Aldara 5%: composition and form
One sachet contains 12.5 mg of imiquimod in 250 mg of cream, that is 5%; per 100 mg of cream this comes to 5 mg of active substance. The sachet is single-use: cream from an opened packet is not used again, even if some is left. The contents of one sachet cover an area of about 20 cm².
The cream is applied to cleansed skin and rubbed in until it disappears — it should be absorbed rather than left as a film. Hands are washed thoroughly before and after applying it. No occlusive dressing is put over the top. The composition includes methyl hydroxybenzoate, propyl hydroxybenzoate, cetyl alcohol and stearyl alcohol — these excipients can cause allergic reactions.
How Aldara 5% works
Imiquimod is an immune response modifier, and that definition is worth taking literally. Binding saturation studies suggest that a membrane receptor for imiquimod exists on the cells of the immune response. Direct antiviral activity the substance does not have: by itself it neither kills the virus nor destroys tumour cells.
What does the work instead is an intermediary — interferon. In animal model studies imiquimod proved an effective antiviral and antitumour agent, chiefly through the induction of interferon α and other cytokines. In clinical studies the induction of interferon α and other cytokines was shown after the cream was applied to genital warts, and pharmacokinetic studies recorded a rise in interferon α and other cytokines in the body after local application. Hence the character of the treatment as well: the skin reaction at the application site is not a complication but the visible part of the medicine's work.
Indications
There are three indications and all of them are cutaneous and local. The first is condylomata acuminata of the external genitals and the perianal area in adults. The second is superficial foci of basal cell carcinoma in adults. The third is actinic keratosis, and it is drawn more precisely than any of them: without signs of hypertrophy or hyperkeratosis, of typical clinical course, on the face or the scalp, in patients with a competent immune system.
The third indication carries a further condition about the choice of method: imiquimod is used when the size or number of lesions limits the effectiveness or the very possibility of cryotherapy, and other local treatments are contraindicated or unsuitable. It is therefore not the first step but the option for cases where the usual burning off will not do. Children and adolescents are not recommended it: there are no data on use in the approved indications, and in molluscum contagiosum it is not used because it lacks efficacy.
Administration and dosage
The frequency and duration of treatment depend on which of the three indications is being treated, and they differ markedly. In every case the cream is applied in the evening before bed and left on the skin overnight; in the morning it must be washed off with water and mild soap, and throughout that time no shower or bath is taken.
| Indication | How often | How long it stays on | How many weeks |
| Genital and perianal warts | 3 times a week | 6-10 hours | until the warts clear, 16 at most |
| Superficial basal cell carcinoma | 5 times a week | about 8 hours | 6 |
| Actinic keratosis | 3 times a week | about 8 hours | 4, and another 4 if needed |
The details differ further still. In basal cell carcinoma the cream is applied with a 1 cm margin of healthy skin around the tumour, and the result is assessed 12 weeks after treatment ends. In actinic keratosis the treatment is started and monitored by a doctor: 4 weeks after the course it is assessed whether the lesions have cleared and, if they persist, they are treated for another 4 weeks, with no single treatment period exceeding four weeks even where doses were missed. If a check about 8 weeks after the last course shows the lesions have not cleared completely, a further four-week period is possible; on relapse after one or two courses the treatment may be repeated after a break of at least 12 weeks. The maximum dose is one sachet. A missed dose is applied as soon as it is remembered and the schedule is then continued, but the cream is not used more than once a day.
Contraindications
The formal prohibition is one: known hypersensitivity to the active substance or to any excipient. Neither age, nor concomitant illness, nor pregnancy has been placed in this section.
The medicine does, however, have a whole set of places where it should not be applied, and they sit in the warnings. Treating warts of the urethra, intravaginal, cervical, anal or intra-anal warts is not recommended. Treatment of basal cell carcinoma closer than 1 cm to the eyelids, nose, lips and hairline has not been assessed. In actinic keratosis efficacy has not been assessed on the eyelids, the inner surfaces of the nostrils and ears or on the vermilion of the lips, and on the skin of the forearms and hands treatment is not recommended — the available data do not confirm its efficacy.
Special warnings and precautions
The first rule is simple: avoid contact with the eyes, lips and nostrils. Imiquimod can aggravate inflammatory conditions of the skin, so it is not started until the skin has healed after previous medicines or surgery: applying it to damaged skin increases systemic absorption and with it the risk of adverse events. Caution is needed in autoimmune disease, where the benefit is weighed against the risk of worsening it, and in organ transplant recipients, where on the other side of the scales sit graft rejection or graft-versus-host disease. Caution is also required with reduced haematopoietic reserve. It is noted separately that rarely, and only after several applications, marked inflammatory skin changes with weeping or erosions may occur, and that local reactions may be accompanied or even preceded by general flu-like symptoms — malaise, fever, nausea, muscle pain, chills; in such cases stopping treatment is considered.
A theme of its own is men with warts under the foreskin. Experience here is limited: the database on uncircumcised men who kept up daily foreskin hygiene covers fewer than 100 patients, while in studies without such hygiene there were two cases of advanced phimosis and one of stricture that led to circumcision. Treatment in this group is therefore recommended only to those able and willing to retract the foreskin daily and wash its whole surface; early signs of stricture — erosion, ulceration, swelling, induration or growing difficulty in retracting it — call for treatment to be stopped at once. There are practical limits for everyone too: the cream must be washed off before sexual intercourse, and it can weaken condoms and diaphragms, so using them at the same time is not recommended and other methods of contraception are advised. Skin to which the cream has been applied is protected from sunlight. Finally, about the local reactions themselves: they are common, their severity usually decreases during treatment, and there is a relationship between complete clearance of the lesions and the strength of the reaction, erythema for instance. In case of intolerance the cream is washed off with water and mild soap and, once the reaction settles, treatment is resumed; where there is discomfort a break of a few days is acceptable.
