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Aldara cream may be used for three different conditions. Your doctor may prescribe Aldara
cream for the treatment of:
● Warts (condylomata acuminata) on the surface of the genitals (sexual organs) and around the
anus (back passage)
● Superficial basal cell carcinoma.
This is a common slow-growing form of skin cancer with a very small likelihood of spread to
other parts of the body. It usually occurs in middle-aged and elderly people, especially those
who are fair-skinned and is caused by too much sun exposure. If left untreated, basal cell
carcinoma can disfigure, especially on the face – therefore early recognition and treatment
are important.
● Actinic keratosis
Actinic keratoses are rough areas of skin found in people who have been exposed to a lot of
sunshine over the course of their lifetime. Some are skin coloured, others are greyish, pink,
red or brown. They can be flat and scaly, or raised, rough, hard and warty. Aldara should
only be used for flat actinic keratoses on the face and scalp in patients with a healthy immune
system where your doctor has decided that Aldara is the most appropriate treatment for you.
Aldara cream helps your body´s own immune system to produce natural substances which help
fight your basal cell carcinoma, actinic keratosis or the virus that has caused your warts.
Do not use Aldara cream:
– If you are allergic to imiquimod (the active ingredient) or any of the ingredients of the cream.
Take special care with Aldara cream:
● If you have previously used Aldara cream or other similar preparations tell your doctor
before starting this treatment.
● Tell your doctor if you have problems with your immune system.
● Do not use Aldara cream until the area to be treated has healed after previous drug or surgical
treatment.
● Avoid contact with the eyes, lips and nostrils. In the event of accidental contact, remove
cream by rinsing with water.
● Do not apply the cream internally.
● Do not use more cream than your doctor has advised.
● Do not cover the treated area with bandages or other dressings after you have applied Aldara
cream.
● If the treated site becomes too uncomfortable, wash the cream off with mild soap and water.
As soon as the problem has stopped you may restart to apply the cream.
● Tell your doctor if you have an abnormal blood count.
Because of the way Aldara works, there is a possibility that the cream may worsen existing
inflammation in the treatment area.
● If you are being treated for genital warts follow these additional precautions:
Men with warts under the foreskin should pull the foreskin back each day and wash
underneath it. If not washed daily the foreskin may be more likely to show signs of tightness,
swelling and wearing away of the skin and result in difficulty in pulling it back. If these
symptoms occur, stop the treatment immediately and call your doctor.
If you have open sores: do not start using Aldara cream until after the sores have healed. If
you have internal warts: do not use Aldara cream in the urethra (the hole from which urine is
passed), the vagina (birth canal), the cervix (internal female organ), or anywhere inside your
anus (rectum).
Do not use this medication for more than one course if you have problems with your immune
system, either due to illness or because of the medicines you are already taking. If you think
this applies to you talk to your doctor.
If you are HIV positive you should inform your doctor as Aldara cream has not been shown
to be as effective in HIV positive patients. If you decide to have sexual relations while you
still have warts, apply Aldara cream after - not before - sexual activity. Aldara cream may
weaken condoms and diaphragms, therefore the cream should not be left on during sexual
activity. Remember, Aldara cream does not protect against giving HIV or other sexually
transmitted diseases to someone else.
● If you are being treated for basal cell carcinoma or actinic keratosis follow these additional
precautions:
Do not use sunlamps or tanning beds, and avoid sunlight as much as possible during
treatment with Aldara cream. Wear protective clothing and wide brimmed hats when
outdoors.
Whilst using Aldara cream and until healed, the treatment area is likely to appear noticeably
different from normal skin.
Using other medicines:
Please inform your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those obtained without a prescription.
There are no medicines known to be incompatible with Aldara cream.
Pregnancy and breast-feeding:
Ask your doctor or pharmacist for advice before taking any medicine.
You must tell your doctor if you are pregnant or intend to become pregnant. Your doctor will
discuss the risks and benefits of using Aldara cream during pregnancy. Studies in animals do not
indicate direct or indirect harmful effects in pregnancy.
Do not breast-feed your infant during treatment with Aldara cream, as it is not known whether
imiquimod is secreted in human milk.
Important information about some of the ingredients of Aldara cream:
Methyl hydroxybenzoate (E218) and propyl hydroxybenzoate (E216) may cause allergic
reactions (possibly delayed). Cetyl and stearyl alcohol may cause local skin reactions (e.g. contact
dermatitis).
Always use Aldara cream exactly as your doctor has told you. Check with your doctor or
pharmacist if you are not sure.
Wash hands carefully before and after applying the cream. Do not cover the treated area with
bandages or other dressings after you have applied Aldara cream.
Open a new sachet each time you use the cream. Dispose of any cream left in the sachet after use.
Do not save the opened sachet for use at a later date.
The treatment frequency and duration differ for genital warts, basal cell carcinoma and actinic
keratosis (see specific instructions for each indication).
● If you are being treated for genital warts:
Application Instructions – (Mon, Wed and Fri)
1. Before going to bed, wash your hands and the treatment area with mild soap and water. Dry
thoroughly.
2. Open a new sachet and squeeze some cream onto your fingertip.
3. Apply a thin layer of Aldara cream onto clean, dry wart area and rub gently into the skin until
cream vanishes.
4. After application of the cream, throw away the opened sachet and wash hands with soap and
water.
