DRUGS & SUPPLEMENTS

Oto Betnovate

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Oto Betnovate uses

Oto Betnovate consists of Betamethasone Valerate, Chlorphenesin, Tetracaine Hydrochloride.

Betamethasone Valerate:



Oto Betnovate (Betamethasone Valerate) Spray is indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.

Oto Betnovate (Betamethasone Valerate) Spray is a corticosteroid indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older. (1)

2 DOSAGE AND ADMINISTRATION

Shake well before use.

Apply Oto Betnovate (Betamethasone Valerate) Spray to the affected skin areas twice daily and rub in gently.

Use Oto Betnovate (Betamethasone Valerate) Spray for up to 4 weeks of treatment. Treatment beyond 4 weeks is not recommended.

Discontinue Oto Betnovate (Betamethasone Valerate) Spray when control is achieved.

Do not use if atrophy is present at the treatment site.

Do not bandage, cover, or wrap the treated skin area unless directed by a physician.

Avoid use on the face, scalp, axilla, groin, or other intertriginous areas.

Oto Betnovate (Betamethasone Valerate) Spray is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

  • Apply to the affected skin areas twice daily. Rub in gently. (2)
  • Use Oto Betnovate (Betamethasone Valerate) Spray for up to 4 weeks and not beyond. (2)
  • Discontinue treatment when control is achieved. (2)
  • Do not use if atrophy is present at the treatment site. (2)
  • Do not use with occlusive dressings unless directed by a physician. (2)
  • Avoid use on the face, scalp, axilla, groin, or other intertriginous areas. (2)
  • Not for oral, ophthalmic, or intravaginal use. (2)
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3 DOSAGE FORMS AND STRENGTHS

Spray, 0.05% for topical use. Each gram of Oto Betnovate (Betamethasone Valerate) Spray contains 0.643 mg Oto Betnovate (Betamethasone Valerate) dipropionate USP (equivalent to 0.5 mg Oto Betnovate (Betamethasone Valerate)) in a slightly thickened, white to off-white oil-in-water emulsion.

Spray: 0.05% (equivalent to 0.5 mg betamethasone/g) (3)

4 CONTRAINDICATIONS

None.

  • None. (4)

5 WARNINGS AND PRECAUTIONS

  • Oto Betnovate Spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1)
  • Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1)
  • Use of topical corticosteroids may require periodic evaluation for HPA axis suppression. (5.1)
  • Modify use if HPA axis suppression develops. (5.1)
  • High potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure and young age may predispose patients to HPA axis suppression. (5.1)
  • Pediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. (5.1, 8.4)

5.1 Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression and Other Unwanted Systemic Glucocorticoid Effects

Oto Betnovate (Betamethasone Valerate) Spray can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age.

Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test.

In a study including 48 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, abnormal ACTH stimulation test results suggestive of adrenal suppression were identified in 5 out of 24 (20.8%) subjects after treatment with Oto Betnovate (Betamethasone Valerate) Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with Oto Betnovate (Betamethasone Valerate) Spray twice daily for 29 days .

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental systemic corticosteroids may be required.

Systemic effects of topical corticosteroids may also manifest as Cushing’s syndrome, hyperglycemia, and glucosuria. These events are rare and generally occur after prolonged exposure to larger than recommended doses, particularly with high-potency topical corticosteroids.

Minimize the unwanted risks from endocrine effects by mitigating the risk factors favoring increased systemic bioavailability and by using the product as recommended .

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios. Use of Oto Betnovate (Betamethasone Valerate) Spray is not recommended in pediatric patients .

5.2 Allergic Contact Dermatitis

Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Corroborate such an observation with appropriate diagnostic patch testing. If irritation develops, discontinue the topical corticosteroid and institute appropriate therapy.

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6 ADVERSE REACTIONS

The most common adverse reactions are application site reactions, including pruritus, burning and/or stinging, pain, and atrophy. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Promius Pharma, LLC. at 1-888-966-8766 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

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.

In two randomized, multicenter, prospective vehicle-controlled clinical trials, subjects with moderate plaque psoriasis of the body applied Oto Betnovate (Betamethasone Valerate) Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied Oto Betnovate (Betamethasone Valerate) Spray and 180 subjects applied vehicle spray.

Adverse reactions that occurred in at least 1% of subjects treated with Oto Betnovate (Betamethasone Valerate) Spray for up to 28 days are presented in Table 1.

Oto Betnovate (Betamethasone Valerate) Spray b.i.d.

(N=352)

Vehicle Spray b.i.d.

(N=180)

Application site pruritus 6.0% 9.4%
Application site burning

and/or stinging

4.5% 10.0%
Application site pain 2.3% 3.9%
Application site atrophy 1.1% 1.7%

Less common adverse reactions (with occurrence lower than 1% but higher than 0.1%) in subjects treated with Oto Betnovate (Betamethasone Valerate) spray were application site reactions including telangiectasia, dermatitis, discoloration, folliculitis and skin rash, in addition to dysgeusia and hyperglycemia. These adverse reactions were not observed in subjects treated with vehicle.

6.2 Postmarketing Experience

Because adverse 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.

Postmarketing reports for local adverse reactions to topical corticosteroids have also included striae, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria.

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8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Oto Betnovate Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Oto Betnovate (Betamethasone Valerate) dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias, cephalocele, and cleft palate.

8.3 Nursing Mothers

Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Oto Betnovate (Betamethasone Valerate) Spray is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Oto Betnovate Spray in patients younger than 18 years of age have not been studied; therefore use in pediatric patients is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at greater risk of systemic toxicity, including HPA axis suppression and adrenal insufficiency, when treated with topical drugs. [see Warnings and Precautions (5.1)]

Rare systemic effects such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids.

Local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients.

8.5 Geriatric Use

Clinical studies of Oto Betnovate (Betamethasone Valerate) Spray did not include sufficient numbers of subjects who were 65 years of age or older to determine whether they respond differently from younger subjects.

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11 DESCRIPTION

Oto Betnovate (Betamethasone Valerate) Spray contains 0.0643% Oto Betnovate (Betamethasone Valerate) dipropionate (equivalent to 0.05% Oto Betnovate (Betamethasone Valerate)), a synthetic, fluorinated corticosteroid.

The chemical name for Oto Betnovate (Betamethasone Valerate) dipropionate is 9-fluoro-11(β), 17, 21-trihydroxy-16(β)-methylpregna-1,4-diene-3,20-dione-17,21-dipropionate. The empirical formula is C28H37FO7 and the molecular weight is 504.6. The structural formula is shown below.

Each gram of Oto Betnovate (Betamethasone Valerate) Spray contains 0.643 mg of Oto Betnovate (Betamethasone Valerate) dipropionate USP (equivalent to 0.5 mg Oto Betnovate (Betamethasone Valerate)) in a slightly thickened, white to off-white, oil-in-water, non-sterile emulsion with the following inactive ingredients:, butylated hydroxytoluene, cetostearyl alcohol, hydroxyethyl cellulose, methylparaben, mineral oil, oleyl alcohol, polyoxyl 20 cetostearyl ether, propylparaben, purified water, and sorbitan monostearate. Oto Betnovate (Betamethasone Valerate) Spray is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing to patients.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Oto Betnovate Spray in psoriasis is unknown.

12.2 Pharmacodynamics

Vasoconstrictor studies performed with Oto Betnovate (Betamethasone Valerate) Spray in healthy subjects indicate that it is in the mid-range of potency as compared with other topical corticosteroids; however, similar blanching scores do not necessarily imply therapeutic equivalence.

The potential for HPA axis suppression by Oto Betnovate (Betamethasone Valerate) Spray was evaluated in a study randomizing 52 adult subjects with moderate to severe plaque psoriasis. Oto Betnovate (Betamethasone Valerate) Spray was applied twice daily for 15 or 29 days, in subjects with psoriasis involving a mean of 29.0% and 26.5% body surface area at baseline across the 2 treatment duration arms, respectively. Forty-eight (48) subjects were evaluated for HPA axis suppression at the end of treatment. The proportion of subjects demonstrating HPA axis suppression was 20.8% (5 out of 24) in subjects treated with Oto Betnovate (Betamethasone Valerate) Spray for 15 days. No subjects (0 out of 24) treated with Oto Betnovate (Betamethasone Valerate) Spray for 29 days had HPA axis suppression. In this study HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30-minutes post-cosyntropin stimulation. In the 4 subjects with available follow-up values, all subjects had normal ACTH stimulation tests at follow-up.

