CALCIPOTRIENE AND BETAMETHASONE DIPROPIONATE suspension

Riik: Ameerika Ühendriigid

keel: inglise

Allikas: NLM (National Library of Medicine)

Toimeaine:

BETAMETHASONE DIPROPIONATE (UNII: 826Y60901U) (BETAMETHASONE - UNII:9842X06Q6M), CALCIPOTRIENE (UNII: 143NQ3779B) (CALCIPOTRIENE - UNII:143NQ3779B)

Saadav alates:

TOLMAR Inc.

Manustamisviis:

TOPICAL

Retsepti tüüp:

PRESCRIPTION DRUG

Näidustused:

Calcipotriene and betamethasone dipropionate topical suspension is indicated for the topical treatment of plaque psoriasis of the scalp in patients 12 years and older and plaque psoriasis of the scalp and body in patients 18 years and older. Additional pediatric use information is approved for LEO Pharma A/S’s Taclonex® (calcipotriene and betamethasone dipropionate) Topical Suspension. However, due to LEO Pharma A/S’s marketing exclusivity rights, this drug product is not labeled with that information. None. Risk Summary Available data with calcipotriene and betamethasone dipropionate topical suspension are not sufficient to evaluate a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Although there are no available data on use of the calcipotriene component in pregnant women, systemic exposure to calcipotriene after topical administration of calcipotriene and betamethasone dipropionate topical suspension is likely to be low [see Clinical Pharmacology ( 12.3 )] . Observational studies suggest an increased risk of having low birth weight infants with the maternal use of potent or super potent topical corticosteroids (see Data). Advise pregnant women that calcipotriene and betamethasone dipropionate topical suspension may increase the potential risk of having a low birth weight infant and to use calcipotriene and betamethasone dipropionate topical suspension on the smallest area of skin and for the shortest duration possible. In animal reproduction studies, oral administration of calcipotriene to pregnant rats during the period of organogenesis resulted in an increased incidence of minor skeletal abnormalities, including enlarged fontanelles and extra ribs (see Data). Oral administration of calcipotriene to pregnant rabbits during the period of organogenesis had no apparent effects on embryo-fetal development. Subcutaneous administration of betamethasone dipropionate to pregnant rats and rabbits during the period of organogenesis resulted in fetal toxicity, including fetal deaths, reduced fetal weight, and fetal malformations (cleft palate and crooked or short tail) (see Data). The available data do not allow the calculation of relevant comparisons between the systemic exposures of calcipotriene and betamethasone dipropionate observed in animal studies to the systemic exposures that would be expected in humans after topical use of calcipotriene and betamethasone dipropionate topical suspension. The estimated background risk of major birth defects and miscarriage of the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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% to 20%, respectively. Data Human Data Available observational studies in pregnant women did not identify a drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency. However, when the dispensed amount of potent or super potent topical corticosteroids exceeded 300 grams during the entire pregnancy, maternal use was associated with an increased risk of low birth weight in infants. Animal Data Embryo-fetal development studies with calcipotriene were performed by the oral route in rats and rabbits. Pregnant rats received dosages of 0, 6, 18, or 54 mcg/kg/day (0, 36, 108, and 324 mcg/m2 /day, respectively) on days 6-15 of gestation (the period of organogenesis). There were no apparent effects on maternal survival, behavior, or body weight gain, no effects on litter parameters, and no effects on the incidence of major malformations in fetuses. Fetuses from dams dosed at 54 mcg/kg/day exhibited a significantly increased incidence of minor skeletal abnormalities, including enlarged fontanelles and extra ribs. Pregnant rabbits were dosed daily with calcipotriene at exposures of 0, 4, 12, or 36 mcg/kg/day (0, 48, 144, and 432 mcg/m2 /day, respectively) on days 6-18 of gestation (the period of organogenesis). Mean maternal body weight gain was reduced in animals dosed at 12 or 36 mcg/kg/day. The incidence of fetal deaths was increased in the group dosed at 36 mcg/kg/day; reduced fetal weight was also observed in this group. The incidence of major malformations among fetuses was not affected. An increase in the incidence of minor skeletal abnormalities, including incomplete ossification of sternebrae, pubic bones, and forelimb phalanges, was observed in the