5. Leave Aldara cream on the warts for 6 to 10 hours. Do not shower or bathe during this time.
6. After 6 to 10 hours wash the area where Aldara cream was applied with mild soap and water.
Apply Aldara cream 3 times per week. For example, apply the cream on Monday, Wednesday
and Friday. One sachet contains enough cream to cover a wart area of 20 cm2 (approx. 3 square
inches). Men with warts under the foreskin should pull the foreskin back each day and wash
underneath it (see section 2 “Take special care with Aldara cream:”)
Continue to use Aldara cream as instructed until your warts have completely gone (half the
females who clear will do so in 8 weeks, half the males who clear will do so in 12 weeks but in
some patients warts may clear as early as 4 weeks).
Do not use Aldara cream for more than 16 weeks in the treatment of each episode of warts.
If you have the impression that the effect of Aldara cream is too strong or too weak, talk to your
doctor or pharmacist.
● If you are being treated for basal cell carcinoma:
Application Instructions – (Mon, Tues, Wed, Thurs and Fri)
1. Before going to bed, wash your hands and the treatment area with mild soap and water. Dry
thoroughly.
2. Open a new sachet and squeeze some cream onto your fingertip.
3. Apply Aldara cream to the affected area and 1cm (approx. 0.5 inch) around the affected area.
Rub gently into the skin until the cream vanishes.
4. After application of the cream, throw away the opened sachet. Wash hands with soap and
water.
5. Leave Aldara cream on the skin for about 8 hours. Do not shower or bathe during this time.
6. After about 8 hours, wash the area where Aldara cream was applied with mild soap and water.
Apply sufficient Aldara cream to cover the treatment area and 1 cm (about ½ an inch) around the
treatment area each day for 5 consecutive days each week for 6 weeks. For example, apply the
cream from Monday to Friday. Do not apply the cream on Saturday and Sunday.
● If you are being treated for actinic keratosis
Application Instructions – (Mon, Wed and Fri)
1. Before going to bed, wash your hands and the treatment area with mild soap and water. Dry
thoroughly.
2. Open a new sachet and squeeze some cream onto your fingertip.
3. Apply the cream to the affected area. Rub gently into the area until the cream vanishes.
4. After application of the cream, throw away the opened sachet. Wash hands with soap and
water.
5. Leave Aldara cream on the skin for about 8 hours. Do not shower or bathe during this time.
6. After about 8 hours, wash the area where Aldara cream was applied with mild soap and water.
Apply Aldara cream 3 times per week. For example, apply the cream on Monday, Wednesday and
Friday. One sachet contains enough cream to cover an area of 25 cm2 (approx. 4 square inches).
Continue treatment for four weeks. Four weeks after finishing this first treatment, your doctor will
assess your skin. If the lesions have not all disappeared, a further four weeks of treatment may be
necessary.
If you use more Aldara cream than you should:
Wash the extra away with mild soap and water. When any skin reaction has gone you may then
continue with your treatment.
If you accidentally swallow Aldara cream please contact your doctor.
If you forget to use Aldara cream:
If you miss a dose, apply cream as soon as you remember and then continue in your regular
schedule.
Do not apply the cream more than once per day.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
The frequency of side effects is classified as follows:
Very common side effects (likely to occur in more than 1 in 10 patients)
Common side effects (likely to occur in fewer than 1 in 10 patients)
Uncommon side effects (likely to occur in fewer than 1 in 100 patients)
Rare side effects (likely to occur in fewer than 1 in 1,000 patients)
Very rare side effects (likely to occur in fewer than 1 in 10,000 patients).
Like all medicines, Aldara cream can cause side effects, although not everybody gets them.
Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using
Aldara cream.
Some patients have experienced changes in skin colour in the area where Aldara cream was
applied. While these changes have tended to improve with time, in some patients they may be
permanent. If your skin reacts badly when using Aldara cream, stop applying the cream, wash the
area with mild soap and water and contact your doctor or pharmacist.
In some individuals a lowering of blood counts was noted. A lowering of blood counts might
make you more susceptible to infections, make you bruise more easily or cause fatigue. If you
notice any of these symptoms, tell your doctor.
Serious skin reactions have been reported rarely. If you experience skin lesions or spots on
your skin that start out as small red areas and progress to look like mini targets, possibly with
symptoms such as itching, fever, overall ill feeling, achy joints, vision problems, burning, painful
or itchy eyes and mouth sores, stop using Aldara cream and tell your doctor immediately.
A small number of patients have experienced hair loss at the treatment site or surrounding area. If
any of the side effects gets serious, or if you notice any side effects not mentioned in this leaflet,
please tell your doctor or pharmacist.
● If you are being treated for genital warts:
Many of the undesirable effects of Aldara cream are due to its local action on your skin.
Very common effects include redness (61% patients), wearing away of the skin (30% patients),
flakiness and swelling. Hardening under the skin, small open sores, a crust that forms during
healing, and small bubbles under the skin may also occur. You might also feel itching (32%
patients), a burning sensation (26% patients) or pain in areas where you have applied Aldara
cream (8% patients). Most of these skin reactions are mild and the skin will return to normal
within about 2 weeks after stopping treatment.
Commonly some patients (4% or less) have experienced headache, uncommonly fevers and flu
like symptoms joint and muscle pains; prolapse of the womb; pain on intercourse in females;
erection difficulties; increase in sweating; feeling sick; stomach and bowel symptoms; ringing in
the ears; flushing; tiredness; dizziness; migraine; pins and needles; insomnia; depression; loss of
appetite; swollen glands; bacterial, viral and fungal infections (e.g. cold sores); vaginal infection
including thrush; cough and colds with sore throat.
