|
|||
DRUGS & SUPPLEMENTS
|
How is the drug helping you? |
Betamethasone Dipropionate:
Betzee-M (Betamethasone Dipropionate) Spray is indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.
Betzee-M (Betamethasone Dipropionate) Spray is a corticosteroid indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older. (1)
Shake well before use.
Apply Betzee-M (Betamethasone Dipropionate) Spray to the affected skin areas twice daily and rub in gently.
Use Betzee-M (Betamethasone Dipropionate) Spray for up to 4 weeks of treatment. Treatment beyond 4 weeks is not recommended.
Discontinue Betzee-M (Betamethasone Dipropionate) 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.
Betzee-M (Betamethasone Dipropionate) Spray is for topical use only. It is not for oral, ophthalmic, or intravaginal use.
Spray, 0.05% for topical use. Each gram of Betzee-M (Betamethasone Dipropionate) Spray contains 0.643 mg Betzee-M (Betamethasone Dipropionate) USP (equivalent to 0.5 mg betamethasone) in a slightly thickened, white to off-white oil-in-water emulsion.
Spray: 0.05% (equivalent to 0.5 mg betamethasone/g) (3)
None.
Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray is not recommended in pediatric patients .
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.
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
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 Betzee-M (Betamethasone Dipropionate) Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied Betzee-M (Betamethasone Dipropionate) Spray and 180 subjects applied vehicle spray.
Adverse reactions that occurred in at least 1% of subjects treated with Betzee-M (Betamethasone Dipropionate) Spray for up to 28 days are presented in Table 1.
Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) 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.
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.
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Betzee-M Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Betzee-M (Betamethasone 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.
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 Betzee-M (Betamethasone Dipropionate) Spray is administered to a nursing woman.
Safety and effectiveness of Betzee-M 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.
Clinical studies of Betzee-M (Betamethasone Dipropionate) 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.
Betzee-M (Betamethasone Dipropionate) Spray contains 0.0643% Betzee-M (Betamethasone Dipropionate) (equivalent to 0.05% betamethasone), a synthetic, fluorinated corticosteroid.
The chemical name for Betzee-M (Betamethasone 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 Betzee-M (Betamethasone Dipropionate) Spray contains 0.643 mg of Betzee-M (Betamethasone Dipropionate) USP (equivalent to 0.5 mg betamethasone) 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. Betzee-M (Betamethasone Dipropionate) Spray is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing to patients.
Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Betzee-M Spray in psoriasis is unknown.
Vasoconstrictor studies performed with Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray was evaluated in a study randomizing 52 adult subjects with moderate to severe plaque psoriasis. Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray for 15 days. No subjects (0 out of 24) treated with Betzee-M (Betamethasone Dipropionate) 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.
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 Betzee-M (Betamethasone Dipropionate), betamethasone-17-propionate, and betamethasone 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 Betzee-M (Betamethasone Dipropionate), while the metabolites, betamethasone-17-propionate and betamethasone, 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) | Betzee-M (Betamethasone Dipropionate) Spray b.i.d. (15 days) | Betzee-M (Betamethasone Dipropionate) Spray b.i.d. (29 days) |
Betamethasone-17-propionate | 120 ± 127 | 63.9 ± 52.6 |
Betamethasone | 119 ± 176 | 57.6 ± 55.9 |
Long-term animal studies have not been performed to evaluate the carcinogenic potential of Betzee-M (Betamethasone Dipropionate).
In a 90-day repeat-dose toxicity study in rats, topical administration of Betzee-M (Betamethasone 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.
Betamethasone 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.
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 Betzee-M (Betamethasone Dipropionate) 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 | |||
Betzee-M (Betamethasone Dipropionate) Spray b.i.d. (N=182) | Vehicle Spray b.i.d. (N=95) | Betzee-M (Betamethasone Dipropionate) 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% |
Betzee-M 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:
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.
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Inform patients of the following:
Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215
Distributed by: Promius Pharma, LLC., Princeton, NJ 08540
Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) (ser-ne-vo) (betamethasone dipropionate) Spray, 0.05% | |
Important: Betzee-M (Betamethasone Dipropionate) Spray is for use on the skin only. Do not get Betzee-M (Betamethasone Dipropionate) Spray near or in your eyes, mouth, or vagina. | |
What is Betzee-M (Betamethasone Dipropionate) Spray?
