Imiquimod - Drug Monograph

Introduction

Imiquimod is a topical immunomodulating agent that belongs to the class of immune response modifiers. Originally approved by the FDA in 1997, it represents a novel approach to treating various dermatological conditions by harnessing the body's own immune system rather than relying on direct cytotoxic effects.

Mechanism of Action

Imiquimod acts as a toll-like receptor 7 (TLR7) agonist, stimulating both innate and adaptive immune responses. Upon application, it activates antigen-presenting cells (primarily dendritic cells and macrophages), leading to increased production and release of various cytokines including interferon-α, tumor necrosis factor-α, and interleukins (IL-1, IL-6, IL-8, and IL-12). This cytokine cascade results in enhanced cell-mediated immunity through Th1-type immune responses, ultimately leading to antiviral and antitumor effects.

Indications

FDA-approved indications:

• Treatment of external genital and perianal warts/condyloma acuminata in adults
• Actinic keratosis on face and scalp
• Superficial basal cell carcinoma (sBCC) ≤ 2.0 cm in diameter

Off-label uses include:

• Treatment of common warts
• Molluscum contagiosum
• Bowen's disease
• Lentigo maligna
• Extramammary Paget's disease

Dosage and Administration

• Apply 3 times per week (e.g., Monday, Wednesday, Friday)
• Leave on skin for 6-10 hours before washing off
• Treatment duration: up to 16 weeks

• Apply 2 times per week for 16 weeks
• Treatment area: 25 cm² of face or scalp

• Apply 5 times per week for 6 weeks
• Treatment area: includes 1 cm margin around tumor

• Apply thin layer to affected area
• Wash hands before and after application
• Do not use occlusive dressings
• Avoid application near eyes, lips, and nostrils

• Renal impairment: Use with caution
• Hepatic impairment: No dosage adjustment needed
• Pediatrics: Safety not established
• Geriatrics: No dosage adjustment needed

Pharmacokinetics

Contraindications

• Hypersensitivity to imiquimod or any component of the formulation
• Use on broken or inflamed skin
• Application to mucous membranes
• Pregnancy (category C)

Warnings and Precautions

• Local skin reactions: Severe inflammatory reactions may occur
• Flu-like symptoms: May experience fatigue, fever, myalgia
• Autoimmune disorders: May exacerbate or trigger autoimmune conditions
• Sun exposure: Increased photosensitivity; avoid excessive sun exposure
• Multiple lesions: Limit treatment area to minimize systemic effects
• Immunocompromised patients: Safety not established
• Pregnancy: Use only if potential benefit justifies potential risk

Drug Interactions

• Other topical medications: Potential for increased irritation
• Immunosuppressants: May diminish therapeutic effect
• CYP1A2 substrates: Potential for altered metabolism
• Vaccines: Theoretical risk of enhanced vaccine response

Adverse Effects

• Local skin reactions: erythema, edema, erosion, flaking/scaling
• Application site reactions: itching, burning, pain
• Fatigue
• Headache

• Flu-like symptoms
• Myalgia
• Fever
• Diarrhea
• Nausea

• Severe local skin reactions requiring discontinuation
• Autoimmune disorders (lupus, psoriasis)
• Lymphadenopathy
• Hypo- or hyperpigmentation

Monitoring Parameters

• Local skin reactions at application site
• Signs of systemic absorption (flu-like symptoms)
• Complete blood count if extensive application
• Liver function tests if extensive application
• Response to therapy (lesion clearance)
• Signs of autoimmune phenomena
• Patient adherence to regimen

Patient Education

• Apply medication exactly as prescribed
• Wash hands thoroughly before and after application
• Use medication at bedtime and wash off after 6-10 hours
• Expect local skin reactions; these indicate medication is working
• Do not share medication with others
• Avoid sexual contact while cream is on skin
• Report severe skin reactions or systemic symptoms
• Use sun protection during treatment
• Do not apply to broken or irritated skin
• Keep out of reach of children
• Store at room temperature (15-30°C)

References

1. FDA Prescribing Information: Aldara (imiquimod) Cream, 5% 2. Gupta AK, Browne M, Bluhm R. Imiquimod: a review. J Cutan Med Surg. 2002;6(6):554-560. 3. Stanley MA. Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential. Clin Exp Dermatol. 2002;27(7):571-577. 4. Lebwohl M, Dinehart S, Whiting D, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol. 2004;50(5):714-721. 5. Geisse JK, Rich P, Pandya A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol. 2002;47(3):390-398. 6. American Society of Health-System Pharmacists. AHFS Drug Information. Imiquimod. Updated 2023.