12.3 Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids are absorbed through normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Plasma concentrations of Oto Betnovate (Betamethasone Valerate) dipropionate, betamethasone-17-propionate, and Oto Betnovate (Betamethasone Valerate) were measured at baseline, and before and after the last dose (1, 3, and 6 hours) in the HPA axis suppression trial in subjects with psoriasis [see Clinical Pharmacology (12.2)]. The majority of subjects had no measurable plasma concentration (<5.00 pg/mL) of Oto Betnovate (Betamethasone Valerate) dipropionate, while the metabolites, betamethasone-17-propionate and Oto Betnovate (Betamethasone Valerate), were detected in the majority of subjects (Table 2). There was high variability in the data but there was a trend toward higher systemic exposure at Day 15 and lower systemic exposure at Day 29.

Analyte (pg/mL) Oto Betnovate (Betamethasone Valerate) Spray b.i.d.

(15 days)

Oto Betnovate (Betamethasone Valerate) Spray b.i.d.

(29 days)

Betamethasone-17-propionate 120 ± 127 63.9 ± 52.6
Oto Betnovate (Betamethasone Valerate) 119 ± 176 57.6 ± 55.9

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Oto Betnovate (Betamethasone Valerate) dipropionate.

In a 90-day repeat-dose toxicity study in rats, topical administration of Oto Betnovate (Betamethasone Valerate) dipropionate spray formulation at dose concentrations of 0.05% and 0.1% (providing dose levels up to 0.5 mg/kg/day in males and 0.25 mg/kg/day in females) resulted in a toxicity profile consistent with long-term exposure to corticosteroids including reduced body weight gain, adrenal atrophy, and histological changes in bone marrow, thymus and spleen indicative of severe immune suppression. A no observable adverse effect level (NOAEL) could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk of carcinogenesis.

Oto Betnovate (Betamethasone Valerate) was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in vitro human lymphocyte chromosome aberration assay, and equivocal in the in vivo mouse bone marrow micronucleus assay.

Studies in rabbits, mice, and rats using intramuscular doses up to 1, 33, and 2 mg/kg, respectively, resulted in dose-related increases in fetal resorptions in rabbits and mice.

14 CLINICAL STUDIES

Two multi-center, randomized, double-blind, vehicle-controlled clinical trials were conducted in subjects aged 18 years and older with moderate plaque psoriasis. In both trials, randomized subjects applied Oto Betnovate (Betamethasone Valerate) Spray or vehicle spray to the affected areas twice daily for 28 days. Enrolled subjects had body surface area of involvement between 10% to 20%, and an Investigator Global Assessment (IGA) score of 3 (moderate).

Efficacy was assessed as the proportion of subjects who were considered a treatment success (defined as having an IGA score of 0 or 1 [clear or almost clear] and at least a 2-grade reduction from baseline). Table 3 presents the efficacy results at Day 15 and Day 29.

a Treatment success is defined as an IGA of 0 or 1 (clear or almost clear) and at least a 2-grade reduction

from baseline.

Study 1 Study 2
Oto Betnovate (Betamethasone Valerate) Spray

b.i.d.

(N=182)

Vehicle Spray

b.i.d.

(N=95)

Oto Betnovate (Betamethasone Valerate) Spray

b.i.d.

(N=174)

Vehicle Spray

b.i.d.

(N=87)

Treatment Success

at Day 15

21.5% 7.4% 19.0% 2.3%
Treatment Success

at Day 29

42.7% 11.7% 34.5% 13.6%

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied/Storage

Oto Betnovate Spray is a slightly thickened, white to off-white, non-sterile emulsion supplied in high density polyethylene bottles with a heat induction seal lined polypropylene cap. The drug is supplied in the following volumes:

  • 60 mL (NDC 67857-808-17)
  • 120 mL (NDC 67857-808-04)

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) .

Each unit is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing.

16.2 Handling/Instructions for the Pharmacist

  • Remove the spray pump from the wrapper.
  • Remove and discard the cap from the bottle.
  • Keeping the bottle upright, insert the spray pump into the bottle and turn clockwise until it is closed tightly.
  • Dispense the bottle with the spray pump inserted.
  • Include the date dispensed in the space provided on the carton.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Inform patients of the following:

  • Discontinue therapy when control is achieved, unless directed otherwise by the physician.
  • Do not use for longer than 4 consecutive weeks.
  • Avoid contact with the eyes.
  • Avoid use of Oto Betnovate (Betamethasone Valerate) Spray on the face, scalp, underarms, groin or other intertriginous areas, unless directed by the physician.
  • Do not occlude the treatment area with bandage or other covering, unless directed by the physician.
  • Local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids.

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

Oto Betnovate (Betamethasone Valerate) is a trademark of Promius Pharma, LLC.

Issued: 02/2016

007465

140728

This Patient Information has been approved by the U.S. Food and Drug Administration Issued: 02/2016
PATIENT INFORMATION

Oto Betnovate (Betamethasone Valerate) (ser-ne-vo)

(betamethasone dipropionate)

Spray, 0.05%

Important: Oto Betnovate (Betamethasone Valerate) Spray is for use on the skin only. Do not get Oto Betnovate (Betamethasone Valerate) Spray near or in your eyes, mouth, or vagina.

What is Oto Betnovate (Betamethasone Valerate) Spray?

  • Oto Betnovate (Betamethasone Valerate) Spray is a prescription corticosteroid medicine used to treat mild to moderate plaque psoriasis in people 18 years of age and older.

It is not known if Oto Betnovate (Betamethasone Valerate) Spray is safe and effective in children under 18 years of age. Oto Betnovate (Betamethasone Valerate) Spray is not recommended for use in patients under 18 years of age.


Before you use Oto Betnovate (Betamethasone Valerate) Spray, tell your doctor about all of your medical conditions, including if you:

  • are allergic to any of the ingredients in Oto Betnovate (Betamethasone Valerate) Spray. See the end of this leaflet for a list of the ingredients in Oto Betnovate (Betamethasone Valerate) Spray.
  • have thinning of the skin (atrophy) at the treatment site
  • are pregnant or plan to become pregnant. It is not known if Oto Betnovate (Betamethasone Valerate) Spray will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Oto Betnovate (Betamethasone Valerate) Spray passes into breast milk.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctor if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids.


How should I use Oto Betnovate (Betamethasone Valerate) Spray?

See the “Instructions for Use” for detailed information about the right way to apply Oto Betnovate (Betamethasone Valerate) Spray.

  • Use Oto Betnovate (Betamethasone Valerate) Spray exactly as your doctor tells you to use it.
  • Your doctor should tell you how much Oto Betnovate (Betamethasone Valerate) Spray to use and where to apply it.
  • Apply Oto Betnovate (Betamethasone Valerate) Spray 2 times a day.
  • Use Oto Betnovate (Betamethasone Valerate) Spray for the shortest amount of time needed to treat your plaque psoriasis. Tell your doctor if your skin condition is not getting better after 4 weeks of using Oto Betnovate (Betamethasone Valerate) Spray. Do not use Oto Betnovate (Betamethasone Valerate) Spray for longer than 4 weeks.
  • Wash your hands after applying Oto Betnovate (Betamethasone Valerate) Spray.
  • Do not use Oto Betnovate (Betamethasone Valerate) Spray on your face, scalp, underarms (armpits), groin, or areas where your skin may touch or rub together.
  • Do not bandage, cover, or wrap the treated skin area, unless your doctor tells you to.

What are the possible side effects of Oto Betnovate (Betamethasone Valerate) Spray?

  • Oto Betnovate (Betamethasone Valerate) Spray can pass through your skin. Too much Oto Betnovate (Betamethasone Valerate) Spray passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check for adrenal gland problems.

