Clarissa Marie Arce

Ease and Efficacy versus Warts and sBCC* *Superficial Basal Cell Carcinoma Sexually active individuals are prone to infections caused by the human papillomavirus (HPV) - external genital warts (EGW) and superficial basal cell carcinomas (sBCC). External genital wart, also known as condylomata acuminata (CA), is one of the most common forms of sexually transmitted diseases affecting the general population.1,2 Easy and effective remedy for EGW Imiquimod (Aldara™), a topical immune response modifier, enhances both the innate and acquired immune responses versus skin viruses and cancers.3 Imiquimod (Aldara™) is a recommended non-invasive treatment for EGW and sBCC.4-8 Treatment of Patient With Genital Warts Genital warts diagnosed. Provide patient education and counselting. Assess wart size, location, and, morphology. ≤10 warts Wart area 0.5 to 1.0 cm2 Treat based on patient and physician preferences: • Patient-applied therapy with podofilox (Condylox) or Imiquimod (Aldara) is preferred. • Cryotherapy if patient prefers. • Podophyllin, TCA, laser, or surgical excision for warts not responding to treatment. >10 warts Wart area > 1.0 cm2 Non-keratinized warts on moist surfaces: • Patient-applied therapy with podofilox or Imiquimod (Aldara) is preferred. • Podophyllin or TCA for warts not respnding to treatment. Keratinized warts on dry surfaces: • Cryotherapy, surgical excision, or other ablative procedure is preferred. Large keratinized warts: > 10 mm in diameter Treat based on patient and physician preferences: • Surgical excision as primary therapy. • Consider pre-treatment with Imiquimod (Aldara) to reduce wart size prior to excision. TCA = trichloroacetic acid Vaginal, anal, or cervical warts: Exclude squamous intraepithelial lesions before treatment for vaginal or cervical warts. Treat based on guidelines and patient and physician preferences: • Cryotherapy with liquid nitrogen is preferred. • TCA if patient or physician prefers. Adapted from reference 2 Even with various therapies, such as cryotherapy, laser, and surgical excision, recurrence of warts commonly occur within 3 months in up to 67% of patients.1,2 Compared to more invasive and expensive regimens, Imiquimod (Aldara™) is a well-tolerated and cost-effective treatment that prevents wart recurrence.2 Comparison of Treatments for Genital Warts Treatment Adverse effects and their incidence (%)* Cryotherapy Pain or blisters at application site (20) Imiquimod (Aldara) Erythema (70), irritation, ulceration and pain (< 10); burning, erosion, flaking, edema, induration, and pigmentary changes at application site: minimal systemic absorption Burning, itching, and irritation at injection site: systemic myalgias, headaches, fever, chills, leukopenia, elevated transaminase levels (6), thrombocytopenia (1) Interferon (Intralesional) Similar to surgical excision; risk for spreading human papillomavirus via smoke plumes Laser treatment Podofilox (Condylox) Burning at application site (75), pain (50), inflammation (70); low risk for systemic toxicity Local irritation, erythema, burning, and soreness at application site (75); possibly mutagenicity, oncogenicity. Pain (100), bleeding (40), scarring (10); risk for burning and allergic reaction from local anesthetic Surgical excision Trichloroacetic acid Placebo Local pain and irritation; no systemic side effects ↕ Clearance rate (%) Risk of recurrence (%)↑ 60 to 90 20 to 40 30 to 50 15 20 to 60 ↕ 25 to 50 5 to 50 45 to 80 5 to 30 30 to 80 20 to 65 35 to 75 20 50 to 80 35 0 to 55 ↕ * - Rates of adverse effects are not compared with rates for placebo ↑ - Recurrence rates are approximated from ranges identified in references. Time until recurrence varies across studies, but recurrence rates typically are measured at three months after treatment ↕ - insufficient data Adapted from reference 2 EASY Home Applica�on (for EGW) 1 3 Wash hands and treatment area with mild soap and water and allow to dry thoroughly. Rub in cream thoroughly and leave undisturbed overnight (6 to 10hrs). 2 Dosage Instruc�ons Apply thin layer of cream to the affected area at bed�me 3 �mes per week (e.g. Mon, Wed, Fri) un�l wart has cleared or up to 16 weeks. 