Imiquimod 5% cream or 12.5mg cream (Recommendation -Grade A)
(Imiquimod 5% (or 12.5 mg cream in 0.25gm sachet) is same as 5% imiquimod is 5mg in 100 mg cream base, that means 10 mg in 200 mg cream base or 12.5 mg in 250 mg cream base or 12.5mg in 0.25gm cream in sachet) - is a patient-applied topical immunomodulatory agent, applied at bedtime 3 times weekly for up to 16 weeks; the treatment area should be washed with soap and water 6-10 hours after the application.
Imiquimod 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/genital warts or for a maximum of 16 weeks per episode of warts.
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 day. Imiquimod cream should be applied in a thin layer and rubbed on the clean wart area until the cream vanishes.
Application of an excess of cream or prolonged contact with the skin may result in a severe application site reaction. 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.
Imiquimod 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.
The use of an occlusive dressing is not recommended with imiquimod cream therapy.
Imiquimod is a synthetic agent with immune response modifying activity.
Imiquimod 5% cream has been used in the treatment of a variety of skin conditions, including basal cell carcinomas and actinic keratoses. Although its precise mechanism of action remains unclear, imiquimod is believed to activate immune cells by binding to the membranous toll-like receptor. This leads to the secretion of multiple cytokines, such as interferon-α, interleukin-6, and tumor necrosis factor-α, which are critical in the induction of an inflammatory response promoting wart clearance.
Imiquimod cream should be used with caution in patients with autoimmune conditions. and inflammatory conditoins. In addition, imiquimod-treated patients have been shown to have a decrease in viral load measured by HPV DNA, a decrease in messenger ribonucleic acid (mRNA) expression for markers of keratinocyte proliferation, and an increase in mRNA expression for markers of tumor suppression.
As an immune response modifier (IRM), imiquimod stimulates cytokine production, especially interferon production. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production.
For the treatment of Condylomata Acuminata, imiquimod is applied at bedtime three times per week for up to 16 weeks.
Commonly encountered local inflammatory side effects, such as itching, erythema, burning, irritation, tenderness, ulceration, and pain, have been long-standing issues with the 5% cream.
Occasionally, patients may experience systemic side effects of headaches, muscle aches, fatigue, and general malaise.
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, the application of the cream should be stopped immediately.
What Conditions does Imiquimod Cream In Packet Treat?
external genital wart
a skin surface basal cell carcinoma
a type of skin cancer
a roughened red patch of skin called actinic keratosis
vulvar intraepithelial neoplasia
This medication is used to treat certain types of growths on the skin. These are precancerous growths (actinic keratoses), a certain type of skin cancer (superficial basal cell carcinoma), and warts on the outside of the genitals/anus. Treating these conditions can decrease complications from them. Imiquimod belongs to a group of drugs called immune response modifiers. It is believed to work by helping to activate your immune system to fight these abnormal skin growths.
This product is not recommended for use on children under 12 years of age
How to use Imiquimod Cream In Packet
Use this medication on the skin only. Apply this medication to the affected area(s) as directed, usually just before you go to sleep for the night. If you are using the single-use packets, use a new packet for each dose. If you are using the pump, prime the pump as directed before using it for the first time.
Before applying, wash your hands and the area to be treated with mild soap and water. Dry the area well. Apply a thin layer of medication on the affected area(s) as directed and rub in. Wash your hands with soap and water after each application. Do not cover the treated area with bandages or waterproof coverings. However, you may cover the area with cotton gauze, or wear cotton underwear if treating the genital area. Leave the cream on overnight, usually for about 8 hours if treating actinic keratoses or basal cell carcinoma, or 6 to 10 hours for warts. Do not shower or bathe during this time. In the morning, wash the treated area with soap and water to remove the cream. Do not leave imiquimod cream on longer than prescribed.
When treating warts, this medication is usually applied 3 times a week for up to 16 weeks.
Use this medication regularly to get the most benefit from it. To help you remember, it may help to mark your calendar.