The most common side effects of Oto Betnovate (Betamethasone Valerate) Spray include itching, burning, stinging, pain, and thinning of skin (atrophy) at the treated site.

These are not all the possible side effects of Oto Betnovate (Betamethasone Valerate) Spray.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


How should I store Oto Betnovate (Betamethasone Valerate) Spray?

  • Store Oto Betnovate (Betamethasone Valerate) Spray at room temperature between 68°F to 77°F (20°C to 25°C)
  • Throw away (discard) any unused Oto Betnovate (Betamethasone Valerate) Spray after 4 weeks.

Keep Oto Betnovate (Betamethasone Valerate) Spray and all medicines out of the reach of children.


General information about the safe and effective use of Oto Betnovate (Betamethasone Valerate) Spray.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Oto Betnovate (Betamethasone Valerate) Spray for a condition for which it was not prescribed. Do not give Oto Betnovate (Betamethasone Valerate) Spray to other people even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about Oto Betnovate (Betamethasone Valerate) Spray that is written for health professionals.


What are the ingredients in Oto Betnovate (Betamethasone Valerate) Spray?

Active ingredient: Oto Betnovate (Betamethasone Valerate) dipropionate

Inactive ingredients: butylated hydroxytoluene, cetostearyl alcohol, hydroxyethyl cellulose, methylparaben, mineral oil, oleyl alcohol, polyoxyl 20 cetostearyl ether, propylparaben, purified water, and sorbitan monostearate

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

007465

140728


Instructions for Use

Oto Betnovate (Betamethasone Valerate) (ser-ne-vo)

(betamethasone dipropionate)

Spray, 0.05%

Important: Oto Betnovate (Betamethasone Valerate) Spray is for use on the skin only. Do not get Oto Betnovate (Betamethasone Valerate) Spray near or in your eyes, mouth, or vagina.

Read this “Instructions for Use” before you start using Oto Betnovate (Betamethasone Valerate) Spray and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

Parts of the Oto Betnovate (Betamethasone Valerate) Spray bottle.

Figure A

How to apply Oto Betnovate (Betamethasone Valerate) Spray:

Step 1: Shake the Oto Betnovate (Betamethasone Valerate) Spray bottle well. Remove the cap from the pump top.

Step 2: Hold the bottle in an upright position while pointing the opening of the pump top in the direction of the affected area. To spray, push down on the pump top. Apply Oto Betnovate (Betamethasone Valerate) Spray to the affected area as instructed by your doctor. (See Figure B )

Figure B

Step 3: Spray only enough Oto Betnovate (Betamethasone Valerate) Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Oto Betnovate (Betamethasone Valerate) Spray gently.

Figure C

Repeat Steps 2 and 3 to apply Oto Betnovate (Betamethasone Valerate) Spray to other affected areas as instructed by your doctor.

Step 4: After applying Oto Betnovate (Betamethasone Valerate) Spray, place the cap back onto the pump top. (See Figure D )

Figure D

How should I store Oto Betnovate (Betamethasone Valerate) Spray?

  • Store Oto Betnovate (Betamethasone Valerate) Spray at room temperature between 68°F to 77°F (20°C to 25°C).
  • Throw away (discard) any unused Oto Betnovate (Betamethasone Valerate) Spray after 28 days.

Keep Oto Betnovate (Betamethasone Valerate) Spray and all medicines out of the reach of children.

This “Instructions for Use” has been approved by the U.S. Food and Drug Administration.

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

Oto Betnovate (Betamethasone Valerate) is a trademark of Promius Pharma, LLC.

Issued: 02/2016

007528

140693

Chlorphenesin:


A centrally acting muscle relaxant. Its mode of action is unknown. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1203)

Indication: Used, along with rest and physical therapy, to treat injuries and other painful muscular conditions. Investigated for use in trigeminal neuralgia (tic douloureux), a neuropathic disorder characterized by severe facial pain. Was investigated as a modulator of histamine release.

Oto Betnovate (Chlorphenesin) is a muscle relaxant. It blocks nerve impulses (or pain sensations) that are sent to the brain.

Tetracaine Hydrochloride:


1 INDICATIONS AND USAGE

Oto Betnovate (Tetracaine Hydrochloride) TM is indicated for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J in adults and children who weigh 40 kg or more.

Oto Betnovate (Tetracaine Hydrochloride) contains Oto Betnovate (Tetracaine Hydrochloride) HCl, an ester local anesthetic, and oxymetazoline HCl, a vasoconstrictor. Oto Betnovate (Tetracaine Hydrochloride) is indicated for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J in adults and children who weigh 40 kg or more ( 1).

2 DOSAGE AND ADMINISTRATION

Oto Betnovate is for intranasal use only ( 2). Administer Oto Betnovate (Tetracaine Hydrochloride) ipsilateral (on the same side) to the maxillary tooth on which the dental procedure will be performed.

Age Group Dose
Adults (≥ 18 years old) 2 sprays (0.2 mL per spray),

4 to 5 minutes apart

1 additional spray (0.2 mL) if adequate anesthesia has not been achieved 10 minutes after the second spray
Children who weigh 40 kg or more 2 sprays (0.2 mL per spray),

4 to 5 minutes apart

2.1 Important Dosage and Administration Instructions

  • Oto Betnovate (Tetracaine Hydrochloride) is for intranasal use only.
  • Administer ipsilateral (same side) to the maxillary tooth on which the dental procedure will be performed.
  • Wait 10 minutes after administration of Oto Betnovate (Tetracaine Hydrochloride) to perform a test drill to confirm that the tooth involved is anesthetized. A patient may not experience the same sensations of numbness or tingling of the lips and cheeks associated with injectable dental anesthetics.

2.2 Dosing in Adults

  • 2 sprays (0.2 mL each) administered 4 to 5 minutes apart in the nostril ipsilateral to the maxillary tooth on which the dental procedure will be performed. Initiate the dental procedure 10 minutes after the second spray.
  • 1 additional spray (0.2 mL) if adequate anesthesia to initiate the dental procedure has not been achieved 10 minutes after the second spray.

2.3 Dosing in Children

  • 2 sprays (0.2 mL each) administered 4 to 5 minutes apart in the nostril ipsilateral to the maxillary tooth on which the dental procedure will be performed. Initiate the dental procedure 10 minutes after the second spray.
Age Group Dose
Adults (≥ 18 years old)
  • 2 sprays (0.2 mL per spray), 4 to 5 minutes apart
  • 1 additional spray (0.2 mL) if adequate anesthesia has not been achieved 10 minutes after the second spray
Children who weigh 40 kg or more
  • 2 sprays (0.2 mL per spray), 4 to 5 minutes apart

3 DOSAGE FORMS AND STRENGTHS

Oto Betnovate (Tetracaine Hydrochloride) Nasal Spray is a pre-filled, single-use, intranasal sprayer containing a clear 0.2 mL aqueous solution at pH 6.0 ± 1.0 comprising 30 mg/mL of Oto Betnovate (Tetracaine Hydrochloride) hydrochloride and 0.5 mg/mL of oxymetazoline hydrochloride (equivalent to 26.4 mg/mL Oto Betnovate (Tetracaine Hydrochloride) and 0.44 mg/mL oxymetazoline).

Each nasal spray unit delivers one 0.2 mL spray.

Each 0.2 mL spray contains 6 mg Oto Betnovate (Tetracaine Hydrochloride) hydrochloride (equivalent to 5.27 mg Oto Betnovate (Tetracaine Hydrochloride)) and 0.1 mg oxymetazoline hydrochloride (equivalent to 0.088 mg oxymetazoline).

Nasal spray in pre-filled, single-use sprayer: 6 mg Oto Betnovate (Tetracaine Hydrochloride) HCl and 0.1 mg oxymetazoline HCl (equivalent to 5.27 mg Oto Betnovate (Tetracaine Hydrochloride) and 0.088 mg oxymetazoline) in each 0.2 mL spray ( 3).

4 CONTRAINDICATIONS

Oto Betnovate (Tetracaine Hydrochloride) is contraindicated in patients with a history of allergy to or intolerance of Oto Betnovate (Tetracaine Hydrochloride), benzyl alcohol, other ester local anesthetics, p-aminobenzoic acid (PABA), oxymetazoline, or any other component of the product .

