FDA Label for Vusion

1 Indications And Usage

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1.1 Indication

VUSION 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.

VUSION 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.

VUSION should not be used as a substitute for frequent diaper changes. VUSION should not be used to prevent the occurrence of diaper dermatitis, since preventative use may result in the development of drug resistance.

1.2 Limitations Of Use

The safety and efficacy of VUSION have not been demonstrated in immunocompromised patients, or in infants less than 4 weeks of age (premature or term).

The safety and efficacy of VUSION have not been evaluated in incontinent adult patients. VUSION 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

VUSION is not for oral, ophthalmic, or intravaginal use.

Before applying VUSION, 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.

Apply VUSION to the affected area at each diaper change for 7 days. Continue treatment for the full 7 days, even if there is improvement. The safety of VUSION when used for longer than 7 days is not known. Do not use VUSION for longer than 7 days. If symptoms have not improved by day 7, see your health care provider.

Gently apply a thin layer of VUSION to the diaper area with the fingertips. Do not rub VUSION into the skin as this may cause additional irritation. Thoroughly wash hands after applying VUSION.

3 Dosage Forms And Strengths

White ointment containing 0.25% miconazole nitrate, 15% zinc oxide, and 81.35% white petrolatum.

4 Contraindications

None

5 Warnings And Precautions

If irritation occurs or if the disease worsens, discontinue use of the medication, and contact the health care provider.

The safety and efficacy of VUSION have not been evaluated in incontinent adult patients. VUSION 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.

6 Adverse Reactions

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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 VUSION 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 VUSION 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 VUSION.

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

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.

7 Drug Interactions

Drug-drug interaction studies were not conducted. Women who take a warfarin anticoagulant and use a miconazole intravaginal cream or suppository may be at risk for developing an increased prothrombin time, international normalized ratio (INR), and bleeding. The potential for this interaction between warfarin and VUSION is unknown.

8 Use In Specific Populations

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8.1 Pregnancy

There are no adequate and well-controlled studies of VUSION in pregnant women. Therefore, VUSION should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Miconazole nitrate administration has been shown to result in prolonged gestation and decreased numbers of live young in rats and in increased number of resorptions and decreased number of live young in rabbits at oral doses of 100 mg/kg/day and 80 mg/kg/day, which are 28 and 45 times the maximum possible topical exposure of caregivers, respectively, assuming 100% absorption.

8.3 Nursing Mothers

Safety and efficacy of VUSION have not been established in nursing mothers. It is not known if the active components of VUSION may be present in milk.

8.4 Pediatric Use

Efficacy was not demonstrated in infants less than 4 weeks of age. Safety and efficacy have not been established in very-low-birth-weight infants.

VUSION should not be used to prevent diaper dermatitis.

The safety of VUSION when used for longer than 7 days is not known. Do not use more than 7 days.

8.5 Geriatric Use

Safety and efficacy in a geriatric population have not been evaluated.

11 Description

VUSION contains the synthetic antifungal agent, miconazole nitrate (0.25%) USP, zinc oxide (15%) USP, and white petrolatum (81.35%) USP.

The chemical name of miconazole nitrate is 1-[2, 4-dichloro-ß-{(2,4-dichlorobenzyl)oxy} phenethyl] imidazole mononitrate with empirical formula C₁₈H₁₄Cl₄N₂O•HNO₃ and molecular weight of 479.15. The structural formula of miconazole nitrate is as follows:

The zinc oxide has an empirical formula of ZnO and a molecular weight of 81.39.

The white petrolatum, which is obtained from petroleum and is wholly or nearly decolorized, is a purified mixture of semisolid saturated hydrocarbons having the general chemical formula C_nH_2n+2. The hydrocarbons consist mainly of branched and unbranched chains. White petrolatum contains butylated hydroxytoluene (BHT) as stabilizer.

Each gram of VUSION contains 2.5 mg of miconazole nitrate USP, 150 mg of zinc oxide USP, and 813.5 mg of white petrolatum USP containing butylated hydroxytoluene, trihydroxystearin, and  Chemoderm^® 1001/B fragrance.¹

VUSION is a smooth, uniform, white ointment.

12 Clinical Pharmacology

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12.1 Mechanism Of Action

The miconazole component of VUSION is an antifungal agent [see Clinical Pharmacology (12.4)]. The mechanism of action of white petrolatum and zinc oxide for the adjunctive treatment of diaper dermatitis is unknown.

12.2 Pharmacodynamics

The human pharmacodynamics of Vusion is unknown [see Clinical Pharmacology (12.4) for fungal pharmacodynamics].

12.3 Pharmacokinetics

The topical absorption of miconazole from VUSION 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.

12.4 Microbiology

The miconazole nitrate component in this product has been shown to have in vitro activity against Candida albicans, an organism that is associated with diaper dermatitis. The activity of miconazole nitrate against C. albicans is based on the inhibition of the ergosterol biosynthesis in the cell membrane. The accumulation of ergosterol precursors and toxic peroxides results in cytolysis of the cell. In vitro minimal inhibitory concentration (MIC) test results for C. albicans isolates obtained from treatment failures in Clinical Study 1 (see Clinical Studies (14)) does not appear to indicate that resistance to miconazole nitrate was the reason for treatment failure. The clinical significance of the in vitro activity of miconazole nitrate against C. albicans in the setting of diaper dermatitis is unclear.

13 Nonclinical Toxicology

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13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

The carcinogenic potential of VUSION in animals has not been evaluated.

Miconazole nitrate was negative in a bacterial reverse mutation test, a chromosome aberration test in mice, and micronucleus assays in mice and rats.

Miconazole nitrate had no adverse effect on fertility in a study in rats at oral doses of up to 320 mg/kg/day, which is 89 times the maximum possible topical exposure of caregivers, assuming 100% absorption.

14 Clinical Studies

Study 1 was a double-blind, multicenter study in which VUSION was compared to the zinc oxide and white petrolatum combination treatment and included 236 infants and toddlers with diaper dermatitis, complicated by candidiasis as documented by KOH tests that demonstrated psuedohyphae and/or budding yeasts. Study medication was applied at every diaper change for 7 days.

The primary endpoint was “Overall Cure” and required that subjects be both clinically cured (total resolution of all signs and symptoms of infection) and microbiologically cured (eradication of candidiasis). Primary efficacy was assessed 1 week following the end of treatment, at Day 14.

Study results are shown in the following table.

Two additional studies provided supportive evidence of the clinical efficacy of VUSION in infants and toddlers with diaper dermatitis, some of whom cultured positive for C. albicans. However, candidal infection was not documented in the culture-positive subjects, as microscopic testing (e.g. KOH) was not done. Therefore, the positive culture results may have reflected colonization rather than infection.

16 How Supplied/Storage And Handling

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16.1 How Supplied

VUSION is a smooth, uniform, white ointment supplied in an aluminum tube, as follows:

50g (NDC 54868-6246-0)

16.2 Storage Conditions

Store at controlled room temperature between 20°C and 25°C (68°F and 77°F); with excursions permitted between 15°C and 30°C (59°F and 86°F).

Keep out of reach of children.

17 Patient Counseling Information

See FDA-Approved Patient Labeling

Patients using VUSION should be informed about the following information:

• VUSION is to be used only for diaper dermatitis that is complicated by documented candidiasis (i.e. documented by microscopic testing).
• VUSION should not be used as a substitute for frequent diaper changes.
• VUSION should not be used to prevent diaper dermatitis.
• VUSION should not be used long term.
• VUSION should be used only as directed by the health care provider.
• VUSION is for external use only. It is not for oral, ophthalmic, or intravaginal use.
• Gently cleanse the diaper area with lukewarm water or a very mild soap and pat the area dry with a soft towel before applying VUSION.
• Gently apply VUSION to the diaper area with the fingertips after each diaper change. Do not rub VUSION into the skin as this may cause additional irritation.
• Thoroughly wash hands after applying VUSION.
• Treatment should be continued for 7 days, even if there is improvement. Do not use VUSION for longer than 7 days. If symptoms have not improved by day 7, see your health care provider.
• VUSION should not be used on children for whom it is not prescribed.

VSN:2PI

Principal Display Panel

NDC 0145-0002-04

image of package label - 6246

Vusion^®

(miconazole nitrate 0.25% USP, zinc oxide 15% USP, white petrolatum 81.35% USP)

Ointment

50 grams

R_x only

For topical use only

Usual Dosage: See package insert.

Caution: Not for oral, ophthalmic, or intravaginal use. Keep out of reach of children. If seal is damaged or punctured, do not use, and return product to place of purchase.

Description: Each gram of VUSION^® Ointment contains 2.5 mg miconazole nitrate USP, 150 mg zinc oxide USP, and 813.5 mg white petrolatum USP containing butylated hydroxytoluene, trihydroxystearin, and Chemoderm^® 1001/B fragrance.

Store at 15^oC (77^oF); excursions permitted to 25^oC -30^oC (59^oF -86^oF).

See tube crimp for lot number and expiration date.