Very rarely severe and painful reactions have occurred, particularly when more cream has been
used than recommended. Painful skin reactions at the opening of the vagina have very rarely
made it difficult for some women to pass urine. If this occurs you should seek medical help
immediately.
● If you are being treated for basal cell carcinoma:
Many of the undesirable effects of Aldara cream are due to its local action on your skin. Local
skin reactions can be a sign that the drug is working as intended.
Very Commonly the treated skin may be slightly itchy.
Common effects include: pins and needles, small swollen areas in the skin, pain, burning,
irritation, bleeding, redness or rash.
If a skin reaction becomes too uncomfortable during treatment, speak to your doctor. He/she may
advise you to stop applying Aldara cream for a few days (i.e. to have a short rest from treatment).
If there is pus (matter) or other suggestion of infection, discuss this with your doctor. Apart from
reactions in the skin, other common effects include swollen glands and back pain.
Uncommonly some patients experience changes at the application site (discharge, inflammation,
swelling, scabbing, skin breakdown, blisters, dermatitis) or irritability, feeling sick, dry mouth,
flu-like symptoms and tiredness.
● If you are being treated for actinic keratosis
Many of the undesirable effects of Aldara cream are due to its local action on your skin. Local
skin reactions can be a sign that the drug is working as intended.
Very commonly the treated skin may be slightly itchy.
Common effects include pain, burning, irritation or redness.
If a skin reaction becomes too uncomfortable during treatment, speak to your doctor. He/she may
advise you to stop applying Aldara cream for a few days (i.e. to have a short rest from treatment).
If there is pus (matter) or other suggestion of infection, discuss this with your doctor. Apart from
reactions in the skin, other common effects include headache, anorexia, nausea, muscle pain, joint
pain and tiredness. Uncommonly some patients experience changes at the application site (bleeding, inflammation,
discharge, sensitivity, swelling, small swollen areas in the skin, pins and needles, scabbing,
scarring, ulceration or a feeling of warmth or discomfort), or inflammation of the lining of the
nose, stuffy nose, flu or flu-like symptoms, depression, eye irritation, swelling of the eyelid, throat
pain, diarrhoea, actinic keratosis, redness, swelling of the face, ulcers, pain in extremity, fever,
weakness or shivering.
Keep out of the reach and sight of children.
Do not store above 25°C.
Do not use after the expiry date stated on the label.
Sachets should not be re-used once opened.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist to
dispose of medicines no longer required. These measures will help to protect the environment.
What Aldara cream contains:
– The active substance is imiquimod. Each sachet contains 250 mg cream (100 mg cream
contains 5 mg imiquimod).
– The other ingredients are isostearic acid, benzyl alcohol, cetyl alcohol, stearyl alcohol, white
soft paraffin, polysorbate 60, sorbitan stearate, glycerol, methyl hydroxybenzoate (E218),
propyl hydroxybenzoate (E216), xanthan gum, purified water.
MEDA Pharma GmbH & Co. KG
Benzstrasse 1
61352 Bad Homburg
Germany
MANUFACTURER:
3M Health Care Limited
Derby Road
Loughborough
Leicestershire
LE11 5SF, United Kingdom
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lmiquimod cream is indicated for the topical treatment of:
• External genital and perianal warts (condylomata acuminata) in adults.
• Small superficial basal cell carcinomas (sBCCs) in adults.
• Clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses (AK.s) on the face or
scalp in immunocompetent adult patients when size or number oflesions limit the efficacy
and/or acceptability of cryotherapy and other topical treatment options are contraindicated or
less appropriate.
Posology
The application frequency and duration of treatment with imiquimod cream is different for each
indication.
External genital warts in adults:
lmiquimod cream should be applied 3 times per week (example: Monday, Wednesday, and Friday; or
Tuesday, Thursday, and Saturday) prior to normal sleeping hours, and should remain on the skin for
6 to 10 hours. Imiquimod cream treatment should continue until the clearance of visible genital or
perianal warts or for a maximum of 16 weeks per episode of warts.
For quantity to be applied see section 4.2 ethod of administration.
Superficial basal cell carcinoma in adults:
Apply imiquimod cream for 6 weeks, 5 times per week (example: Monday to Friday) prior to normal
sleeping hours, and leave on the skin for approximately 8 hours.
For quantity to be applied see 4.2 Method of administration.
Actinic keratosis in adults
Treatment should be initiated and monitored by a physician. Imiquimod cream should be applied
3 times per week (example: Monday, Wednesday and Friday) for four weeks prior to normal sleeping
hours, and left on the skin for approximately 8 hours. Sufficient cream should be applied to cover the
treatment area. After a 4-week treatment-free period, clearance of AKs should be assessed. If any
lesions persist, treatment should be repeated for another four weeks.
The maximum recommended dose is one sachet. The maximum recommended treatment duration is
8 weeks.
An interruption of dosing should be considered if intense local inflammatory reactions occur (see
section 4.4) or if infection is observed at the treatment site. In this latter case, appropriate other
measures should be taken. Each treatment period should not be extended beyond 4 weeks due co
missed doses or rest periods.
lf the treated lesion(s) show an incomplete response at the follow-up examination at 4-8 weeks after
the second treatment period, a different therapy should be used (see section 4.4)
Information applicable to all indications:
If a dose is missed, the patient should apply the cream as soon as he/she remember and then he/she
should continue with the regular schedule. However the cream should not be applied more than once
a
Paediatric population
Use in the paediatric patient population is not recommended. There are no data available on the use of
imiquimod in children and adolescents in the approved indications.
Aldara should not be used in children with molluscum contagiosum due to lack of efficacy in this
indication (see section 5.1).