Known hypersensitivity to Oto Betnovate (Tetracaine Hydrochloride), benzyl alcohol, other ester local anesthetics, p-aminobenzoic acid (PABA), oxymetazoline, or any other component of the product ( 4).

5 WARNINGS AND PRECAUTIONS

Hypertension and Thyroid Disease: Shown to increase blood pressure in some clinical trial patients. Monitor blood pressure. Use in patients with inadequately controlled hypertension or active thyroid disease is not advised.

Epistaxis: Use is not recommended in patients with a history of frequent nose bleeds (≥5 per month). If a decision to use is made, monitor these patients carefully ( 5.2).

Dysphagia: Carefully monitor patients for dysphagia ( 5.3).

Methemoglobinemia: May cause methemoglobinemia, particularly when used with methemoglobin-inducing agents. Use in patients with history of congenital or idiopathic methemoglobinemia not advised. If central cyanosis unresponsive to oxygen therapy occurs, suspect methemoglobinemia, confirm diagnosis with CO-oximetry, and treat with a standard clinical regimen ( 5.4).

Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs ( 5.5).

5.1 Risk of Hypertension

Oto Betnovate (Tetracaine Hydrochloride) has not been studied in Phase 3 trials in adult dental patients with blood pressure greater than 150/100 or in those with inadequately controlled active thyroid disease. Oto Betnovate (Tetracaine Hydrochloride) has been shown to increase blood pressure in some patients in clinical trials. Monitor patients for increased blood pressure. Use in patients with uncontrolled hypertension or inadequately controlled active thyroid disease of any type is not advised .

5.2 Epistaxis

In clinical trials, epistaxis occurred more frequently with Oto Betnovate than placebo. Either do not use Oto Betnovate (Tetracaine Hydrochloride) in patients with a history of frequent nose bleeds (≥ 5 per month) or monitor patients with frequent nose bleeds more carefully if Oto Betnovate (Tetracaine Hydrochloride) is used. [see Adverse Reactions ( 6.1 )].

5.3 Dysphagia

In clinical trials, dysphagia occurred more frequently with Oto Betnovate (Tetracaine Hydrochloride) than placebo. Carefully monitor patients for this adverse reaction.

5.4 Methemoglobinemia

Oto Betnovate may cause methemoglobinemia, particularly in conjunction with methemoglobin-inducing agents. Based on the literature, patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia. Use of Oto Betnovate (Tetracaine Hydrochloride) in patients with a history of congenital or idiopathic methemoglobinemia is not advised.

Patients taking concomitant drugs associated with drug-induced methemoglobinemia, such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, p-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine, may be at greater risk for developing methemoglobinemia.

Initial signs and symptoms of methemoglobinemia (which may be delayed for up to several hours following exposure) are characterized by a slate grey cyanosis seen in, e.g., buccal mucous membranes, lips and nail beds. In severe cases, symptoms may include central cyanosis, headache, lethargy, dizziness, fatigue, syncope, dyspnea, CNS depression, seizures, dysrythmia and shock. Methemoglobinemia should be considered if central cyanosis unresponsive to oxygen therapy occurs, especially if methemoglobinemia-inducing agents have been used. Calculated oxygen saturation and pulse oximetry are inaccurate in the identification of methemoglobinemia. Confirm diagnosis by measuring methemoglobin level with co-oximetry. Normally, methemoglobinemia levels are <1%, and cyanosis may not be evident until a level of at least 10% is present.

Treat clinically significant symptoms of methemoglobinemia with a standard clinical regimen such as a slow intravenous infusion of methylene blue at a dosage of 1-2 mg/kg given over a 5 minute period.

5.5 Anaphylactic Reactions

Allergic or anaphylactic reactions have been associated with Oto Betnovate (Tetracaine Hydrochloride), and may occur with other components of Oto Betnovate (Tetracaine Hydrochloride). They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, seek emergency help immediately.

6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

  • Hypertension
  • Epistaxis
  • Dysphagia
  • Methemoglobinemia
  • Anaphylatic Reactions

The most common adverse reactions occurring in >10% of patients include rhinorrhea, nasal congestion, nasal discomfort, oropharyngeal pain, and lacrimation increased ( 6).

Transient, asymptomatic elevations in systolic blood pressure (≥ 25 mm Hg from baseline) and diastolic blood pressures (≥ 15 mm Hg from baseline) have been reported ( 6).

To report SUSPECTED ADVERSE REACTIONS, contact St. Renatus, LLC at 800-865-4925 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The adverse reactions information described below is from Phase 3 randomized, controlled clinical trials [see Clinical Studies ( 14)] . These data reflect exposure to Oto Betnovate (Tetracaine Hydrochloride) in 154 adult dental patients and 20 pediatric dental patients (aged 7 to 17 years) with a need for an operative restorative dental procedure requiring local anesthesia for a single vital maxillary tooth (other than a maxillary first, second, or third molar) with no evidence of pulpal pathology. .

Common Adverse Reactions in Adult Dental Patients and Pediatric Patients Weighing 40 kg or More

The most common adverse reactions to occur in Phase 3 trials with Oto Betnovate (Tetracaine Hydrochloride) in adult dental patients and pediatric dental patients weighing 40 kg or more were rhinorrhea, nasal congestion, nasal discomfort, oropharyngeal pain, and lacrimation increased [ Table 1] .

No serious adverse events with Oto Betnovate (Tetracaine Hydrochloride) have occurred .

SOC / Preferred Term Oto Betnovate (Tetracaine Hydrochloride) (N=174) Active Comparator* (N=54) Placebo (N=88)
Respiratory System Disorders 141 (81%) 50 (93%) 18 (21%)
Rhinorrhea (runny nose) 91 (52%) 20 (37%) 3 (3%)
Nasal congestion 56 (32%) 34 (63%) 6 (7%)
Nasal discomfort 45 (26%) 7 (13%) 5 (6%)
Oropharyngeal pain (sore throat) 25 (14%) 5 (9%) 0 (0%)
Intranasal hypoesthesia 18 (10%) 8 (15%) 5 (6%)
Pharyngeal hypesthesia (numb throat) 17 (10%) 10 (19%) 0 (0%)
Throat Irritation 15 (9%) 1 (2%) 0 (0%)
Rhinalgia 10 (6%) 3 (6%) 2 (2%)
Sneezing 7 (4%) 2 (4%) 1 (1%)
Epistaxis 4 (2%) 2 (4%) 0 (0%)
Nasal Dryness 4 (2%) 0 (0%) 1 (1%)
Nervous System Disorders 39 (22%) 5 (9%) 6 (7%)
Headache 18 (10%) 3 (6%) 4 (5%)
Dysgeusia 14 (8%) 1 (2%) 1 (1%)
Sinus headache 5 (3%) 0 (0%) 0 (0%)
Dizziness 5 (3%) 0 (0%) 1 (1%)
Sensory Disturbance 4 (2%) 0 (0%) 0 (0%)
Eye Disorders 29 (17%) 8 (15%) 4 (5%)
Lacrimation increased (watery eye) 23 (13%) 6 (11%) 4 (5%)
Gastrointestinal Disorders 16 (9%) 5 (9%) 3 (3%)
Oral Discomfort 4 (2%) 0 (0%) 0 (0%)
Investigations 12 (7%) 0 (0%) 4 (5%)
BP systolic increased 8 (5%) 0 (0%) 2 (2%)
BP diastolic increased 6 (3%) 0 (0%) 1 (1%)
Cardiac Disorders 8 (5%) 5 (9%) 1 (1%)
Bradycardia 5 (3%) 3 (6%) 1 (1%)
Vascular Disorders 6 (3%) 2 (4%) 1 (1%)
Hypertension 5 (3%) 1 (2%) 1 (1%)
* Active Comparator was Oto Betnovate (Tetracaine Hydrochloride) only spray used in two clinical studies in adults.

