NDC 0299-3823 Soolantra

Ivermectin

NDC Product Code 0299-3823

NDC 0299-3823-00

Package Description: 2 g in 1 TUBE

NDC 0299-3823-02

Package Description: 1 TUBE in 1 BLISTER PACK > 2 g in 1 TUBE

NDC 0299-3823-30

Package Description: 1 TUBE in 1 CARTON > 30 g in 1 TUBE

NDC 0299-3823-45

Package Description: 1 TUBE in 1 CARTON > 45 g in 1 TUBE

NDC 0299-3823-60

Package Description: 1 TUBE in 1 CARTON > 60 g in 1 TUBE

NDC Product Information

Soolantra with NDC 0299-3823 is a a human prescription drug product labeled by Galderma Laboratories, L.p.. The generic name of Soolantra is ivermectin. The product's dosage form is cream and is administered via topical form.

Labeler Name: Galderma Laboratories, L.p.

Dosage Form: Cream - An emulsion, semisolid3 dosage form, usually containing > 20% water and volatiles5 and/or < 50% hydrocarbons, waxes, or polyols as the vehicle. This dosage form is generally for external application to the skin or mucous membranes.

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.

Soolantra 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.

  • IVERMECTIN 10 mg/g

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.

  • CARBOMER COPOLYMER TYPE B (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 809Y72KV36)
  • CETYL ALCOHOL (UNII: 936JST6JCN)
  • CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)
  • DIMETHICONE (UNII: 92RU3N3Y1O)
  • EDETATE DISODIUM (UNII: 7FLD91C86K)
  • GLYCERIN (UNII: PDC6A3C0OX)
  • ISOPROPYL PALMITATE (UNII: 8CRQ2TH63M)
  • METHYLPARABEN (UNII: A2I8C7HI9T)
  • OLEYL ALCOHOL (UNII: 172F2WN8DV)
  • PHENOXYETHANOL (UNII: HIE492ZZ3T)
  • POLYOXYL 20 CETOSTEARYL ETHER (UNII: YRC528SWUY)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • PROPYLPARABEN (UNII: Z8IX2SC1OH)
  • WATER (UNII: 059QF0KO0R)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SORBITAN MONOSTEARATE (UNII: NVZ4I0H58X)
  • STEARYL ALCOHOL (UNII: 2KR89I4H1Y)

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.

  • Antiparasitic - [EPC] (Established Pharmacologic Class)
  • Pediculicide - [EPC] (Established Pharmacologic Class)

Product Labeler Information

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

Labeler Name: Galderma Laboratories, L.p.
Labeler Code: 0299
FDA Application Number: NDA206255 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: 01-01-2015 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".

* Please review the disclaimer below.

Soolantra 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

1 Indications And Usage

SOOLANTRA cream is indicated for the treatment of inflammatory lesions of rosacea.

2 Dosage And Administration

Apply to the affected areas of the face once daily. Use a pea-size amount for each area of the face (forehead, chin, nose, each cheek) that is affected. Spread as a thin layer, avoiding the eyes and lips. SOOLANTRA cream is not for oral, ophthalmic, or intravaginal use.

3 Dosage Forms And Strengths

Cream, 1%.Each gram of SOOLANTRA cream contains 10 mg of ivermectin in a white to pale yellow cream base. SOOLANTRA cream is supplied in tubes of 30 g, 45 g and 60 g.

4 Contraindications

None.

6 Adverse Reactions

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. During clinical trials, 2047 subjects with inflammatory lesions of rosacea received SOOLANTRA cream once daily. A total of 1555 subjects were treated once daily for more than 12 weeks, and 519 for approximately one year. Adverse reactions, reported in ≤ 1% of subjects treated with SOOLANTRA cream for at least 3 months in vehicle-controlled clinical trials, included skin burning sensation and skin irritation.In postmarketing use with Soolantra, occurrences of contact dermatitis and allergic dermatitis have been reported.

7 Drug Interactions

In vitro studies have shown that SOOLANTRA cream, at therapeutic concentrations, neither inhibits nor induces cytochrome P450 (CYP450) enzymes.

