulvar lesions.

General reactions: very often - itching and pain at the site of application; often - burning and irritation at the site of application, fatigue; infrequently - hyperthermia, flu-like symptoms, pain, asthenia, discomfort, chills.

Superficial basal cell carcinoma. When applying the cream 5 times a week, reactions were observed at the cream application site: erythema, erosion, a severe form of scab and peeling, as well as some systemic adverse reactions, including back pain and flu-like symptoms.

Infections and infestations: often - a tendency to bacterial infections, acne.

From the lymphatic system: often - lymphadenopathy.

From the psyche: infrequently - irritability.

From the gastrointestinal tract: infrequently - nausea, dry mouth.

On the part of the skin and subcutaneous tissue: infrequently - dermatitis.

From the side of musculoskeletal and connective tissue: often - back pain.

General reactions: very often - itching at the site of application; often - burning, irritation and pain at the site of application, erythema, bleeding in the area of ​​application, the formation of papules, paresthesia and rashes at the site of application; infrequently - flu-like symptoms, discharge at the site of application, inflammation, swelling and swelling at the site of application, scab formation, destruction of the site of application, vesicle formation, lethargy.

Actinic keratosis. With a 3-time use of the cream per week in 2 courses lasting 4 weeks, reactions were noted at the site of application of the cream, namely itching and burning. Severe erythema and severe scabs and peeling were often detected. Some systemic adverse reactions have also been noted, namely muscle pain.

Infections and infestations: infrequently - a tendency to bacterial infections, acne, flu, rhinitis.

From the blood system and lymphatic system: infrequently - lymphadenopathy.

From the side of metabolism: often - anorexia.

From the psyche: infrequently - depression.

From the side of the central nervous system: often - a headache.

From the side of the organ of vision: infrequently - swelling of the eyelids, inflammation of the conjunctiva.

From the respiratory system: infrequently - sore throat, nasal congestion.

From the digestive tract: often - nausea; infrequently - diarrhea.

On the part of the skin and subcutaneous tissue: infrequently - erythema, actinic keratosis, swelling of the face, ulcers on the skin.

From the side of musculoskeletal and connective tissue: often - pain in muscles, joints; infrequently - pain in the limbs.

General reactions: very often - itching in the area of ​​application; often - fatigue, burning, irritation and pain in the field of application, erythema, reaction at the site of application; infrequently - bleeding in the field of application, papule formation, paresthesia, hyperthermia, asthenia, chills, dermatitis, discharge at the application site, hyperesthesia of the application site, edema, scabs and scars, swelling and ulceration at the application site, blistering, fever at the site of application, discomfort, inflammation.

Adverse reactions that were noted with all indications are hypo- and hyperpigmentation after applying the cream, alopecia in the area of ​​application or the surrounding area.In isolated cases, a decrease in the level of hemoglobin, the level of white blood cells, the absolute number of neutrophils and platelets was noted, but this did not require intervention. In separate reports, an elevated level of liver enzymes and an exacerbation of autoimmune conditions were noted. Severe skin reactions reported in clinical trials include polymorphic erythema, Stevens-Johnson syndrome, and cutaneous manifestations of systemic lupus erythematosus.

special instructions

Application features for all indications

Contact with the mucous membranes of the eyes, lips and nose should be avoided.

Imiquimod can exacerbate inflammatory processes on the skin.

The cream must be used with caution in patients with autoimmune diseases, as well as in those who underwent organ transplantation.

Cream treatment is not recommended if the skin after the previous drug or surgical treatment is still impaired. Applying the cream to the affected skin can increase the systemic absorption of imiquimod, which will increase the risk of adverse reactions.

The use of an occlusive dressing is not recommended.

In rare cases, an acute inflammatory reaction is possible, including weeping or erosion after several applications of imiquimod cream. Local acute inflammatory reactions may accompany or even precede systemic signs and symptoms resembling influenza, including malaise, fever, nausea, muscle pain and chills.

Imiquimod should be used carefully in patients with anemia.