Do not apply this medication in the eyes, nose, mouth, rectum, or vagina. If you get this medication in those areas, flush with plenty of water. If irritation occurs, contact your doctor right away.
Treatment area reactions may include redness, swelling, itching, burning, pain/tenderness, thickening/hardening of the skin, peeling/flaking/scabbing/crusting, or leaking a clear fluid. Also, changes in skin color may occur and may not go away. The most frequently reported local skin reactions were erythema, other skin reactions are excoriation, itching, erosions, excoriation and pain can be present. The local reactions noted with imiquimod are most likely due to cytokine-induced inflammation and/or an immune response. An inflammatory response was not required to achieve clearance of the
warts; however, patients with such a response were more likely to have wart clearance.
If the skin reaction is severe (bleeding, formation of sores/blisters/ulcers), imiquimod may need to be temporarily stopped so that the skin can heal.
Flu-like symptoms (such as fever, tiredness, muscle aches), runny/stuffy nose, cough, diarrhea, nausea, and back pain may also occur.
Rare but serious side effects occur: swollen glands (lymph nodes), new unusual skin growths/changes, chest pain, trouble urinating.
A very serious allergic reaction to this drug is rare.
However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.
Genital/anal warts are caused by a virus called human papillomavirus (HPV). Since imiquimod does not destroy the virus but only helps to eliminate the wart, new warts may form, even while you are being treated. You may also be able to infect any sexual partner who comes into contact with the areas of skin infected with HPV.
To reduce the risk of spreading HPV to others, always use effective barrier protections (such as latex or polyurethane condoms, dental dams) during all sexual activity. Consult your doctor or pharmacist for more details.
During treatment of genital/anal warts, avoid all sexual contact while the cream is on the skin. Condoms, dental dams, and diaphragms may be weakened by the cream, and therefore they may not work as well to prevent pregnancy or spreading of HPV or HIV.
This medicine may be harmful if swallowed.
If you miss a dose, wait until the next night to apply it. Do not double the dose to catch up. Continue with your regular scheduled doses as directed.
Mechanism of action of imiquimod cream
The exact mechanism of action through which imiquimod and its analogs activate the immune system is not known. However, imiquimod activates immune cells through the toll-like receptor 7none (TLR7), commonly involved in pathogen recognition, on the cell surface. Cells activated by imiquimod via TLR-7 secrete cytokines [primarily interferon-α (IFN-α), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)]. Imiquimod, when applied to skin, can lead to the activation of Langerhans cells, which subsequently migrates to local lymph nodes to activate the adaptive immune system. Other cell types activated by imiquimod include natural killer cells, macrophages and B-lymphocytes. Topical application of imiquimod elevates the production of cytokines, including the principal cytokine for antiviral activity, interferon-α. This is the initial event in an immunological cascade resulting in the stimulation of the innate immune response as well as the cell-mediated pathway of acquired immunity. This immune modification mediates the indirect antiviral, antiproliferative and antitumor activity of imiquimod. These properties are responsible for imiquimod to be effective treatment for genital warts and Molluscum Contigiosum.
Imiquimod, an imidazoquinoline amine, is an immune response modifier, which acts as a stimulator of a local cell-mediated immune response and in addition induces the production of antiviral cytokines.23 The imiquimod acts as agonist on Toll-like receptor 7, stimulating the dermal dendritic cells to express cytokines, such as tumor necrosis factor-a, interferon-a (IFN-a), as well as interleukins 1, 6, 8, and 12. The immediate effect of the cytokines is that initially plasmacytoid dendritic cells are attracted from the bloodstream and second great amounts of IFN-a are being produced. As consequence, the increased levels of cytokines stimulate natural killer cells to target both the HPV-infected and the carcinogenic cells. Furthermore, imiquimod also induces the Langerhans cells to mature and migrate to the lymph nodes, where they present antigen and induce a Th1 response. Tumor-specific T-cells are multiplied and infiltrate the affected area3.