4 Indica�on Dosing Dura�on External Genital Warts and Perianal Warts Once a day; 3 �mes per week e.g.: Mon / Wed / Fri or Sun / Tue / Thurs Total wart clearance or maximum of 16 weeks Once a day, 5 �mes per week e.g.: 6 weeks (condyloma acuminata) Wash cream off with mild soap and water upon waking. Avoid ge�ng Aldara™ cream in or near eyes lips or nostrils. Superficial Basal Cell Carcinoma Monday through Friday Clinical trial efficacy and safety results are based on single-use sachets for approved indica�ons. First-line non-invasive treatment option for sBCC BCC Treatment Strategy Low-risk BCC Superficial Nodular First-Line Treatment: First-Line Treatment: • Surgery (3-4 mm) • Imiquimod • PDT • Cryosurgery • Curettage • Laser • Surgery (3-4 mm) • Curettage High-risk BCC Pluridisciplinary committee Intermediary-risk BCC Second-Line Treatment: • Cryotheraphy • PDT • Imiquimod Surgery Possible First-Line Treatment: • Surgery (margins > 4 mm) • Mohs Surgery •2-step Surgery Second-Line Treatment: If surgery not possible (4 mm) • Radiotheraphy Third Line Treatment: Surgery Not Possible First-Line Treatment: • Mohs Surgery • 2-step surgery Second-Line Treatment: • Surgery (margins 510mm) • Radiotheraphy • Chimiotheraphy • Cryotheraphy • PDT • Imiquimod PDT = photodynamic therapy Adapted from reference 7. Success Rate Imiquimod Surgery 3-Year 83.6% (178/213) 98.4% (185/188) 5-Year 82.5% (170/206) 97.7% (173/177) relative risk of imiquimod success = 0.84, 95% confidence interval = 0.77-0.91, P < 0.001. "The absolute response rate for topical imiquimod of 83% at five years, although clearly inferior to the 98% for excisional surgery for low-risk BCC, might still represent a clinically useful treatment modality, because a cream treatment can be carried out in a primary care setting, and some patients may also prefer the option of a cream rather than surgery." - Hywel C. Williams, DSc, FMedSci, NIHR Senior Investigator, Professor of Dermato-Epidemiology and Co-Director of the Centre of Evidence-Based Dermatology at the University of Nottingham, Nottingham, UK.11 References: 1. Kodner C and Nasraty S. Management of genital warts. Am Fam Physician. 2004;70(12):-. Scheinfeld N and Lehman D. An evidence-based review of medical and surgical treatments of genital warts. Dermatol Online J. 2006;12(3):5. 3. Sapijaszko MJA. Imiquimod 5% cream (Aldara®) in the treatment of basal cell carcinoma. Skin Therapy Letter. Available at: http://www.skintherapyletter.com/2005/10.6/1.html. Accessed December 19, 2017. 4. Moore RA, et al. Imiquimod for the treatment of genital warts: a quantitative systematic review. BMC Infect Dis. 2001;1:3. 5. Karnes JB, Usatine RP. Management of external genital warts. Am Fam Physician. 2014;90(5):312-8. 6. Anogenital warts. 2015 Sexually transmitted diseases treatment guidelines. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/std/tg2015/warts.htm. Accessed December 19, 2017. 7. van der Meijden WI, et al. 2016 European guideline for the management of vulval conditions. European Academy of Dermatology and Venereology. Available at: https://www.iusti.org/regions/europe/pdf/2017/Vulvalconditions.pdf. Accessed December 19, 2017. 8. Bichakjian C, et al. Basal cell skin cancer, version 1.2016. Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. J Natl Compr Canc Netw. 2016;14:574-97. 9. Trakatelli M, et al. Update of the European guidelines for basal cell carcinoma management developed by the Guideline Subcommittee of the European Dermatology Forum. Eur J Dermatol. 2014;24(3):-. Williams HC, et al. Surgery versus 5% imiquimod for nodular and superficial basal cell carcinoma: 5-year results of the SINS randomized controlled trial. J Invest Dermatol. 2017;137(3):614-9. 