warnings and cautions
5 WARNINGS AND PRECAUTIONS • Intense local inflammatory reactions can occur (e.g., skin weeping, erosion). Dosing interruption may be required. ( 2 , 5.1 , 6 ) • Severe local inflammatory reactions of the female external genitalia can lead to severe vulvar swelling. Severe vulvar swelling can lead to urinary retention; dosing should be interrupted or discontinued. ( 5.1 ) • Flu-like systemic signs and symptoms including fatigue, nausea, fever, myalgias, arthralgias, and chills can occur. Dosing interruption may be required. ( 2.1 , 2.2 , 5.2 , 6 ) • Avoid concomitant use of Imiquimod Cream and any other imiquimod cream because of increased risk for adverse reactions. ( 5.4 ) 5.1 Local Skin Reactions Intense local skin reactions including skin weeping or erosion can occur after a few applications of Imiquimod Cream and may require an interruption of dosing [see Dosage and Administration (2) and Adverse Reactions (6) ] . Imiquimod 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. Dosing should be interrupted or discontinued for severe vulvar swelling. Administration of Imiquimod Cream is not recommended until the skin is healed from any previous drug or surgical treatment. 5.2 Systemic Reactions Flu-like signs and symptoms may accompany, or even precede, local skin reactions and may include fatigue, nausea, fever, myalgias, arthralgias, malaise, and chills. An interruption of dosing and an assessment of the patient should be considered [see Adverse Reactions (6) ] . Lymphadenopathy occurred in 2% of subjects with actinic keratosis treated with Imiquimod Cream, 3.75% and in 3% of subjects treated with Imiquimod Cream, 2.5% [see Adverse Reactions (6) ] . This reaction resolved in all subjects by 4 weeks after completion of treatment. 5.3 Ultraviolet Light Exposure Risks Exposure to sunlight (including sunlamps) should be avoided or minimized during use of Imiquimod Cream. Patients should be warned to use protective clothing (e.g., a hat) when using Imiquimod Cream. Patients with sunburn should be advised not to use Imiquimod Cream until fully recovered. Patients who may have considerable sun exposure (e.g., due to their occupation) and those patients with inherent sensitivity to sunlight should exercise caution when using Imiquimod Cream. In an animal photocarcinogenicity study, imiquimod cream shortened the time to skin tumor formation [see Nonclinical Toxicology (13.1) ] . The enhancement of ultraviolet carcinogenicity is not necessarily dependent on phototoxic mechanisms. Therefore, patients should minimize or avoid natural or artificial sunlight exposure. 5.4 Increased Risk of Adverse Reactions with Concomitant Imiquimod Use Concomitant use of Imiquimod Cream and any other imiquimod products, in the same treatment area, should be avoided since they contain the same active ingredient (imiquimod) and may increase the risk for and severity of local skin reactions. The safety of concomitant use of Imiquimod Cream and any other imiquimod products has not been established and should be avoided since they contain the same active ingredient (imiquimod) and may increase the risk for and severity of systemic reactions. 5.5 Immune Cell Activation in Autoimmune Disease Imiquimod Cream should be used with caution in patients with pre-existing autoimmune conditions because imiquimod activates immune cells [see Clinical Pharmacology (12.2) ] .