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DRUGS & SUPPLEMENTS
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How long you have been taking the medicine? |
Betamethasone Dipropionate:
Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray is indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.
Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray to the affected skin areas twice daily and rub in gently.
Use Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray for up to 4 weeks of treatment. Treatment beyond 4 weeks is not recommended.
Discontinue Cronolevel con Lidocaina (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.
Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray contains 0.643 mg Cronolevel con Lidocaina (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.
Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray and 180 subjects applied vehicle spray.
Adverse reactions that occurred in at least 1% of subjects treated with Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray for up to 28 days are presented in Table 1.
Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (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. Cronolevel con Lidocaina Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray is administered to a nursing woman.
Safety and effectiveness of Cronolevel con Lidocaina 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 Cronolevel con Lidocaina (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.
Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray contains 0.0643% Cronolevel con Lidocaina (Betamethasone Dipropionate) (equivalent to 0.05% betamethasone), a synthetic, fluorinated corticosteroid.
The chemical name for Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray contains 0.643 mg of Cronolevel con Lidocaina (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. Cronolevel con Lidocaina (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 Cronolevel con Lidocaina Spray in psoriasis is unknown.
Vasoconstrictor studies performed with Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray was evaluated in a study randomizing 52 adult subjects with moderate to severe plaque psoriasis. Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray for 15 days. No subjects (0 out of 24) treated with Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (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) | Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray b.i.d. (15 days) | Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate).
In a 90-day repeat-dose toxicity study in rats, topical administration of Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (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 | |||
Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray b.i.d. (N=182) | Vehicle Spray b.i.d. (N=95) | Cronolevel con Lidocaina (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% |
Cronolevel con Lidocaina 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
Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) (ser-ne-vo) (betamethasone dipropionate) Spray, 0.05% | |
Important: Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray is for use on the skin only. Do not get Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray near or in your eyes, mouth, or vagina. | |
What is Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray?
It is not known if Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray is safe and effective in children under 18 years of age. Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray is not recommended for use in patients under 18 years of age. | |
Before you use Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray? See the “Instructions for Use” for detailed information about the right way to apply Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray.
| |
What are the possible side effects of Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray?
The most common side effects of Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray?
Keep Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray and all medicines out of the reach of children. | |
General information about the safe and effective use of Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray for a condition for which it was not prescribed. Do not give Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray that is written for health professionals. | |
What are the ingredients in Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray? Active ingredient: Cronolevel con Lidocaina (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
Cronolevel con Lidocaina (Betamethasone Dipropionate) (ser-ne-vo)
(betamethasone dipropionate)
Spray, 0.05%
Important: Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray is for use on the skin only. Do not get Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray near or in your eyes, mouth, or vagina.
Read this “Instructions for Use” before you start using Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray bottle.
Figure A
How to apply Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray:
Step 1: Shake the Cronolevel con Lidocaina (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 Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray to the affected area as instructed by your doctor. (See Figure B )
Figure B
Step 3: Spray only enough Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray gently.
Figure C
Repeat Steps 2 and 3 to apply Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray to other affected areas as instructed by your doctor.
Step 4: After applying Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray, place the cap back onto the pump top. (See Figure D )
Figure D
How should I store Cronolevel con Lidocaina (Betamethasone Dipropionate) Spray?
Keep Cronolevel con Lidocaina (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
Cronolevel con Lidocaina (Betamethasone Dipropionate) is a trademark of Promius Pharma, LLC.
Issued: 02/2016
007528
140693
Betamethasone Sodium Phosphate:
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray to the affected skin areas twice daily and rub in gently.
Use Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray for up to 4 weeks of treatment. Treatment beyond 4 weeks is not recommended.
Discontinue Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is for topical use only. It is not for oral, ophthalmic, or intravaginal use.
Spray, 0.05% for topical use. Each gram of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray contains 0.643 mg Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) dipropionate USP (equivalent to 0.5 mg Cronolevel con Lidocaina (Betamethasone Sodium Phosphate)) in a slightly thickened, white to off-white oil-in-water emulsion.
Spray: 0.05% (equivalent to 0.5 mg betamethasone/g) (3)
None.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray and 180 subjects applied vehicle spray.
Adverse reactions that occurred in at least 1% of subjects treated with Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray for up to 28 days are presented in Table 1.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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. Cronolevel con Lidocaina Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is administered to a nursing woman.
Safety and effectiveness of Cronolevel con Lidocaina 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray contains 0.0643% Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) dipropionate (equivalent to 0.05% Cronolevel con Lidocaina (Betamethasone Sodium Phosphate)), a synthetic, fluorinated corticosteroid.
The chemical name for Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray contains 0.643 mg of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) dipropionate USP (equivalent to 0.5 mg Cronolevel con Lidocaina (Betamethasone Sodium Phosphate)) 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. Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina Spray in psoriasis is unknown.
Vasoconstrictor studies performed with Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray was evaluated in a study randomizing 52 adult subjects with moderate to severe plaque psoriasis. Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray for 15 days. No subjects (0 out of 24) treated with Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) dipropionate, betamethasone-17-propionate, and Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) dipropionate, while the metabolites, betamethasone-17-propionate and Cronolevel con Lidocaina (Betamethasone Sodium Phosphate), 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) | Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray b.i.d. (15 days) | Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray b.i.d. (29 days) |
Betamethasone-17-propionate | 120 ± 127 | 63.9 ± 52.6 |
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) | 119 ± 176 | 57.6 ± 55.9 |
Long-term animal studies have not been performed to evaluate the carcinogenic potential of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) dipropionate.
In a 90-day repeat-dose toxicity study in rats, topical administration of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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.
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 | |||
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray b.i.d. (N=182) | Vehicle Spray b.i.d. (N=95) | Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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% |
Cronolevel con Lidocaina 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
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) (ser-ne-vo) (betamethasone dipropionate) Spray, 0.05% | |
Important: Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is for use on the skin only. Do not get Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray near or in your eyes, mouth, or vagina. | |
What is Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray?
It is not known if Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is safe and effective in children under 18 years of age. Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is not recommended for use in patients under 18 years of age. | |
Before you use Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray? See the “Instructions for Use” for detailed information about the right way to apply Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray.
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What are the possible side effects of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray?
The most common side effects of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray include itching, burning, stinging, pain, and thinning of skin (atrophy) at the treated site. These are not all the possible side effects of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray?
Keep Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray and all medicines out of the reach of children. | |
General information about the safe and effective use of Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray for a condition for which it was not prescribed. Do not give Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray that is written for health professionals. | |
What are the ingredients in Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray? Active ingredient: Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) (ser-ne-vo)
(betamethasone dipropionate)
Spray, 0.05%
Important: Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray is for use on the skin only. Do not get Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray near or in your eyes, mouth, or vagina.
Read this “Instructions for Use” before you start using Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray bottle.
Figure A
How to apply Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray:
Step 1: Shake the Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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 Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray to the affected area as instructed by your doctor. (See Figure B )
Figure B
Step 3: Spray only enough Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray gently.
Figure C
Repeat Steps 2 and 3 to apply Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray to other affected areas as instructed by your doctor.
Step 4: After applying Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray, place the cap back onto the pump top. (See Figure D )
Figure D
How should I store Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) Spray?
Keep Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) 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
Cronolevel con Lidocaina (Betamethasone Sodium Phosphate) is a trademark of Promius Pharma, LLC.
Issued: 02/2016
007528
140693
Depending on the reaction of the Cronolevel con Lidocaina after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Cronolevel con Lidocaina 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 Cronolevel con Lidocaina 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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The information was verified by Dr. Rachana Salvi, MD Pharmacology