11. Elsevier. Topical skin cream for treatment of basal cell carcinoma shows promise as an alternative to surgery. Science Daily. Available at: https://www.sciencedaily.com/releases/2016/12/-.htm. Accessed December 19, 2017. Please review Product Informa�on before prescribing. Product Informa�on available upon request from iNova Pharmaceu�cals. ABRIDGED PRESCRIBING INFORMATION: Imiquimod (Aldara™) Cream INDICATIONS AND USAGE: Treatment of external genital and perianal warts/condyloma acuminata in individuals 12 years old and above. Topical treatment of biopsy-confirmed, primary superficial basal cell carcinoma (sBCC) in immunocompetent adults, with a maximum tumor diameter of 2.0 cm, located on the trunk (excluding anogenital skin), neck, or extremi�es (excluding hands and feet), only when surgical methods are medically less appropriate and pa�ent follow-up can be reasonably assured. CONTRAINDICATIONS: Individuals with a history of sensi�vity reac�ons to any of its components. It should be discon�nued if hypersensi�vity to any of its ingredients is noted. PRECAUTIONS: Local skin reac�ons such as erythema, erosion, excoria�on/flaking, and edema are common. Should severe local skin reac�on occur, the cream should be removed by washing the treatment area with mild soap and water. Treatment with Aldara cream can be resumed a�er the skin reac�on has subsided. Aldara cream administra�on is not recommended un�l genital/perianal �ssue is healed from any previous drug or surgical treatment. Aldara cream has a poten�al to exacerbate inflammatory condi�ons of the skin. The safety and efficacy of trea�ng superficial basal cell carcinoma (sBCC) lesions on the face, head and anogenital area have not been established. The efficacy and safety of Aldara cream have not been established for pa�ents with Basal Cell Nevus Syndrome or Xeroderma Pigmentosum. INFORMATION FOR PATIENTS: General Informa�on: 1. This medica�on is to be used as directed by a physician. It is for external use only. Eye contact should be avoided. 2. The treatment area should not be bandaged or otherwise covered or wrapped as to be occlusive. 3. Some reports have been received of localized hypopigmenta�on and hyperpigmenta�on following Aldara cream use. Follow-up informa�on suggests that these skin color chages may be permanent in some pa�ents. Pa�ents Being Treated for External Genital Warts: 1. It is recommended that the treatment area should be washed with mild soap and water 6-10 hours following Aldara cream applica�on. 2. It is common for pa�ents to experience local skin reac�ons: erythema, erosion, excoria�on/flaking and edema at the site of applica�on or surrounding areas. Most skin reac�ons are mild to moderate. Severe skin reac�ons can occur and should be promptly reported to the prescribing physician. Should severe local skin reac�on occur, the cream should be removed by washing the treatment area with mild soap and water. Treatment with Aldara cream can resumed a�er the skin reac�on has subsided. 3. Sexual (genital, anal, oral) contact should be avoided while the cream is on the skin. 4. Applica�on of Aldara cream in the vagina is considered internal and should be avoided. Female pa�ents should take special care if applying the cream at the opening of the vagina because local skin reac�ons on the delicate moist surfaces can result in pain or swelling, and may cause difficulty in passing urine. 5. Uncircumcised males trea�ng warts under the foreskin should retract the foreskin and clean the area daily. 6. Pa�ents should be aware that new warts may develop during therapy, as Aldara cream is not a cure. 7. The effect of the Aldara cream on the transmission of genital/perianal warts is unknown. 8. Aldara cream may weaken condoms and vaginal diaphragms, therefore concurrent use is not recommended. Pa�ents Being Treated for Superficial Basal Cell Carcinoma: 1. It is recommended that the treatment area be washed with mild soap and water 8 hours following Aldara cream applica�on. 2. Most pa�ents using Aldara cream for the treatment of sBCC experience erythema, edema, indura�on, erosion, scabbing/crushing and flaking/scaling at the applica�on with normal dosing. These local skin reac�ons generally decrease in intensity or resolve a�er cessa�on of Aldara cream therapy. Pa�ents may also experience applica�on site reac�ons such as itching and/or burning. Local skin reac�ons may be of such an intensity that pa�ents may require rest periods from treatment. Treatment with Aldara cream can be resumed a�er the skin reac�on has subsided, as determined by the physician. 3. During treatment and un�l healed, affected skin is likely to appear no�ceably different from normal skin. 4. It is prudent for pa�ents to minimize or avoid exposure to natural or ar�ficial sunlight. 