CLOTIC (clotrimazole) otic solution

1 INDICATIONS AND USAGE CLOTIC is indicated for the treatment of fungal otitis externa (otomycosis) due to Aspergillus species and Candida species in patients 18 years of age and older. Limitations of Use CLOTIC has only been studied in patients with intact tympanic membranes. The use of CLOTIC is not recommended for the treatment of otomycosis in patients with perforated tympanic membranes. CLOTIC is an azole antifungal indicated for the treatment of fungal otitis externa (otomycosis) due to Aspergillus species and Candida species in patients 18 years of age and older. ( 1 ) Limitations of Use CLOTIC has only been studied in patients with intact tympanic membranes. The use of CLOTIC is not recommended for the treatment of otomycosis in patients with perforated tympanic membranes

2 DOSAGE AND ADMINISTRATION CLOTIC is for otic use only. ( 2 ) Instill the contents of one single-dose CLOTIC vial into the affected ear canal twice daily, morning and evening, preferably 12 hours apart for 14 consecutive days. ( 2 ) See full prescribing information for preparation and administration instructions 2.1 Recommended Dosage and Administration CLOTIC is for otic use only. Instill the contents of one single-dose CLOTIC vial into the affected ear canal twice daily morning and evening, preferably 12 hours apart, for 14 consecutive days. 2.2 Preparation and Administration Instructions Warm the solution by holding the vial in the hand for 1 to 2 minutes. This is to avoid dizziness which may result from the instillation of a cold solution into the ear canal. The patient should lie with the affected ear upward, and then instill the medication. Gently pull the outer ear lobe upward and outward. This will allow the ear drops to flow down into the ear canal. Maintain this position for 1 minute after the drug administration. Repeat, if necessary, for the opposite ear [see Instructions for Use ].

5 WARNINGS AND PRECAUTIONS None. None. ( 5 )

4 CONTRAINDICATIONS CLOTIC is contraindicated in patients with known hypersensitivity to clotrimazole. CLOTIC is contraindicated in patients with known hypersensitivity to clotrimazole. ( 4 )

8.1 Pregnancy Risk Summary Systemic absorption of clotrimazole following topical administration appears to be minimal, and maternal use of CLOTIC is not expected to result in fetal exposure to the drug. The background risk of major birth defects and miscarriage for the indicated population is unknown All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

6 ADVERSE REACTIONS The most common adverse reactions that occurred in ≥ 1 patient were headache, application site pain, tinnitus, tympanic membrane perforation, and paresthesia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Carwin Pharmaceutical Associates, LLC at phone 1-844-700-5011 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two randomized, placebo-controlled, phase 3 trials, 393 adult patients with otomycosis and intact tympanic membranes were treated with CLOTIC or placebo (Trial 1 and Trial 2) twice daily for a median duration of 14 days. There were 261 patients who received at least one dose of CLOTIC and 132 patients received at least one dose of placebo. These patients had a mean age of 51 years (range 19 to 89 years); 55% were male, 87% were White, and 26% were Hispanic or Latino ethnicity. Adverse Reactions Leading to Discontinuation Treatment discontinuation due to an adverse reaction occurred in 1% (3/261) of patients receiving CLOTIC and 3% (4/132) of patients receiving placebo. Adverse reactions leading to discontinuation of CLOTIC were application site pain in two patients and tympanic membrane perforation in one patient. Most Common Adverse Reactions Selected adverse reactions that occurred in 1 or more patients receiving CLOTIC are presented in Table 1. Table 1: Selected Adverse Reactions Occurring in 1 or more Patients in Trials 1 and 2 Adverse Reactions CLOTIC N=261 n (%) Placebo N=132 n (%) Headache 4 (1.5) 2 (1.5) Application site pain 2 (0.8) 0 Tinnitus 2 (0.8) 0 Tympanic membrane perforation 2 (0.8) 1 (0.8) Paresthesia 1 (0.4) 0