It is not known if Betzee-M (Betamethasone Dipropionate) Spray is safe and effective in children under 18 years of age. Betzee-M (Betamethasone Dipropionate) Spray is not recommended for use in patients under 18 years of age. | |
Before you use Betzee-M (Betamethasone Dipropionate) Spray, tell your doctor about all of your medical conditions, including if you:
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 Betzee-M (Betamethasone Dipropionate) Spray? See the “Instructions for Use” for detailed information about the right way to apply Betzee-M (Betamethasone Dipropionate) Spray.
| |
What are the possible side effects of Betzee-M (Betamethasone Dipropionate) Spray?
The most common side effects of Betzee-M (Betamethasone Dipropionate) Spray include itching, burning, stinging, pain, and thinning of skin (atrophy) at the treated site. These are not all the possible side effects of Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray?
Keep Betzee-M (Betamethasone Dipropionate) Spray and all medicines out of the reach of children. | |
General information about the safe and effective use of Betzee-M (Betamethasone Dipropionate) Spray. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Betzee-M (Betamethasone Dipropionate) Spray for a condition for which it was not prescribed. Do not give Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray that is written for health professionals. | |
What are the ingredients in Betzee-M (Betamethasone Dipropionate) Spray? Active ingredient: Betzee-M (Betamethasone 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
Betzee-M (Betamethasone Dipropionate) (ser-ne-vo)
(betamethasone dipropionate)
Spray, 0.05%
Important: Betzee-M (Betamethasone Dipropionate) Spray is for use on the skin only. Do not get Betzee-M (Betamethasone Dipropionate) Spray near or in your eyes, mouth, or vagina.
Read this “Instructions for Use” before you start using Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray bottle.
Figure A
How to apply Betzee-M (Betamethasone Dipropionate) Spray:
Step 1: Shake the Betzee-M (Betamethasone Dipropionate) 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 Betzee-M (Betamethasone Dipropionate) Spray to the affected area as instructed by your doctor. (See Figure B )
Figure B
Step 3: Spray only enough Betzee-M (Betamethasone Dipropionate) Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Betzee-M (Betamethasone Dipropionate) Spray gently.
Figure C
Repeat Steps 2 and 3 to apply Betzee-M (Betamethasone Dipropionate) Spray to other affected areas as instructed by your doctor.
Step 4: After applying Betzee-M (Betamethasone Dipropionate) Spray, place the cap back onto the pump top. (See Figure D )
Figure D
How should I store Betzee-M (Betamethasone Dipropionate) Spray?
Keep Betzee-M (Betamethasone Dipropionate) 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
Betzee-M (Betamethasone Dipropionate) is a trademark of Promius Pharma, LLC.
Issued: 02/2016
007528
140693
Miconazole Nitrate:
Betzee-M (Miconazole Nitrate) Ointment is indicated for the adjunctive treatment of diaper dermatitis only when complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast), in immunocompetent pediatric patients 4 weeks and older. A positive fungal culture for Candida albicansis not adequate evidence of candidal infection since colonization with C. albicans can result in a positive culture. The presence of candidal infection should be established by microscopic evaluation prior to initiating treatment.
Betzee-M (Miconazole Nitrate) should be used as part of a treatment regimen that includes measures directed at the underlying diaper dermatitis, including gentle cleansing of the diaper area and frequent diaper changes.
Betzee-M (Miconazole Nitrate) should not be used as a substitute for frequent diaper changes. Betzee-M (Miconazole Nitrate) should not be used to prevent the occurrence of diaper dermatitis, since preventative use may result in the development of drug resistance.
The safety and efficacy of Betzee-M (Miconazole Nitrate) have not been demonstrated in immunocompromised patients, or in infants less than 4 weeks of age (premature or term).
The safety and efficacy of Betzee-M (Miconazole Nitrate) have not been evaluated in incontinent adult patients. Betzee-M (Miconazole Nitrate) should not be used to prevent the occurrence of diaper dermatitis, such as in an adult institutional setting, since preventative use may result in the development of drug resistance.
Betzee-M (Miconazole Nitrate) is not for oral, ophthalmic, or intravaginal use.
Before applying Betzee-M (Miconazole Nitrate), gently cleanse the skin with lukewarm water and pat dry with a soft towel. Avoid using any scented soaps, shampoos, or lotions on the diaper area.