5. The clinical outcome of the therapy can be determined a�er regenera�on of the treated skin, approximately 12 weeks a�er the end of treatment. 6. Pa�ents should contact their physician if they experience any sign or symptom at the applica�on site that restricts or prohibits their daily ac�vity or makes con�nued applica�on of the cream difficult. 7. Pa�ents with sBCC treated with Aldara cream are recommended to have regular follow-ups to re-evaluate the treatment site. USE IN PREGNANCY: There are no adequate and well-controlled studies in pregnant women. Aldara cream is not recommended for use during pregnancy. USE IN LACTATION: Aldara cream is not recommended for use during lacta�on. It is unknown whether topically applied imiquimod is excreted in breastmilk. ADVERSE EFFECTS: The most commonly reported adverse reac�ons are edema, erosion, erythema, flaking/scaling, indura�on, scabbing/crushing, ulcera�on and vesicles. Applica�on site disorders: Wart Site Reac�ons (burning, hypopigmenta�on, irrita�on, itching, pain, rash, sensi�vity, soreness, s�nging, tenderness); Remote Site Reac�ons: (bleeding, burning, itching, pain, tenderness, �nea cruris); Body as a Whole: fa�gue, fever, influenza-like symptoms; Central and Peripheral Nervous System Disorders: headache; Gastrointes�nal System Disorders: diarrhea; Musculoskeletal System Disorders: myalgia. DRUG INTERACTION: It is unlikely that drug interac�ons will occur since imiquimod has limited systemic availability when applied topically. DOSAGE AND ADMINISTRATION: External Genital Warts: Aldara cream is applied 3 �mes per week, prior to normal sleeping hours, and le� on the skin for 6 to 10 hours. Aldara cream treatment should con�nue un�l there is total clearance of the genital/perianal warts or for a maximum of 16 weeks. Local skin reac�ons (erythema) at the treatment site are common. A rest period of several days may be taken if required by the pa�ent’s discomfort or severity of the local skin reac�on. Treatment may resume once the reac�on subsides. Superficial Basal Cell Carcinoma: Aldara cream should be applied 5 �mes per week for six weeks to a biopsy-confirmed superficial basal cell carcinoma. The target tumor should have a maximum diameter of no more than 2 cm and be located on the trunk (excluding anogenital skin), neck or extremi�es (excluding hands and feet). The treatment area should include a 1 cm margin of skin around the tumor. Aldara cream is to be applied 5 �mes per week, prior to normal sleeping hours, and le� on the skin for approximately 8 hours. Before applying the cream, the pa�ent should wash the treatment area with mild soap and water and allow the area to dry thoroughly. Sufficient cream should be applied to cover the treatment area, including one cen�meter of skin surrounding the tumor. A thin layer is applied to the wart/treatment area and rubbed in un�l the cream is no longer visible. The applica�on site is not to be occluded. Following the treatment period, cream should be removed by washing the treatment area with mild soap and water. Hand washing before and a�er the cream applica�on is recommended. AVAILABLE FORMS: 50mg/g (5%) cream supplied in boxes of 12 single-use sachets or packets each containing 250mg of the cream. ROUTE OF ADMINISTRATION: Topical. SPECIAL PATIENT GROUPS: Pediatric use: Safety and efficacy in pa�ents with external genital/perianal warts below the age of 12 years have not been established, sBCC is not generally seen within pediatric popula�on. The safety and efficacy of Aldara cream for sBCC in pa�ents less than 18 years of age have not been established. Geriatric use: No other clinical experience has iden�fied differences in responses between the elderly and younger pa�ents, but greater sensi�vity of some older individuals cannot be ruled out. Aldara cream is not recommended for use during pregnancy or lacta�on. Manufactured by: 3M Healthcare Limited Derby Road, Loughborough, Leicestershire, LE11 5SF, United Kingdom For: iNova Pharmaceu�cals (Aust) Pty Ltd. 9-15 Chilvers Road, Thornleigh, NSW 2120 Australia Imported and Distributed by: Metro Drug Inc. Compound Mañalac Ave., Bagumbayan, Taguig City Philippines 1632 Addi�onal informa�on is available upon request from