NDC 24208-630 Bepotastine Besilate

Bepotastine Besilate

NDC Product Code 24208-630

NDC CODE: 24208-630

Proprietary Name: Bepotastine Besilate What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Bepotastine Besilate What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat itching of the eyes due to allergies. Bepotastine is an antihistamine. It works by blocking a certain natural substance (histamine) that causes allergic symptoms. Do not use this medication to treat red or irritated eyes due to wearing contact lenses. Contact your doctor for further instructions if this occurs.

NDC Code Structure

NDC 24208-630-05

Package Description: 1 BOTTLE, DROPPER in 1 CARTON > 5 mL in 1 BOTTLE, DROPPER

NDC 24208-630-10

Package Description: 1 BOTTLE, DROPPER in 1 CARTON > 10 mL in 1 BOTTLE, DROPPER

NDC Product Information

Bepotastine Besilate with NDC 24208-630 is a a human prescription drug product labeled by Bausch & Lomb Incorporated. The generic name of Bepotastine Besilate is bepotastine besilate. The product's dosage form is solution/ drops and is administered via ophthalmic form.

Labeler Name: Bausch & Lomb Incorporated

Dosage Form: Solution/ Drops - A solution which is usually administered in a drop-wise fashion.

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.

Bepotastine Besilate 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.

  • BEPOTASTINE BESILATE 15 mg/mL

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.

  • BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)
  • SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)
  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

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

  • Ophthalmic - Administration to the external eye.

Pharmacological Class(es)

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

  • Histamine-1 Receptor Antagonist - [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: Bausch & Lomb Incorporated
Labeler Code: 24208
FDA Application Number: NDA022288 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 AUTHORIZED GENERIC - A product marketed as a “generic” drug under an approved New Drug Application (NDA), rather than an Abbreviated New Drug Application (ANDA),. 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: 05-28-2021 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: 12-31-2022 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.

Bepotastine Besilate 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

Bepotastine Besilate Ophthalmic Solution, 1.5% is a histamine H1 receptor antagonist indicated for the treatment of itching associated with signs and symptoms of allergic conjunctivitis.

2 Dosage And Administration

Instill one drop of Bepotastine Besilate Ophthalmic Solution into the affected eye(s) twice a day. Remove contact lenses prior to instillation of Bepotastine Besilate Ophthalmic Solution.

3 Dosage Forms And Strengths

Ophthalmic solution containing bepotastine besilate 15 mg/mL (1.5%).

4 Contraindications

Bepotastine Besilate Ophthalmic Solution is contraindicated in patients with a history of hypersensitivity reactions to bepotastine or any of the other ingredients [see Adverse Reactions (6.2)].

5.1 Contamination Of Tip And Solution

To minimize contaminating the dropper tip and solution, advise the patient not to touch the eyelids or surrounding areas with the dropper tip of the bottle and to keep the bottle tightly closed when not in use.

5.2 Contact Lens Wear

Bepotastine Besilate Ophthalmic Solution should not be used to treat contact lens-related irritation. Bepotastine Besilate Ophthalmic Solution should not be instilled while wearing contact lenses. Patient should remove contact lenses prior to instillation of Bepotastine Besilate Ophthalmic Solution, because benzalkonium chloride may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of Bepotastine Besilate Ophthalmic Solution.

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 clinical practice. The most common reported adverse reaction occurring in approximately 25% of subjects was a mild taste following instillation. Other adverse reactions occurring in 2-5% of subjects were eye irritation, headache, and nasopharyngitis.

6.2 Post-Marketing Experience

Hypersensitivity reactions have been reported rarely during the post-marketing use of Bepotastine Besilate Ophthalmic Solution. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The hypersensitivity reactions may include itching, body rash, and swelling of lips, tongue and/or throat.

8.1 Pregnancy

Risk SummaryThere are no available human data for the use of Bepotastine Besilate Ophthalmic Solution during pregnancy to inform any drug-associated risks.Oral administration of bepotastine besilate to pregnant rats or rabbits during organogenesis or during the pre/postnatal period did not produce adverse embryofetal or offspring effects at clinically relevant systemic exposures. Maternal toxicity was observed in the rabbits at the lowest dose administered, 20 mg/kg/day (215 times the maximum recommended human ophthalmic dose, RHOD, on a mg/m2 basis) [see Data].The background risk of major birth defects and miscarriage for the indicated population is unknown. However, 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.DataAnimal DataIn embryofetal development studies, oral administration of bepotastine besilate to pregnant rabbits throughout organogenesis did not produce teratogenic effects at maternal doses up to 500 mg/kg/day (approximately 5400 times the maximum RHOD, on a mg/m2 basis). A maternal no observed adverse effect level (NOAEL) was not identified in this study due to spontaneous abortion observed at the lowest dose tested, 20 mg/kg/day (approximately 215 times higher than the maximum RHOD, on a mg/m2 basis). Oral administration of bepotastine besilate to pregnant rats throughout organogenesis produced skeletal anomalies at 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis), a dose that also produced maternal toxicity and lethality. No teratogenic effects were observed in rats at maternal doses up to 200 mg/kg/day (corresponding to an estimated blood plasma concentration 3300 times higher than that anticipated in humans at the maximum RHOD). A maternal NOAEL was observed at 10 mg/kg/day (54 times higher than the maximum RHOD, on a mg/m2 basis). Following a single 3 mg/kg oral dose in rats (16 times higher than the maximum RHOD, on a mg/m2 basis), the concentration of radio-labeled bepotastine besilate was similar in fetal liver and maternal blood plasma. The concentration in other fetal tissues was one-third to one-tenth the concentration in maternal blood plasma.In a pre/postnatal development study, oral administration of bepotastine besilate to rats during the perinatal and lactation periods produced an increase in stillbirths and decreased growth and development in offspring at a maternal dose of 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis). There were no observed adverse effects on offspring of rats treated with 100 mg/kg/day (540 times higher than the maximum RHOD, on a mg/m2 basis). Effects on parturition and maternal lethality were observed at 100 mg/kg/day and 1000 mg/kg/day, respectively. A maternal NOAEL was observed at 10 mg/kg/day (54 times higher than the maximum RHOD, on a mg/m2 basis).

8.2 Lactation

Risk SummaryThere are no data on the presence of Bepotastine Besilate Ophthalmic Solution in human milk, the effects on the breastfed infant or the effects on milk production.The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for Bepotastine Besilate Ophthalmic Solution, and any potential adverse effects on the breastfed infant from Bepotastine Besilate Ophthalmic Solution.Animal DataFollowing a single 3 mg/kg oral dose (16 times the maximum RHOD, on a mg/m2 basis) of radiolabeled bepotastine besilate to nursing rats 11 days after delivery, the maximum concentration of radioactivity in milk was 0.40 mcg-eq/mL 1 hour after administration; at 48 hours after administration, the radioactivity concentration was below detection limits. The milk radioactivity concentration was higher than the maternal blood plasma radioactivity concentration at each time of measurement. It is not known whether bepotastine besilate would be present in maternal milk following topical ocular administration.

8.4 Pediatric Use

Safety and efficacy of Bepotastine Besilate Ophthalmic Solution, 1.5% have not been established in pediatric patients under 2 years of age. Efficacy in pediatric patients under 10 years of age was extrapolated from clinical trials conducted in pediatric patients greater than 10 years of age and from adults.

8.5 Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

11 Description

  • Bepotastine Besilate Ophthalmic Solution, 1.5% is a sterile, topically administered drug for ophthalmic use. Each mL of Bepotastine Besilate Ophthalmic Solution contains 15 mg bepotastine besilate. Bepotastine besilate is designated chemically as (+) -4-[[(S)-p-chloro-alpha -2-pyridylbenzyl]oxy]-1-piperidine butyric acid monobenzenesulfonate. The chemical structure for bepotastine besilate is: Bepotastine besilate is a white to pale yellowish-white crystalline powder. The molecular weight of bepotastine besilate is 547.06 daltons. Bepotastine Besilate Ophthalmic Solution is supplied as a sterile, aqueous 1.5% solution, with an approximate pH of 6.8. The osmolality of Bepotastine Besilate Ophthalmic Solution, 1.5% is approximately 295 mOsm/kg. Each mL of Bepotastine Besilate Ophthalmic Solution, 1.5% contains: •Active: bepotastine besilate 15 mg (equivalent to 10.7 mg bepotastine) •Inactives:monobasic sodium phosphate dihydrate, sodium chloride, sodium hydroxide to adjust pH, and water for injection, USP. •Preservative: benzalkonium chloride 0.005%

12.1 Mechanism Of Action

Bepotastine is a topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from mast cells.

12.3 Pharmacokinetics

Absorption: The extent of systemic exposure to bepotastine following topical ophthalmic administration of bepotastine besilate 1% and 1.5% ophthalmic solutions was evaluated in 12 healthy adults. Following one drop of 1% or 1.5% bepotastine besilate ophthalmic solution to both eyes four times daily (QID) for 7 days, bepotastine plasma concentrations peaked at approximately 1 to 2 hours post-instillation. Maximum plasma concentrations for the 1% and 1.5% strengths were 5.1 ± 2.5 ng/mL and 7.3 ± 1.9 ng/mL, respectively. Plasma concentrations at 24 hours post-instillation were below the quantifiable limit (2 ng/mL) in 11/12 subjects in the two dose groups. Distribution: The extent of protein binding of bepotastine is approximately 55% and independent of bepotastine concentration. Metabolism: In vitrometabolism studies with human liver microsomes demonstrated that bepotastine is minimally metabolized by CYP450 isozymes. In vitrostudies demonstrated that bepotastine besilate does not inhibit the metabolism of various cytochrome P450 substrates via inhibition of CYP3A4, CYP2C9, and CYP2C19. The effect of bepotastine besilate on the metabolism of substrates of CYP1A2, CYP2C8 and CYP2D6 was not studied. Bepotastine besilate has a low potential for drug interaction via inhibition of CYP3A4, CYP2C9, and CYP2C19. Excretion: The main route of elimination of bepotastine besilate is urinary excretion (with approximately 75-90% excreted unchanged in urine).

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisLong-term dietary studies in mice and rats were conducted to evaluate the carcinogenic potential of bepotastine besilate. Bepotastine besilate did not significantly induce neoplasms in mice receiving a nominal dose of up to 200 mg/kg/day for 21 months, or in rats receiving a nominal dose of up to 97 mg/kg/day for 24 months. These dose levels correspond to systemic exposures approximately 350 and 200 times higher than that achieved at the RHOD, respectively. The no observable adverse effect level for bepotastine besilate based on nominal dose levels in carcinogenicity tests were 18.7 to 19.9 mg/kg/day in mice and 9.6 to 9.8 mg/kg/day in rats (corresponding to systemic exposures approximately 60 and 20 times higher than that anticipated in humans at RHOD, respectively). MutagenesisThere was no evidence of genotoxicity in the Ames test (mutagenicity), in CHO cells (chromosome aberration), in mouse hepatocytes (unscheduled DNA synthesis), or in the mouse micronucleus test. Impairment of FertilityOral administration of bepotastine to male and female rats at doses up to 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis) resulted in reduction in fertility index and surviving fetuses. Oral administration of bepotastine besilate produced no observed adverse effects on fertility or reproduction in rats at oral doses up to 200 mg/kg/day (corresponding to an estimated blood plasma concentration 3300 times higher than that anticipated in humans at the RHOD).

14 Clinical Studies

Clinical efficacy was evaluated in two conjunctival allergen challenge (CAC) studies (237 patients). Bepotastine Besilate Ophthalmic Solution, 1.5% was more effective than its vehicle for relieving ocular itching induced by an ocular allergen challenge, both at a CAC 15 minutes post-dosing and a CAC 8 hours post-dosing of Bepotastine Besilate Ophthalmic Solution. The safety of Bepotastine Besilate Ophthalmic Solution was evaluated in a randomized clinical study of 861 subjects over a period of 6 weeks.

16 How Supplied/Storage And Handling

Bepotastine Besilate Ophthalmic Solution, 1.5% is supplied in a white low density polyethylene bottle with a sterile linear low density polyethylene controlled dropper tip and a white polyproplyene cap in the following sizes: NDC 24208-630-05        5 mL Bottle NDC 24208-630-10      10 mL BottleStorage:Store at 15° to 25°C (59° to 77°F).

17 Patient Counseling Information

  • •Sterility of Dropper TipAdvise patients not to touch the dropper tip to any surface, as this may contaminate the solution and to keep the bottle tightly closed when not in use. •Concomitant Use of Contact LensesAdvise patients not to wear a contact lens if their eye is red and that Bepotastine Besilate Ophthalmic Solution should not be used to treat contact lens-related irritation. Patients should also be advised to remove contact lenses prior to instillation of Bepotastine Besilate Ophthalmic Solution, which may be reinserted after 10 minutes following administration.Distributed by:Bausch + Lomb, a division ofBausch Health US, LLCBridgewater, NJ 08807 USAManufactured by:Bausch & Lomb IncorporatedTampa, FL 33637 USAUnder license from: Senju Pharmaceutical Co., Ltd.Osaka, Japan 541-0046U.S. Patent Numbers: 8,784,789 and 8,877,168© 2020 Bausch & Lomb Incorporated or its affiliates9751300 (folded)9751400 (flat)

* Please review the disclaimer below.