8.1 Pregnancy

Pregnancy Category C.There are no adequate and well-controlled studies in pregnant women. SOOLANTRA cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Note: The animal multiples of human exposure calculations were based on AUC comparisons. The maximum topical human dose (MTHD) of SOOLANTRA cream is 1 g applied once daily.Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 1.5, 4, and 12 mg/kg/day ivermectin were administered during the period of organogenesis (gestational days 6–17) to pregnant female rats. Maternal death occurred at 12 mg/kg/day (1909X MTHD). Cleft palate occurred in the fetuses from the 12 mg/kg/day (1909X MTHD) group. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 4 mg/kg/day (708X MTHD). Oral doses of 0.5, 1.5, 2.5, 3.5 and 4.5 mg/kg/day ivermectin were administered during the period of organogenesis (gestational days 7–20) to pregnant female rabbits. Maternal death occurred at doses >2.5 mg/kg/day (72X MTHD). Carpal flexure occurred in the fetuses from the 4.5 mg/kg/day (354X MTHD) group. Fetal weight decrease was noted at 3.5 mg/kg/day (146X MTHD). No treatment related effects on embryofetal toxicity were noted at 2.5 mg/kg/day (72X MTHD) and no treatment related effects on teratogenicity were noted at 3.5 mg/kg/day (146X MTHD).A pre- and postnatal development study was conducted in rats. Oral doses of 1, 2 and 4 mg/kg/day ivermectin were administered to pregnant female rats during gestational days 6-20 and lactation days 2-20. Neonatal death occurred at doses >2 mg/kg/day. Behavior development of newborn rats was adversely affected at all doses.

8.3 Nursing Mothers

Following oral administration, ivermectin is excreted in human milk in low concentrations. Excretion in human milk following topical administration has not been evaluated. In oral studies in rats, ivermectin was excreted in the milk of nursing mothers and neonatal toxicity was observed in the litters. The blood-brain barrier in neonatal rats may not be fully developed at birth. Because of the potential for serious adverse reactions from SOOLANTRA cream in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness of SOOLANTRA cream in pediatric patients have not been established.

8.5 Geriatric Use

Of the 1371 subjects in the two pivotal clinical studies of SOOLANTRA cream, 170 (12.4%) were 65 and over, while 37 (2.7%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

10 Overdosage

In accidental or significant exposure to unknown quantities of veterinary formulations of ivermectin in humans, either by ingestion, inhalation, injection, or exposure to body surfaces, the following adverse effects have been reported most frequently: rash, edema, headache, dizziness, asthenia, nausea, vomiting, and diarrhea. Other adverse effects that have been reported include: seizure, ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis.In case of accidental ingestion, supportive therapy, if indicated, should include parenteral fluids and electrolytes, respiratory support (oxygen and mechanical ventilation if necessary) and pressor agents if clinically significant hypotension is present. Induction of emesis and/or gastric lavage as soon as possible, followed by purgatives and other routine anti-poison measures, may be indicated if needed to prevent absorption of ingested material.

11 Description

SOOLANTRA (ivermectin) cream, 1% is a white to pale yellow hydrophilic cream. Each gram of SOOLANTRA cream contains 10 mg of ivermectin. It is intended for topical use.Ivermectin is a semi-synthetic derivative isolated from the fermentation of Streptomyces avermitilis that belongs to the avermectin family of macrocyclic lactones.Ivermectin is a mixture containing not less than 95.0% and not more than 102.0% of 5-O-demethyl-22,23-dihydroavermectin A1a plus 5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl)-22,23-dihydroavermectin A1a, generally referred to as 22,23-dihydroavermectin B1a and B1b or H2B1a and H2B1b, respectively; and the ratio (calculated by area percentage) of component H2B1a/(H2B1a + H2B1b) is not less than 90.0%. The respective empirical formulas of H2B1a and H2B1b are C48H74O14 and C47H72O14 with molecular weights of 875.10 and 861.07 respectively.The structural formulas are:Component H2B1a: R = C2H5, Component H2B1b: R = CH3.SOOLANTRA cream contains the following inactive ingredients: carbomer copolymer type B, cetyl alcohol, citric acid monohydrate, dimethicone, edetate disodium, glycerin, isopropyl palmitate, methylparaben, oleyl alcohol, phenoxyethanol, polyoxyl 20 cetostearyl ether, propylene glycol, propylparaben, purified water, sodium hydroxide, sorbitan monostearate, and stearyl alcohol.

