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****** DATA-MÉDICOS ******

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EL IMIQUIMOD  I/ THE IMIQUIMOD

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***** DERMAGIC-EXPRESS No. 6 ****

****** 21 OCTUBRE DE 1.998 ******* 

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EDITORIAL ESPAÑOL

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El imiquimod (imidazoquinolinamine), nombre comercial ALDARA, es producido por 3MPharmaceutical y fue aprobado por la FDA de los Estados Unidos en febrero de 1.997para el tratamiento de las verrugas anogenitales, es un modificador de la respuesta inmunológica y tiene actividad antitumoral: eleva los niveles del factor de necrosis tumoral(TNF), e induce la producción de interferón (INF) alfa, los primeros estudios que encontré datan de 1.992, con el nombre de R-837, En noviembre 1.997 STAURT MADDIN hace una revisión del producto, en enero de 1.998 se publica un artículo sobre su efectividad en verrugas genitales, luego se encontro ser efectivo en queratosis actínicas, seborreicas y molusco contagioso.

Este producto hay que manejarlo con mucho detalle y cuidado, pues su principal efecto secundario son quemaduras en el sitio de colocación que pueden dejar ulceraciones. 

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DERMAGIC/EXPRESS(6)

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E L  I M I Q U I M O D  / THE IMIQUIMOD 

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REFERENCIA 1: imiquimod y citoquinas

REFERENCIA 2: imiquimod, actividad antitumoral

REFERENCIA 3: imiquimod, actividad antitumoral

REFERENCIA 4: imiquimod, actividad antitumoral

REFERENCIA 5: imiquimod, actividad antiviral

REFERENCIA 6: imiquimod, antivirales en dermatologia

REFERENCIA 7: imiquimod en la WEB: Aldara Cream Effective For Genital Warts 

REFERENCIA 8: imiquimod, Self-administered Topical 5% Imiquimod Cream for External Anogenital Warts, Archivos Dermatología, Enero 1.998. 

REFERENCIA 9: imiquimod y verruga genital

REFERENCIA 10: imiquimod y papiloma virus

REFERENCIA 11: imiquimod: Revision, THE SKIN THERAPY LETTER, STUART MADDIN.

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1.) TI: Cytokine induction in mice by the immunomodulator imiquimod

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AU: Reiter-MJ; Testerman-TL; Miller-RL; Weeks-CE; Tomai-MA

AD: 3M Pharmaceuticals, 3M Center 270-2S-06, St. Paul, MN 55144, United States

SO: J-LEUKOCYTE-BIOL. 55/2 (234-240) 1994

CO: JLBIE

PY: 1994

LA: English

CP: United-States

PT: Journal-Article

AB-A: Imiquimod has been identified as a potent antiviral and antitumor agent in animal models. The biological activity associated with imiquimod has been attributed to its induction of interferon (IFN)-alpha . The present studies evaluated imiquimod administered orally for its ability to stimulate production of IFN and other cytokines in mice. The cytokine profile induced by imiquimod was compared with other known immunomodulators. Imiquimod was found to stimulate increased serum IFN in mice. Daily dosing of imiquimod for five consecutive days led to diminished production of IFN in mice as measured after the final dose. Elevated levels of serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 but not IL-1 alpha were found in serum from mice treated with imiquimod. Imiquimod produced significantly higher levels of IFN but lower levels of TNF and IL-6 and IL-1 alpha than lipopolysaccharide. Polyinosinic acid:polycytidylic acid induced significantly higher amounts of IFN but lower levels of TNF and IL-6 than imiquimod. Imiquimod stimulated significantly higher levels of IFN when compared with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and similar levels of IFN when compared with tilorone. Neither ABPP nor tilorone-induced TNF or IL-6. Finally, imiquimod stimulated TNF, IFN, and IL-6 production in cultures of mouse spleen and bone marrow cells. These studies demonstrate that imiquimod induces not only IFN but other cytokines as well, all of which may contribute to its biological activity. 

