Instructions for use Aldara cream 5% sachet 250 mg No. 12
Composition
active ingredient: imiquimod;
1 mg of cream contains 0.05 mg of imiquimod;
excipients: isostearic acid, benzyl alcohol, stearyl alcohol, cetyl alcohol, white soft paraffin, polysorbate 60, sorbitan stearate, glycerin, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), xanthan gum, purified water.
Dosage form
Cream.
Main physicochemical properties: homogeneous cream from white to light yellow in color.
Pharmacotherapeutic group
Topical chemotherapeutic agents. Antiviral agents. Imiquimod.
ATX code D06B B10.
Pharmacological properties
Pharmacodynamics.
Imiquimod is an immune response modifier. Saturated binding studies suggest the presence of imiquimod-responsive protein receptors on immune cell membranes. Imiquimod has no direct antiviral activity. In experimental animal models, imiquimod is effective against viral infections and acts as an antitumor agent, mainly by inducing the synthesis of α-interferon and other cytokines. Induction of the synthesis of α-interferon and other cytokines after application of the cream to tissues affected by genital warts has also been demonstrated in clinical studies.
An increase in systemic levels of α-interferon and other cytokines after topical application of imiquimod has been demonstrated in pharmacokinetic studies.
External genital warts
Clinical efficacy
Results from three pivotal phase III efficacy studies showed that imiquimod treatment for sixteen weeks was significantly more effective than placebo treatment, as measured by complete clearance of treated warts.
In 119 patients treated with imiquimod, the overall complete clearance rate was 60% compared with 20% in 105 patients treated with the cream base (95% CI for the difference in incidence: 20% to 61%, p < 0.001). In patients treated with imiquimod who achieved complete clearance of warts, the median time to clearance was 8 weeks.
In 157 male patients treated with imiquimod, the overall complete clearance rate was 23% compared with 5% in 161 patients treated with the cream base (95% CI for the difference in incidence: 3% to 36%, p < 0.001). In patients treated with imiquimod who achieved complete clearance of warts, the median time to clearance was 12 weeks.
Superficial basal cell carcinoma
Clinical efficacy
The efficacy of imiquimod 5 times a week for 6 weeks was studied in two double-blind, placebo-controlled clinical trials. Target tumors were histologically confirmed single primary superficial basal cell carcinomas with a minimum size of 0.5 cm2 and a maximum diameter of 2 cm. Tumors located within 1 cm of the eyes, nose, mouth, ears, or hairline were excluded.
In the pooled analysis of these two studies, histological clearance was observed in 82% (152/185) of patients. Clinically, clearance as assessed by the composite endpoint was observed in 75% (139/185) of patients. These results were statistically significant (p < 0.001) compared with the corresponding figures in the placebo group: 3% (6/179) and 2% (3/179), respectively. There was a significant association between the intensity of local skin reactions (e.g. erythema) observed during treatment and complete clearance of basal cell carcinoma.
Data from a five-year long-term open-label uncontrolled study show that 77.9% [95% CI (71.9%, 83.8%)] of all subjects initially treated experienced clinical resolution of symptoms and this was maintained for 60 months.
Actinic keratosis (AK)
Clinical efficacy
The efficacy of imiquimod 3 times a week for one or two courses of 4 weeks each, separated by a 4-week treatment-free period, was studied in two double-blind, placebo-controlled clinical trials.
Patients had clinically typical, visible, discrete, non-hyperkeratotic, non-hypertrophic AK lesions on the balding scalp or face within 2 adjacent 25 cm2 treatment areas. 4–8 AK lesions were treated. The complete clearance rate (imiquimod minus placebo) for the combined studies was 46.1% (CI 39.0%, 53.1%).
One-year data from two combined observational studies indicate a relapse rate of 27% (35/128 patients) of those patients who had resolved clinical signs after one or two courses of treatment.
The recurrence rate for individual lesions was 5.6% (41/737). The corresponding recurrence rates for the cream base were 47% (8/17 patients) and 7.5% (6/80 lesions).
A total of 482 patients were enrolled in these studies, of whom 481 patients received the study treatment: 243 patients were treated with imiquimod and 238 patients with topical diclofenac. The treated area of AK was located on the bald scalp or face with an adjacent area of approximately 40 cm², and in both treatment groups the median number of clinically typical AK lesions was 7 at baseline. Available clinical experience 90 patients received 3 or more courses of imiquimod treatment, 80 patients received 5 or more courses of imiquimod treatment during the 3-year study period.