12.1 Mechanism Of Action

The mechanism of action of SOOLANTRA cream in treating rosacea lesions is unknown.

12.2 Pharmacodynamics

Cardiac ElectrophysiologyAt therapeutic doses, SOOLANTRA cream is not expected to prolong QTc interval.

12.3 Pharmacokinetics

AbsorptionThe absorption of ivermectin from SOOLANTRA cream was evaluated in a clinical trial in 15 adult male and female subjects with severe papulopustular rosacea applying 1 g SOOLANTRA cream, 1% once daily. At steady state (after 2 weeks of treatment), the highest mean ± standard deviation plasma concentrations of ivermectin peaked (Tmax) at 10 ± 8 hours post dose, the maximum concentration (Cmax) was 2.10 ± 1.04 ng/mL (range: 0.69 - 4.02 ng/mL) and the area under the concentration curve (AUC0-24hr) was 36.14 ± 15.56 ng.hr/mL (range: 13.69-75.16 ng.hr/mL). In addition, systemic exposure assessment in longer treatment duration (Phase 3 studies) showed that there was no plasma accumulation of ivermectin over the 52-week treatment period.DistributionAn in vitro study demonstrated that ivermectin is greater than 99% bound to plasma proteins and is bound primarily to human serum albumin. No significant binding of ivermectin to erythrocytes was observed.MetabolismIn vitro studies using human hepatic microsomes and recombinant CYP450 enzymes have shown that ivermectin is primarily metabolized by CYP3A4. In vitro studies show that ivermectin at therapeutic concentrations does not inhibit the CYP450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 or 4A11, or induce 1A2, 2B6, 2C9 or 3A4.ExcretionThe apparent terminal half-life averaged 6.5 days (mean ± standard deviation: 155± 40 hours, range 92-238 hours) in patients receiving a once daily cutaneous application of SOOLANTRA cream for 28 days.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a 2-year dermal mouse carcinogenicity study, ivermectin was administered to CD-1 mice at topical doses of 1, 3, and 10 mg/kg/day (0.1%, 0.3% and 1% ivermectin cream applied at 2 ml/kg/day). No drug-related tumors were noted in this study up to the highest dose evaluated in this study of 10 mg/kg/day (747X maximum topical human dose [MTHD]).In a 2-year oral rat carcinogenicity study, ivermectin was administered to Wistar rats at gavage doses of 1, 3, and 9 mg/kg/day. A statistically significant increase in the incidence of hepatocellular adenoma was noted in males treated with 9 mg/kg/day (1766X MTHD) ivermectin. The clinical relevance of this finding is unknown. No drug-related tumors were noted in females up to the highest dose evaluated in this study of 9 mg/kg/day (1959X MTHD). No drug-related tumors were noted in males at doses ≤ 3 mg/kg/day (599X MTHD).Ivermectin revealed no evidence of genotoxic potential based on the results of two in vitro genotoxicity tests (the Ames test and the L5178Y/TK+/- mouse lymphoma assay) and one in vivo genotoxicity test (rat micronucleus assay).In a fertility study, oral doses of 0.1, 1 and 9 mg/kg/day ivermectin were administered to male and female rats. Mortality occurred at 9 mg/kg/day (1027X MTHD). The precoital period was generally prolonged at 9 mg/kg/day. No treatment-related effects on fertility or mating performance were noted at doses ≤ 1 mg/kg/day (68X MTHD).