Method of administration
External genital warts:
hniquimod cream should be applied in a thin layer and rubbed on the clean wart area until the cream
vanishes. Only apply to affected areas and avoid any application on internal surfaces. Imiquimod
cream should be applied prior to nonnal sleeping hours. During the 6 to IO hour treatment period,
showering or bathing should be avoided. After this period it is essential that imiquimod cream is
removed with mild soap and water. Application of an excess of cream or prolonged contact with the
skin may result in a severe application site reaction (see sections 4.4, 4.8 and 4.9). A single-use sachet
is sufficient to cover a wart area of 20 cm2 (approx. 3 inches2). Sachets should not be re-used once
opened. Hands should be washed carefully before and after application of cream.
Uncircumcised males treating warts under the foreskin should retract the foreskin and wash the area
daily (see section 4.4).
Superficial basal cell carcinoma:
Before applying imiquimod cream, patients should wash the treatment area with mild soap and water and dry thoroughly, Sufficient cream should be applied to cover the treatment area including one centimetre of skin surrounding the tumour. The cream should be rubbed into the treatment area until
the cream vanishes. The cream should be applied prior to normal sleeping hours and remain on the
skin for approximately 8 hours. During this period, showering and bathing should be avoided. After
this period it is essential that imiquimod cream is removed with mild soap and water.
Sachets should not be re-used once opened. Hands should be washed carefully before and after
application of cream.
Response of the treated tumour to imiquimod cream should be assessed 12 weeks after the end of
treatment. If the treated tumour shows an incomplete response, a different therapy should be used (see
section 4.4).
A rest period of several days may be taken (see section 4.4) if the local skin reaction to imiquimod
cream causes excessive discomfort to the patient, or if infection is observed at the treatment site. In
this latter case, appropriate other measures should be taken.
Actinic keratosis:
Before applying imiquimod cream, patients should wash the treatment area with mild soap and water
and dry thoroughly. Sufficient cream should be applied to cover the treatment area. The cream should
be rubbed into the treatment area until the cream vanishes. The cream should be applied prior to
normal sleeping hours and remain on the skin for approximately 8 hours. During this period,
showering and bathing should be avoided. After this period it is essential that imiquimod cream is
removed with mild soap and water. Sachets should not be re-used once opened. Hands should be
washed carefully before and after application of cream.
External genital warts. superficial basal cell carcinoma and actinic keratosis:
Avoid contact with the eyes, lips and nostrils.
lmiquimod has the potential to exacerbate inflammatory conditions of the skin.
lmiquimod cream should be used with caution in patients with autoimmune conditions (refer to
section 4.5). Consideration should be given to balancing the benefit of imiquimod treatment for these
patients with the risk associated with a possible worsening of their autoimmune condition.
lmiquimod cream should be used witycaution in organ transplant patients (refer to section 4.5).
Consideration should be given to balancing the benefit of imiquimod treatment for these patients with
the risk associated with the possibility of organ rejection or graft-versus-host disease.
lmiquimod cream therapy is not recommended until the skin has healed after any previous drug or
surgical treatment. Application to broken skin could result in increased systemic absorption of
imiquimod leading to a greater risk of adverse events (re!er to section 4.8 and 4.9)
The use of an occlusive dressing is not recommended with imiquimod cream therapy.
/
The excipients methyl hydroxybenzoate (E 218) and propyl hydroxybenzoate (E 216) may cause
allergic reactions (possibly delayed). Cetyl alcohol and stearyl alcohol may cause local skin reactions
(e.g. contact dermatitis).
Rarely, intense local inflammatory reactions including skin weeping or erosion can occur after only a
few applications of imiquimod cream. Local inflammatory reactions may be accompanied, or even
preceded, by flu-like systemic signs and symptoms including malaise, pyrexia, nausea, myalgias and
rigors. An interruption of dosing should be considered.
Imiquimod should be used with caution in patients with reduced haematologic reserve (refer to
section 4.8d).
External genital warts:
There is limited experience in the use of imiquimod cream in the treatment of men with foreskinassociated
warts. The safety database in uncircumcised men treated with imiquimod cream three times
weekly and carrying out a daily foreskin hygiene routine is less than 100 patients. In other studies, in
which a daily foreskin hygiene routine was not followed, there were two cases of severe phimosis and
one case of stricture leading to circumcision. Treatment in this patient population is therefore
recommended only in men who are able or willing to follow the daily foreskin hygiene routine. Early
signs of stricture may include local skin reactions ( e.g. erosion, ulceration, oedema, induration), or
increasing difficulty in retracting the foreskin. If these symptoms occur, the treatment should be
stopped immediately. Based on current knowledge, treating urethral, intra-vaginal, cervical, rectal or
intra-anal warts is not recommended. Imiquimod cream therapy should not be initiated in tissues
where open sores or wounds exist until after the area has healed.
Local skin reactions such as erythema, erosion, excoriation, flaking and oedema are common. Other
local reactions such as induration, ulceration, scabbing, and vesicles have also been reported. Should
an intolerable skin reaction occur, the cream should be removed by washing the area with mild soap
and water. Treatment with imiquimod cream can be resumed after the skin reaction has moderated.
The risk of severe local skin reactions may be increased when imiquimod is used at higher than
recommended doses (see section 4.2). However, in rare cases severe local reactions that have required
treatment and/or caused temporary incapacitation have been observed in patients who have used
imiquimod according to the instructions. Where such reactions have occurred at the urethral meatus,
some women have experienced difficulty in urinating, sometimes requiring emergency catheterisation
and treatment of the affected area.
No clinical experience exists with imiquimod cream immediately following treatment with other
cutaneously applied drugs for treatment of external genital or perianal warts. Imiquimod cream should
be washed from the skin before sexual activity. Imiquimod cream may weaken condoms and
diaphragms, therefore concurrent use with imiquimod cream is not recommended. Alternative forms
of contraception should be considered.
In immunocompromised patients, repeat treatment with imiquimod cream is not recommended.
While limited data have shown an increased rate of wart reduction in HIV positive patients,
imiquimod cream has not been shown to be as effective in terms of wart clearance in this patient
group.
Superficial basal cell carcinoma:
lmiquimod bas not been evaluated for the treatment of basal cell carcinoma within 1 cm of the
eyelids, nose, lips or hairline.
During therapy and until healed, affected skin is likely to appear noticeably different from normal
skin. Local skin reactions are common but these reactions generally decrease in intensity during
therapy or resolve after cessation of imiquimod cream therapy. There is an assoc1ation between the
comlete clearance rate and the itensit7 of local sn reactions (e.g. erytha).''fna! skin
reacaons may be related to the st11nulat10n of local immune response. If required by the patient's
discomfort or the severity of the local skin reaction, a rest period of several days may be taken.
Treatment with imiquimod cream can be resumed after the skin reaction has moderated.
The clinical outcome of therapy can be determined after regeneration of the treated skin,
approximately l2 weeks after the end of treatment.
No clinical experience exists with the use of irniquimod cream in immunocompromised patients.
No clinical experience exists in patients with recurrent and previously treated BCCs, therefore use for
previously treated tumours is not recommended.
Data from an open label clinical trial suggest that large tumours {>7.25 cm
2
) are less likely to respond
to imiquimod therapy.
The skin surface area treated should be protected from solar exposure.
Actinic keratosis
Lesions clinically atypical for AK or suspicious for malignancy should be biopsied to determine
appropriate treatment.
Imiquimod has not been evaluated for the treatment of actinic keratoses on the eyelids, the inside of
the nostrils or ears, or the lip area inside the vermilion border.
There are very limited data available on the use of irniquimod for the treatment of actinic keratoses in
anatomical locations other than the face and scalp. The available data on actinic keratosis on the
foreanns and hands do not support efficacy in this indication and therefore such use is not
recommended.
Imiquimod is not recommended for the treatment of AK lesions with marked hyperkeratosis or
hypertrophy as seen in cutaneous horns.
During therapy and until healed, affected skin is likely to appear noticeably different from normal
skin. Local skin reactions are common but these reactions generally decrease in intensity during
therapy or resolve after cessation of imiquimod cream therapy. There is an association between the
complete clearance rate and the intensity of local skin reactions ( e.g. erythema). These local skin
reactions may be related to the stimulation of local immune response. If required by the patient's
discomfort or the intensity of the local skin reaction, a rest period of several days may be taken.
Treatment with imiquimod cream can be resumed after the skin reaction has moderated.
Each treatment period should not be extended beyond 4 weeks due to missed doses or rest periods.
The clinical outcome of therapy can be determined after regeneration of the treated skin,
approximately 4-8 weeks after the end of treatment.
No clinical experience exists with the use of imiquimod cream in immunocompromised patients.
No data are available on re-treating actinic keratoses that have cleared after one or two courses of
treatment and subsequently recur, and any such use is therefore not recommended.
Data from an open-label clinical trial suggest that subjects with more than 8 AK lesions showed a
decreased rate of complete clearance compared to patients with less than 8 lesions.
The skin surface area treated should be protected from solar exposure.
No interaction studies have been perfonned. Tltis includes studies with immunosuppressive drugs.
Interactions with systemic drugs would be limited by the minimal percutaneous absorption of
imiquimod cream.
Due to its immunostimulating properties, imiquimod cream should be used with caution in patients
who are receiving immunosuppressive medication (see section 4.4).
Pregnancy
For imiquimod no clinical data on exposed pregnancies are available. Animal studies do not indicate
direct or indirect hannful effects with respect to pregnancy, embryonal/foetal development,
parturition or postnatal development (see section 5.3). Caution should be exercised when prescribing
to pregnant women.
Breast-feeding
As no quantifiable levels (> 5 ng/ml) of irniquimod are detected in the serum after single and multiple
topical doses, no specific advice can be given on whether to use or not in lactating mothers.
Aldara cream has no or negligible influence on the ability to drive and use machines.
a) General Description:
External genital warts:
In the pivotal trials with 3 times a week dosing, the most frequently reported adverse drug reactions
judged to be probably or possibly related to imiquimod cream treatment were application site
reactions at the wart treatment site (33.7% of imiquimod treated patients). Some systemic adverse
reactions, including headache (3.7%), influenza-like symptoms (i. l %), and myalgia (1.5%) were also
reported.
Patient reported adverse reactions from 2292 patients treated with imiquimod cream in placebo
controlled and open clinical studies are presented below. These adverse events are considered at least
possibly causally related to treatment with imiquimod.
Superficial basal cell carcinoma:
In trials with 5 times per week dosing 58% of patients experienced at least one adverse event. The
most frequently reported adverse events from the trials judged probably or possibly related to
irniquimod cream are application site disorders, with a frequency of 28.1 %. Some systemic adverse
reactions, including back pain (1.1 %) and influenza-like symptoms (0.5%) were reported by
irniquimod cream patients.
Patient reported adverse reactions from 185 patients treated with irniquimod cream in placebo
controlled phase III clinical studies for superficial basal cell carcinoma are presented below. These
adverse events are considered at least possibly causally related to treatment with imiquimod.
Actinic keratosis
In the pivotal trials with 3 times per week dosing for up to 2 courses each of 4 weeks, 56% of
imiquimod patients reported at least one adverse event. The most fr equently reported adverse event
from these trials judged probably or possibly related to imiquimod cream was application site
reactions (22% of imiquimod treated patients). Some systemic adverse reactions, including myalgia
(2%) were reported by imiquimod treated patients.
Patient reported adverse reactions from 252 patients treated with imiquimod cream in vehicle I
controlled phase III clinical studies for actinic keratosis are presented below. These adverse events are
considered at least possibly causally related to treatment with imiquimod. I
I
b) Tabular Listing of adverse events:
Frequencies are defined as Very common (:2:1/10), Common (:2:l/100 to <l/10) and Uncommon
(:2:1/1,000 to <l/100). Lower frequencies from clinical trials are not reported here.
External genital Superficial basal Actinic keratosis
warts cell carcinoma
(3x/ wk,16wks) (Sx/wk, 6 wks) (3x/wk, 4 or 8 wks)
N=2292 N= 185 N=252
Infections and infestations:
Infection Common Common Uncommon
Pustules Common Uncommon
Herpes simplex Uncommon
Genital candidiasis Uncommon
Vaginitis Uncommon
Bacterial infe.ction Uncommon
Fungal infection Uncommon
Upper respiratory tract infection Uncommon
Vulvitis Uncommon
Rhinitis Uncommon
Influenza Uncommon
Blood and lymphatic system
disorders:
Lymphadenopathy Uncommon Common Uncommon
Metabolism and nutrition disorders:
Anorexia Uncommon
--
Common
Psychiatric disorders:
Insomnia Uncommon
Depression Uncommon Uncommon
Irritability Uncommon
Nervous system disorders:
Headache Common Common
Paraesthesia Uncommon
Dizziness Uncommon
Migraine Uncommon
Somnolence Uncommon
Eve disorders -
Conjunctiva] irritation Uncommon
Eyelid oedema Uncommon
Ear and labyrinth disorders:
Tinnitus Uncommon
Vascular disorders:
Flushing
Respiratory, thoracic and
mediastinal disorders:
Pharvngitis
Rhinitis
Nasal congestion
Pharvngo laryngeal pain
Gastrointestinal disorders:
Nausea
Abdominal pain
Diarrhoea
Votniting
Rectal disorder
Rectal tenesmus
Drvmouth
Skin and subcutaneous tissue
disorders:
Pruritus
Dermatitis
Folliculitis
Rash erythematous
Eczema
Rash
Sweating increased
Urticaria
Actinic keratosis
Erythema
Face oedema
Skin ulcer
Musculoikeletal and connective
tissue disorders:
Myalgia
Arthralgia
Back pain
Pain in extremity
Renal and urinary disorders:
Dvsuria
Reproductive system and breast
disorders:
Genital pain male
Penile disorder
Oyspareunia
Erectile dysfunction
Uterovaginal prolapse
Vaginal pain
Vacinitis atrophic
Vulva! disorder
General disorders and
administration site conditions:
Anolication site pruritus
Annlication site pain
Aoolication site burning
Application site irritation
Application site erythema
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Common Uncommon Common
Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Common Common
Uncommon Common
Uncommon Common
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Vervcommon Very common Very common
Vervcommon Common Common
Common Common Common
Common Common Common
Common Common
Aoolication site reaction
Anolication site bleeding
Application site oapules
Aoolication site oaraesthesia
Annlication site rash
Fatime Common
Pvrexia Uncommon
Influenza-like illness Uncommon
Pain Uncommon
Asthenia Uncommon
Malaise Uncommon
Rigors Uncommon
Annlication site dermatitis
Annlication site discharge
Annlication site hvoeraesthesia
Aoolication site inflammation
Annlication site oedema
Annlication site scabbing
Application site scar
APnlication site skin breakdown
Anolication site swelling
Annlication site ulcer
Application site vesicles
Apnlication site warmth
LetharP-Y
Discomfort
Inflammation
Frequently occurring adverse events:
External genital warts:
Common
Common Uncommon
Common Uncommon
Common Uncommon
Common
Common
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
c)
Aoolication site reaction
Anolication site bleeding
Application site oapules
Aoolication site oaraesthesia
Annlication site rash
Fatime Common
Pvrexia Uncommon
Influenza-like illness Uncommon
Pain Uncommon
Asthenia Uncommon
Malaise Uncommon
Rigors Uncommon
Annlication site dermatitis
Annlication site discharge
Annlication site hvoeraesthesia
Aoolication site inflammation
Annlication site oedema
Annlication site scabbing
Application site scar
APnlication site skin breakdown
Anolication site swelling
Annlication site ulcer
Application site vesicles
Apnlication site warmth
LetharP-Y
Discomfort
Inflammation
Frequently occurring adverse events:
External genital warts:
Common
Common Uncommon
Common Uncommon
Common Uncommon
Common
Common
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon Uncommon
Uncommon
Uncommon
Uncommon
Uncommon
Investigators of placebo controlled trials were required to evaluate protocol mandated clinical signs
(skin reactions). These protocol mandated clinical sign assessments indicate that local skin reactions
including erythema (61%), erosion (30%), excoriation/flaking/scaling (23%) and oedema (14%) were
common in these placebo controlled clinical trials with imiquimod cream applied three times weekly
(see section 4.4). Local skin reactions, such as erythema, are -probably an extension of the
pharmacologic effects of imiquimod cream.