For the primary endpoint (histological progression), a total of 13 of 242 patients (5.4%) in the imiquimod group and 26 of 237 patients (11.0%) in the diclofenac group had histological progression to in situ or invasive PCA within 3 years; the difference was -5.6% (95% confidence interval [CI]: -10.7% to -0.7%). In contrast, 4 of 242 patients (1.7%) in the imiquimod group and 7 of 237 patients (3.0%) in the diclofenac group had histological progression to invasive PCA within 3 years.
Overall, 126 of 242 patients treated with imiquimod (52.1%) and 84 of 237 patients treated with topical diclofenac (35.4%) had complete clinical clearance of the treated AK area at week 20 (i.e. approximately 8 weeks after the end of the initial course of treatment); the difference was 16.6% (95% CI: 7.7–25.1%). In this group of patients with complete clinical clearance of the treated AK area, recurrence of AK was assessed. In these studies, recurrence was considered if the patient had at least one lesion of AK in the completely cleared area, whereby a recurrence could be a lesion that occurred at the same site as a previously cleared lesion or a lesion that was newly detected at any site of the treated AK area. The risk of recurrence of AK in the treated area (as defined above) was 39.7% (50 of 126 patients) in the imiquimod group compared with 50.0% (42 of 84 patients) in the topical diclofenac group up to 12 months (difference -10.3% [95% CI: -23.6% to 3.3%]); and 66.7% (84 of 126 patients) in the imiquimod group and 73.8% (62 of 84 patients) in the topical diclofenac group up to 36 months (difference -7.1% [95% CI: -19.0% to 5.7%]). The probability of complete recovery in a patient with recurrent AK (as defined above) in a completely cleared area was approximately 80% after an additional course of imiquimod treatment compared with approximately 50% with retreatment with topical diclofenac.
Children
The registered indications, genital warts, actinic keratosis and superficial basal cell carcinoma, are generally not seen in children and have not been studied.
Aldara cream was evaluated in four double-blind, randomized, placebo-controlled trials in children aged 2 to 15 years with molluscum contagiosum (imiquimod n = 576, placebo n = 313).
These studies failed to demonstrate the efficacy of imiquimod in any of the tested treatment regimens (3 times/week for ≤16 weeks and 7 times/week for ≤8 weeks).
Pharmacokinetics.
External genital warts, superficial basal cell carcinoma, and actinic keratosis
When applied topically, less than 0.9% of a single dose of labeled imiquimod was absorbed through the skin in humans. The small amount of cream that was absorbed into the general circulation was rapidly excreted via the urinary system and the intestines in an average ratio of 3:1. Serum levels (> 5 ng/mL) of the drug were not quantifiable after single or multiple topical applications.
Systemic exposure (through skin penetration) was calculated from the recovery of carbon-14 [14C] from imiquimod in urine and feces.
Minimal systemic absorption of imiquimod 5% cream through the skin of 58 patients with actinic keratosis was observed when applied 3 times a week for 16 weeks. The extent of transdermal absorption between the first and last doses of this study did not change significantly. Peak serum concentrations of the active substance at the end of week 16 were achieved between 9 and 12 hours after the start of administration and were 0.1, 0.2 and 1.6 ng/mL when applied to the face (12.5 mg, 1 single-use sachet), scalp (25 mg, 2 sachets) and hands (75 mg, 6 sachets), respectively. The surface area of application was not controlled in the scalp and hands/arms application groups. Dose proportionality was not observed. The apparent half-life was approximately 10-fold greater than the 2-hour half-life observed after subcutaneous administration in a previous study, suggesting prolonged drug retention in the skin. Urinary excretion in these patients was less than 0.6% of the dose applied at 16 weeks.
Children
The pharmacokinetics of imiquimod following single and multiple administration were investigated in a paediatric population with molluscum contagiosum (MC). Systemic exposure data showed that the extent of absorption of imiquimod following dermal application in children aged 6–12 years with MC was low and comparable to that in healthy adults and adults with actinic keratosis or superficial basal cell carcinoma. In younger patients aged 2–5 years, absorption was higher based on Cmax values compared to adults.
Indication
external genital and perianal warts (condyloma acuminatum);
small superficial basal cell carcinomas (BCC);
Clinically typical, non-hyperkeratic, non-hypertrophic actinic keratosis (AK) on the face or scalp in patients with a normally functioning immune system, when the size or number of lesions limits the effectiveness and/or feasibility of cryotherapy, and other topical treatments are contraindicated or less appropriate.