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2.) TI: Curative effectiveness of the interferon-inducing imiquimod asa single agent in mouse bladder tumors (Meeting abstract).

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AU: Sidky-YA; Borden-EC; Weeks-CE

AD: Cancer Center, Medical Coll. of Wisconsin, Milwaukee, WI 53226

SO: Proc-Annu-Meet-Am-Assoc-Cancer-Res. 34:A2789 1993

PY: 1993

LA: ENGLISH

PT: MEETING-ABSTRACT

AB-A: 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (imiquimod) is a low mol wt oral inducer of interferon-alpha. Treatment with imiquimod reduced the growth of MC-26 colon carcinoma, RIF-1 sarcoma and B16-F10 melanoma. Treatment with 150 mg/kg imiquimod on days 1, 5, 9, 13, and 17 cured 90% of C57BL/6 mice inoculated sc with FCB bladder carcinoma. Oral imiquimod was also effective in curing another mouse bladder tumor, MB49. Tumors continued to grow until about day 15 when they started to regress and totally disappeared by day 25. Cured mice remained tumor-free for 100 days when experiments were terminated. MB49 was also instilled by transurethral catheter in the bladder. In one experiment mice were sacrificed on day 17. Bladders of all vehicle-treated mice had visible tumors of different sizes; 4/6 of the imiquimod-treated mice had no visible tumors and the remaining two had small tumor remnants. Bladders of vehicle-treated mice were significantly heavier than those of mice treated with imiquimod 50.3 vs 31.7 mg (p less than 0.05). Imiquimod as a single agent is curative for murine bladder tumors. (Abstract from CANCERLIT)

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3.) TI: Phase I trial of an oral immunomodulator and interferon inducer in cancer patients

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AU: Witt-PL; Ritch-PS; Reding-D; McAuliffe-TL; Westrick-L; Grossberg-SE; Borden-EC

AD: Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-4801, United States

SO: Cancer-Res. 53(21):5176-80 1993

CO: CNREA

PY: 1993

LA: ENGLISH

CP: United-States

PT: CLINICAL-TRIAL; CLINICAL-TRIAL,-PHASE-I; JOURNAL-ARTICLE

AB-A: Imiquimod [1-(2-methylpropyl)-1H-imidazo[4,5c]quinolin-4-amine] is a compound of low molecular weight that, when administered p.o., induces interferon-alpha in several animal species and inhibits tumor growth in mice. To determine maximum tolerated dose, toxicity, and biological response in humans, a phase I clinical trial was conducted with 14 eligible cancer patients who received 100-500 mg imiquimod p.o. either once or twice weekly. Imiquimod induced interferon-alpha in serum in 10 of 19 doses of 200-300 mg. Interferon serum levels peaked 8-24 h after treatment and reached a maximum of 23,000 IU/ml in one patient. Significant mean increases (P < 0.01) in serum beta 2-microglobulin (1.5-fold), serum neopterin (3.5-fold), and 2-5A synthetase activity in peripheral blood mononuclear cells (7.9-fold) indicated that 200-300 mg imiquimod had biological and immunological activity in all evaluable patients. Increases in serum interferon, beta 2-microglobulin, and neopterin correlated significantly with dose (P < 0.001). No patient developed measurable antibody to interferon-alpha. Dose-limiting side effects included fatigue, malaise, fever, headache, and lymphocytopenia; no hepatic or renal toxicity or other hematological changes exceeded the normal range. Patients tolerated weekly doses of up to 500 mg, with the longest treatment lasting 4 weeks at 200 mg weekly. Twice-weekly doses up to to 300 mg were tolerated, with the longest twice-weekly treatments being 200 mg for 9 weeks and 100 mg for 25 weeks. No clinical responses were observed. Imiquimod, as an oral inducer of interferon, may have therapeutic usefulness in human cancers, viral infections, and other diseases. However, before initiation of phase II trials, additional work will be required to establish a tolerated dose and schedule for continued administration. (Abstract from CANCERLIT AND EMBASE)