Intranasal ulcerations, some of which were transient, were noted to have occurred following treatment with Oto Betnovate (Tetracaine Hydrochloride). In Phase 3 trials, 6 (3%) patients who received Oto Betnovate (Tetracaine Hydrochloride), but no patients who received placebo, developed nasal ulcers that were present on exam the same day as Oto Betnovate (Tetracaine Hydrochloride) dosing. Three (2%) Oto Betnovate (Tetracaine Hydrochloride) and 2 (2%) placebo-treated patients without nasal ulcerations on the day of Oto Betnovate (Tetracaine Hydrochloride) or placebo dosing were observed to have nasal ulcerations at the next day follow-up visit.

Less Common Adverse Reactions in Phase 3 Clinical Trials Adult Dental Patients and Pediatric Dental Patients Weighing 40 kg or More

Dysphagia (i.e., the sensation of difficult swallowing) is a notable adverse reaction reported in Phase 3 trials, occurring in 1.15% of patients.

For medical advice about adverse reactions, contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact St. Renatus, LLC at 800-865-4925 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch/.

7 DRUG INTERACTIONS

Monoamine oxidase inhibitors : Concomitant use of MAOIs, nonselective beta adrenergic antagonists, or tricyclic antidepressants may cause hypertension and is not recommended ( 7.1).

Oxymetazoline-containing products: Discontinue use 24 hours prior to Oto Betnovate (Tetracaine Hydrochloride) administration ( 7.2).

Intranasal products: Avoid concomitant use ( 7.3).

7.1 Monoamine Oxidase Inhibitors

Use of Oto Betnovate (Tetracaine Hydrochloride) in combination with monoamine oxidase inhibitors (MAOIs), nonselective beta adrenergic antagonists, or tricyclic antidepressants may cause hypertension and is not recommended. Alternative anesthetic agents should be chosen for patients who cannot discontinue use of MAOIs, nonselective beta adrenergic antagonists, or tricyclic antidepressants.

7.2 Oxymetazoline-containing Products

Concomitant use with other oxymetazoline-containing products has not been adequately studied. Use of Oto Betnovate (Tetracaine Hydrochloride) with other products containing oxymetazoline may increase risk of hypertension, bradycardia, and other adverse events associated with oxymetazoline. Discontinue use 24 hours prior to administration of Oto Betnovate (Tetracaine Hydrochloride).

7.3 Intranasal Products

Oxymetazoline has been known to slow the rate, but not affect the extent of absorption of concomitantly administered intranasal products. Do not administer other intranasal products with Oto Betnovate (Tetracaine Hydrochloride).

7.4 Drugs That May Cause Methemoglobinemia When Used with Oto Betnovate

Oto Betnovate (Tetracaine Hydrochloride) may cause methemoglobinemia, particularly in conjunction with methemoglobin-inducing agents such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, p- aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine. Monitor patients carefully for signs of methemoglobinemia if Oto Betnovate (Tetracaine Hydrochloride) is used in the setting of these drugs.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Limited published data on Oto Betnovate use in pregnant women are not sufficient to inform any risks. Published epidemiologic studies of nasal oxymetazoline used as a decongestant during pregnancy do not identify a consistent association with any specific malformation or pattern of malformations . In animal reproduction and development studies, oxymetazoline given subcutaneously to rats during the period of organogenesis caused structural abnormalities at a dose approximately 7.6 times the exposure of oxymetazoline HCl at the 0.3 mg maximum recommended human dose (MRHD) of Oto Betnovate (Tetracaine Hydrochloride). In a pre- and post-natal development study, oxymetazoline given subcutaneously to rats caused embryo-fetal toxicity manifested by reduced implantation sites and live litter sizes at approximately 1.5 times the MRHD and increased pup mortality at 6 times the MRHD. No adverse developmental effects were observed following subcutaneous administration of Oto Betnovate (Tetracaine Hydrochloride) HCl only to rats and rabbits during organogenesis at 32 and 6 times, respectively, the estimated exposure of Oto Betnovate (Tetracaine Hydrochloride) HCl at the 18 mg MRHD of Oto Betnovate (Tetracaine Hydrochloride) .

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 and to 20%, respectively.

Data

Human Data

Published epidemiologic studies of nasal oxymetazoline used as a decongestant during pregnancy do not identify a consistent association with any specific malformation or pattern of malformations. These data are limited by the small number of cases exposed, multiple comparisons which may have resulted in chance findings, and analyses based on decongestants as a group.

Animal Data

In an embryo-fetal development study, pregnant rats were administered subcutaneous doses of oxymetazoline HCl only at 0.1 mg/kg, Oto Betnovate (Tetracaine Hydrochloride) HCl only at 7.5 mg/kg, or oxymetazoline HCl at 0.01, 0.03, and 0.1 mg/kg/day in combination with 7.5 mg/kg Oto Betnovate (Tetracaine Hydrochloride) HCl during the period of organogenesis (Gestational Days [GD] 7-17). Oxymetazoline HCl treatment at 0.1 mg/kg/day (7.6 times the oxymetazoline AUC exposure at the maximum recommended human dose [MRHD] of Oto Betnovate (Tetracaine Hydrochloride) [3 mg oxymetazoline HCl and 18 mg Oto Betnovate (Tetracaine Hydrochloride) HCl]) caused reduced fetal weight and structural abnormalities including external and skeletal malformations (e.g., short forelimb digits, fused arches in thoracic vertebrae, fused ribs, and irregular number of ribs), and variations (e.g., irregularly shaped arches and increased bifid centra in thoracic vertebrae, and un-ossified forelimb phalanx) in the presence of maternal toxicity (reduced food consumption, body weight gain, and absolute body weight); however, the structural abnormality findings cannot be clearly attributed to the maternal toxicity. Adverse developmental effects were not observed when pregnant rats were co-administered the same dose of oxymetazoline HCl in combination with 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl, or with 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl alone. The no-observed-adverse-effect-level (NOAEL) for fetal effects was 0.03 mg/kg/day oxymetazoline HCl (1.5 times the oxymetazoline AUC exposure at the MRHD) and 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl (30 times the AUC exposure as measured by PBBA [major Oto Betnovate (Tetracaine Hydrochloride) metabolite] at the MRHD).

In other embryo-fetal development studies, Oto Betnovate (Tetracaine Hydrochloride) base alone administered subcutaneously did not cause structural abnormalities in rats at doses up to 10 mg/kg/day (approximately 6.1 times the MRHD level of 18 mg Oto Betnovate (Tetracaine Hydrochloride) HCl by body surface area (BSA) comparison) or in rabbits at subcutaneous doses up to 5 mg/kg/day (approximately 6.1 times the MRHD level by BSA comparison).

In a prenatal and postnatal development study, pregnant rats were given subcutaneous doses of oxymetazoline HCl only at 0.1 mg/kg/day, Oto Betnovate (Tetracaine Hydrochloride) HCl only at 7.5 mg/kg/day, and oxymetazoline HCl at 0.01, 0.03, and 0.1 mg/kg/day in combination with 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl from GD 7 to Lactation Day [LD] 20 (corresponding to the beginning of organogenesis through parturition and subsequent pup weaning). Oxymetazoline HCl treatment decreased the mean number of implant sites/litter at ≥ 0.03 mg/kg (≥ 1.5 times the oxymetazoline AUC exposure at the MRHD) when administered with 7.5 mg/kg Oto Betnovate (Tetracaine Hydrochloride) HCl (approximately 9%) and without Oto Betnovate (Tetracaine Hydrochloride) HCl (5.5%), which resulted in a reduction in live litter sizes in these groups. At the end of the lactation period, fetal body weights were significantly decreased at 0.1 mg/kg oxymetazoline HCl (6 times the oxymetazoline AUC exposure at the MRHD) when administered alone (19%) and co-administered with 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl (11%). In addition, a decrease in pup survival was observed at the 0.1/7.5 mg/kg oxymetazoline HCl/tetracaine HCl dose (91.9%) compared to the control (99.6%), but no effects in any other groups. Maternal toxicity (e.g., mortality and reduced body weight gain, absolute body weight and food consumption) occurred in groups administered 0.1 mg/kg/day oxymetazoline HCl; however, the adverse developmental findings observed at this dose cannot clearly be attributed to the maternal toxicity. There were no adverse effects on sexual maturation, neurobehavioral, or reproductive function in the offspring at any maternal dose. The no-effect level for oxymetazoline HCl for maternal reproduction was 0.01 mg/kg/day (0.5 times oxymetazoline AUC exposure at the MRHD) and for pup growth and development was 0.03 mg/kg/day (1.5 times oxymetazoline AUC exposure at the MRHD). The no-effect level for Oto Betnovate (Tetracaine Hydrochloride) HCl for maternal reproduction and pup growth and development was 7.5 mg/kg/day (12 times the AUC exposure as measured by PBBA at the MRHD).