Contraindication
Hypersensitivity to the active substance or excipients.
Interaction with other medicinal products and other types of interactions
No interaction studies have been conducted, including interactions with immunosuppressive drugs. Interactions with systemic drugs will be limited to minimal absorption of imiquimod creams through the skin.
Since Aldara stimulates the immune system, the cream should be prescribed with caution to patients receiving immunosuppressants (see section "Special instructions").
Application features
Features of use for all indications.
Contact with the mucous membranes of the eyes, lips and nose should be avoided.
Imiquimod may exacerbate inflammatory processes on the skin.
The cream should be used with caution in patients with autoimmune diseases and in patients who have undergone organ transplantation (see section 4.5). The benefit of imiquimod treatment in these patients should be weighed against the potential for worsening of their autoimmune disease and the risk of organ rejection or graft-versus-host disease.
Treatment with the cream is not recommended if the skin has not healed after previous medical or surgical treatment. Applying the cream to affected skin may increase the systemic absorption of imiquimod, which may increase the risk of adverse reactions (see sections "Adverse reactions", "Overdose").
The use of an occlusive dressing is not recommended.
The excipients methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) may cause allergic reactions (possibly delayed). Cetyl alcohol and stearyl alcohol may cause local skin reactions (e.g. contact dermatitis).
In isolated cases, an acute inflammatory reaction, including oozing or erosion, may occur after multiple applications of imiquimod cream. Local acute inflammatory reactions may accompany or even precede systemic flu-like signs and symptoms, including malaise, fever, nausea, myalgia, and chills. Discontinuation of use should be considered.
Imiquimod should be used with caution in patients with reduced hematological reserve (see section 4.8).
External genital warts.
There is limited experience with the use of imiquimod cream in men with warts under the foreskin. The safety database in uncircumcised men who used imiquimod cream three times a week and maintained daily foreskin hygiene includes fewer than 100 patients. In other studies in which patients did not maintain foreskin hygiene, two cases of severe phimosis and one case of stricture leading to circumcision were reported.
Treatment of men with genital warts in the foreskin area is possible only if they are willing or able to perform daily hygiene procedures. Early signs of stricture may include local skin reactions (e.g. erosion, ulceration, swelling, induration) or difficulty in retracting the foreskin. If such symptoms appear, treatment should be discontinued immediately.
Treatment of urethral, intravaginal, cervical, rectal, or intraanal warts is not recommended. Treatment of tissues with open ulcers or wounds is not indicated until they are completely healed.
Local skin reactions such as redness, erosion, excoriation, scaling and swelling are common. Other local reactions such as induration, ulceration, scabbing and vesicles have also been reported. Therefore, if the skin reaction becomes intolerable, the area of application of the cream should be washed with warm water and mild soap. Treatment with the cream may be resumed after the skin reactions have subsided. The risk of severe local skin reactions may be increased when imiquimod is used at doses higher than those recommended (see section 4.2). However, in isolated cases, patients who used imiquimod as directed have experienced severe local reactions requiring treatment and/or causing temporary incapacity. When such reactions occurred in the urethral canal, some women experienced difficulty urinating, sometimes requiring emergency catheterization and treatment of the affected area.
There are no clinical data on the application of the cream immediately after treatment of genital and perianal warts with other medications.
Repeated treatment with the cream is not recommended for patients with weakened immunity.
Although limited data suggest an increased incidence of wart reduction in HIV-positive patients when treated for genital warts, the use of the cream has not always been effective in HIV-positive patients.
Superficial basal cell carcinomas.
When treating basal cell carcinoma, the cream should be applied no closer than 1 cm from the hairline, the edge of the eyes, mouth or nose.
During treatment and until complete recovery, the affected skin is significantly different from healthy skin. Local skin reactions are common, but the severity of these reactions usually decreases during treatment and they disappear after discontinuation of treatment.
There is a correlation between the degree of complete clearance and the occurrence of local skin reactions (e.g. erythema). These local skin reactions may be associated with stimulation of the local immune response. Treatment may be interrupted for a few days due to patient discomfort or severe local skin reactions. Treatment may be resumed after the skin reactions have subsided.
The clinical outcome of the treatment can be assessed after the recovery of the treated skin approximately 12 weeks after the end of treatment.
There is no clinical data on the use of the cream in immunocompromised patients.
There are no clinical data on the use of the cream in patients with recurrent and previously treated basal cell carcinoma, therefore therapy in this category of patients is not recommended.
Data from an open-label clinical trial showed that large tumors (>7.25 cm2) are less responsive to imiquimod treatment.