14 Clinical Studies

SOOLANTRA cream applied once daily at bedtime was evaluated in the treatment of inflammatory lesions of rosacea in two randomized, double-blind, vehicle controlled clinical trials, which were identical in design. The trials were conducted in 1371 subjects aged 18 years and older who were treated once daily for 12 weeks with either SOOLANTRA cream or vehicle cream.Overall, 96% of subjects were Caucasian and 67% were female. Using the 5-point Investigator Global Assessment (IGA) scale (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), 79% of subjects were scored as moderate (IGA=3) and 21% scored as severe (IGA= 4) at baseline.The co-primary efficacy endpoints in both pivotal trials were the success rate based on the IGA outcome (percentage of subjects “clear” and “almost clear”) and absolute change from baseline in inflammatory lesion counts at Week 12. Table 1 presents the co-primary efficacy results at Week 12. SOOLANTRA cream was more effective than vehicle cream on the co-primary efficacy endpoints starting from 4 weeks of treatment in both studies, see Figures 1 through 4.Table 1: Co-Primary Efficacy Results at Week 12Study 1Study 2  SOOLANTRA              VehicleCream (N=451)       Cream (N=232)  SOOLANTRA              VehicleCream (N=459)       Cream (N=229)Investigator Global Assessment:Number (%) of Subjects Clear or Almost Clear173 (38.4%)             27 (11.6%)184 (40.1%)               43 (18.8%)Inflammatory Lesion Counts:Mean Absolute (%) Change from Baseline20.5 (64.9%)             12.0 (41.6%)22.2 (65.7%)             13.4 (43.4%)Figures 1 and 2: IGA Success Rates Over TimeFigures 3 and 4: Mean Absolute Change in Inflammatory Lesion Counts from Baseline Over Time

16 How Supplied/Storage And Handling

SOOLANTRA (ivermectin) cream, 1% is a white to pale yellow cream, supplied in a laminated tube with a child resistant cap in the following sizes:30 gram NDC 0299-3823-3045 gram NDC 0299-3823-4560 gram NDC 0299-3823-60StorageStore at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature].

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).Patients using SOOLANTRA cream should receive the following instruction:Keep out of reach of children.Marketed by:GALDERMA LABORATORIES, L.P.Fort Worth, Texas 76177 USAMade in Canada.P52476-1

Instructions For Use

SOOLANTRA (soo lan' trah) (ivermectin) cream, 1%Important: SOOLANTRA® cream is for use on the face only. Do not use SOOLANTRA cream in your eyes, mouth or vagina.Read and follow the steps below so that you use SOOLANTRA cream correctly:1. Open the tube of SOOLANTRA cream by gently pressing down on the child resistant cap and twist in the direction of the arrow (counterclockwise) as shown below. See Figures A and B. To avoid spilling, do not squeeze the tube while opening or closing.2. To apply SOOLANTRA cream to your face, squeeze a pea-sized amount of SOOLANTRA cream from the tube onto your fingertip. See Figure C.3. Apply SOOLANTRA to the affected areas of your face once a day. Use a pea-sized amount of SOOLANTRA cream for each area of your face (forehead, chin, nose, each cheek) that is affected. Spread the cream smoothly and evenly in a thin layer. Avoid contact with your eyes and lips.4. To close SOOLANTRA cream, gently press down on the child resistant cap and twist to the right (clockwise). See Figure D.How should I store SOOLANTRA cream?Store SOOLANTRA cream at room temperature between 68°F to 77°F (20°C to 25°C).Keep SOOLANTRA cream out of the reach of children.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Marketed by:GALDERMA LABORATORIES, L.P.Fort Worth, TX 76177 USAMade in Canada.Issued: September 2017P52476-1

Package Label - 30 G

NDC 0299-3823-30soolantra®(ivermectin) cream, 1%Rx onlyFor Topical Use OnlyKeep Out of Reach of ChildrenNET WT. 30 gGALDERMAGTIN: 00302993823308SN:LOT:EXP:Marketed by:GALDERMA LABORATORIES, L.P.Fort Worth, TX 76177 USAMade in CanadaP52477-1 Rev.: 03/17Not for oral, ophthalmic, or intravaginal use.To Open Tube: Push cap in and turn counterclockwise to remove cap.Usual Dosage: Apply to the affected areas once daily. See package insert for complete prescribing information.Each gram contains the active ingredient ivermectin 10 mg (1%) with the inactive ingredients carbomer copolymer type B, cetyl alcohol, citric acid monohydrate, dimethicone, edetate disodium, glycerin, isopropyl palmitate, methylparaben, oleyl alcohol, phenoxyethanol, polyoxyl 20 cetostearyl ether, propylene glycol, propylparaben, purified water, sodium hydroxide, sorbitan monostearate, and stearyl alcohol.Storage: Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).[See USP Controlled Room Temperature].See carton closure for lot number and expiration.

* Please review the disclaimer below.