External genital warts. Treatment of men with condylomas in the foreskin is possible only with daily hygiene procedures. In their absence, a stricture or an increase in difficulty in shifting the foreskin is possible, which can lead to phimosis and stricture.

Treatment of urethral, ​​intravaginal, cervical, rectal or intraanal warts is not recommended. Treatment of tissues with open sores or wounds until they are completely healed is not prescribed.

When treating with cream, skin reactions are common. In this regard, if the skin reaction becomes unbearable, the area for applying the cream must be washed with warm water and soap. Cream treatment can be resumed after a decrease in the severity of skin reactions.

Clinical data on the use of the cream immediately after the treatment of genital and perianal warts with other drugs are not available.

Cream with imiquimod should be washed off before intercourse. It can reduce the effect of condoms and vaginal diaphragms. It is necessary to use other contraceptives.

Repeated cream treatment is not recommended for immunocompromised patients.

When treating genital warts in HIV-positive patients, the use of a cream was not always effective.

Superficial basal cell carcinoma. When treating basal cell carcinoma, the cream should be applied no closer than 1 cm from the border of hair growth, the edges of the eyes, mouth or nose.

The clinical outcome of treatment can be assessed after skin restoration approximately 12 weeks after the end of treatment.

There is no clinical data on the use of the cream in immunocompromised patients.

Large tumors (7.25 cm²) are less susceptible to imiquimod treatment.

The surface area of ​​the skin undergoing treatment must be protected from exposure to ultraviolet radiation.

Actinic keratosis. If the lesions are clinically atypical for actinic keratosis or if a malignant neoplasm is suspected, a biopsy is necessary.

In the treatment of actinic keratosis, the cream should not be applied to the eyelids, the inner surface of the nose or ears, or to the red border of the lips.

There is very limited evidence regarding the use of cream for treatment in other anatomical locations than the skin of the face or head. The treatment data for axillary keratosis and on the hands do not confirm effectiveness.

Imiquimod is not recommended for the treatment of actinic lesions with severe hyperkeratosis or hypertrophy, which are characteristic of horn keratoma.

During treatment and until complete recovery, the affected skin is markedly different from healthy. Local skin reactions are normal, but the severity of these reactions usually decreases during treatment or they disappear after treatment with the cream is discontinued. There is a relationship between the rate of recovery and the severity of local skin reactions (eg, erythema). These local reactions may be associated with stimulation of the local immune response. You can take a break in treatment for several days due to discomfort in the patient or severe local skin reactions. Treatment can be resumed after a decrease in the severity of skin reactions.

Each treatment period should not exceed 4 weeks due to missed doses.

The clinical outcome of treatment can be assessed after skin restoration approximately 4-8 weeks after the end of treatment.

There is no clinical data on the use of the cream in immunocompromised patients.

The area of ​​the skin undergoing treatment must be protected from ultraviolet radiation.

Use during pregnancy and lactation. The drug should not be prescribed to pregnant women and women who are breast-feeding.

Children. Contraindicated in children.

The ability to influence the speed of reactions when driving vehicles or working with other mechanisms. During treatment, care should be taken when driving vehicles or working with other mechanisms, as well as when performing work that requires an increased concentration of attention, in connection with the possible occurrence of weakness, dizziness.

Interactions

Since aldara stimulates the immune system, the cream should be used with caution in patients who receive immunosuppressive drugs.

Overdose

With topical application of the drug, a general overdose of cream with imiquimod is unlikely due to the low skin absorption of the drug. constant overdose with cutaneous application of the cream can cause severe local skin reactions.

After accidentally swallowing a single dose of 200 mg of imiquimod, which corresponds to approximately 16 sachets, nausea, vomiting, headache, muscle pain, and fever may occur. The most serious adverse event that occurred after repeated administration of an oral dose of 200 mg was arterial hypotension, which was resolved after oral or iv infusion therapy.

Storage conditions

At a temperature not exceeding 25 ° C. reuse of open sachets is not allowed.