Interactions with other medicines
No interaction studies have been carried out — including with immunosuppressants. The formal reason for the absence of problems is given right there: interactions with systemically acting medicines are limited because of the minimal absorption of imiquimod through the skin. In other words, the substance barely reaches the bloodstream, and ordinary drug interactions are therefore not characteristic of it.
One warning does exist, and it arises not from pharmacokinetics but from the mechanism. The medicine stimulates the immune system, that is, it acts in the direction opposite to immunosuppressive therapy. So in patients receiving such treatment imiquimod is used with caution. Adjacent to this is what the warnings say: in immunocompromised patients repeat treatment is not recommended, and in HIV infection, although limited data showed a greater degree of wart reduction, the medicine did not prove as effective at clearing them.
Pregnancy and breastfeeding
There are no clinical data on the use of imiquimod during pregnancy. Animal studies showed no direct or indirect harmful effect on the course of pregnancy, on embryonic or fetal development, on labour or on postnatal development. Even so, the conclusion in the product information is cautious: caution should be exercised when prescribing it to pregnant women.
With breastfeeding the position is unusual: the product information gives neither permission nor prohibition, and explains why. After a single dose and after repeated locally applied doses, measurable serum concentrations of imiquimod — that is, above 5 ng/ml — were not detected. Since the substance essentially does not enter the blood, no specific advice can be given on using or not using it in breastfeeding women. The decision stays with the doctor and rests on common sense: do not apply the cream where the child may come into contact with it.
Adverse reactions
The adverse reaction profile is described separately for each indication, and the figures show that what matters most in it are the reactions at the application site. In warts, on the three-times-a-week schedule, they were reported in 33.7% of patients; of the general ones, headache was recorded in 3.7%, flu-like symptoms in 1.1% and muscle pain in 1.5%. In superficial basal cell carcinoma, on the five-times-a-week schedule, at least one adverse event occurred in 58% of patients, local reactions in 28.1%, back pain in 1.1% and flu-like symptoms in 0.5%. In actinic keratosis, where up to two four-week courses were used, at least one event was recorded by 56% of patients, application-site reactions by 22% and muscle pain by 2%.
By frequency the picture is this. Very commonly: itching and pain at the application site and, in actinic keratosis, very commonly itching in particular. Commonly: burning and irritation at the application site, erythema, fatigue, headache, nausea, muscle and joint pain, loss of appetite, infection. Uncommonly: herpes, genital candidiasis, vaginitis and vulvitis, bacterial and fungal infections, upper respiratory tract infections, lymphadenopathy, insomnia, depression, paraesthesia, dizziness, migraine, drowsiness, tinnitus, hot flushes, pharyngitis, rhinitis, abdominal pain, diarrhoea, vomiting, rectal discomfort, itching, dermatitis, folliculitis, eczema, rash, urticaria, sweating, back pain, dysuria, genital pain and erectile dysfunction in men, vaginal pain and dyspareunia in women, fever, chills, weakness, conjunctival irritation and eyelid oedema. Of the rare but significant ones: severe local reactions have been described in people who used the cream exactly as directed — they required treatment and sometimes caused a temporary inability to father a child, and in some women reactions around the urethral opening caused difficulty passing urine, at times requiring catheterisation.
Overdose
Systemic overdose with local application is not possible, because absorption through the skin is minimal. That sentence opens the section in the product information and takes away the main fear. A reference point for the order of magnitude comes from the preclinical work: in rabbits the lethal dose on application proved to be above 5 g per kilogram of body weight.
Two other situations are dangerous, however. The first is exceeding the dose over a long period: it can cause severe local skin reactions. The second is swallowing the cream. After accidental ingestion of a single 200 mg dose of imiquimod, corresponding to the contents of about 16 sachets, nausea, vomiting, headache, muscle pain and fever are possible. With repeated oral doses of 200 mg or more, the clinically most serious reported adverse event was a fall in blood pressure, which resolved after fluids were given by mouth or intravenously.
How to get a prescription for Aldara 5% online
One and the same cream treats three different diseases on three different schedules, and a mistake in the schedule costs either the result or a severe skin inflammation. So the first thing the doctor needs is the exact diagnosis and the location of the lesions. At e-zdrowie.com you fill in a medical questionnaire, the doctor examines the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and with it any Polish pharmacy will hand over the pack.
In the questionnaire say what exactly you are treating — warts, superficial basal cell carcinoma or actinic keratosis — and give the precise site: for the latter two indications this is essential, because around the eyelids, nose, lips and hairline, and on the hands and forearms, the medicine is either unstudied or not recommended. Write how many lesions there are and how large. Be sure to report autoimmune disease, an organ transplant, the use of immunosuppressants and HIV infection, blood disorders, and also whether the area was treated before — surgically, with cryotherapy or with other creams — and whether the skin has healed. Men with warts under the foreskin should state separately whether they are circumcised: whether the medicine is prescribed at all depends on it. And state pregnancy or breastfeeding if either applies.
