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Pronunciation
(i mi KWI mod)
Generic Available (U.S.)
Yes
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of external genital and perianal warts/condyloma acuminata; nonhyperkeratotic actinic keratosis on face or scalp; superficial basal cell carcinoma (sBCC) with a maximum tumor diameter of 2 cm located on the trunk, neck, or extremities (excluding hands or feet)
Use: Unlabeled/Investigational
Treatment of common warts
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were noted in some animal studies following oral administration. Safety and efficacy have not been established in pregnant women.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
There are no contraindications listed within the approved manufacturer's labeling.
Canadian labeling (not in U.S. labeling): Hypersensitivity to imiquimod or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Local inflammatory reactions: Intense local inflammatory reactions may occur after a few applications and may be accompanied by systemic symptoms (fever, malaise, myalgia); reactions may extend beyond the application site. Interruption of therapy may be necessary.
• Photosensitivity: May increase sunburn susceptibility; patients should protect themselves from the sun and artificial forms of sunlight.
Disease related concerns:
• Actinic keratosis: Appropriate use: Treatment should be limited to areas ≤25 cm2 (Aldara®) or <200 cm2 (Zyclara® 3.75%). Safety and efficacy of repeated use of Aldara® or Zyclara® 3.75% in a previously treated area have not been established. Prescribed course of therapy should be completed even if all lesions appear to be gone.
• Autoimmune disorders: Use caution in patients with pre-existing autoimmune disorders (onset or exacerbation of disease has been reported rarely with imiquimod).
• Basal cell carcinoma: Appropriate use: Should be limited to superficial carcinomas with a maximum diameter of 2 cm. Safety and efficacy in treatment of sBCC lesions of the face, head, and anogenital area, or other subtypes of basal cell carcinoma (including nodular and morpheaform), have not been established.
• Basal cell nevus syndrome: Safety and efficacy have not been established for basal cell nevus syndrome.
• Genital warts: Appropriate use: Zyclara® 3.75%: Safety and efficacy in the treatment of external genital warts have not been established. Imiquimod has not been evaluated for the treatment of urethral, intravaginal, cervical, rectal, or intra-anal human papilloma viral disease and is not recommended for these conditions.
• Skin inflammatory conditions: Has the potential to exacerbate inflammatory conditions of the skin (including chronic graft-versus-host disease).
• Xeroderma pigmentosum: Safety and efficacy have not been established for xeroderma pigmentosum.
Special populations:
• Immunocompromised patients: Safety and efficacy have not been established in immunosuppressed patients.
• Pediatrics: Zyclara® 3.75%: Safety and efficacy in children <18 years of age have not been established. Aldara®: Safety and efficacy have not been established in children <12 years of age; following 2 randomized, double-blind, placebo-controlled trials, efficacy was not established for molluscum contagiosum in children 2-12 years of age.
Other warnings/precautions:
• Administration: Not intended for oral, nasal, intravaginal, or ophthalmic use. Administration is not recommended until tissue is healed from any previous drug or surgical treatment. Treatment should not be prolonged beyond recommended period due to missed doses or rest periods.
Adverse Reactions
Note: Frequency may depend on indication/formulation.
>10%:
Local: Application site reactions are common. Frequency of reactions vary, and are related to the degree of inflammation associated with the treated disease, number of weekly applications, and individual sensitivity.
Burning, edema, erosion/ulceration, erythema, excoriation, flaking, induration, itching, scabbing/crusting, scaling/dryness, vesicles, weeping/exudate
Respiratory: Upper respiratory infection
Miscellaneous: Fungal infection
1% to 10%:
Cardiovascular: Chest pain
Central nervous system: Anxiety, dizziness, fatigue, fever, headache, pain
Dermatologic: Alopecia, eczema, seborrhoeic keratosis
Endocrine & metabolic: Blood glucose increased
Gastrointestinal: Anorexia, diarrhea, dyspepsia, nausea, vomiting
Genitourinary: Urinary tract infection
Local: Bleeding, hypopigmentation, infection, irritation, pain, papule, paresthesia, pruritus, rash, scar, sensitivity, soreness, stinging, tenderness
Neuromuscular & skeletal: Back pain, myalgia, rigors
Respiratory: Coughing, pharyngitis, rhinitis, sinusitis
Miscellaneous: Herpes simplex, influenza-like syndrome, lymphadenopathy, squamous cell carcinoma, tinea cruris
Postmarketing and/or case reports (limited to important and/or life-threatening): Abdominal pain, agitation, anemia, angioedema, arrhythmias (atrial fibrillation, palpitations, tachycardia), arthralgia, capillary leak syndrome, cardiac failure, cardiomyopathy, cerebrovascular accident, cheilitis, chills, depression, dyspnea, erythema multiforme, exfoliative dermatitis, dysuria, Henoch-Schönlein purpura syndrome, herpes zoster, hyperpigmentation, hypertrophic scar, idiopathic thrombocytopenia purpura, insomnia, ischemia, lethargy, leukopenia, liver function abnormal, lymphoma, MI, multiple sclerosis aggravated, pancytopenia, paresis, proteinuria, psoriasis (onset or exacerbated), pulmonary edema, seizure, spondyloarthropathy (onset or exacerbated), syncope, thrombocytopenia, thyroiditis, tingling, ulcerative colitis (onset or exacerbated), urinary retention, urticaria
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Storage
Aldara®: Store at 4°C to 25°C (39°F to 77°F); do not freeze.