Apply Betzee-M (Miconazole Nitrate) to the affected area at each diaper change for 7 days. Continue treatment for the full 7 days, even if there is improvement. The safety of Betzee-M (Miconazole Nitrate) when used for longer than 7 days is not known. Do not use Betzee-M (Miconazole Nitrate) for longer than 7 days. If symptoms have not improved by day 7, see your health care provider.
Gently apply a thin layer of Betzee-M (Miconazole Nitrate) to the diaper area with the fingertips. Do not rub Betzee-M (Miconazole Nitrate) into the skin as this may cause additional irritation. Thoroughly wash hands after applying Betzee-M (Miconazole Nitrate).
White ointment containing 0.25% Betzee-M (Miconazole Nitrate) nitrate, 15% zinc oxide, and 81.35% white petrolatum.
None
If irritation occurs or if the disease worsens, discontinue use of the medication, and contact the health care provider.
The safety and efficacy of Betzee-M (Miconazole Nitrate) have not been evaluated in incontinent adult patients. Betzee-M (Miconazole Nitrate) should not be used to prevent the occurrence of diaper dermatitis, such as in an adult institutional setting, since preventative use may result in the development of drug resistance.
To report SUSPECTED ADVERSE REACTIONS, contact Prestium Pharma, Inc. at 1-866-897-5002 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Because clinical trials are conducted under widely varying conditions, adverse reaction rate observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
A total of 835 infants and young children were evaluated in the clinical development program. Of 418 subjects in the Betzee-M group, 58 (14%) reported one or more adverse events. Of 417 subjects in the zinc oxide/white petrolatum control group, 85 (20%) reported one or more adverse events. Adverse events that occurred at a rate of ≥ 1% for subjects who were treated with Betzee-M (Miconazole Nitrate) were approximately the same in type and frequency as for subjects who were treated with zinc oxide/white petrolatum ointment.
The following adverse reactions have been identified during post approval use of Betzee-M (Miconazole Nitrate).
GASTROINTESTINAL DISORDERS: vomiting
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: burning sensation, condition aggravated, inflammation, pain
INJURY, POISONING AND PROCEDURAL COMPLICATIONS: accidental exposure
SKIN AND SUBCUTANEOUS TISSUE DISORDERS: blister, dermatitis contact, diaper dermatitis, dry skin, erythema, pruritus, rash, skin exfoliation
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Drug-drug interaction studies were not conducted. Women who take a warfarin anticoagulant and use a Betzee-M (Miconazole Nitrate) intravaginal cream or suppository may be at risk for developing an increased prothrombin time, international normalized ratio (INR), and bleeding. The potential for this interaction between warfarin and Betzee-M (Miconazole Nitrate) is unknown.
There are no adequate and well-controlled studies of Betzee-M in pregnant women. Therefore, Betzee-M (Miconazole Nitrate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Betzee-M (Miconazole Nitrate) nitrate administration has been shown to result in prolonged gestation and decreased numbers of live young in rats and in increased number of resorptions and decreased number of live young in rabbits at oral doses of 100 mg/kg/day and 80 mg/kg/day, which are 28 and 45 times the maximum possible topical exposure of caregivers, respectively, assuming 100% absorption.
Safety and efficacy of Betzee-M (Miconazole Nitrate) have not been established in nursing mothers. It is not known if the active components of Betzee-M (Miconazole Nitrate) may be present in milk.
Efficacy was not demonstrated in infants less than 4 weeks of age. Safety and efficacy have not been established in very-low-birth-weight infants.
Betzee-M should not be used to prevent diaper dermatitis.
The safety of Betzee-M (Miconazole Nitrate) when used for longer than 7 days is not known. Do not use more than 7 days.
Safety and efficacy in a geriatric population have not been evaluated.
Betzee-M (Miconazole Nitrate) contains the synthetic antifungal agent, Betzee-M (Miconazole Nitrate) nitrate (0.25%) USP, zinc oxide (15%) USP, and white petrolatum (81.35%) USP.
The chemical name of Betzee-M (Miconazole Nitrate) nitrate is 1-[2, 4-dichloro-ß-{(2,4-dichlorobenzyl)oxy} phenethyl] imidazole mononitrate with empirical formula C18H14Cl4N2O-HNO3 and molecular weight of 479.15. The structural formula of Betzee-M (Miconazole Nitrate) nitrate is as follows:
The zinc oxide has an empirical formula of ZnO and a molecular weight of 81.39.
