FABIOR

5 WARNINGS AND PRECAUTIONS Fetal Risk: FABIOR Foam contains tazarotene, which is a teratogenic substance. FABIOR Foam is contraindicated in pregnancy. Females of childbearing potential should have a negative pregnancy test within 2 weeks prior to initiating treatment and use an effective method of contraception during treatment. ( 5.1 ) Local Irritation: Use with caution in patients with a history of local tolerability reactions or local hypersensitivity. ( 5.2 ) Potential Irritant Effect with Concomitant Topical Medications: Use with caution because a cumulative irritant effect may occur. ( 5.3 ) Photosensitivity and Risk for Sunburn: Avoid exposure to sunlight, sunlamps, and weather extremes. Wear sunscreen daily. ( 5.4 ) Contents are flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. ( 5.5 ) 5.1 Fetal Risk Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically over sufficient body surface area, exposure could be in the same order of magnitude as in orally treated animals. Tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans [see Clinical Pharmacology (12) ] . There were 5 reported pregnancies in subjects who participated in clinical trials for topical tazarotene foam. One of the subjects was found to have been treated with topical tazarotene for 25 days, 2 were treated with vehicle foam, and the other 2 did not receive either tazarotene foam or vehicle foam. The subjects were discontinued from the trials when their pregnancy was reported. The one pregnant woman who was inadvertently exposed to topical tazarotene during the clinical trial delivered a full-term healthy infant. Females of Childbearing Potential: Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when tazarotene foam is used. The possibility of pregnancy should be considered in females of child-bearing potential at the time of institution of therapy. A negative serum or urine result for pregnancy test having a sensitivity down to at least 25 mIU/mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to therapy with FABIOR Foam, which should begin during a normal menstrual period for females of childbearing potential. Advise patients of the need to use an effective method of contraception to avoid pregnancy [see Use in Specific Populations (8.1) ] . 5.2 Local Irritation FABIOR Foam should be used with caution in patients with a history of local tolerability reactions or local hypersensitivity. Retinoids should not be used on abraded or eczematous skin, as they may cause severe irritation. Contact with the mouth, eyes, and mucous membranes should be avoided. In case of accidental contact, rinse well with water. Some individuals may experience skin redness, peeling, burning or excessive pruritus. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the dosing should be reduced to an interval the patient can tolerate. However, efficacy at reduced frequency of application has not been established. Weather extremes, such as wind or cold, may be more irritating to patients using FABIOR Foam. 5.3 Potential Irritant Effect with Concomitant Topical Medications Concomitant topical acne therapy should be used with caution because a cumulative irritant effect may occur. If irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. Treatment should be discontinued if the irritation persists. 5.4 Photosensitivity and Risk for Sunburn Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided. Patients must be warned to use sunscreens and protective clothing when using FABIOR Foam. Patients with sunburn should be advised not to use FABIOR Foam until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using FABIOR Foam and ensure that the precautions are observed [see FDA-approved patient labeling ]. Due to the potential for photosensitivity resulting in greater risk for sunburn, FABIOR Foam should be used with caution in patients with a personal or family history of skin cancer. FABIOR Foam should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. 5.5 Flammability The propellant in FABIOR Foam is flammable. Instruct the patient to avoid fire, flame, and/or smoking during and immediately following application.

6 ADVERSE REACTIONS Most common adverse reactions reported at an incidence ≥6% are application site irritation, application site dryness, application site erythema, and application site exfoliation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data reflect exposure to FABIOR Foam in 744 subjects with acne vulgaris. Subjects were aged 12 to 45 years and were treated once daily in the evening for 12 weeks. Adverse reactions reported in ≥ 1% of subjects treated with FABIOR Foam are presented in Table 1. Most adverse reactions were mild to moderate in severity. Severe adverse reactions represented 3.0% of the subjects treated. Overall, 2.7% (20/744) of subjects discontinued FABIOR Foam because of local skin reactions. Table 1. Incidence of Adverse Reactions in ≥1 % of Subjects Treated with FABIOR Foam FABIOR Foam N = 744 Vehicle Foam N = 741 Patients with any adverse reaction, n (%) 163 (22) 19 (3) Application site irritation 107 (14) 9 (1) Application site dryness 50 (7) 8 (1) Application site erythema 48 (6) 3 (<1) Application site exfoliation 44 (6) 3 (<1) Application site pain 9 (1) 0 Application site photosensitivity (including sunburn) 8 (1) 3 (<1) Application site pruritus 7 (1) 3 (<1) Application site dermatitis 6 (1) 1 (<1) Additional adverse reactions that were reported in <1% of subjects treated with FABIOR Foam included application site reactions (including discoloration, discomfort, edema, rash, and swelling), dermatitis, impetigo, and pruritus. Local skin reactions, dryness, erythema, and peeling actively assessed by the investigator and burning/stinging and itching reported by the subject were evaluated at baseline, during treatment, and end of treatment. During the 12 weeks of treatment, each local skin reaction peaked at Week 2 and gradually reduced thereafter with the continued use of FABIOR Foam.

<table width="75%"><caption>Table 1. Incidence of Adverse Reactions in &#x2265;1 % of Subjects Treated with FABIOR Foam</caption><col width="60%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">FABIOR Foam N = 744 </th><th styleCode="Rrule">Vehicle Foam N = 741 </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Patients with any adverse reaction, n (%)</td><td styleCode="Rrule">163 (22)</td><td styleCode="Rrule">19 (3)</td></tr><tr><td styleCode="Lrule Rrule">Application site irritation</td><td styleCode="Rrule">107 (14)</td><td styleCode="Rrule">9 (1)</td></tr><tr><td styleCode="Lrule Rrule">Application site dryness</td><td styleCode="Rrule">50 (7)</td><td styleCode="Rrule">8 (1)</td></tr><tr><td styleCode="Lrule Rrule">Application site erythema</td><td styleCode="Rrule">48 (6)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site exfoliation</td><td styleCode="Rrule">44 (6)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site pain</td><td styleCode="Rrule">9 (1)</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule">Application site photosensitivity (including sunburn)</td><td styleCode="Rrule">8 (1)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site pruritus</td><td styleCode="Rrule">7 (1)</td><td styleCode="Rrule">3 (&lt;1)</td></tr><tr><td styleCode="Lrule Rrule">Application site dermatitis</td><td styleCode="Rrule">6 (1)</td><td styleCode="Rrule">1 (&lt;1)</td></tr></tbody></table>