B-cells start producing antibodies that subsequently increase antigen presentation. Conversely, the innate immune response can also lead to adverse events like edema, local redness, burning sensation, and itching. These synergistic effects exert the antiviral and antitumor qualities of imiquimod3.
FAQs about imiquimod cream
What is Imiquimod cream?
It is a cream used to treat genital warts and has also proven to be an effective treatment for Anal warts / anal intra-epithelial neoplasia (AIN). AIN is caused by the human papilloma virus (HPV) which is generally passed from person to person through sexual contact.
Is Imiquimod cream like other treatments?
Imiquimod cream works differently to other treatments. It helps your body’s own immune system to fight HPV, which in turn helps to clear the AIN.
How do I use Imiquimod Cream packets?
- Open a packet of Imiquimod Cream just before use.
- Apply Imiquimod Cream as described above.
- After applying Imiquimod Cream safely throw away the opened packet so that children and pets cannot get it.
- The opened packet should be thrown away even if all the Imiquimod Cream was not completely used.
How do I Apply Imiquimod Cream:
- Wash the area where the cream will be applied with mild soap and water.
- Allow the area to dry.
- Wash your hands.
- Place the amount of cream to be used in your palm.
- Apply a thin layer of Imiquimod Cream only to the affected area or areas to be treated. Do not use more Imiquimod Cream than is needed to cover the treatment area.
- Rub the cream in all the way to the affected area or areas.
- After you apply Imiquimod Cream, wash your hands well.
- Leave the cream on the affected area or areas for the time prescribed by your healthcare provider. Do not bathe or get the treated area wet before the prescribed time has passed.
- Do not leave Imiquimod Cream on your skin longer than prescribed.
- After about 8 hours, wash the treated area or areas with mild soap and water.
- If you forget to apply Imiquimod Cream, just apply the next dose of Imiquimod Cream at your regular time.
When using Imiquimod Cream for external genital warts what precautions do I take?
- Do not get Imiquimod Cream in or on your anus or vagina.
- Apply a thin layer of Imiquimod Cream only to the affected area or areas to be treated. Do not use more Imiquimod Cream than is needed to cover the treatment area.
- Rub the cream into your skin until you cannot see the Imiquimod Cream.
- Imiquimod Cream is usually left on the skin for approximately 8 hours. Treatment should continue until the warts are completely gone or for up to 8 weeks.
- Uncircumcised males treating warts under their penis foreskin must pull their foreskin back and clean before treatment and clean daily during treatment.
- Female patients treating genital warts must be careful when applying Imiquimod Cream around the vaginal opening. Do not put Imiquimod Cream in your vagina.
- If you have been prescribed Imiquimod Cream packets, do not use more than one packet for each daily application.
- If you have been prescribed Imiquimod Cream pump, do not use more than one actuation of the pump for each daily application.
What should I avoid while using Imiquimod Cream?
- Do not cover the treated area with bandages or other closed dressings.
- Cotton gauze dressings can be used. Cotton underwear can be worn after applying Imiquimod Cream to the genital or perianal area.
- Do not use sunlamps or tanning beds, and avoid sunlight as much as possible during treatment with Imiquimod Cream. Use sunscreen and wear protective clothing if you go outside during daylight.
- Do not have sexual contact including genital, anal, or oral sex when Imiquimod Cream is on your genital or perianal skin. Imiquimod Cream may weaken condoms and vaginal diaphragms. This means they may not work as well to prevent pregnancy.
What are the possible side effects of Imiquimod Cream?
Imiquimod Cream may cause serious side effects, including:
- Local Skin Reactions: Skin drainage (weeping) or breakdown of the outer layer of your skin (erosion). Swelling outside of the vagina (vulvar swelling) may happen in female patients. You should take special care if applying the cream at the opening of the vagina because local skin reactions on the delicate moist surfaces can cause pain or swelling, and may cause problems passing urine. Tell your healthcare provider if this happens.
- Flu-like symptoms: Tell your healthcare provider if you have tiredness, nausea, vomiting, fever, chills, muscle pain, and joint pain.
