Imiquimod

What is imiquimod?

Imiquimod is an immune response modifier. It is manufactured as a 5% (50 mg/g) cream called Aldara™. Generic forms of imiquimod cream are also available. The Perrigo brand is funded by PHARMAC in New Zealand (2019).

A 3.75% cream called Zyclara™ has also been approved by the FDA in the USA but is not yet available in New Zealand (March 2017).

What is imiquimod used for?

Imiquimod is mainly used to treat:

• Actinic keratoses (also called solar keratoses or AKs).
• Basal cell carcinoma (BCC), especially superficial BCC and sometimes low-risk nodular BCC
• Intraepidermal carcinoma (also known as Bowen disease, or in-situ squamous cell carcinoma (SCC)), an unregistered indication at this time (June 2016)

It was first approved for use in genital warts. It may also be helpful in the unapproved treatment of common warts (once they have been thinned down by other means), plane warts, and herpes simplex. Experimentally it has been successful in reducing some keloid scars, granuloma annulare, vitiligo, melanoma in situ (lentigo maligna type) and, in combination with diphencyprone, metastatic melanoma (see topical and intralesional immunotherapy for melanoma.

Although sometimes prescribed for molluscum contagiosum, clinical trials have not shown imiquimod to be of benefit.

Before starting, a biopsy may be performed to confirm the diagnosis. Imiquimod is particularly useful in areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs. 

How does imiquimod work?

Imiquimod works by stimulating the immune system to release a number of chemicals called cytokines, which are important in fighting viruses and destroying cancer cells.

When used to treat skin cancers and pre-cancerous lesions it results in inflammation, which destroys the lesion. The degree of inflammation is quite variable from person to person, in part due to the type of skin lesion and in part due to genetic factors. The imiquimod is taken up by the so-called ‘toll-like receptor 7’ on certain immune cells that are found in the outside part of the skin (the epidermis); these receptors are expressed more in some individuals and in some skin lesions than in others.

Treatment regimes for imiquimod cream

Various imiquimod treatment regimes are used. For example:

• Actinic keratoses: imiquimod is typically used two or three times weekly for four to six weeks, repeated if necessary after a break of four weeks. Very scaly lesions should be frozen with liquid nitrogen about three weeks before starting imiquimod.
• Basal cell carcinomas and intraepidermal carcinoma: imiquimod is used five times weekly for six weeks. 
• Genital warts: imiquimod is used three times weekly; or, if available, 3.75% cream daily; until total clearance or for up to 8 weeks.
• (Off label) lentigo maligna: imiquimod is used three to seven times per week for six to 16 weeks. Close follow-up is essential.  

The imiquimod should be applied less often if the reaction is excessive, and more often if no reaction occurs (perhaps accompanied by a topical retinoid to enhance absorption of imiquimod into the skin). The course can be repeated, and treatment is sometimes continued for up to 16 weeks.

Treatment should be carefully monitored, because the cream may need to be applied more or less frequently than originally planned or for a shorter or longer course, depending on response. Once the inflammation has settled there is generally a good or excellent cosmetic result with little scarring. 

How to use imiquimod cream

The 5% product is supplied either as a box of sachets, each containing 250 mg, or as a pump-pack (2 g). Wash hands before and after applying imiquimod cream. 

Cut the top off the sachet or pierce the sachet with a needle and squeeze out a tiny amount of cream onto your fingertip. If using the pump pack, remove the protective cap and prime several times before pressing the pump once only to dispense the cream. Apply the cream to the affected areas.

Although the information on the packet states that the sachet is for single-use, some people seal it using a paper clip or tape and store it in a closed container to prevent the cream drying out.

Imiquimod is usually used during the winter months but, as it is not photosensitising, it may be used at any time of year. Sun protection with clothing and sunscreen can continue as usual.

Imiquimod in the genital area should be washed off before having sexual intercourse. It can weaken rubber condoms.

What to expect from imiquimod cream

Areas treated with imiquimod will become inflamed. The effects include itching, burning, redness, ulceration (sores), scabbing, flaking and pain. These reactions indicate that the cream is likely to be effective - if there is no inflammation, imiquimod is unlikely to clear the lesions. An exaggerated response may clear the skin lesion sooner than expected — sometimes after as few as three or four applications. In some patients, surrounding untreated areas also become inflamed but this will settle when treatment is discontinued.

If black scabs and ulceration occur or there are severe systemic symptoms, the cream should be discontinued.

BCC

Imiquimod to BCC

Imiquimod to BCC

Imiquimod to actinic keratosis

Imiquimod to actinic keratosis

Imiquimod to actinic keratosis

More images of the effect of imiquimod.

Systemic side effects from imiquimod cream

When using imiquimod cream, 'flu-like symptoms may develop, such as fever, fatigue, headache, nausea, diarrhoea and muscle pain. These are generally mild and may be treated with paracetamol. Side effects should resolve within a few days of stopping treatment. They may also resolve with continuing treatment.