Clinical Overview

References: 1. Vazquez JA, Patton LL, Epstein JB, et al; SMiLES Study Group. Randomized, comparative, double-blind, double-dummy, multicenter trial of miconazole buccal tablet and clotrimazole troches for the treatment of oropharyngeal candidiasis: study of miconazole Lauriad® efficacy and safety (SMiLES). HIV Clin Trials. 2010;11(4):186-196. 2. Data on file, Midatech Pharma US Inc.

References: 1. Bensadoun R-J, Daoud J, El Gueddari B, et al. Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis: a prospective, randomized, single-blind, multicenter, comparative, phase III trial in patients treated with radiotherapy for head and neck cancer. Cancer. 2008;112:204-211. 2. Data on file, Midatech Pharma US Inc

Important Safety Information

• Because concomitant administration of miconazole and warfarin has resulted in enhancement of anticoagulant effect, patients should be closely monitored.
• Oravig^® should be administered with caution in patients with hepatic impairment.
• There is no information regarding cross-hypersensitivity between miconazole and other azole antifungal agents. Monitor patients with a history of hypersensitivity to azoles.
• Most commonly reported adverse reactions (incidence 2%) in clinical studies include diarrhea, nausea, upper abdominal pain, vomiting, headache and dysgeusia

Safety & Tolerability

Contraindications

Oravig^® is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to miconazole, milk protein concentrate, or any other component of the product.

Warnings, Precautions and Adverse Reactions

Allergic reactions, including anaphylactic reactions and hypersensitivity, have been reported with the administration of miconazole products, including Oravig^®. Discontinue Oravig^® immediately at the first sign of hypersensitivity.

There is no information regarding cross-hypersensitivity between miconazole and other azole antifungal agents. Monitor patients with a history of hypersensitivity to azoles.

Drug Interactions

Wafarin

Concomitant administration of miconazole and warfarin has resulted in enhancement of anticoagulant effect. Cases of bleeding and bruising following the concomitant use of warfarin and topical, intravaginal, or oral miconazole were reported. Closely monitor prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests if Oravig^® is administered concomitantly with warfarin. Also monitor for evidence of bleeding.

Drugs Metabolized Through CYP2C9 and 3A4

No formal drug interaction studies have been performed with Oravig^®. Miconazole is a known inhibitor of CYP2C9 and CYP3A4. Although the systemic absorption of miconazole following Oravig^® administration is minimal and plasma concentrations of miconazole are substantially lower than when given intravenously, the potential for interaction with drugs metabolized through CYP2C9 and CYP3A4 such as oral hypoglycemics, phenytoin, or ergot alkaloids cannot be ruled out.

Adverse Reactions

Adverse Reactions Reported in ≥ 2% of Patients and Healthy Subjects who Received Oravig^® in Clinical Trials.

Discontinuation of Oravig^® due to adverse drug reactions occurred in 0.6% overall.

Dosing & Administration

Dosing

The recommended dosing schedule for Oravig^® is the application of one 50 mg buccal tablet to the upper gum region (canine fossa) once daily for 14 consecutive days. Oravig^® is a buccal tablet containing 50 mg of miconazole. Oravig^® tablets are round, off-white tablets, with a rounded side and a flat side. The tablets are marked with an “L” on the flat side.

Instructions on Usage

Oravig^® should be applied in the morning, after brushing the teeth. The tablet should be applied with dry hands. The rounded side surface of the tablet should be placed against the upper gum just above the incisor tooth (canine fossa) and held in place with slight pressure over the upper lip for 30 seconds to ensure adhesion. The tablet is round on one side for comfort, but either side of the tablet can be applied to the gum.

Once applied, Oravig^® stays in position and gradually dissolves. Subsequent applications of Oravig^® should be made to alternate sides of the mouth. Before applying the next tablet, the patient should clear away any remaining tablet material. In addition,

• Oravig^® should not be crushed, chewed or swallowed.
• Food and drink can be taken normally when Oravig^® is in place but chewing gum should be avoided.
• If Oravig^® does not adhere or falls off within the first 6 hours, the same tablet should be repositioned immediately. If the tablet still does not adhere, a new tablet should be placed.
• If Oravig^® is swallowed within the first 6 hours, the patient should drink a glass of water and a new tablet should be applied only once.
• If Oravig^® falls off or is swallowed after it was in place for 6 hours or more, a new tablet should not be applied until the next regularly scheduled dose.