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4.) TI: Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine

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AU: Sidky-YA; Borden-EC; Weeks-CE; Reiter-MJ; Hatcher-JF; Bryan-GT

AD: Cancer Center, Medical College of Wisconsin, 8901 Watertown Plank Road, Milwaukee, WI 53226, United States

SO: Cancer-Res. 52(13):3528-33 1992

CO: CNREA

PY: 1992

LA: ENGLISH

CP: United-States

PT: JOURNAL-ARTICLE

AB-A: The low-molecular-weight imidazoquinolinamine derivative, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (imiquimod, previously described as R-837), induced alpha-interferon (IFN-alpha) in mice. IFN induction was identified at oral doses as low as 3 mg/kg. The 10% lethal dose for daily treatment with imiquimod was 200 mg/kg. Oral treatment with 30 mg/kg imiquimod once every three days significantly inhibited MC-26 colon carcinoma. Delay of treatment from day 1 to day 5, when tumors were easily palpable, did not reduce benefits. Ten daily treatments were slightly more effective than five. However, delivery of the same total dose of imiquimod either once every day for 20 days, once every 4 days, once every 7 days, or once every 10 days inhibited tumor growth to the same level. The antitumor effects of imiquimod were significantly abrogated by an antiserum to murine IFN-alpha, suggesting that the antitumor effect was to a substantial extent mediated by IFN induction. Imiquimod also significantly reduced the number of lung colonies in mice inoculated i.v. with MC-26 tumor cells. Combination of treatment with imiquimod and cyclophosphamide was significantly (P less than 0.01) better than treatment with either drug alone. Combination treatment with cyclophosphamide led to cures in some of the mice inoculated either s.c. or i.v. with MC-26 cells. Treatment with imiquimod also inhibited the growth of RIF-1 sarcoma and Lewis lung carcinoma but was ineffective for P388 leukemia. Imiquimod is an oral IFN-alpha inducer with antitumor effectiveness for transplantable murine tumors. (Abstract from CANCERLIT AND EMBASE)

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5.) TI: Immunomodulating and antiviral activities of the imidazoquinoline S-28463.

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AU: Tomai-MA; Gibson-SJ; Imbertson-LM; Miller-RL; Myhre-PE; Reiter-MJ; Wagner-TL; Tamulinas-CB; Beaurline-JM; Gerster-JF; et-al

AD: Department of Pharmacology, 3M Pharmaceuticals, St. Paul, MN 55144, USA.

SO: Antiviral-Res. 1995 Nov; 28(3): 253-64

ISSN: 0166-3542

PY: 1995

LA: ENGLISH

CP: NETHERLANDS

AB: Recently, a new class of immunomodulating agents, represented by the molecules imiquimod and R-842, has demonstrated potent antiviral and antitumor activities in animal models. In this study, another representative of this class, S-28463 (4-amino-2-ethoxymethyl-alpha,alpha-dimethyl-1H-imidazo[4,5-c]quinoline- 1- ethanol) was evaluated for its immunomodulating and antiviral activities. S-28463 induced IFN and other cytokines in vivo in mice, rats, monkeys and in vitro in human peripheral blood mononuclear cell cultures. S-28463 showed potent antiviral activity against herpes simplex virus-challenged guinea pigs when given subcutaneously, dermally, or intravaginally 24 h before infection. Antiviral activity in guinea pigs correlated with the induction of serum 2',5'-oligoadenylate synthetase activity. Thus, S-28463, like the other imidazoquinolines, demonstrates potent antiviral and immunomodulating effects in a number of models.

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6.) TI: Antiviral agents in dermatology: current status and future prospects.

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AU: Memar-OM; Tyring-SK

AD: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.

SO: Int-J-Dermatol. 1995 Sep; 34(9): 597-606

ISSN: 0011-9059

PY: 1995

LA: ENGLISH

CP: UNITED-STATES

AB: The majority of current antiviral agents have become available only during the past decade. The above mentioned antiviral drugs, especially the viral-TK-specific agents have attempted to bring antiviral therapy on par with antimicrobial therapy. The fact, that cells infected with viruses can be selected against the relatively low toxicity to the patient, highlights the present state of antiviral therapy. Since viral infection can be viewed as an integral component of the self (i.e., a condition that cannot simply be surgically eliminated), the science of medicine is turning to the components of the self to overcome such conditions. By administering immune-system-derived agents (e.g., interferons) or compounds that stimulate the immune system (e.g., adjuvants like imiquimod), previously unmanageable conditions become manageable. The future of antiviral therapy will undoubtedly be at the molecular level. With greater understanding of the virus and the immune system with which it interacts, more specific and efficacious antiviral agents will be added to the arsenal of the clinician.

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7.) Aldara Cream Effective For Genital Warts 

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ST. PAUL, MN -- February 12, 1998 -- Results from a clinical trial show that

Aldara(TM) (imiquimod) cream 5% is a safe, effective treatment for genital warts.

The trial results were published in the January edition of the journal Archives of

Dermatology. In a clinical trial with 311 patients, 72 percent of women and 33 percent of men using 5% Aldara cream achieved total wart clearance after a maximum of 16 weeks compared to 11 percent of patients using vehicle cream. In addition, 72

percent of those who cleared using Aldara and 82 percent of the vehicle group

remained wart clear after 12 weeks.

"This study highlights that Aldara cream, used three times a week, is a safe and

effective patient-applied therapy," said Mary Owens, MD, associate director of

clinical research, 3M Pharmaceuticals.

The newest in a class of drugs called immune response modifiers and

representing the first new therapeutic approach to genital warts in five years,

Aldara was approved by the United States Food and Drug Administration in

March, 1997 and has been available to patients since June, 1997.

Genital warts is a sexually transmitted disease (STD) caused by the human

papillomavirus (HPV). HPV is one of the most common -- and least talked

about -- of all STDs. At least 10 to 20 percent of sexually-active Americans

are thought to be infected. 

Genital warts is growing at a rate of 750,000 new cases each year, is spread

by sexual contact with an infected partner and is highly contagious. This life long

virus can cause warts in the genital and perianal areas in females and males.

Male sexual partners of infected women often have HPV penile infection.

Genital warts may cause itching, burning, pain and tenderness. Although there is

no cure for genital warts, treatment can alleviate physical symptoms and

psychological reactions such as problems with sexuality, shame, embarrassment

and self-blame.

Until recently, most treatment options for genital warts were tissue destructive

Involving chemical agents, procedures such as loop electrocautery excision

(burning), surgery, cryotherapy (freezing) and tissue destructive drugs such as

podofilox and podophyllin.

"Many patients have previously avoided treatment for genital warts because of

fear of chemical and surgical procedures," said Karl Beutner, MD, PhD,

associate clinical professor, University of California, San Francisco and chief

investigator in the clinical trial of Aldara. "Self-administered Aldara cream is an

effective, patient-friendly treatment that can be applied in the privacy of home

to clear up warts."

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8.)Archives of Dermatology Abstracts - January 1998

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Self-administered Topical 5% Imiquimod Cream for External Anogenital Warts 

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Libby Edwards, MD; Alex Ferenczy, MD; Lawrence Eron, MD; David Baker, MD; Mary L. Owens, MD; Terry L. Fox, MS; Andrina J.

Hougham; Kathy A. Schmitt; and the HPV Study Group 

Objective: To compare the safety and effectiveness of 5% and 1%

imiquimod cream with vehicle cream in the treatment of external anogenital warts. 

Design: Randomized, double-blind, placebo-controlled comparison that

evaluated patients for total clearance of their warts. Patients who

experienced total clearance were evaluated for recurrence in a 12-week

follow-up. 

Setting: Eleven ambulatory offices, including both private physician offices

and referral medical centers. 

Patients: Three hundred eleven healthy men and women aged 18 years or

older with 2 to 50 external anogenital warts were recruited from the

practices of investigators, referring physicians, and advertisements.

Eighty-two additional patients were screened but did not qualify. Four

patients discontinued use of the medication because of adverse effects. 

Interventions: Five percent imiquimod (Aldara) cream, 1% imiquimod

cream, or vehicle cream was applied to all external warts overnight 3 times

each week for 16 weeks, or until all treated warts disappeared, whichever

occurred first. 

Main Outcome Measurements: The number of patients experiencing the

elimination of all baseline warts and the recurrence rate of these warts. In

addition, the reduction in baseline wart area, the duration of therapy required

To eliminate warts, and the frequency and severity of adverse reactions were

principal measurements. 

Results: In the intent-to-treat analysis, 54 (50%) of 109 patients who

received 5% imiquimod cream, 21 (21%) of 102 of those who received 1%

imiquimod cream, and 11 (11%) of 100 patients treated with vehicle cream

experienced eradication of all treated baseline warts. The difference between

the effectiveness of 5% imiquimod cream and the vehicle cream was

statistically significant (P<.001). Of those patients whose warts cleared

during therapy, 13% of patients who received 5% imiquimod experienced a

recurrence of at least 1 wart. Recurrences occurred in none of the patients

who used 1% imiquimod cream and in 10% of patients who used the vehicle

cream. Local erythema was the most common adverse reaction, but the

majority of patients in each group experienced no or only mild local

inflammatory reactions. There were no differences in incidences of flulike

symptoms among treatment groups. 

Conclusions: Five percent imiquimod cream is an effective and safe

self-administered therapy for external anogenital warts when applied 3 times

a week overnight for up to 16 weeks. The recurrence rate is low. 

Arch Dermatol. 1998;134:25-30

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9.) Therapeutic approaches to genital warts.

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Beutner KR; Ferenczy A Department of Dermatology, University of California at San Francisco, USA.

Am J Med (UNITED STATES) May 5 1997 102 (5A) p28-37 ISSN: 0002-9343

Language: ENGLISH

Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 

Journal Announcement: 9710

Subfile: AIM; INDEX MEDICUS

Although many treatments are available for genital warts caused by human 

papillomavirus (HPV), none are uniformly successful in the treatment of this disease. 

Most current treatment options work by destroying affected tissue, either by a 

cytotoxic or a physically ablative mode of action. Interferons have antiviral, 

antiproliferative, and immunomodulatory activities, but these have not translated 

into a high level of cure rates against warts. With all current treatments, 

recurrent warts are common. Therapies currently being investigated include a 5-

fluorouracil/epinephrine collagen gel that achieves high concentrations of 5-

fluorouracil at the site of injection. Other new treatment modalities focus on 

activating the host's immune system or improving the delivery of therapeutic 

compounds to the affected site. Imiquimod, a novel immune-response modifier, induces 

interferon and a number of other endogenous cytokines. A cream formulation 

containing 5% imiquimod resulted in good total clearance rates and generally 

tolerable side effects in controlled clinical trials of patients with external 

genital warts. Perhaps the most effective means for managing HPV disease would be a 

vaccine that prevents the occurrence of genital warts. Although it is unlikely that 

such a vaccine will be introduced in the near future, preliminary studies indicate 

that it may be possible to develop suitable prophylactic and therapeutic vaccines. 

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10.) Therapeutic approaches to papillomavirus infections.

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Baker GE; Tyring SK

Department of Dermatology, Microbiology/Immunology, University of Texas Medical 

Branch, Galveston, USA.

Dermatol Clin (UNITED STATES) Apr 1997 15 (2) p331-40 ISSN: 0733-8635

Language: ENGLISH

Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 

Journal Announcement: 9708

Subfile: INDEX MEDICUS

Human papillomaviruses (HPVs) cause benign tumors (i.e., warts) and are 

occasionally responsible for malignant tumors such as squamous-cell carcinomas. 

Therapy for most warts is commonly via surgical or cytodestructive methods. 

Presently, only one antiviral/immunomodulatory drug is available for wart therapy; 

this agent, interferon alpha (IFN alpha), is approved only for genital warts 

(condylomata acuminata) and is expensive, relatively difficult to use, associated 

with systemic side effects, and somewhat slow acting. Two new 

antiviral/immunomodulatory drugs, imiquimod and cidofovir, have been proved to be 

effective and able to overcome many of the shortcomings of IFN alpha. While these 

two agents are pending approval, other treatments are being evaluated, such as 

antisense oligonucleotides and therapeutic HPV vaccines. In contrast to surgical and 

cytodestructive therapies, the goal of these new antiviral/immunomodulatory agents is 

not just to remove the tumor but also to reduce sufficiently the amount of latent and 

subclinical HIV so as to reduce the rate of recurrence. (71 References)

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11.) Imiquimod THE SKIN THERAPHY LETTTER STUART MADDIN

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Imiquimod cream 5% (Aldara R, 3M Pharmaceuticals) was approved by

the FDA February, 1997 for the treatment of external genital and perianal

warts/condyloma acuminata in adults. Anogenital warts are very common, sexually transmitted, virally induced tumors that although benign

themselves, have been associated with the development of squamous cell

carcinoma, particularly cervical carcinoma.1

Imiquimod is an immune response modifier. Studies have shown that it has

potent immunomodulatory effects and stimulates human peripheral mononuclear

cells to release interferon alpha, sub-types alpha1,alpha2, alpha5, alpha6, and alpha8. It also induces monocytes and macrophages to produce other cytokines

including interleukins 1, 6, 8 and tumor necrosis factor alpha.2 The clinical

relevance of these findings is not fully understood.

Imiquimod's advantages 

Low recurrence rate. 

Self-application. 

limited systemic effects and only mild (rarely moderate) local inflammation. 

Previously available treatments (e.g. cryotherapy, laser vaporization,

electrocautery and excision) for anogenital warts are often painful and

expensive. Local therapy with podophyllin, or podophyllotoxin or

trichloracetic acids, requires multiple applications, is slow acting and often causes problems associated with local inflammation.1 5-Fluorouracil, although sometimes used for external anogenital warts, is not yet approved for this

indication, has neither antiviral nor immunomodulatory effects, earlier

formulations were irritating and intralesional injections are painful.3,4

Unfortunately, recurrence often follows cessation of treatment following the use of these therapies.1

Recent reports suggest that multiple injections of interferon alpha produce

clearance rates of 36 - 62% and are well tolerated locally; however, such

treatments are time-consuming, expensive and are associated with systemic side effects.5,6

Efficacy

In early multicenter, double-blind, dose-ranging, vehicle controlled clinical trials,

imiquimod 5% has proven effective in treating anogenital warts. In 311 patients, imiquimod 5% three times weekly completely cleared warts in 50% of patients, compared to 11% clearance in patients treated with the vehicle (p < 0.0001, intent-to-treat analysis). In a subsequent trial, daily application of the 5% cream completely cleared the warts of 52% of patients compared to 3% clearance of

warts in patients using the vehicle alone (p < 0.0001, intent-to-treat analysis). In these two trials, following cessation of treatment, wart recurrence rates were 13% and 19% respectively.7

Combination treatment, using this new topical immunomodulator,

imiquimod, and ablative destructive therapy, is currently under study.8

Although results are not available, it seems logical to combine imiquimod with and ablative therapy so that imiquimod could induce an immune response which has the potential to affect the virus, eliminate residual lesions, and possibly reduce recurrence rates.

Side Effects

The trials discussed above revealed that erythema and increased skin irritation

was the most common reaction and was severe in 4% of both male and female patients

treated three times weekly.9 Other adverse events reported by more than 1% of patients include fatigue, fever, influenza like symptoms, headache, diarrhea, myalgia and fungal infections.9

Safety During Pregnancy & Lactation

There are no adequate and well controlled studies in pregnancy and it is not

known whether topically applied imiquimod is excreted in breast milk.