Remote site skin reactions, mainly erythema ( 44%), were also reported in the placebo controlled
trials. These reactions were at non-wart sites which may have been in contact with imiquimod cream.
Most skin reactions were mild to moderate in severity and resolved within 2 weeks of treatment
discontinuation. However, in some cases these reactions have been severe, requiring treatment and/or
causing incapacitation. In very rare cases, severe reactions at the urethral meatus have resulted in
dysuria in women (see section 4.4).
Superficial basal cell carcinoma:
Investigators of the placebo controlled clinical trials were required to evaluate protocol mandated
clinical signs (skin reactions). These protocol mandated clinical sign assessments indicate that severe
erythema (31%) severe erosions (13%) and severe scabbing and crusting (19%) were very common in
these trials with imiquimod cream applied 5 times weekly. Local skin reactions, such as erythema, are
probably an extension of the pharmacologic effect of imiquimod cream.
Skin infections during treatment with imiquimod have been observed. While serious sequelae have
not resulted, the possibility of infection in broken skin should always be considered.
Actinic keratosis
In clinical trials of imiquimod cream 3 times weekly for 4 or 8 weeks the most frequently occurring
application site reactions were itching at the target site (14%) and burning at the target site (5%).
Severe erythema (24%) and severe scabbing and crusting (20%) were very common. Local skin
reactions, such as erythema, are probably an extension of the pharmacologic effect of irniquimod
cream. See 4.2 and 4.4 for information on rest periods.
Skin infections during treatment with imiquimod have been observed. While serious sequelae have
not resulted, the possibility of infection in broken skin should always be considered.
d) Adverse events applicable to all indications:
Reports have been received of localised hypopigmentation and hyperpigmentation following
imiquimod cream use. Follow-up information suggests that these skin colour changes may be
permanent in some patients. In a follow-up of 162 patients five years after treatment for sBCC a mild
hypopigmentation was observed in 37% of the patients and a moderate hypopigmentation was
observed in 6% of the patients. 56% of the patients have been free of hypopigmentation;
hyperpigmentation has not been reported.
Clinical studies investigating the use of irniquimod for the treatment of actinic keratosis have detected
a 0.4% (5/1214) frequency of alopecia at the treatment site or surrounding area. Postrnarketing reports
of suspected alopecia occurring during the treatment of sBCC and EGW have been received.
Reductions in haemoglobin, white blood cell count, absolute neutrophils and platelets have been
observed in clinical trials. These reductions are not considered to be clinically significant in patients
with normal haematologic reserve. Patients with reduced haematologic reserve have not been studied
in clinical trials. Reductions in haematological parameters requiring clinical intervention have been
reported from postrnarketing experience. There have been postrnarketing reports of elevated liver
enzymes.
Rare reports have been received of exacerbation of autoimmune conditions.
Rare cases of remote site dermatologic drug reactions, including erythema multiforme, have been
reported from clinical trials. Serious skin reactions reported from postmarketing experience include
erythema multiforme, Stevens Johnson syndrome and cutaneous lupus erythematosus.
e) Paediatric population:
Imiquimod was investigated in controlled clinical studies with paediatric patients (see sections 4.2
and 5.1 ). There was no evidence for systemic reactions. Application site reactions occurred more
frequently after imiquimod than after vehicle, however, incidence and intensity of these reactions
were not different from that seen in the licensed indications in adults. There was no evidence for
serious adverse reaction caused by imiquimod in paediatric patients.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance uf the medicinal ·product. Healthcare
professionals are asked to report any suspected adverse reactions via the national reJ)Orting system
listed in Appendix V.
When applied topically, systemic overdosage with imiquimod cream is unlikely due to minimal
percutaneous absorption. Studies in rabbits reveal a dermal lethal dose of greater than 5 g,'kg.
Persistent dermal overdosing of imiquimod cream could result in severe local skin reactions.
Following accidental ingestion, nausea, emesis, headache, myalgia and fever could occur after a
single dose of 200 mg imiquimod which corresponds to the content of approximately 16 sachets. The
most clinically serious adverse event reported following multiple oral doses of 200 mg was
hypotension which resolved following oral or intravenous fluid administration.
Pharmacotherapeutic group: Chemotherapeutics for topical use, antivirals, ATC Code: D06BB 10
Imiquimod is an immune response modifier. Saturable binding studies suggest a membrane receptor
for imiquimod exists on responding immune cells. Imiquimod has no direct antiviral activity. In
animal models imiquimod is effective against viral infections and acts as an antitumour agent
principally by induction of alpha interferon and other cytokines. The induction of alpha interferon and
other cytokines following imiquimod cream application to genital wart tissue has also been
demonstrated in clinical studies.
Increases in systemic levels of alpha interferon and other cytokines following topical application of
imiquimod were demonstrated in a pharmacokinetic study.
External genital warts:
Clinical Efficacy
The results of 3 phase III pivotal efficacy studies showed that treatment with imiquimod for sixteen
weeks was significantly more effective than treatment with vehicle as measured by total clearance of
treated warts.
In 119 imiquimod-treated female patients, the combined total clearance rate was 60% as compared to
20% in I 05 vehicle-treated patients (95% CI for rate difference: 20% to 61 o/o, p<0.001). In those
imiquimod patients who achieved total clearance of their warts, the median time to clearance was
8 weeks.
In 157 imiquimod-treated male patients, the combined total clearance rate was 23% as compared to
5% in 161 vehicle-treated patients (95%CI for rate difference: 3% to 36%, p<0.001 ). In those
imiquimod patients who achieved total clearance of their warts, the median time to clearance was
12 weeks.