The most common side effects of Imiquimod Cream include:
- local skin reactions including skin redness, scabbing, crusting, flaking, scaling, dryness, swelling
- itching at the treatment area
- skin irritation
- pain at the treatment area
1. Minh PPT, Thi LP, Lan AT, Van TN, Van HL, Cam VT, Gandolfi M, Feliciani C, Satolli F, Tirant M, Vojvodic A, Lotti T. Early Treatment with Imiquimod 5% Cream of Periungual Warts in Vietnam: The Poorer, the Better. Open Access Maced J Med Sci. 2019 Jan 25;7(2):214-216. doi: 10.3889/oamjms.2019.053. PMID: 30745962; PMCID: PMC6364714.
2. Puri N. A study on the use of imiquimod for the treatment of genital molluscum contagiosum and genital warts in female patients. Indian J Sex Transm Dis AIDS. 2009 Jul;30(2):84-8. doi: 10.4103/0253-7184.62763. PMID: 21938126; PMCID: PMC3168064
3.Gkegkes ID, Iavazzo C, Stamatiadis AP. Intra-anal use of imiquimod: what is the clinical evidence? Int J STD AIDS. 2019 Sep;30(10):1018-1024. doi: 10.1177/0956462419855828. Epub 2019 Jul 8. PMID: 31284838.
Intra-anal application of Imiquimod 5% cream
In 2001, imiquimod was for the first time applied intra-anally, as off-label use, for the treatment of HPV-related anal lesions3,4. Nevertheless, until now the intra-anal use of imiquimod has not been officially approved and is considered off-label 3.
Most HPV infections are cleared spontaneously by the innate immune system. Imiquimod is an immune response modifier that works by stimulating both innate and adaptive immunity, as well as inducing apoptosis.
Local adverse events are common and may include burning, itching, and pain at the application site due to mucocutaneous inflammation after application of imiquimod. The problem arises in intra-anal warts as the imiquimod is not recommended for intra-anal use due to increased risk of absorbtion and inflammation.
Intra-anal application of imiquimod has been shown to be effective against intra-anal warts and but also associated with increased risk of burning, itching and swelling. To reduce the adverse effect of intra-anal imiquimod half dose of the recommended dose is used intra-anally every alternate day for 4 months and further maintainence was used once a week for 48 week (almost 1 year) was shown to be effective in removing the HPV virus from the body
Imiquimod therapy generally leads to a rapid decrease in high-risk HPV DNA loads within the first 4 to 8 weeks of therapy2.
Regimen intra-anal imiquad therapy for HIV + person is to apply 6.25 mg imiquimod intra-anally and peri-anally 3 doses per week for 16 weeks initially and then one dose per week for a further 48 weeks in followup period1.
The cream is inserted into the anal canal, using half a sachet (half the dose used for anogenital warts) to reduce the likelihood of systemic absorption through the anal mucosa. The adverse effect experienced are irritation, itching and tenderness (Pain).
The absorption of imiquimod from the rectal mucosa can cause flulike symptoms, a sign of systemic immune activation. In addition, in order to avoid the absorption from the rectal mucosa, imiquimod is advised to be intra-anally inserted till the dentate line of the anus3.
The adverse effects correlated to the intra-anal use of imiquimod seem to be minor in comparison to its effect on both anal HSIL and on benign anal HPV lesions (warts). The intra-anal administration of imiquimod either as anal tampon or as self-applied cream seems to be well tolerated. The present clinical evidence suggests that imiquimod may be proposed as effective as well as safe, when applied intra-anally for HPV related lesions (warts).
Application of imiquimod cream intra-vaginally either directly or as tampons is associated with number of adverse reactions like Malaise, Persisting nausea, Mild diarrhoea, Asymptomatic hyponatremia, Leukopenia, headache, Light-headedness, Abdominal pain, Fatigue, Fever, Erosion of the cornea5. These adverse effects reverse on stopping application of imiquimod cream.
How to use Imiquimod cream to treat Intra-anal warts / anal intraepithelial neoplasia (AIN).
