ALDARA^™

Imiquimod 5% w/w cream

Presentation

ALDARA is a white cream with a uniform appearance. Each sachet contains 250 mg of cream for use as a single application.

Uses

Actions

Imiquimod is an immune response modifier and its mechanism of action is believed to be secondary to local cytokine induction in the skin. In animal models imiquimod is an effective antiviral and antitumour agent. Imiquimod is not a nucleoside analogue and its activity is principally due to induction of alpha interferon but other cytokines are also involved. Saturable binding studies suggest a membrane receptor for imiquimod exists on responding cells. Binding kinetics indicate a high and low affinity binding site. When imiquimod cream is applied topically to the back of mice, mRNA for alpha interferon and increased protein levels of interferon and tumour necrosis factor alpha are detected in the skin.

Pharmacokinetics

Less than 0.9% of a single 5 mg dose of radiolabelled imiquimod was absorbed through the skin of human subjects. The small amount of imiquimod which was absorbed into the systemic circulation was promptly excreted by both urinary and faecal routes at a ratio of approximately 3:1. No quantifiable levels (> 5 ng/ml) of imiquimod were detected in serum of patients after topical dosing.

Indications

ALDARA cream is indicated for the topical treatment of external genital warts and perianal warts (condyloma acuminata).

Dosage and Administration

Adult male and female patients self-administer the cream by applying to external warts once a day, 3 times per week (every other day followed by a 2 day treatment-free interval).

Treatment should be applied until wart clearance is achieved or up to a maximum of 16 weeks.

ALDARA cream should be applied onto the fingertip and rubbed onto a clean, dry wart area until the cream vanishes. ALDARA cream should be applied prior to normal sleeping hours. Showering or bathing during the period that the cream is on the treated wart area should be avoided. After this treatment period, ALDARA cream should be removed with soap and water. Cream in a single use sachet is sufficient to cover a wart area of 20 cm² and should not be reused after opening.

It is recommended that ALDARA is applied after, rather than before, sexual activity.

Contraindications

ALDARA cream is contraindicated in patients with hypersensitivity to imiquimod or cream excipients.

Warnings and Precautions

ALDARA cream has not been evaluated for the treatment of internal genital warts and should not be used to treat urethral, intra-vaginal, cervical, rectal or intra-anal warts.

Local reactions such as erythema, erosion, excoriation/flaking and oedema are expected and are believed to be the pharmacological response of the body's immune system to ALDARA. Should an intolerable skin reaction occur, the cream should be removed by washing the area with mild soap and water. Treatment with ALDARA can be resumed after the skin reaction has moderated.

An occlusive dressing should not be applied with ALDARA therapy. Higher than recommended doses may lead to increased local skin reactions. Uncircumcised males with warts under the foreskin should retract the foreskin and clean the area daily.

The effect of ALDARA 5% cream on the transmission of genital/perianal warts is unknown. ALDARA 5% cream may weaken condoms and vaginal diaphragms. Therefore, concurrent use is not recommended.

No clinical experience exists with ALDARA therapy immediately following treatment with other cutaneously applied drugs for treatment of external genital and perianal warts. ALDARA therapy is therefore not recommended for such patients until the genital skin has healed.

ALDARA has been applied to traumatised genital skin following wart ablation by electrocautery or cryotherapy in two pilot trials. Wound healing was not prolonged for these patients.

Use of ALDARA in transplant recipient patients has not been studied and ALDARA should only be used if the potential benefit justifies the potential risk.

While limited data has shown an increased rate of wart reduction in HIV positive patients, ALDARA has not been shown to be as effective in terms of wart clearance in this patient group.

Toxicology

Two year biostudies in Wistar rats (up to 3 mg/kg orally per day) and CD-1 mice (up to 4.5 mg/kg applied topically 3 times per week) showed no evidence of a carcinogenic effect in male and female rats and female mice. Liver tumours were increased in male mice exposed to the highest dose concentration, compared to the unexposed controls. However, the number of tumours was within the range seen historically for male CD-1 mice. It is generally accepted that an increase in liver tumours in male mice, in the absence of other neoplastic responses in mice or rats, is not indicative of a carcinogenic risk for humans.

Pregnancy and lactation

Animal studies with imiquimod have not revealed any teratogenic effects in rats and rabbits. No adverse effects were found on reproduction in a second generation rat study. There are no data in pregnant or lactating women and ALDARA cream should only be used during pregnancy if the potential benefit justifies the potential risk to the foetus.

Adverse Effects

The most frequent adverse events associated with ALDARA cream therapy are local application site reactions which include itching, pain and burning sensation at the wart treatment site. Local skin reactions (including erythema, erosion, oedema, vesicles, scabbing, desquamation/flaking and induration) are seen in conjunction with decreasing wart size and are believed to be secondary to the pharmacological activity of imiquimod. Most of the local skin reactions are mild to moderate in severity and resolved without sequelae within two weeks of discontinuing ALDARA. Isolated 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.

Interactions

No interactions have been identified.

Overdosage

Symptoms and Signs

Topical overdosage with ALDARA is unlikely due to minimal systemic absorption. Animal studies reveal a dermal lethal dose of greater than 5000 mg/kg and an oral lethal dose ranging from 400 to 1600 mg/kg. Persistent overdosing of ALDARA 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 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.

Pharmaceutical Precautions

Store below 25°C.

Medicine Classification

Prescription Medicine

Package Quantities

Each packet of ALDARA contains 12 single use sachets