8.2 Lactation

Risk Summary

There are no data on the presence of Oto Betnovate (Tetracaine Hydrochloride), oxymetazoline, or their metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Detectable levels of oxymetazoline, Oto Betnovate (Tetracaine Hydrochloride) and the major metabolite of Oto Betnovate (Tetracaine Hydrochloride), p-butylaminobenzoic acid (PBBA), were found in the milk of lactating rats following subcutaneous administration of oxymetazoline HCl in combination with Oto Betnovate (Tetracaine Hydrochloride) HCl during the period of organogenesis through parturition and subsequent pup weaning . Due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Oto Betnovate (Tetracaine Hydrochloride) and any potential adverse effects on the breastfed infant from Oto Betnovate (Tetracaine Hydrochloride) or from the underlying maternal condition.

Data

In a pre- and post-natal development study, rats were given oxymetazoline HCl subcutaneously at doses of 0.01, 0.03, and 0.1 mg/kg/day (0.6, 1.5, and 7.6 times, respectively, the oxymetazoline AUC exposure at the MRHD) in combination with 7.5 mg/kg Oto Betnovate (Tetracaine Hydrochloride) HCl (12 times the AUC exposure as measured by PBBA at the MRHD) from Gestational Day [GD] 7 to Lactation Day [LD] 20. Concentrations of oxymetazoline, Oto Betnovate (Tetracaine Hydrochloride), and PBBA were measured in the milk of lactating rats at approximately 2 hours postdose on LD 15. The concentrations of oxymetazoline were generally dose dependent (2.5, 7.0, and 33.8 ng/mL at 0.01, 0.03, and 0.1 mg/kg/day, respectively). The concentrations of Oto Betnovate (Tetracaine Hydrochloride) and PBBA were generally similar across all 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl dosing groups regardless of the presence of oxymetazoline (54.2 – 72.9 ng/mL for Oto Betnovate (Tetracaine Hydrochloride), and 100.5 – 131.2 ng/mL for PBBA).

8.3 Females and Males of Reproductive Potential

Infertility

No information is available on fertility effects in humans.

Females

Based on animal data, Oto Betnovate may reduce fertility in females of reproductive potential. In female rats, decreased fertility noted as a decrease in litter size occurred at 0.7 times the oxymetazoline AUC exposure at the MRHD of Oto Betnovate (Tetracaine Hydrochloride). It is not known if the effects on fertility are reversible [ see Nonclinical Toxicology ( 13.1)] .

Males

Based on animal data, Oto Betnovate (Tetracaine Hydrochloride) may reduce male fertility. In male rats, decreased sperm motility and sperm concentration occurred at approximately 2 times the oxymetazoline AUC exposure at the MRHD of Oto Betnovate (Tetracaine Hydrochloride) .

8.4 Pediatric Use

Oto Betnovate (Tetracaine Hydrochloride) has not been studied in pediatric patients under 3 years of age and is not advised for use in pediatric patients weighing less than 40 kg because efficacy has not been demonstrated in these patients .

8.5 Geriatric Use

Clinical studies of Oto Betnovate did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Monitor geriatric patients for signs of local anesthetic toxicity, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Of note, comparisons of Oto Betnovate (Tetracaine Hydrochloride) safety and efficacy results were generally similar among dental patients who were > 50 years old (n=66) and ≤ 50 years old (n=148). However, a trend toward a higher incidence of notable increases in systolic blood pressure was observed in dental patients > 50 years of age compared with patients ≤ 50 years of age (16.6% vs 1.4, respectively) [see Adverse Reactions ( 6.1 )]. These increases in blood pressure measurements were generally asymptomatic and transient in nature, and all spontaneously resolved without the need for medical intervention [see Clinical Studies ( 14.1 )] .

8.6 Hepatic Disease

Because of an inability to metabolize local anesthetics, those patients with severe hepatic disease may be at a greater risk of developing toxic plasma concentrations of Oto Betnovate (Tetracaine Hydrochloride). Monitor patients with hepatic disease for signs of local anesthetic toxicity.

8.7 Pseudocholinesterase Deficiency

Because of an inability to metabolize local anesthetics, those patients with pseudocholinesterase deficiency may be at a greater risk of developing toxic plasma concentrations of Oto Betnovate (Tetracaine Hydrochloride). Monitor patients with pseudocholinesterase deficiency for signs of local anesthetic toxicity.

10 OVERDOSAGE

No addictive properties have been reported in the literature for either Oto Betnovate (Tetracaine Hydrochloride) or oxymetazoline, but there have been numerous case reports of unintended overdose for both compounds. Side effects in adults and children associated with oxymetazoline overdose include dizziness, chest pain, headaches, myocardial infarction, stroke, visual disturbances, arrhythmia, hypertension, or hypotension. Side effects of Oto Betnovate (Tetracaine Hydrochloride) overdose include rapid circulatory collapse, cardiac arrest, and cerebral events.

Possible rebound nasal congestion, irritation of nasal mucosa, and adverse systemic effects (particularly in children), including serious cardiac events, have been associated with overdosage and/or prolonged or too frequent intranasal use of oxymetazoline containing agents.

Accidental ingestion of imidazoline derivatives (i.e., oxymetazoline, naphazoline, tetrahydrozoline) in children has resulted in serious adverse events requiring hospitalization (e.g., coma, bradycardia, decreased respiration, sedation, and somnolence).

Patients should be instructed to avoid using oxymetazoline-containing products (such as Afrin ®) and other α-adrenergic agonists within 24 hours prior to their scheduled dental procedure .

Management of an overdose includes close monitoring, supportive care, and symptomatic treatment.

11 DESCRIPTION

Oto Betnovate (Tetracaine Hydrochloride) (tetracaine HCl and oxymetazoline HCl) Nasal Spray is a clear aqueous solution in a pre-filled, single-use intranasal sprayer. The solution pH is 6.0 ± 1.0. The product contains two active ingredients: 30 mg/mL Oto Betnovate (Tetracaine Hydrochloride) HCl (equivalent to 26.4 mg/mL Oto Betnovate (Tetracaine Hydrochloride)) and 0.5 mg/mL oxymetazoline hydrochloride (equivalent to 0.44 mg/mL oxymetazoline). Each spray delivers 0.2 mL of solution containing 6 mg Oto Betnovate (Tetracaine Hydrochloride) hydrochloride (equivalent to 5.27 mg Oto Betnovate (Tetracaine Hydrochloride)) and 0.1 mg of oxymetazoline hydrochloride (equivalent to 0.088 mg oxymetazoline). The product also contains citric acid, sodium citrate, hydroxyethylcellulose, benzyl alcohol, and water. Sodium hydroxide and/or hydrochloric acid are added for pH adjustment as needed.

Oto Betnovate (Tetracaine Hydrochloride) hydrochloride is an ester local anesthetic. Chemically it is 2-(dimethylamino)ethyl 4-(butylamino)benzoate hydrochloride. Its molecular weight is 300.8 for the hydrochloride salt and 264.4 for the free base. It is freely soluble in water and soluble in ethanol. Its structural formula is:

Oxymetazoline hydrochloride is a vasoconstrictor. Chemically it is 3-[(4,5-dihydro-1 H-imidazol-2-yl)methyl]-6-(1,1,-dimethylethyl)-2,4-dimethylphenol mono-hydrochloride. Its molecular weight is 296.8 for the hydrochloride salt and 260.4 for the free base. It is freely soluble in water and ethanol and has a partition coefficient of 0.1 in octanol/water. Its structural formula is:

Oto Betnovate (Tetracaine Hydrochloride) Hydrochloride Structural Formula Oxymetazoline Hydrochloride Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Oto Betnovate is a local anesthetic of the ester type and exerts its activity by blocking sodium ion channels required for the initiation and conduction of neuronal impulses. Oxymetazoline is an imidazoline derivative with sympathomimetic activity. It is believed to be a mixed α 12-adrenoceptor agonist and, by stimulating adrenergic receptors, it elicits vasoconstriction of dilated arterioles and reduces nasal blood flow.