How do I use Imiquimod cream intra-anally?
It should be applied in the anal canal (the first 4-5 centimetres (cm) inside your anus). Do not take it by mouth or use it in or near your eyes.
When do I apply Imiquimod cream?
Use it three times a week, just before going to bed. Apply it on either Mondays, Wednesdays and Fridays or Tuesdays, Thursdays and Saturdays, using it more often than that does not have greater effect.
How long should I use the cream for?
As Imiquimod works with your immune system it takes time to be effective. We usually recommend a course of 16 weeks of treatment.
How do I apply Imiquimod cream?
- Before going to bed, wash and dry your hands and around your anus.
- Use half a sachet each time. Squeeze the cream onto your index finger (pointing finger).
- You may want to cover your finger with cling film or use a latex glove to insert the cream.
- Part your buttocks and push the cream up into your anus. If any is left around the outside, then continue pushing the cream inside until it is all gone.
- Wash your hands with soap and water.
- Discard the remaining cream, after folding the top of the packet over.
- You should avoid emptying your bowels, bathing, douching or sexual contact after applying the cream.
What changes will I notice?
Reddening, soreness and wearing away of the skin around the anus is normal. Not all patients will notice this, but the cream may still be working inside. Rarely, you can develop more significant blistering, pain and flu-like symptoms.
What should I do if undesirable effects occur?
If you notice severe itching or burning when the cream is applied, then stop the treatment and contact your doctor.
Can I have sex whilst using Imiquimod cream?
- If you have sex on your treatment day, then you should apply the cream after sex, not before sex
- Avoid sexual contact while the cream is in place
- Durukan D, Phillips TR, Murray GL, Ong JJ, Grulich AE, Poynten IM, Jin F, Bradshaw CS, Aguirre I, Silvers J, Kent H, Atchison S, Balgovind P, Cornall A, Chen MY, Fairley CK, Chow EPF. Intra-Anal Imiquimod Cream against Human Papillomavirus Infection in Men Who Have Sex with Men Living with HIV: A Single-Arm, Open-Label Pilot Study. J Clin Med. 2021 Sep 28;10(19):4477. doi: 10.3390/jcm10194477. PMID: 34640496; PMCID: PMC8509144.
- Wieland U, Brockmeyer NH, Weissenborn SJ, Hochdorfer B, Stücker M, Swoboda J, Altmeyer P, Pfister H, Kreuter A. Imiquimod treatment of anal intraepithelial neoplasia in HIV-positive men. Arch Dermatol. 2006 Nov;142(11):1438-44. doi: 10.1001/archderm.142.11.1438. PMID: 17116834.
- Gkegkes ID, Iavazzo C, Stamatiadis AP. Intra-anal use of imiquimod: what is the clinical evidence? Int J STD AIDS. 2019 Sep;30(10):1018-1024. doi: 10.1177/0956462419855828. Epub 2019 Jul 8. PMID: 31284838.
- Pehoushek J, Smith KJ. Imiquimod and 5% Fluorouracil Therapy for Anal and Perianal SquamousCell Carcinoma In Situ in an HIV-1–Positive Man. Arch Dermatol. 2001;137(1):14–16. doi:10.1001/archderm.137.1.14
Wouters T, Hendriks N, Koeneman M, Kruse AJ, van de Sande A, van Beekhuizen HJ, Gerestein KG, Bekkers RLM, Piek JMJ. Systemic adverse events in imiquimod use for cervical intraepithelial neoplasia - A case series. Case Rep Womens Health. 2019 Mar 6;21:e00105. doi: 10.1016/j.crwh.2019.e00105. PMID: 30906696; PMCID: PMC6411488.
Werner RN, Westfechtel L, Dressler C, Nast A. Anogenital warts and other HPV-associated anogenital lesions in the HIV-positive patient: a systematic review and meta-analysis of the efficacy and safety of interventions assessed in controlled clinical trials. Sex Transm Infect. 2017 Dec;93(8):543-550. doi: