NDC 0378-6140 Avita

Tretinoin

NDC Product Code 0378-6140

NDC 0378-6140-44

Package Description: 20 g in 1 TUBE

NDC 0378-6140-45

Package Description: 45 g in 1 TUBE

Price per Unit: $1.67769 per GM

NDC Product Information

Avita with NDC 0378-6140 is a a human prescription drug product labeled by Mylan Pharmaceuticals Inc.. The generic name of Avita is tretinoin. The product's dosage form is gel and is administered via topical form. The RxNorm Crosswalk for this NDC code indicates multiple RxCUI concepts are associated to this product: 208332 and 313451.

Dosage Form: Gel - A semisolid3 dosage form that contains a gelling agent to provide stiffness to a solution or a colloidal dispersion.4 A gel may contain suspended particles.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Avita Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • BUTYLATED HYDROXYTOLUENE (UNII: 1P9D0Z171K)
  • HYDROXYPROPYL CELLULOSE, UNSPECIFIED (UNII: 9XZ8H6N6OH)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Topical - Administration to a particular spot on the outer surface of the body. The E2B term TRANSMAMMARY is a subset of the term TOPICAL.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Retinoid - [EPC] (Established Pharmacologic Class)
  • Retinoids - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Mylan Pharmaceuticals Inc.
Labeler Code: 0378
FDA Application Number: NDA020400 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-18-1998 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Information for Patients

Tretinoin Topical

Tretinoin Topical is pronounced as (tret' i noyn)

Why is tretinoin topical medication prescribed?
Tretinoin is used to treat acne. It promotes peeling of affected skin areas and unclogs pores. Tretinoin controls acne but does not cure it.This medication is sometimes p...
[Read More]

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Avita Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

For Topical Use Only

Description

AVITA® Gel, a topical retinoid, contains tretinoin 0.025% by weight in a gel vehicle of butylated hydroxytoluene, hydroxypropyl cellulose, polyolprepolymer-2, and ethanol (denatured with tert-butyl alcohol and brucine sulfate) 83% w/w. Chemically, tretinoin is all-trans-retinoic acid (C20H28O2; molecular weight 300.44 vitamin A acid) and has the following structural formula:

Clinical Pharmacology

Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.

Pharmacokinetics

In vitro and in vivo pharmacokinetic studies with AVITA® Gel indicate that less than 0.3% of the topically applied dose is bioavailable. Circulating plasma levels of both tretinoin and isotretinoin are only slightly elevated above those found in healthy normal controls.

Clinical Studies

In two large vehicle-controlled clinical trials, AVITA® (tretinoin gel) Gel 0.025%, applied once daily was more effective than vehicle in the treatment of facial acne vulgaris of mild to moderate severity. Percent reductions in lesion counts after treatment for 12 weeks in these studies are shown in the following Tables:Study 1AVITA® Gel,0.025%VehicleGelN = 198N = 204Noninflammatory Lesions-36%-27%Inflammatory Lesions-35%-25%Total Lesions-36%-27%Study 2AVITA® Gel,0.025%VehicleGelN = 58N = 58N = Number of SubjectsNoninflammatory Lesions-42%-26%Inflammatory Lesions-38%-23%Total Lesions-41%-26%

Indications And Usage

AVITA® Gel is indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of this product in the treatment of other disorders have not been established.

Contraindications

The product should not be used if there is hypersensitivity to any of the ingredients.

Warnings

GELS ARE FLAMMABLE. Note: Keep away from heat and flame. Keep tube tightly closed.

General

If a reaction suggesting sensitivity or chemical irritation occurs, use of the medication should be discontinued. Exposure to sunlight, including sunlamps, or artificial sunlight should be minimized during the use of AVITA® Gel, and patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with tretinoin.AVITA® (tretinoin gel) Gel, 0.025% should be kept away from the eyes, the mouth, the paranasal creases, and mucous membranes.Topical use may induce severe local erythema and peeling at the site of application. If the degree of local irritation warrants, patients should be directed to temporarily use the medication less frequently, discontinue use temporarily, or discontinue use altogether. Efficacy at reduced frequencies of application has not been established. Tretinoin has been reported to cause severe irritation on eczematous skin and should be used with utmost caution in patients with this condition.

Information For Patients

See attached Patient Package Insert.

Drug Interactions

Concomitant topical medication, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime should be used with caution because of possible interaction with tretinoin. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid with AVITA® Gel. It also is advisable to "rest" a patient's skin until the effects of such preparations subside before use of AVITA® Gel is begun.

Carcinogenesis, Mutagenesis And Impairment Of Fertility

In a dermal mouse carcinogenicity study with AVITA® Gel, tretinoin was administered to CD-1 mice at topical doses of 0.027 mg/kg (0.003% gel), 0.072 mg/kg (0.008% gel), and 0.225 mg/kg (0.025% gel) for 2 years (5 doses/week). No drug-related tumors were noted in this mouse carcinogenicity study up to the highest dose evaluated in this study of 0.225 mg/kg in both male and female mice, which was 2.6 times the recommended human topical clinical dose (based on weekly dose BSA comparison). For purposes of comparisons of the animal exposure to human exposure, the “recommended human topical clinical dose” is defined as 1.0 g of 0.025% AVITA® Gel applied daily to a 50 kg person. In a chronic, two-year bioassay of vitamin A acid in mice performed by Tsubura and Yamamoto, generalized amyloid deposition was reported in all vitamin A treated groups in the basal layer of the skin. In CD-1 mice, a similar study reported hyalinization at the treated skin sites and the incidence of this finding was 0/50, 3/50, 3/50, and 2/50 in male mice and 1/50, 0/50, 4/50, and 2/50 in female mice from the vehicle control, 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg groups, respectively.Studies in hairless albino mice suggest that tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVA and UVB light from a solar simulator. In other studies, when lightly pigmented hairless mice treated with tretinoin were exposed to carcinogenic doses of UVA/UVB light, the incidence and rate of development of skin tumors were either reduced or no effect was seen. Due to significantly different experimental conditions, no strict comparison of these disparate data is possible at this time. Although the significance of these studies to humans is not clear, patients should minimize exposure to sun.The mutagenic potential of tretinoin was evaluated in the Ames assay and in the in vivo mouse micronucleus assay, both of which were negative.Dermal Segment I and III studies with AVITA® Gel have not been performed in any species. In oral Segment I and Segment III studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (> 400 times the average recommended human topical clinical dose).

Pregnancy

Pregnancy Category C.

Teratogenic Effects

Oral tretinoin has been shown to be teratogenic in rats, mice, rabbits, hamsters, and sub-human primates. It was teratogenic and fetotoxic in rats when given orally in doses 1000 times the average recommended human topical clinical dose. However, variations in teratogenic doses among various strains of rats have been reported. In the cynomolgus monkey, which metabolically is closer to humans for tretinoin than other species examined, fetal malformations were reported at oral doses of 10 mg/kg/day or greater, but none were observed at 5 mg/kg/day (1000 times the average recommended human topical clinical dose), although increased skeletal variations were observed at all doses. Dose-related increased embryolethality and abortion were reported. Similar results have also been reported in pigtail macaques.Topical tretinoin in animal teratogenicity tests has generated equivocal results. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in Wistar rats at doses greater than 1 mg/kg/day (200 times the recommended human topical clinical dose). Anomalies (humerus: short 13%, bent 6%; os parietal incompletely ossified 14%) have also been reported in rats when 10 mg/kg/day was dermally applied.Topical tretinoin (AVITA® Gel, 0.025%) has been shown to be teratogenic in rabbits when given in doses 364 times the topical human dose for gel (assuming a 50 kg adult applies 1.0 g of 0.025% gel topically). In this study, increased incidence of cleft palate and hydrocephaly was reported in the tretinoin-treated animals.There are other reports, in New Zealand White rabbits with doses of approximately 80 times the recommended human topical clinical dose, of an increased incidence of domed head and hydrocephaly, typical of retinoid-induced fetal malformations in this species.When given subcutaneously to rabbits, tretinoin was teratogenic at 2 mg/kg/day but not at 1 mg/kg/day. These doses are approximately 400 and 200 times, respectively, the human topical dose of tretinoin gel, 0.025% (assuming a 50 kg adult applies 1.0 g of 0.025% gel topically).In contrast, several well-controlled animal studies have shown that dermally applied tretinoin was not teratogenic at doses of 100 and 200 times the recommended human topical clinical dose, in rats and rabbits, respectively.With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin (Retin-A). Although no definite pattern of teratogenicity and no causal association have been established from these cases, 5 of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these spontaneous reports in terms of risk to the fetus is not known.

Nonteratogenic Effects

Dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 100 times the recommended topical human clinical dose. Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 500 times the recommended topical human clinical dose. There are, however, no adequate and well-controlled studies in pregnant women. AVITA® (tretinoin gel) Gel, 0.025% should not be used during pregnancy.

Nursing Mothers

It is not known whether this drug is excreted in human milk, caution should be exercised when AVITA® Gel is administered to a nursing woman.

Adverse Reactions

The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the medication dosing frequency should be adjusted temporarily to a level the patient can tolerate. However, efficacy has not been established for lower dosing frequencies. True contact allergy to topical tretinoin is rarely encountered.Temporary hyper- or hypopigmentation has been reported with repeated application of AVITA® Gel. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with AVITA® Gel. Adverse effects of AVITA® Gel have been reversible upon discontinuation of therapy (see Dosage and Administration Section).

Overdosage

If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of vitamin A.

Dosage And Administration

AVITA® Gel should be applied once a day, in the evening, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Application may cause a transient feeling of warmth or slight stinging. In cases where it has been necessary to temporarily discontinue therapy or reduce the frequency of application, therapy may be resumed or frequency of application increased when the patients become able to tolerate the treatment. Alterations of dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. Efficacy has not been established for less than once-daily dosing frequencies.During the early weeks of therapy, an apparent increase in number and exacerbation of inflammatory acne lesions may occur. This is due, in part, to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy. Therapeutic results should be noticed after two to three weeks, but more than six weeks of therapy may be required before definite beneficial effects are seen. Patients treated with AVITA® Gel may use cosmetics, but the areas to be treated should be cleansed thoroughly before the medication is applied (see Precautions Section).

How Supplied

AVITA® (tretinoin gel) Gel, 0.025% is supplied as:NDC CodeStrengthQuantity0378-6140-440.025%20 g0378-6140-450.025%45 g

Storage Conditions

Keep this and all medications out of the reach of childrenStore below 30°C (86°F). Avoid freezing.Rx OnlyManufactured for:Mylan Pharmaceuticals Inc.Morgantown, WV 26505 U.S.A.REVISED NOVEMBER 2013022.6Patent #’s: 5,650,171 Remove this portion before dispensing

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