The white petrolatum, which is obtained from petroleum and is wholly or nearly decolorized, is a purified mixture of semisolid saturated hydrocarbons having the general chemical formula CnH2n+2. The hydrocarbons consist mainly of branched and unbranched chains. White petrolatum contains butylated hydroxytoluene (BHT) as stabilizer.
Each gram of Betzee-M (Miconazole Nitrate) contains 2.5 mg of Betzee-M (Miconazole Nitrate) nitrate USP, 150 mg of zinc oxide USP, and 813.5 mg of white petrolatum USP containing butylated hydroxytoluene, trihydroxystearin, and Chemoderm® 1001/B fragrance.1
Betzee-M (Miconazole Nitrate) is a smooth, uniform, white ointment.
Structural formula of Betzee-M (Miconazole Nitrate) nitrate
The Betzee-M component of Betzee-M (Miconazole Nitrate) is an antifungal agent. The mechanism of action of white petrolatum and zinc oxide for the adjunctive treatment of diaper dermatitis is unknown.
The human pharmacodynamics of Betzee-M (Miconazole Nitrate) is unknown.
The topical absorption of Betzee-M from Betzee-M (Miconazole Nitrate) was studied in immunocompetent male and female infants and children (n=17) with diaper dermatitis complicated by documented candidiasis (microscopic evidence of pseudohyphae and/or budding yeast) ranging in age from 1 month to 21 months. After multiple daily applications to the affected area at every diaper change (approximately 5-12 times per day) for 7 days, the plasma concentrations of Betzee-M (Miconazole Nitrate) were below the lower limit of quantitation (LOQ) of 0.5 ng/mL in 15 out of 17 (88%) subjects. In the other 2 remaining subjects, the plasma concentrations of Betzee-M (Miconazole Nitrate) were 0.57 and 0.58 ng/mL, respectively at a single timepoint (4 hours after the last application) on Day 7.
The Betzee-M (Miconazole Nitrate) nitrate component in this product has been shown to have in vitro activity against Candida albicans, an organism that is associated with diaper dermatitis. The activity of Betzee-M (Miconazole Nitrate) nitrate against C. albicans is based on the inhibition of the ergosterol biosynthesis in the cell membrane. The accumulation of ergosterol precursors and toxic peroxides results in cytolysis of the cell. In vitro minimal inhibitory concentration (MIC) test results for C. albicans isolates obtained from treatment failures in Clinical Study 1 (see Clinical Studies (14)) does not appear to indicate that resistance to Betzee-M (Miconazole Nitrate) nitrate was the reason for treatment failure. The clinical significance of the in vitro activity of Betzee-M (Miconazole Nitrate) nitrate against C. albicans in the setting of diaper dermatitis is unclear.
The carcinogenic potential of Betzee-M (Miconazole Nitrate) in animals has not been evaluated.
Betzee-M (Miconazole Nitrate) nitrate was negative in a bacterial reverse mutation test, a chromosome aberration test in mice, and micronucleus assays in mice and rats.
Betzee-M (Miconazole Nitrate) nitrate had no adverse effect on fertility in a study in rats at oral doses of up to 320 mg/kg/day, which is 89 times the maximum possible topical exposure of caregivers, assuming 100% absorption.
Study 1 was a double-blind, multicenter study in which Betzee-M (Miconazole Nitrate) was compared to the zinc oxide and white petrolatum combination treatment and included 236 infants and toddlers with diaper dermatitis, complicated by candidiasis as documented by KOH tests that demonstrated psuedohyphae and/or budding yeasts. Study medication was applied at every diaper change for 7 days.
The primary endpoint was “Overall Cure” and required that subjects be both clinically cured (total resolution of all signs and symptoms of infection) and microbiologically cured (eradication of candidiasis). Primary efficacy was assessed 1 week following the end of treatment, at Day 14.
Study results are shown in the following table.
Overall Cure at Day 14 | ||
Betzee-M (Miconazole Nitrate) n=112 | Zinc Oxide/White Petrolatum n=124 | |
26 (23%) | 12 (10%) |
Two additional studies provided supportive evidence of the clinical efficacy of Betzee-M (Miconazole Nitrate) in infants and toddlers with diaper dermatitis, some of whom cultured positive for C. albicans. However, candidal infection was not documented in the culture-positive subjects, as microscopic testing (e.g. KOH) was not done. Therefore, the positive culture results may have reflected colonization rather than infection.
Betzee-M is a smooth, uniform, white ointment supplied in an aluminum tube, as follows:
50g (NDC 40076-002-50)
Store at controlled room temperature between 20°C and 25°C (68°F and 77°F); with excursions permitted between 15°C and 30°C (59°F and 86°F).
Keep out of reach of children.
See FDA-Approved Patient Labeling
Patients using Betzee-M (Miconazole Nitrate) should be informed about the following information:
Manufactured for:
Prestium Pharma, Inc.
Newtown, PA 18940
Manufactured by:
GlaxoSmithKline
Mississauga, ON, Canada
Made in Canada
© 2013 Delcor Asset Corporation, an affiliate of Prestium Pharma, Inc.
Revised Oct 2013 VSN:3PI
FDA-Approved Patient Labeling
Betzee-M (Miconazole Nitrate)® (Vu-sion) Ointment
(0.25% Betzee-M (Miconazole Nitrate) nitrate, 15% zinc oxide and 81.35% white petrolatum)
IMPORTANT: For Skin Use Only. Do not use in the mouth, eyes, or vagina.
Read the Patient Information that comes with Betzee-M (Miconazole Nitrate) before you use it on your child. This leaflet does not take the place of talking to your health care provider about your child’s medical condition or treatment. If you have any questions or if you are not sure about any of the information on Betzee-M (Miconazole Nitrate), ask your health care provider, or pharmacist.
What is Betzee-M (Miconazole Nitrate)?
Betzee-M (Miconazole Nitrate) is a prescription skin medicine used to treat diaper rash that also has a yeast infection in children who are at least 4 weeks old and who have a normal immune system. Betzee-M (Miconazole Nitrate) contains medicines that will help treat the yeast infection and the diaper rash, but you must also change your child’s diapers very often so that your child is not wearing a wet or soiled diaper. Even if you use Betzee-M (Miconazole Nitrate), diaper rash will not go away if you do not keep your child’s diaper area clean and dry. You should use water or a very mild cleanser to clean your child’s diaper area. Betzee-M (Miconazole Nitrate) is not to be used to prevent diaper rash or to be used for more than 7 days.
Your health care provider will need to do a special test to tell if your child’s diaper rash also has a yeast infection. Do not use Betzee-M (Miconazole Nitrate) on your child’s diaper rash unless your health care provider tells you that there is also a yeast infection.
Who should not use Betzee-M (Miconazole Nitrate)?
Betzee-M (Miconazole Nitrate) is not for treatment of all cases of diaper rash. Betzee-M (Miconazole Nitrate) is only for diaper rash that also has a yeast infection. Most cases of diaper rash do not need the yeast medicine that is in Betzee-M (Miconazole Nitrate) because most cases of diaper rash do not also have a yeast infection.
Do not use Betzee-M (Miconazole Nitrate) on any other children or other family member.
Do not use Betzee-M (Miconazole Nitrate) on your child’s diaper rash if they are allergic to anything in it. See the end of this leaflet for a list of ingredients in Betzee-M (Miconazole Nitrate).
Do not use on infants less than 4 weeks of age.
Do not use in infants or children who do not have a normal immune system.
How should I use Betzee-M (Miconazole Nitrate) on my child?
Betzee-M (Miconazole Nitrate) is applied to the skin on your child’s diaper area at each diaper change for 7 days.
Apply Betzee-M (Miconazole Nitrate) for the full 7 days even if the diaper rash starts to go away. Call your child’s health care provider if the diaper rash gets worse or does not go away with 7 days of treatment with Betzee-M (Miconazole Nitrate). Betzee-M (Miconazole Nitrate) should not be used for more than 7 days.
To apply Betzee-M (Miconazole Nitrate):
Betzee-M (Miconazole Nitrate) is for skin use only.
Call your child’s health care provider or poison control center right away if any Betzee-M (Miconazole Nitrate) is swallowed. Call your child’s health care provider if Betzee-M (Miconazole Nitrate) gets in the eye.
Keep out of reach of children.
What other steps will help diaper rash go away?
What are the possible side effects of Betzee-M (Miconazole Nitrate)?
Betzee-M (Miconazole Nitrate) may cause irritation. You should call your child’s health care provider if irritation appears or if the diaper rash gets worse.
How should I store Betzee-M (Miconazole Nitrate)?
General information about Betzee-M (Miconazole Nitrate)
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets.
Do not use Betzee-M (Miconazole Nitrate) for a condition for which it was not prescribed. Do not give Betzee-M (Miconazole Nitrate) to other children or family members, even if they have the same symptoms your child has. It may harm them.
This leaflet summarizes the most important information about Betzee-M (Miconazole Nitrate). If you would like more information, talk to your child’s health care provider. You can ask your child’s health care provider or pharmacist for information about Betzee-M (Miconazole Nitrate) that is written for healthcare professionals.
Side effects may be reported to Prestium Pharma, Inc. at 1-866-897-5002 or the FDA at 1-800-FDA-1088.
What are the ingredients in Betzee-M (Miconazole Nitrate)?
Active Ingredients: Betzee-M (Miconazole Nitrate) nitrate, zinc oxide, and white petrolatum
Inactive Ingredients: trihydroxystearin, butylated hydroxyltoluene (BHT), and Chemoderm® 1001/B fragrance
This Patient Information leaflet has been approved by the U.S. Food and Drug Administration.
The Patient Information leaflet was last revised: October 2013
Manufactured for:
Prestium Pharma, Inc.
Newtown, PA 18940
Manufactured by:
GlaxoSmithKline
Mississauga, ON, Canada
Made in Canada
© 2013 Delcor Asset Corporation, an affiliate of
Prestium Pharma, Inc.
Revised Oct 2013
VSN:3PIL
Principal Display Panel
NDC 40076-002-50
Betzee-M (Miconazole Nitrate)®
(miconazole nitrate 0.25% USP, zinc oxide 15% USP, white petrolatum 81.35% USP)
Ointment
50 grams
Rx only
Principal Display Panel NDC 40076-002-50 Vusion® (miconazole nitrate 0.25% USP, zinc oxide 15% USP, white petrolatum 81.35% USP) Ointment 50 grams Rx only
Zinc Sulfate:
Betzee-M (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Betzee-M (Zinc Sulfate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.
None known.
Direct intramuscular or intravenous injection of Betzee-M (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and Betzee-M (Zinc Sulfate) doses because these elements are primarily eliminated in the urine.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Betzee-M (Zinc Sulfate) from a bolus injection. Administration of Betzee-M (Zinc Sulfate) in the absence of copper may cause a decrease in serum copper levels.
Periodic determinations of serum copper as well as Betzee-M (Zinc Sulfate) are suggested as a guideline for subsequent Betzee-M (Zinc Sulfate) administration.
Long-term animal studies to evaluate the carcinogenic potential of Betzee-M 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Betzee-M (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
Pregnancy Category C. Animal reproduction studies have not been conducted with Betzee-M chloride. It is also not known whether Betzee-M (Zinc Sulfate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Betzee-M (Zinc Sulfate) chloride should be given to a pregnant woman only if clearly needed.
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
None known.
None known.
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Betzee-M (Zinc Sulfate) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Betzee-M (Zinc Sulfate) concentration of 207 mcg/dl. Symptoms abated within three hours.
Hyperamylasemia may be a sign of impending Betzee-M (Zinc Sulfate) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).
Death resulted from an overdosage in which 1683 mg Betzee-M (Zinc Sulfate) was delivered intravenously over the course of 60 hours to a 72 year old patient.
Symptoms of Betzee-M (Zinc Sulfate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Betzee-M (Zinc Sulfate) level of 4184 mcg/dl.
Calcium supplements may confer a protective effect against Betzee-M (Zinc Sulfate) toxicity.
Betzee-M (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Betzee-M (Zinc Sulfate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Betzee-M (Zinc Sulfate).
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
Betzee-M (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
Revised: October, 2004
© Hospira 2004 EN-0488 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
10 mL Vial
Betzee-M (Zinc Sulfate)
1 mg/mL
Betzee-M (Zinc Sulfate) Chloride Inj., USP
Rx only
FOR I.V. USE ONLY AFTER DILUTION.
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
Depending on the reaction of the Betzee-M after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Betzee-M 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 Betzee-M 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.
There are no reviews yet. Be the first to write one! |
The information was verified by Dr. Rachana Salvi, MD Pharmacology