of application. if the degree of local irritation warrants, patients should be directed to temporarily use the medication less frequently, discontinue use temporarily, or discontinue use altogether. efficacy at reduced frequencies of application has not been established. tretinoin has been reported to cause severe irritation on eczematous skin and should be used with utmost caution in patients with this condition.

d be noticed after two to three weeks, but more than six weeks of therapy may be required before definite beneficial effects are seen. patients treated with avita ® gel may use cosmetics, but the areas to be treated should be cleansed thoroughly before the medication is applied (see precautions section).

study 1 avita ® gel, 0.025% vehicle gel n = 198 n = 204 noninflammatory lesions -36% -27% inflammatory lesions -35% -25% total lesions -36% -27% study 2 avita ® gel, 0.025% vehicle gel n = 58 n = 58 n = number of subjects noninflammatory lesions -42% -26% inflammatory lesions -38% -23% total lesions -41% -26%

zation at the treated skin sites and the incidence of this finding was 0/50, 3/50, 3/50, and 2/50 in male mice and 1/50, 0/50, 4/50, and 2/50 in female mice from the vehicle control, 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg groups, respectively. studies in hairless albino mice suggest that tretinoin may enhance the tumorigenic potential of carcinogenic doses of uva and uvb light from a solar simulator. in other studies, when lightly pigmented hairless mice treated with tretinoin were exposed to carcinogenic doses of uva/uvb light, the incidence and rate of development of skin tumors were either reduced or no effect was seen. due to significantly different experimental conditions, no strict comparison of these disparate data is possible at this time. although the significance of these studies to humans is not clear, patients should minimize exposure to sun. the mutagenic potential of tretinoin was evaluated in the ames assay and in the in vivo mouse micronucleus assay, both of which were negative. dermal segment i and iii studies with avita ® gel have not been performed in any species. in oral segment i and segment iii studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (> 400 times the average recommended human topical clinical dose).

exposure to the sun. therapy with avita ® gel may make your skin more susceptible to sunburn and other adverse effects of the sun, so unprotected exposure to natural or artificial sunlight should be minimized. laboratory findings: when laboratory mice are exposed to artificial sunlight, they often develop skin tumors. these sunlight-induced tumors may appear more quickly and in greater number if the mouse is also topically treated with the active ingredient in avita ® gel, tretinoin. in some studies, under different conditions, however, when mice treated with tretinoin were exposed to artificial sunlight, the incidence and rate of development of skin tumors was reduced. there is no evidence to date that tretinoin alone will cause the development of skin tumors in either laboratory animals or humans. use caution in the sun: when outside, even on hazy days, areas treated with avita ® gel should be protected. an effective sunscreen should be used any time you are outside (consult your physician for a recommendation of an spf level which will provide you with the necessary high level of protection). for extended sun exposure, protective clothing, like a hat, should be worn. do not use artificial sunlamps or artificial sunlight while you are using avita ® (tretinoin gel) gel, 0.025%. if you do become sunburned, stop your therapy with avita ® gel until your skin has recovered. avoid excessive exposure to wind or cold: extremes of climate tend to dry or burn normal skin. skin treated with avita ® gel may be more vulnerable to these extremes.your physician can recommend ways to manage your acne treatment under such conditions. possible problems: the skin of certain sensitive individuals may become excessively red, swollen, blistered, or crusted. if you are experiencing severe or persistent irritation, discontinue the use of avita ® gel and consult your physician. there have been reports that, in some patients, areas treated with avita ® gel developed a temporary increase or decrease in the amount of skin pigment (color) present. use other medication only on your physician’s advice: only your physician knows which other medications may be helpful during treatment and will recommend them to you if necessary. follow the physician’s instructions carefully. in addition, you should avoid preparations that may dry or irritate your skin. these preparations may include certain astringents, toiletries containing alcohol, spices or lime, or certain medicated soaps, shampoos, and hair permanent solutions. do not allow anyone else to use this medication. do not use other medications with avita ® gel which are not recommended by your doctor. the medications you have used in the past might cause unnecessary redness or peeling. if you are pregnant, think you are pregnant, or are nursing an infant: no studies have been conducted in humans to establish the safety of avita ® gel in pregnant women. if you are pregnant, think you are pregnant, or are nursing a baby, consult your physician before using this medication. and while you’re on avita ® therapy use a mild non-medicated soap. avoid frequent washings and harsh scrubbing. acne isn’t caused by dirt, so no matter how hard you scrub, you can’t wash it away. washing too frequently or scrubbing too roughly may at times actually make your acne worse. wash your skin gently with a mild, bland soap. two or three times a day should be sufficient. pat skin dry with a towel. let the face dry 20 to 30 minutes before applying avita ® (tretinoin gel) gel, 0.025%. remember, excessive irritation such as rubbing, too much washing, use of other medications not suggested by your physician, etc., may worsen your acne. how to use avita ® (tretinoin) gel to get the best results with avita ® gel therapy, it is necessary to use it properly. forget about the instructions given for other products and the advice of friends. just stick to the special plan your doctor has laid out for you and be patient. remember, when avita ® gel is used properly, many users see improvement by 12 weeks. again, follow instructions - be patient – don’t start and stop therapy on your own - if you have questions, ask your doctor. to help you use the medication correctly, keep these simple instructions in mind. • avita ® gel should be applied once a day, in the evening, or as directed by your physician, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. first, wash with a mild soap and dry your skin gently. wait 20 to 30 minutes before applying medication; it is important for skin to be completely dry in order to minimize possible irritation. • it is better not to use more than the amount suggested by your physician or to apply more frequently than instructed. too much may irritate the skin, waste medication, and won’t give faster or better results. • keep the medication away from the corners of the nose, mouth, eyes, and open wounds. spread away from these areas when applying. • gel: squeeze about a half inch or less of medication onto the fingertip. while that should be enough for your whole face, after you have had some experience with the medication you may find you need slightly more or less to do the job. the medication should become invisible almost immediately. if it is still visible, or if dry flaking occurs from the gel within a minute or so you are using too much. cover the affected area lightly with avita ® gel by first dabbing it on your forehead, chin, and both cheeks, then spreading it over the entire affected area. smooth gently into the skin. • if needed, you may apply a moisturizer or a moisturizer with sunscreen that will not aggravate your acne (noncomedogenic) in the morning after you wash. what to expect with your new treatment avita ® (tretinoin gel) gel, 0.025% works deep inside your skin and this takes time. you cannot make avita ® gel work any faster by applying more than one dose each day, but an excess amount of avita ® gel may irritate your skin. be patient. there may be some discomfort or peeling during the early days of treatment. some patients also notice that their skin begins to take on a blush. these reactions do not happen to everyone. if they do, it is just your skin adjusting to avita ® gel and this usually subsides within two to four weeks. these reactions can usually be minimized by following instructions carefully. should the effects become excessively troublesome, consult your doctor. by three to six weeks, some patients notice an appearance of new blemishes (papules and pustules). at this stage it is important to continue using avita ® gel. if avita ® gel is going to have a beneficial effect for you, you should notice an improvement in your appearance by 6 to 12 weeks of therapy. don’t be discouraged if you see no immediate improvement. don’t stop treatment at the first signs of improvement. once your acne is under control, you should continue regular application of avita ® gel until your physician instructs otherwise. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. manufactured for: mylan pharmaceuticals inc. morgantown, wv 26505 u.s.a. revised: 1/2018 022.7pl printed in u.s.a.