Superficial basal cell carcinoma:
Clinical efficacy:
I 39/185) of patients. These results were statistically significant (p<0.00 I) by comparison with the
vehicle group, 3% (6/179) and 2% (3/179) respectively. There was a significant association between
the intensity of local skin reactions ( e.g. erythema) seen during the treatment period and complete
clearance of the basal cell carcinoma.
Five -year data from a long-term open-label uncontrolled study indicate that an estimated 77.9%
[95% Cl (71.9%, 83.8%)] of all the subjects who initially received treatment became clinically clear
and remained clear at 60 months.
Actinic keratosis:
Clinical efficacy:
The efficacy of imiquimod applied 3 times per week for one or two courses of 4 weeks, separated by a
4 week treatment-free period, was studied in two double-blind vehicle controlled clinical trials.
Patients had clinically typical, visible, discrete, nonhyperkeratotic, nonhypertrophic AK lesions on the
balding scalp or face within a contiguous 25 cm2 treatment area. 4-8 AK lesions were treated. The
complete clearance rate (imiquimod minus placebo) for the combined trials was 46.1 % (Cl 39.0%,
53.1%).
One-year data from two combined observational studies indicate a recurrence rate of 27%
(35/128 patients) in those patients who became clinically clear after one or two courses of treatment.
The recurrence rate for individual lesions was 5.6% (41/737). Corresponding recurrence rates for
vehicle were 47% (8/17 patients) and 7.5% (6/80 lesions). The rate of progression to squamous cell
carcinoma (SCC) was reported in 1.6% (2/128 patients).
There are no data on recurrence and pro gression rates beyond 1 year.
Paediatric population
The approved indications genital warts, actinic keratosis and superficial basal cell carcinoma are
conditions not generally seen within the paediatric population and were not studied.
Aldara Cream has been evaluated in four randomised, vehicle controlled, double-blind trials in
children aged 2 to 15 years with molluscum contagiosum (imiquimod n = 576, vehicle n = 313).
These trials failed to demonstrate efficacy of imiquimod at any of the tested dosage regimens
(3x/week for 16 weeks and 7x/week for 8 weeks).
External genital warts, superficial basal cell carcinoma and actinic keratosis:
Less than 0.9% of a topically applied single dose of radiolabelled imiquimod was absorbed through
the skin of human subjects. The small amount of drug which was absorbed into the systemic
circulation was promptly excreted by both urinary and faecal routes at a mean ratio of approximately
3 to 1. No quantifiable levels (>5 ng/ml) of drug were detected in serum after single or multiple
topical doses.
Systemic exposure (percutaneous penetration) was calculated from recovery of carbon-14 from [ I 4C]
imiquimod in urine and faeces.
scalp and hands/ anns groups. Dose proportionality was not observed. An apparent half-life was
calculated that was approximately 10 times greater than the 2 hour half-life seen following
subcutaneous dosing in a previous study, suggesting prolonged retention of drug in the skin. Urinary
recovery was less than 0.6% of the applied dose at week 16 in these patients.
Paediatric population
The pharmacokinetic properties of imiquimod following single and multiple topical application in
paediatric patients with molluscum contagiosurn (MC) have been investigated. The systemic exposure
data demonstrated that the extent of absorption of imiquimod following topical application to the MC
lesional skin of the paediatric patients aged 6-12 years was low and comparable to that observed in
healthy adults and adults with actinic keratosis or superficial basal cell carcinoma. In younger patients
aged 2-5 years absorption, based on C,nax values, was higher compared to adults.
Non-clinical data revealed no special hazard for humans based on conventional studies of safety
pharmacology, mutagenicity and teratogenicity.
In a four-month rat dermal toxicity study, significantly decreased body weight and increased spleen
weight were observed at 0.5 and 2.5 mg/kg; similar effects were not seen in a four month mouse
dermal study. Local dermal irritation, especially at higher doses, was observed in both species.
A two-year mouse carcinogenicity study by dermal administration on three days a week did not
induce tumours at the application site. However, the incidences of hepatocellular tumours among
treated animals were greater than those for controls. The mechanism for this is not known, but as
imiquimod has low systemic absorption from human skin, and is not mutagenic, any risk to humans
from systemic exposure is likely to be low. Furthermore, tumours were not seen at any site in a 2-year
oral carcinogenicity study in rats.
hniquimod cream was evaluated in a photocarcinogenicity bioassay in alhino hairless mice exposed to
simulated solar ultraviolet radiation (UVR). Animals were administered imiquimod cream three ti.mes
per week and were irradiated 5 days per week for 40 weeks. Mice were maintained for an additional
12 weeks for a total of 52 weeks. Tumours occurred earlier and in greater number in the group of
mice administered the vehicle cream in comparison with the low UVR control group. The significance
for man is unknown. Topical administration of imiquimod cream resulted in no tumour enhancement
at any dose, in comparison with the vehicle cream group.
isostearic acid
benzyl alcohol
cetyl alcohol
stearyl alcohol
white soft paraffin
polysorbate 60
sorbitan stearate
glycerol
methyl hydroxybenzoate (E 218)
propyl hydroxybenzoate (E 216)
xanthan gum
purified water.
Not applicable.
Do not store above 25 °C.
Sachets should not be re-used once opened.
Boxes of 12 or 24 single-use polyester/aluminium foil sachets, containing 250 mg of cream.
Not all pack sizes may be marketed.
No special requirements.