12.3 Pharmacokinetics

Absorption

Following nasal administration of 0.6 mL Oto Betnovate (Tetracaine Hydrochloride) in adult subjects (n=24), oxymetazoline attained maximum concentrations within approximately 10 minutes following the end of dosing. The observed mean oxymetazoline C max and AUC 0-inf value were 1.78 ng/mL and 4.24 ng.h/mL, respectively. The observed median T max was 5 minutes.

Plasma concentrations of Oto Betnovate (Tetracaine Hydrochloride) in all subjects were at or below the limit of assay quantification (0.05 ng/mL). Of all plasma samples analyzed, only one quantifiable Oto Betnovate (Tetracaine Hydrochloride) concentration was observed in a single sample from one subject, which was at the limit of assay quantification. The primary metabolite of Oto Betnovate (Tetracaine Hydrochloride), p-butylaminobenzoic acid (PBBA) achieved peak concentrations within approximately 25 minutes following the end of Oto Betnovate (Tetracaine Hydrochloride) dosing. The observed mean PBBA C max and AUC 0-inf value were 465 ng/mL and 973 ng.h/mL, respectively. The observed median T max was 20 minutes.

Distribution

Protein binding and distribution of oxymetazoline and PBBA have not been determined. Plasma protein binding of Oto Betnovate (Tetracaine Hydrochloride) has been reported to be 75% to 85%.

Elimination

The terminal half-life of oxymetazoline in plasma following nasal administration of Oto Betnovate (Tetracaine Hydrochloride) to adult subjects is approximately 5.2 hours.

The elimination half-life and apparent clearance of Oto Betnovate (Tetracaine Hydrochloride) could not be determined after Oto Betnovate (Tetracaine Hydrochloride) administration because it is rapidly and thoroughly hydrolyzed in plasma. The plasma half-life of PBBA is approximately 2.6 hours in adult subjects.

Metabolism

Oxymetazoline is converted to a glucuronide conjugate in vitro by UGT1A9.

Oto Betnovate (Tetracaine Hydrochloride) is rapidly and thoroughly cleaved by esterases in plasma and other tissues to PBBA and dimethylaminoethanol. These metabolites have an unspecified activity.

Excretion

The apparent clearance of oxymetazoline after nasal administration of Oto Betnovate (Tetracaine Hydrochloride) has not been determined. It is thought that the primary route of oxymetazoline elimination at clinically relevant concentrations is by renal excretion.

PBBA clearance cannot be determined after administration of Oto Betnovate (Tetracaine Hydrochloride).

Special Populations

Pediatrics:

In subjects 4-15 years of age (n=18) that received Oto Betnovate (Tetracaine Hydrochloride) doses of 0.1 mL (10 to < 20 kg body weight), 0.2 mL (20 to < 40 kg), or 0.4 mL (≥ 40 kg), oxymetazoline attained maximum concentrations within approximately 10 minutes to 30 minutes (median time) following the end of dosing. The observed oxymetazoline mean C max values were 0.37 ± 0.43, 0.85 ± 0.45, and 1.2 ± 0.39 ng/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. The observed oxymetazoline mean AUC 0-inf values were 0.99 (AUC can be calculated only in one subject), 2.53 ± 1.08, and 2.64 ± 0.41 ng.h/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. Mean elimination half-life values for oxymetazoline were approximately 1.6 to 4.3 hours across pediatric dose groups.

Plasma concentrations of Oto Betnovate (Tetracaine Hydrochloride) were below the limit of assay quantification (0.05 ng/mL) in all subjects.

PBBA attained maximum concentrations within approximately 20 minutes to 30 minutes (median time) following the end of dosing. The observed PBBA mean C max values were 166 ± 71, 345 ± 172, and 365 ± 30 ng/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. The observed PBBA mean AUC 0-inf values were 529 ± 222, 826 ± 606, and 665 ± 86 ng.h/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. Mean elimination half-life values for PBBA were approximately 1.6 to 2.8 hours across pediatric dose groups.

Elderly: The pharmacokinetics of Oto Betnovate (Tetracaine Hydrochloride) were not evaluated in subjects greater than 50 years of age.

Renal or Hepatic Impairment: The pharmacokinetics of oxymetazoline, Oto Betnovate (Tetracaine Hydrochloride), and PBBA were not evaluated after nasal administration of Oto Betnovate (Tetracaine Hydrochloride) in subjects with renal or hepatic impairment.

Race: There were insufficient data to evaluate the effect of race on oxymetazoline, Oto Betnovate (Tetracaine Hydrochloride), and PBBA pharmacokinetics after nasal administration of Oto Betnovate (Tetracaine Hydrochloride).

13 NON-CLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Oto Betnovate (Tetracaine Hydrochloride) or oxymetazoline.

Mutagenesis

Oto Betnovate (Tetracaine Hydrochloride) base was negative in the in vitro Ames bacterial reverse mutation assay and the in vivo mouse micronucleus assay. In the in vitro chromosome aberration assay using Chinese hamster ovary cells, Oto Betnovate (Tetracaine Hydrochloride) base was negative in the absence of metabolic activation, and equivocal in the presence of metabolic activation. No studies have been conducted to evaluate the mutagenic potential of oxymetazoline.

Impairment of Fertility

Male and female rats were given subcutaneous doses of oxymetazoline HCl alone at 0.1 mg/kg/day, Oto Betnovate (Tetracaine Hydrochloride) HCl alone at 7.5 mg/kg/day, or the combination of oxymetazoline HCl at 0.01, 0.03, or 0.1 mg/kg/day oxymetazoline with 7.5 mg/kg/day Oto Betnovate (Tetracaine Hydrochloride) HCl prior to and during mating. Oxymetazoline HCl at ≥ 0.03 mg/kg/day reduced the percentage of motile sperm and sperm counts at 2 times the oxymetazoline AUC exposure at the MRHD of Oto Betnovate (Tetracaine Hydrochloride). There were no effects on male mating behavior at any dose tested. The no-effect level for sperm effects was 0.01 mg/kg/day (0.7 times the oxymetazoline AUC exposure at the MRHD of Oto Betnovate (Tetracaine Hydrochloride)).

In female rats, a reduction in the number of viable embryos was observed at oxymetazoline AUC exposures equivalent to 0.7 times the MRHD and higher, given alone or in combination with Oto Betnovate (Tetracaine Hydrochloride) HCl. Reduced numbers of corpora lutea and implantation sites were observed at 7.5 times the oxymetazoline AUC exposure at the MRHD in animals given oxymetazoline HCl alone or in combination with Oto Betnovate (Tetracaine Hydrochloride) HCl. These effects were attributed to oxymetazoline HCl because similar effects were not observed in rats given Oto Betnovate (Tetracaine Hydrochloride) HCl alone. A no-effect level for fertility in female rats was not established in this study.

No effects on male or female fertility were attributed to Oto Betnovate (Tetracaine Hydrochloride) HCl at 7.5 mg/kg/day (28 and 33 times the AUC exposure for males and females, respectively, as measured by PBBA [major Oto Betnovate (Tetracaine Hydrochloride) metabolite] at the MRHD of Oto Betnovate (Tetracaine Hydrochloride)).

14 CLINICAL STUDIES

The efficacy of Oto Betnovate Nasal Spray for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J has been evaluated in three adult dental patient studies, as well as one pediatric dental patient study. The primary endpoint for all four studies was the successful completion of a restorative operative dental procedure without the need for a rescue injection. One adult dental study was terminated early for reasons related to the administration of Oto Betnovate (Tetracaine Hydrochloride). Unlike the other studies conducted, in this study all three sprays were delivered horizontally.