The treated skin surface area should be protected from exposure to ultraviolet radiation.
Actinic keratosis.
If lesions are clinically atypical for actinic keratosis or malignancy is suspected, a biopsy should be performed to determine appropriate treatment.
When treating actinic keratosis, the cream should not be applied to the eyelids, the inside of the nose or ears, or the red border of the lips.
There is very limited data on the use of the cream for treatment of anatomical sites other than the face or scalp. Data on the treatment of actinic keratosis in the axilla and hands do not support efficacy, therefore such treatment is not recommended.
Imiquimod is not recommended for the treatment of actinic lesions with marked hyperkeratosis or hypertrophy, which are seen in keratoma corneum.
During treatment and until complete recovery, the affected skin is significantly different from healthy skin. Local skin reactions are common, but the severity of these reactions usually decreases during treatment and they disappear after discontinuation of the cream. There is a relationship between the degree of complete clearance and the manifestation of local skin reactions (e.g. erythema). These local reactions may be associated with stimulation of the local immune response. Treatment may be interrupted for a few days due to patient discomfort or severe local skin reactions. Treatment may be resumed after the skin reactions have subsided.
Each treatment period should not exceed 4 weeks due to missed doses or rest periods.
The clinical result of the treatment can be assessed after the recovery of the treated skin approximately 4 to 8 weeks after the end of treatment.
There is no clinical data on the use of the cream in immunocompromised patients.
Information on retreatment of actinic keratosis lesions that have cleared after one or two courses of treatment and subsequently recur is provided in the sections “Method of administration and dosage” and “Pharmacodynamics”.
Data from an open-label clinical trial suggest that subjects with more than 8 AK lesions had a reduced incidence of complete skin clearance compared to patients with fewer than 8 lesions.
Areas of skin to be treated must be protected from ultraviolet radiation.
Use during pregnancy or breastfeeding
The drug is not recommended for pregnant and breastfeeding women.
The ability to influence the speed of reactions when driving vehicles or other mechanisms
Aldara cream has no or negligible influence on the ability to drive or use machines.
Method of administration and doses
The frequency and duration of use is determined by the doctor individually for each patient.
External genital warts in adults.
The cream should be applied in a thin layer and rubbed into the clean surface of the areas affected by warts until completely absorbed. The cream should be applied only to the affected areas and avoid internal surfaces. For 6-10 hours after applying the cream to the skin, you should avoid taking a shower or bath. After the specified period, the cream should be washed off with warm water and mild soap. Applying an excessive amount of cream or prolonged contact with the skin may cause a reaction at the site of application (see sections "Special instructions", "Adverse reactions", "Overdose"). The cream from one sachet is enough to apply to an area of skin with warts of 20 cm2. The cream from a previously opened sachet cannot be reused. Before and after applying the cream, wash your hands thoroughly with warm water and soap.
Men who have not undergone circumcision should, during treatment for genital warts, retract the foreskin and wash the area under it daily (see section "Special Instructions for Use").
Superficial basal cell carcinoma in adults.
Apply imiquimod cream 5 days a week for 6 weeks (for example, Monday through Friday) before going to bed and leave on the skin for about 8 hours.
Before applying imiquimod cream, wash the affected areas with mild soap and allow them to dry. Apply a sufficient amount of cream to the entire affected area, including healthy skin 1 centimeter from the edge of the tumor. The cream should be rubbed into the affected area until completely absorbed. The cream should be applied before bedtime and should remain on the skin for 8 hours. During this time, showering or bathing should be avoided. After the specified period, the cream should be washed off with warm water and mild soap.
Do not reuse the cream from a previously opened sachet. Wash your hands thoroughly with warm water and soap before and after applying the cream.
The response of the treated tumor to the cream should be assessed 12 weeks after the end of treatment. If the treated tumor does not respond sufficiently, another treatment should be used (see section "Special instructions").
If a local skin reaction to the cream causes increased discomfort to the patient or if infection of the treated area occurs, treatment should be interrupted for several days (see section "Special instructions"). In the latter case, other appropriate measures should be taken.
Actinic keratosis in adults.
Treatment is prescribed and monitored by a doctor. Imiquimod cream should be applied three times a week (e.g. Monday, Wednesday and Friday or Tuesday, Thursday and Saturday) before going to bed for 4 weeks and left on the skin for 8 hours. A sufficient amount of cream should be applied to the entire affected area. Actinic keratosis should be assessed 4 weeks after stopping treatment. If any symptoms persist, treatment should be continued for another four weeks.