Zyclara® 3.75%: Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze.
Mechanism of Action
Precise mechanism of action is unknown; Toll-like receptor 7 agonist that induces cytokines, including interferon-alpha and others
Pharmacodynamics/Kinetics
Absorption: Minimal; systemic absorption more dependent upon surface area of application as opposed to dose
Time to peak: 9 hours
Excretion: Urine (≤2% of applied dose as imiquimod and metabolites)
Dosage
Topical: Note: A rest period of several days may be taken if required by the patient's discomfort or severity of the local skin reaction. Treatment may resume once the reaction subsides. Imiquimod treatment should not be prolonged beyond recommended period due to missed doses or rest periods.
Children ≥12 years and Adults (Aldara®): External genital and/or perianal warts/condyloma acuminata: Apply a thin layer 3 times/week prior to bedtime and leave on skin for 6-10 hours. Remove with mild soap and water. Examples of 3 times/week application schedules are: Monday, Wednesday, Friday; or Tuesday, Thursday, Saturday. Continue treatment until there is total clearance of the warts (maximum duration of therapy: 16 weeks).
Adults:
Aldara®:
Actinic keratosis: Apply twice weekly for 16 weeks to a treatment area on face or scalp (but not both concurrently); no more than 1 packet should be applied at each application and no more than 36 packets applied per 16 weeks; apply prior to bedtime and leave on skin for 8 hours. Remove with mild soap and water.
Common oral warts (dental use; unlabeled use): Apply once daily prior to bedtime
Common warts (unlabeled use): Apply once daily prior to bedtime for 5 days/week for up to 16 weeks (Hengge, 2000) or apply twice daily for up to 24 weeks (Grussendorf-Conen, 2002)
Superficial basal cell carcinoma: Apply once daily prior to bedtime, 5 days/week for 6 weeks. No more than 36 packets should be used during the 6-week treatment period. Treatment area should include a 1 cm margin of skin around the tumor. Leave on skin for 8 hours. Remove with mild soap and water.
Zyclara® 3.75%: Actinic keratosis: Treatment consists of 2 cycles (14 days each) separated by 1 rest period (14 days) with no treatment. Apply up to 2 packets once daily at bedtime to affected area on either face or balding scalp (but not both concurrently); apply no more than 2 packets at each application and no more than 56 packets per 2 cycles of treatment. Leave on skin for 8 hours. Remove with mild soap and water. Note: Canadian labeling recommends avoiding application to areas larger than the face or balding scalp (~200 cm2).
Administration: Topical
Topical: Wash hands prior to and following application. Do not occlude the application site. Partially used packets should be discarded and not reused.
Actinic keratosis: Apply Aldara® over a single contiguous area (approximately 25 cm2) on the face or scalp or Zyclara® 3.75% over an area <200 cm2 on the face or scalp; the treatment area should be washed and thoroughly dried prior to application. Both areas should not be treated concurrently. Apply a thin layer to the affected area and rub in until the cream is no longer visible. Avoid contact with the eyes, lips, and nostrils.
External genital warts: Aldara®: Instruct patients to apply to external or perianal warts; not for vaginal use. Apply a thin layer to the wart area and rub in until the cream is no longer visible. Single-use packets contain sufficient cream to cover a wart area of up to 20 cm2; avoid use of excessive amounts of cream. Nonocclusive dressings (such as cotton gauze or cotton underwear) may be used in the management of skin reactions.
Superficial basal cell carcinoma: Aldara®: Treatment area should have a maximum diameter no more than 2 cm on the trunk, neck, or extremities (excluding the hands, feet, and anogenital skin). Treatment area should include a 1 cm margin around the tumor. Wash and thoroughly dry treatment area prior to application; apply a thin layer to the affected area (and margin) and rub in until the cream is no longer visible. Avoid contact with the eyes, lips, and nostrils.
Monitoring Parameters
Reduction in lesion size is indicative of a therapeutic response; patients should be monitored for signs and symptoms of hypersensitivity to imiquimod
Patient Education
This medication will not eliminate nor prevent the transmission of the virus. For external use only; avoid contact with eyes, mouth, nostrils, or vagina. Exposure to sun should be avoided or minimized. Use sunscreen or wear protective clothing if sun exposure is unavoidable. Sexual contact (vaginal, anal, or oral) should be avoided while cream is on skin. May cause pain, itching, redness, burning, flaking, swelling, or scabbing in treated area. If these effects persist or become severe or open sores develop, stop treatment and notify prescriber. Report fever, malaise, myalgia, or flu-like symptoms. Prescriber may recommend a rest period of several days before resuming treatment. Apply treatment just prior to sleeping and leave on 6-10 hours. Wash hands thoroughly before and after application. Wash and dry area to be treated before applying cream. After treatment period, remove cream with mild soap and water. Apply a thin layer to external warts and rub in until cream is no longer visible. Avoid use of excessive cream. May cover area with light gauze dressing or cotton underwear; do not apply occlusive dressing.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
Imiquimod cream 5% has been used for actinic cheilitis or keratosis. Imiquimod 3.75% cream is FDA approved to treat actinic keratosis. Adverse events of erosion/ulcerations have been reported with topical use. Imiquimod use in the treatment of oral papilloma virus remains inadequately studied.
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, topical: 5% (24s) [0.25 g/packet]
Aldara®: 5% (24s) [contains benzyl alcohol; 0.25 g/packet]
Zyclara®: 3.75% (28s) [contains benzyl alcohol; 0.25 g/packet]
Pricing: U.S. (www.drugstore.com)
Cream (Aldara)
5% (1): $26.99
Cream (Imiquimod)
5% (1): $35.99
Cream (Zyclara)
3.75% (28): $601.01
References
Centers for Disease Control and Prevention (CDC), "Sexually Transmitted Diseases Treatment Guidelines, 2010," MMWR Recomm Rep, 2010, 59(RR-12):1-110.
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):390-8.
Goldgeier M, Fox CA, Zavislan JM, et al, “Noninvasive Imaging, Treatment, and Microscopic Confirmation of Clearance of Basal Cell Carcinoma,” Dermatol Surg, 2003, 29(3):205-10.
Grussendorf-Conen EI, Jacobs S, Rubben A, et al, “Topical 5% Imiquimod Long-Term Treatment of Cutaneous Warts Resistant to Standard Therapy Modalities,” Dermatology, 2002, 205(2):139-45.
Hengge UR, Esser S, Schultewolter T, et al, “Self-Administered Topical 5% Imiquimod for the Treatment of Common Warts and Molluscum Contagiosum,” Br J Dermatol, 2000, 143(5):1026-31.
Housman TS and Jorizzo JL, “Anecdotal Reports of 3 Cases Illustrating a Spectrum of Resistant Common Warts Treated With Cryotherapy Followed by Topical Imiquimod and Salicylic Acid,” J Am Acad Dermatol, 2002, 47(4 Suppl):217-20.
Oster-Schmidt C, Altmeyer P, and Stucker M, “Successful Treatment of Basal Cell Carcinoma on the Face With Imiquimod 5% Cream,” Acta Derm Venereol, 2002, 82(6):477.
Shumack S, Robinson J, Kossard S, et al “Efficacy of Topical 5% Imiquimod Cream for the Treatment of Nodular Basal Cell Carcinoma: Comparison of Dosing Regimens,” Arch Dermatol, 2002, 138(9):1165-71.
Swanson N, Abramovits W, Berman B, et al, “Imiquimod 2.5% and 3.75% for the Treatment of Actinic Keratoses: Results of Two Placebo-Controlled Studies of Daily Application to the Face and Balding Scalp for Two 2-Week Cycles,” J Am Acad Dermatol, 2010, 62(4):582-90.
Tyring S, Conant M, Marini M, et al, “Imiquimod; An International Update on Therapeutic Uses in Dermatology,” Int J Dermatol, 2002, 41(11):810-6.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
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