14.1 Studies in Adults

Study 1

Study 1 was a Phase 3, multicenter, randomized, double-blind, placebo and active-controlled, parallel-groups study designed to compare the efficacy and safety of intranasally administered Oto Betnovate (Tetracaine Hydrochloride) to both Oto Betnovate (Tetracaine Hydrochloride) HCl alone and placebo, for providing dental anesthesia sufficient to allow completion of the standard dental procedure on a single maxillary tooth (#4-13) in adults.

A total of 110 patients were enrolled in two clinical centers and randomized to receive three 0.2 mL intranasal sprays of either Oto Betnovate (Tetracaine Hydrochloride) (n=44), Oto Betnovate (Tetracaine Hydrochloride) alone (n=44), or placebo (n=22). All randomized patients completed the study dental procedure.

Fifty-three percent (53%) of randomized patients were female and 76% were White, with a mean age of 35 years (range 18 to 73 years).

Eighty-four percent (95% CI: 70%, 93%) of Oto Betnovate (Tetracaine Hydrochloride) patients were able to complete the dental procedure without the need for rescue medication compared to 27% (95% CI: 15%, 43%) who received Oto Betnovate (Tetracaine Hydrochloride) alone and 27% (95% CI: 11%, 50%) who received placebo.

Oto Betnovate (Tetracaine Hydrochloride) had a lower success rate for dental procedures on the 2 nd pre-molar (teeth #4 and #13) compared with more anterior teeth (#5 through #12): 63% for the 2 nd pre-molars vs 96% for more anterior teeth.

In this trial, the median duration of a dental procedure successfully completed with Oto Betnovate (Tetracaine Hydrochloride) was 11 minutes, although one successfully completed dental procedure was as long as 43 minutes. Of the people that needed rescue medication in the Oto Betnovate (Tetracaine Hydrochloride) arm, they required it within the first 6 minutes following the start of the dental procedure.

Study 2

Study 2 was a Phase 3, multicenter, randomized, double-blind, parallel-groups study designed to compare the efficacy and safety of intranasally administered Oto Betnovate (Tetracaine Hydrochloride) to placebo, for providing dental anesthesia sufficient to allow completion of the standard dental procedure on a single maxillary tooth (#4-13) in adults.

A total of 150 adult patients were enrolled at three study centers and received either Oto Betnovate (Tetracaine Hydrochloride) (n=100) or placebo (n=50) as a dose of two or three 0.2 mL intranasal sprays. All except two randomized patients (one each in the Oto Betnovate (Tetracaine Hydrochloride) and placebo groups) completed the study dental procedure.

Fifty-five percent (55%) of randomized patients were female and 63% were White, with a mean age of 41 years (range 18 to 78 years).

Eighty-eight percent (95% CI: 80%, 94%) of Oto Betnovate (Tetracaine Hydrochloride) patients were able to complete the dental procedure without the need for rescue medication compared to 28% (95% CI: 16%, 43%) of patients who received placebo.

Oto Betnovate (Tetracaine Hydrochloride) had a lower success rate for dental procedures on the 2 nd pre-molar (teeth #4 and #13) compared with more anterior teeth (#5 through #12): 64% for the 2 nd pre-molars vs 96% for more anterior teeth.

14.2 Study in Children

Study 3

Study 3 was a Phase 3, multicenter, randomized, double-blind, parallel-groups study designed to compare the efficacy and safety of intranasally administered Oto Betnovate (Tetracaine Hydrochloride) to placebo for providing dental anesthesia sufficient to allow completion of the standard dental procedure on a single maxillary tooth (permanent teeth 4-13 or primary teeth A-J) for pediatric patients aged 3 through 17.

A total of 90 patients, 3 through 17 years of age inclusive, were enrolled at two study centers. Patients received one or two intranasal sprays of either Oto Betnovate (Tetracaine Hydrochloride) (n=60) or placebo (n=30) based on body weight: one 0.1 mL spray for patients weighing 10 kg to less than 20 kg; two 0.1 mL sprays for 20 kg to less than 40 kg; or two 0.2 mL sprays for patients weighing 40 kg or more. All except one randomized patient in the Oto Betnovate (Tetracaine Hydrochloride) group completed the study dental procedure.

Fifty-one percent (51%) of randomized patients were male and 89% were White, with a mean age of 8 years (range 3 to 17 years).

Even though a greater percentage of patients were able to complete the dental procedure without the need for rescue anesthesia for Oto Betnovate (Tetracaine Hydrochloride): 77% for Oto Betnovate (Tetracaine Hydrochloride) (95% CI: 64%, 87%) compared to 53% for placebo (95% CI: 34%, 72%) an analysis by weight indicated that efficacy was only established for patients weighing 40 kg or more .

Successful Anesthetic Response by Weight

N (%)

Oto Betnovate (Tetracaine Hydrochloride)

(N = 60)

Placebo

(N = 30)

40 kg or more 18/20 (90%) 4/10 (40%)
20 to less than 40 kg 14/24 (58%) 5/12 (42%)
10 to less than 20 kg 14/16 (88%) 7/8 (88%)

16 HOW SUPPLIED/STORAGE AND HANDLING

Oto Betnovate (Tetracaine Hydrochloride) Nasal Spray is supplied as pre-filled, single-use sprayers containing a clear aqueous solution of 30 mg/mL of Oto Betnovate (Tetracaine Hydrochloride) hydrochloride (equivalent to 26.4 mg/mL Oto Betnovate (Tetracaine Hydrochloride)) and 0.5 mg/mL of oxymetazoline hydrochloride (equivalent to 0.44 mg/mL oxymetazoline). Each sprayer delivers 0.2 mL.

The product is available as:

  • NDC 69803-100-10: Box of 30 sprayers

Store between 2° and 8°C (36° and 46°F); excursions permitted between 0° and 15°C (32° and 59°F).

Discard any unused solution. DO NOT use if drug is left out at room temperature for more than 5 days.

17 PATIENT COUNSELING INFORMATION

  • Inform patients of the likelihood of expected side effects (including runny nose, nasal congestion, mild nose bleeds, dizziness, and/or a sensation of difficulty in swallowing) that should resolve within the same day. Instruct patients to contact their dentist or health care professional if these symptoms persist .
  • Advise patients to inform the dental practitioner if they are taking monoamine oxidase inhibitors (MAOIs), nonselective beta adrenergic antagonists, or tricyclic antidepressants .
  • Instruct patients to avoid using oxymetazoline-containing products (such as Afrin ® and other α-adrenergic agonists) within 24 hours prior to their scheduled dental procedure. .
  • Advise patients of the signs and symptoms of hypersensitivity reactions and to seek immediate medical attention should they occur .

St. Renatus, LLC

Manufactured for:

St. Renatus, LLC

Fort Collins, CO 80526

Oto Betnovate (Tetracaine Hydrochloride) is a trademark of St. Renatus, LLC.

Principal Display Panel - Box Label

NDC 69803-100-10

Oto Betnovate (Tetracaine Hydrochloride)

(tetracaine HCl and oxymetazoline HCl)

NASAL SPRAY

0.2 mL per sprayer

Containing 6 mg Oto Betnovate (Tetracaine Hydrochloride) HCl and 0.1 mg oxymetazoline HCl

(equivalent to 5.27 mg Oto Betnovate (Tetracaine Hydrochloride) and 0.088 mg oxymetazoline)

Contents: 30 sprayers

Rx only

NOT FOR INJECTION

Store refrigerated at 2 to 8°C (36 to 46°F)

Manufactured for

St. Renatus, LLC

Fort Collins, CO 80526

Oto Betnovate pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Oto Betnovate available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Oto Betnovate destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Oto Betnovate Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Oto Betnovate pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."LUXIQ (BETAMETHASONE VALERATE) AEROSOL, FOAM [PRESTIUM PHARMA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."TETRAVISC FORTE (TETRACAINE HYDROCHLORIDE) LIQUID [OCUSOFT, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."TETRACAINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Oto Betnovate?

Depending on the reaction of the Oto Betnovate after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Oto Betnovate not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Oto Betnovate addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Oto Betnovate, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Oto Betnovate consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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