The maximum recommended dose is one sachet.
If a local acute inflammatory reaction is observed (see section "Special instructions for use") or if infection of the treated area occurs, treatment should be discontinued. In the latter case, appropriate measures should be taken. Each treatment period should not exceed 4 weeks due to missed doses or rest.
If complete clearance of the treated area is not evident at follow-up approximately 8 weeks after the last 4-week course of treatment, an additional 4-week course of Aldara may be considered.
Alternative therapy is recommended if the treated lesion(s) show insufficient response to Aldara.
Actinic keratosis lesions that have cleared after one or two courses of treatment and subsequently recur may be re-treated with Aldara cream for one or two additional courses after a treatment break of at least 12 weeks (see section 5.1).
Before applying the cream, wash the affected areas with mild soap and allow them to dry. Apply a sufficient amount of cream to the entire affected surface. The cream should be rubbed into the affected area until completely absorbed. The cream should be applied before bedtime and should remain on the skin for approximately 8 hours. During this time, showering or bathing should be avoided. After the specified period, the cream should be washed off with warm water and mild soap.
Do not reuse the cream from a previously opened sachet. Wash your hands thoroughly with warm water and soap before and after applying the cream.
Information on all indications.
If a 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 once a day.
Children
Use in pediatric patients is not recommended. There are no data on the use of imiquimod in children and adolescents for the approved indications.
Aldara should not be used in children with molluscum contagiosum due to lack of efficacy for this indication (see section "Pharmacodynamics").
Overdose
When applied topically, a general overdose of imiquimod cream is unlikely due to the low absorption of the drug through the skin. Animal studies have shown that the lethal dose for topical application is more than 5 g/kg. Continuous overdose of topical cream may cause severe local skin reactions.
Accidental ingestion of a single dose of 200 mg imiquimod, equivalent to approximately 16 sachets, may cause nausea, vomiting, headache, myalgia and fever. The most serious adverse event observed after multiple oral doses ≥ 200 mg was hypotension, which resolved after oral or intravenous infusion therapy.
Side effects
General description
External genital warts
In the pivotal 3 times weekly studies, the most commonly reported adverse reactions considered probably or possibly related to imiquimod cream treatment were wart application site reactions (33.7% of imiquimod-treated patients). Some systemic adverse reactions were also reported, including headache (3.7%), flu-like symptoms (1.1%), and myalgia (1.5%).
Adverse reactions reported in placebo-controlled and open-label clinical trials involving 2292 patients treated with imiquimod cream are presented below. These adverse reactions are considered to have at least a possible causal relationship to imiquimod treatment.
Superficial basal cell carcinoma
In the 5 times a week studies, 58% of patients experienced at least one adverse reaction. The most common adverse reactions reported in clinical trials that were probably or possibly related to imiquimod cream were application site reactions with a frequency of 28.1%. Patients using imiquimod cream reported some systemic adverse reactions, including back pain (1.1%) and flu-like symptoms (0.5%).
Adverse reactions reported in a placebo-controlled phase III clinical trial in superficial basal cell carcinoma involving 185 patients treated with imiquimod cream are presented below. These adverse reactions are considered to have at least a possible causal relationship to imiquimod treatment.
Actinic keratosis
In pivotal studies of 3 times weekly application for 2 courses of 4 weeks, 56% of patients treated with imiquimod reported at least one adverse reaction. The most common adverse reactions reported in clinical trials that were probably or possibly related to imiquimod cream treatment were application site reactions (22% of patients treated with imiquimod). Some systemic adverse reactions, including myalgia (2%), were reported by treated patients.
Adverse reactions reported in a placebo-controlled phase III clinical trial in actinic keratosis involving 252 patients using imiquimod cream are presented below. These adverse reactions are considered to have at least a possible causal relationship to imiquimod treatment.
Adverse reactions in tabular form
Adverse reactions are defined by frequency as very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1000 to <1/100).
External genital warts. When the cream was applied 3 times a week, the most common adverse reactions were reactions at the application site, namely erythema, erosion, desquamation and swelling. Some systemic adverse reactions were also observed, including headache, flu-like symptoms and myalgia.
Delayed skin reactions, mainly erythema, have also been observed in non-lesional areas that may have come into contact with Aldara cream. Most of these reactions resolved within 2 weeks after the end of treatment. However, in some cases these reactions were severe and caused dysuria in women.
Infections and invasions.
Common: susceptibility to bacterial infections.
