VYLOMA

Adverse Drug Reaction Overview In controlled clinical trials the most frequently observed or reported adverse reactions were local skin and application site reactions, including erythema, edema, erosion/ulceration, weeping/exudate, flaking/scaling/dryness, scabbing/crusting, pain and irritation at the application site; some patients also reported systemic reactions.

The incidence of adverse events, including treatment related and application site reactions, tended to be higher in women than in men. , rest periods, withdrawal from study) were local skin and application site reactions. Both the incidence and severity of local skin reactions were significantly higher for the VYLOMA Cream in comparison to the placebo cream.

5% (126/400) patients treated with VYLOMA took rest periods, with more women taking a rest period than men. 5% (6/400) subjects discontinued the study due to safety reasons. Less than 2% (7/400) of patients reported serious adverse events, all of which were considered “not related” to the study drug by the investigator.

Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse drug reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. In two double-blind, placebo-controlled studies for genital warts, 602 subjects applied up to one packet of VYLOMA Cream or placebo daily for up to 8 weeks.

The most frequently reported adverse reactions were local skin and application site reactions. Overall, less than 1% (3/400) of the subjects treated with VYLOMA Cream discontinued due to local skin/application site reactions. The incidence and severity of local skin reactions during controlled clinical studies are shown in Table 1 PrVYLOMA® Product Monograph Page 7 of 28 Table 1: Local Skin Reactions in the Treatment Area Assessed by the Investigator VYLOMA Cream Placebo Females n=217 Males n=183 Females n=106 Males n=96 All Grades * Severe All Grades * Severe All Grades * Severe All Grades * Severe Any local skin reaction 77% 18% 82% 18% 33% 1% 41% 1% Erythema 74% 10% 78% 10% 23% 0% 37% 1% Edema (induration) 41% 2% 48% 2% 8% 0% 9% 0% Weeping/ Exudate 35% 1% 39% 3% 5% 0% 0% 0% Flaking/ Scaling/ Dryness 26% 0% 39% 0% 11% 0% 11% 0% Scabbing/ Crusting 18% <1% 34% 1% 6% 0% 2% 0% Erosion/ Ulceration 36% 13% 42% 10% 7% 1% 2% 0% *Mild, Moderate, or Severe Local skin reactions were recorded as adverse events if they extended beyond the treatment area, if they required any medical intervention, or they resulted in patient discontinuation from the study.

VYLOMA

Cream is contraindicated in individuals with a history of sensitivity reactions to imiquimod or to any of the components in the formulation. It should be discontinued if hypersensitivity to any of its ingredients is noted or to any components of the formulation (See WARNINGS AND PRECAUTIONS, Sensitivity).

For a complete listing see the Dosage Forms, Composition and Packaging section of the Product Monograph. WARNINGS AND PRECAUTIONS General Treatment of urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease is not recommended.

Local Inflammatory Reactions Local skin reactions such as erythema, scabbing/crusting, flaking/scaling/dryness, and edema are common. Intense local skin reactions including erythema, scabbing/crusting and erosion/ulceration can occur after a few applications of VYLOMA Cream and may require an interruption of dosing (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).

VYLOMA Cream has the potential to exacerbate inflammatory conditions of the skin, including chronic graft versus host disease. Severe local inflammatory reactions of the female external genitalia can lead to severe vulvar swelling. Severe vulvar swelling can lead to urinary retention.

If severe vulvar swelling occurs, dosing should be interrupted or discontinued. Administration of VYLOMA Cream is not recommended until the skin is healed from any previous drug or surgical treatment. Should a severe local skin reaction occur, the cream should be removed by washing the treatment area with mild soap and water and drying the area thoroughly.

Treatment with VYLOMA Cream may be temporarily interrupted and can be resumed after consultation with the treating physician, and once the skin reaction has subsided. Systemic Reactions Flu-like signs and symptoms may accompany, or even precede, local skin reactions and may include fatigue, nausea, fever, myalgias, arthralgias, and chills.