Miconazole Nitrate, Zinc Oxide, White Petrolatum

1 INDICATIONS AND USAGE • Miconazole nitrate, zinc oxide and white petrolatum ointment is indicated for adjunctive treatment of diaper dermatitis when complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast) in immunocompetent pediatric patients 4 weeks and older. ( 1.1 ) • Miconazole nitrate, zinc oxide and white petrolatum ointment should not be used as a substitute for frequent diaper changes. ( 1.1 ) • Miconazole nitrate, zinc oxide and white petrolatum ointment should not be used to prevent the occurrence of diaper dermatitis, since preventative use may result in the development of drug resistance. ( 1.2 ) 1.1 Indication Miconazole nitrate, zinc oxide and white petrolatum ointment is indicated for the adjunctive treatment of diaper dermatitis only when complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast), in immunocompetent pediatric patients 4 weeks and older. A positive fungal culture for Candida albicans is not adequate evidence of candidal infection since colonization with C. albicans can result in a positive culture. The presence of candidal infection should be established by microscopic evaluation prior to initiating treatment. Miconazole nitrate, zinc oxide and white petrolatum ointment should be used as part of a treatment regimen that includes measures directed at the underlying diaper dermatitis, including gentle cleansing of the diaper area and frequent diaper changes. Miconazole nitrate, zinc oxide and white petrolatum ointment should not be used as a substitute for frequent diaper changes. 1.2 Limitations of Use The safety and efficacy of miconazole nitrate, zinc oxide and white petrolatum ointment have not been demonstrated in immunocompromised patients, or in infants less than 4 weeks of age (premature or term). The safety and efficacy of miconazole nitrate, zinc oxide and white petrolatum ointment have not been evaluated in incontinent adult patients. Miconazole nitrate, zinc oxide and white petrolatum ointment should not be used to prevent the occurrence of diaper dermatitis, such as in an adult institutional setting, since preventative use may result in the development of drug resistance.

2 DOSAGE AND ADMINISTRATION Miconazole nitrate, zinc oxide and white petrolatum ointment is not for oral, ophthalmic, or intravaginal use. Before applying miconazole nitrate, zinc oxide and white petrolatum ointment, gently cleanse the skin with lukewarm water and pat dry with a soft towel. Avoid using any scented soaps, shampoos, or lotions on the diaper area. Gently apply a thin layer of miconazole nitrate, zinc oxide and white petrolatum ointment to the diaper area with each diaper change for 7 days. Do not rub miconazole nitrate, zinc oxide and white petrolatum ointment into the skin as this may cause additional irritation. Thoroughly wash hands after applying miconazole nitrate, zinc oxide and white petrolatum ointment. Continue treatment for the full 7 days, even if there is improvement. Do not use miconazole nitrate, zinc oxide and white petrolatum ointment for longer than 7 days. The safety of miconazole nitrate, zinc oxide and white petrolatum ointment when used for longer than 7 days is not known. If symptoms have not improved by day 7, see your health care provider. • Miconazole nitrate, zinc oxide and white petrolatum ointment is for topical use only. Miconazole nitrate, zinc oxide and white petrolatum ointment is not for oral, ophthalmic, or intravaginal use. ( 2 ) • Miconazole nitrate, zinc oxide and white petrolatum ointment should be applied as a thin layer to the affected area at each diaper change for 7 days. ( 2 ) • Miconazole nitrate, zinc oxide and white petrolatum ointment should be used as part of a treatment regimen that includes gentle cleansing of the diaper area and frequent diaper changes. ( 2 )

6 ADVERSE REACTIONS To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) 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 rate observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 835 infants and young children were evaluated in the clinical development program. Of 418 subjects in the miconazole nitrate, zinc oxide and white petrolatum ointment group, 58 (14%) reported one or more adverse events. Of 417 subjects in the zinc oxide/white petrolatum control group, 85 (20%) reported one or more adverse events. Adverse events that occurred at a rate of ≥ 1% for subjects who were treated with miconazole nitrate, zinc oxide and white petrolatum ointment were approximately the same in type and frequency as for subjects who were treated with zinc oxide/white petrolatum ointment. 6.2 Post-marketing Experience The following adverse reactions have been identified during post approval use of miconazole nitrate, zinc oxide and white petrolatum ointment. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: vomiting General Disorders and Administration Site Conditions: burning sensation, condition aggravated, inflammation, pain Injury, Poisoning and Procedural Complications: accidental exposure Skin and Subcutaneous Tissue Disorders: blister, dermatitis contact, diaper dermatitis, dry skin, erythema, pruritus, rash, skin exfoliation

12.3 Pharmacokinetics The topical absorption of miconazole from miconazole nitrate, zinc oxide and white petrolatum ointment was studied in immunocompetent male and female infants and children (n = 17) with diaper dermatitis complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast) ranging in age from 1 month to 21 months. After multiple daily applications to the affected area at every diaper change (approximately 5-12 times per day) for 7 days, the plasma concentrations of miconazole were below the lower limit of quantitation (LOQ) of 0.5 ng/mL in 15 out of 17 (88%) subjects. In the other 2 remaining subjects, the plasma concentrations of miconazole were 0.57 and 0.58 ng/mL, respectively at a single timepoint (4 hours after the last application) on Day 7.