Pharmacokinetics

Percutaneous absorption was minimal (less than 0.9%) following a single dose,

topical application of 5 mg of imiquimod to the skin of six healthy volunteers.

Dosage and Administration of Imiquimod

Prior to retiring, a thin layer of the cream is applied to the wart area, rubbed in

until cream is no longer visible, left on the skin overnight and then in the morning

washed off with mild soap and water. Hands should be washed before and after

being used to apply the cream. The anogenital warts should be treated three

times per week. For those patients who respond, clearance of warts requires on

average 8 weeks for female patients and 12 weeks for male patients.

Patient Information

Local skin reactions are common but are usually mild to moderate in

severity. Severe skin reactions should be reported to the physician

promptly. Do not occlude the treatment area. Uncircumcised males treating warts

under the foreskin should clean the area daily. 

The cream is for external use. Avoid contact with the eyes. Avoid sexual

(genital, anal, oral) contact while the cream is on the skin. 

Imiquimod cream may weaken condoms and vaginal diaphragms and should not be used concurrently. 

Clinical Assessment

Imiquimod has not yet been compared to any other treatment for anogenital

warts. Podophyllin, the most frequently used topical treatment, is not a

standardised preparation10, has an unknown shelf life10, contains potentially

carcinogenic mutagens and has no known antiviral/immunomodulatory activity.

Imiquimod has no mutagenic activity, is immunomodulatory/antiviral and would

appear to be the drug of choice3 for multiple warts when cryotherapy is

inappropriate and cost is not a problem.

Imiquimod's place in therapy: 

Imiquimod provides a new and practical treatment option to previously

available treatments.10 First line therapy3,8 for patients who do not demand immediate removal of warts - it takes as long as eight weeks and sometimes longer to

achieve clearance of warts. Alternative therapy for persons who have failed another first line treatment and who have experienced recurrences of genital warts. 

A potential component of combination therapy for patients with

large/multiple warts.8 The immune response engendered by imiquimod

may affect the virus, eliminate residual lesions, and possibly reduce

recurrence rates. Applying imiquimod three times per week costs the patient approximately US $100 per month for the cream. 

Preliminary clinical data suggests that this new treatment approach utilizing

imiquimod to treat external genital and perianal warts/condyloma can be

justified on phamacoeconomic grounds.

Dr. Stephen Tyring, Galveston, Texas.

This review was prepared by Rodger Hall, Vancouver.

References

1.Edwards L, Ferenczy A, Eron L. Self-administered 5% imiquimod cream

for external

anogenital warts. Arch Dermatol. In press. 

2.Megyeri K, Au WC, Rosztoczy I et al. Stimulation of interferon and

cytokine gene expression by imiquimod and stimulation by Sendai virus

utilize similar signal transduction pathways. Molecular and Cellular

Biology 1995; 15: 2207-2218. 

3.Tyring SK. Personal communication. August 1997. 

4.Krebs Hans-B. Treatment of genital condylomata with topical

5-fluorouracil. Dermatol Clin 1991; 9: 333-341. 

5.Eron SJ, Judson F, Tucker S et al. Interferon therapy for condyloma

acuminata. N Eng J Med 1986; 315: 1059-1064 

6.Friedman-Kein AE, Eron LJ, Conant M et al. Natural interferon alfa for

treatment of condyloma acuminata. JAMA. 1988; 259: 533-538. 

7.Edwards L, Beutner K, Tyring S et al. Comparison of results from two

vehicle controlled clinical trials evaluating topical imiquimod for the

treatment of genital/perianal warts. Clinical Dermatology 2000,

Vancouver, British Columbia, May 28-31, 1996. 

8.Sauder DN. Personal communication. August 1997. 

9.Physician Packet Insert. 

10.Beutner KR. Personal communication. October, 1997

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DATA-MEDICOS/DERMAGIC-EXPRESS No (6) 21/10/98 DR. JOSE LAPENTA R. 

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Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810