Uncommon: herpes simplex, genital candidiasis, vaginitis, bacterial infection, mycosis, upper respiratory tract infection, vulvitis.
Blood and lymphatic system disorders: Uncommon: lymphadenopathy.
Metabolic disorders: Uncommon: anorexia.
Psychiatric disorders: Uncommon: insomnia, depression.
Nervous system disorders: Common: headache.
Uncommon: paresthesia, dizziness, hemicrania, drowsiness.
Hearing and balance disorders: Uncommon: tinnitus.
Vascular disorders: Uncommon: hyperemia.
Respiratory system disorders: Uncommon: pharyngitis, rhinitis.
Gastrointestinal: Common: nausea.
Uncommon: vomiting, abdominal pain, diarrhoea, painful defecation, rectal disorders.
On the skin and subcutaneous tissue.
Uncommon: pruritus, dermatitis, folliculitis, erythematous rash, eczema, rash, increased sweating, urticaria.
On the part of muscle and connective tissue.
Common: muscle pain.
Uncommon: joint pain, back pain.
Renal and urinary disorders: Uncommon: dysuria.
Uncommon: male genital pain, penile disorders, dyspareunia, erectile dysfunction, uterine and vaginal prolapse, vaginal pain, atrophic vaginitis, vulvar disorders.
General reactions: Very common: itching and pain at the application site.
Common: burning and irritation at the application site, increased fatigue.
Uncommon: hyperthermia, influenza-like symptoms, pain, asthenia, malaise, chills.
Superficial basal cell carcinomas.
Infections and invasions.
Common: susceptibility to bacterial infections, acne.
From the lymphatic system.
Common: lymphadenopathy.
Psychiatric disorders: Uncommon: irritability.
Gastrointestinal: Uncommon: nausea, dry mouth.
Skin and subcutaneous tissue disorders: Uncommon: dermatitis.
Musculoskeletal and connective tissue disorders: Common: back pain.
General reactions: Very common: itching at the application site.
Common: burning, irritation and pain at the application site, erythema, application site bleeding, application site papules, application site paresthesia, application site rash.
Uncommon: flu-like symptoms, application site discharge, inflammation, swelling and edema at the application site, scabbing, edema, application site destruction, blistering, lethargy.
Actinic keratosis.
Infections and invasions.
Uncommon: susceptibility to bacterial infections, acne, influenza, rhinitis.
Blood and lymphatic system disorders: Uncommon: lymphadenopathy.
Metabolic disorders: Common: anorexia.
Psychiatric disorders: Uncommon: depression.
Nervous system disorders: Common: headache.
On the part of the organs of vision. Uncommon: eyelid edema, conjunctival inflammation.
Respiratory system: Uncommon: sore throat, nasal congestion.
Gastrointestinal: Common: nausea.
Uncommon: diarrhea.
On the skin and subcutaneous tissue.
Uncommon: erythema, actinic keratosis, facial edema, skin ulceration.
Musculoskeletal and connective tissue disorders: Common: muscle and joint pain.
Uncommon: pain in extremities.
General reactions: Very common: itching at the application site.
Common: fatigue, burning, irritation and pain at the application site, erythema, application site reaction.
Uncommon: application site bleeding, papule formation, paresthesia, hyperthermia, asthenia, chills, dermatitis, application site discharge, application site hyperesthesia, edema, scabbing and scarring, application site swelling and ulceration, blistering, application site heat, discomfort, inflammation.
Common side effects
External genital warts
In the placebo-controlled studies, protocol-specified clinical signs (skin reactions) were assessed. The results of this assessment indicate that local skin reactions, including erythema (61%), erosion (30%), excoriation/desquamation/scaling (23%), and edema (14%), were common in these placebo-controlled clinical studies of imiquimod cream applied three times a week (see section 4.4). Local skin reactions such as erythema are likely to be a continuation of the pharmacological effects of imiquimod cream.
Delayed local skin reactions, mainly erythema (44%), were also reported in placebo-controlled studies. These reactions occurred in areas without warts that may have been exposed to imiquimod cream.
Most skin reactions were mild to moderate in severity and resolved within 2 weeks of discontinuation of treatment. However, in some cases these reactions were severe, required treatment and/or were disabling. In very rare cases, severe reactions in the urethral tract have resulted in dysuria in women (see section 4.4).
Superficial basal cell carcinoma
In placebo-controlled studies, protocol-specified clinical signs (skin reactions) were assessed. The results of this assessment indicate that severe erythema (31%), pruritus (31%), and pruritus (31%) were the most common.