group dosed at 36 mcg/kg/day. Embryo-fetal development studies with betamethasone dipropionate were performed via subcutaneous injection in mice and rabbits. Pregnant mice were administered doses of 0, 156, 625, or 2500 mcg/kg/day (0, 468, 1875, and 7500 mcg/m2 /day, respectively) on days 7 through 13 of gestation (the period of organogenesis). Betamethasone dipropionate induced fetal toxicity, including fetal deaths, reduced fetal weight, malformations (increased incidence of the cleft palate and crooked or short tail), and minor skeletal abnormalities (delayed ossification of vertebra and sternebrae). Fetal toxicity was observed at the lowest exposure that was evaluated (156 mcg/kg/day). Pregnant rabbits were injected subcutaneously at dosages of 0, 0.625, 2.5, and 10 mcg/kg/day (0, 7.5, 30, and 120 mcg/m2 /day, respectively) on days 6 through 18 of gestation (the period of organogenesis). Betamethasone dipropionate induced fetal toxicity, including fetal deaths, reduced fetal weight, external malformations (including malformed ears, cleft palate, umbilical hernia, kinked tail, club foot, and club hand), and skeletal malformations (including absence of phalanges of the first digit and cranial dysplasia) at dosages of 2.5 mcg/kg/day and above. Calcipotriene was evaluated for effects on peri- and post-natal development when orally administered to pregnant rats at dosages of 0, 6, 18 or 54 mcg/kg/day (0, 36, 108, and 324 mcg/m2 /day, respectively) from gestation day 15 through day 20 postpartum. No remarkable effects were observed on any parameter, including survival, behavior, body weight, litter parameters, or the ability to nurse or rear pups. Betamethasone dipropionate was evaluated for effects on peri- and post-natal development when orally administered to pregnant rats at dosages of 0, 100, 300, and 1000 mcg/kg/day (0, 600, 1800, and 6000 mcg/m2 /day, respectively) from gestation day 6 through day 20 postpartum. Mean maternal body weight was significantly reduced on gestation day 20 in animals dosed at 300 and 1000 mcg/kg/day. The mean duration of gestation was slightly, but statistically significantly, increased at 100, 300, and 1000 mcg/kg/day. The mean percentage of pups that survived to day 4 was reduced in relation to dosage. On lactation day 5, the percentage of pups with a reflex to right themselves when placed on their back was significantly reduced at 1000 mcg/kg/day. No effects on the ability of pups to learn were observed, and the ability of the offspring of treated rats to reproduce was not affected. Risk Summary There is no information regarding the presence of topically administered calcipotriene and betamethasone dipropionate in human milk, the effects on the breastfed infant, or the effects on milk production. Concentrations of calcipotriene in plasma are low after topical administration, and therefore, concentrations in human milk are likely to be low [see Clinical Pharmacology ( 12.3 )]. It is not known whether topical administration of large amounts of betamethasone dipropionate could result in sufficient systemic absorption to produce detectable quantities in human milk (see Clinical Considerations ). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for calcipotriene and betamethasone dipropionate topical suspension and any potential adverse effects on the breastfed child from calcipotriene and betamethasone dipropionate topical suspension or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use calcipotriene and betamethasone dipropionate topical suspension on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply calcipotriene and betamethasone dipropionate topical suspension directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations ( 8.4 )] . The safety and effectiveness of calcipotriene and betamethasone dipropionate topical suspension for the treatment of plaque psoriasis of the scalp has been established in pediatric patients age 12 to 17 years. The use of calcipotriene and betamethasone dipropionate topical suspension for this indication is supported by evidence from adequate and well-controlled trials in adults and from uncontrolled trials in pediatric subjects that enrolled 109 adolescents with moderate psoriasis of the scalp. After 4 weeks of once daily treatment with calcipotriene and betamethasone dipropionate topical suspension, HPA axis suppression was observed in 3% of adolescents with psoriasis of the scalp and 16% of adolescents with psoriasis of the scalp and body. [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 ), and Clinical Pharmacology ( 12.2 )]. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic toxicity when treated with topical corticosteroids. Pediatric patients are, therefore, also at greater risk of HPA axis suppression and adrenal insufficiency with the use of topical corticosteroids including calcipotriene and betamethasone dipropionate topical suspension [see Clinical Pharmacology (12.2)] . Rare systemic toxicities 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 striae have also been reported with use of topical corticosteroids in pediatric patients. The safety and effectiveness of calcipotriene and betamethasone dipropionate topical suspension in pediatric patients less than 12 years of age have not been established. Additional pediatric use information is approved for LEO Pharma A/S’s Taclonex® (calcipotriene and betamethasone dipropionate) Topical Suspension. However, due to LEO Pharma A/S’s marketing exclusivity rights, this drug product is not labeled with that information. Clinical studies of calcipotriene and betamethasone dipropionate topical suspension in plaque psoriasis on non-scalp areas included 124 subjects who were 65 years of age or older, and 36 were 75 years of age or older. Clinical studies of calcipotriene and betamethasone dipropionate topical suspension in subjects with psoriasis of the scalp included 334 subjects who were 65 years or older and 84 subjects who were 75 years or older. No overall differences in safety or effectiveness of calcipotriene and betamethasone dipropionate topical suspension were observed between these subjects and younger subjects, and other reported clinical experience has not identified any differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Calcipotriene and Betamethasone Dipropionate Topical Suspension (kal si poe trye’ een and bay’’ ta meth’ a sone dye proe’ pee oh nate) Important: Calcipotriene and betamethasone dipropionate topical suspension is for use on skin only (topical). Do not get calcipotriene and betamethasone dipropionate topical suspension near or in your mouth, eyes, or vagina. Read this Instructions for Use before you start using calcipotriene and betamethasone dipropionate topical suspension  and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. How to apply calcipotriene and betamethasone dipropionate topical suspension to your body: Follow your healthcare provider’s instructions of how much calcipotriene and betamethasone dipropionate topical suspension to use and where to use it. Apply calcipotriene and betamethasone dipropionate topical suspension directly to areas affected by plaque psoriasis and gently rub in. Wash your hands after applying calcipotriene and betamethasone dipropionate topical suspension, unless you are treating areas on your hands. How to apply calcipotriene and betamethasone dipropionate topical suspension to your scalp: You do not need to wash your hair before you apply calcipotriene and betamethasone dipropionate topical suspension. Diagram of Instructions for Use How should I store calcipotriene and betamethasone dipropionate topical suspension? - Store the calcipotriene and betamethasone dipropionate topical suspension at room temperature between 68°F to 77°F (20°C to 25°C). - Do not refrigerate calcipotriene and betamethasone dipropionate topical suspension. - Keep bottle in the carton when not in use. - Discard unused calcipotriene and betamethasone dipropionate topical suspension 6 months after it has been opened.   Keep calcipotriene and betamethasone dipropionate topical suspension and all medicines out of reach of children.   This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured and Distributed by: Tolmar, Inc. Fort Collins, CO 80526 04006030 Rev. 0 12/19

Toote kokkuvõte:

Calcipotriene and betamethasone dipropionate topical suspension is a viscous, nearly odorless, almost clear, colorless to slightly off-white suspension. It is available as: Store between 20°C - 25°C (68°F - 77°F); excursions permitted between 15°C - 30°C (59°F - 86°F). [See USP controlled room temperature.] Do not refrigerate. Keep the bottle in the carton when not in use. Unused product should be discarded six months after the bottle has been opened. Shake before use. Keep out of reach of children.

Volitamisolek:

Abbreviated New Drug Application

Toote omadused

CALCIPOTRIENE AND BETAMETHASONE DIPROPIONATE- CALCIPOTRIENE AND
BETAMETHASONE DIPROPIONATE SUSPENSION
TOLMAR INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CALCIPOTRIENE AND
BETAMETHASONE DIPROPIONATE TOPICAL SUSPENSION, 0.005%/0.064% SAFELY
AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CALCIPOTRIENE AND
BETAMETHASONE
DIPROPIONATE TOPICAL SUSPENSION, 0.005%/0.064%.
CALCIPOTRIENE AND BETAMETHASONE DIPROPIONATE TOPICAL SUSPENSION,
0.005%/0.064%
INITIAL U.S. APPROVAL: 2006
RECENT MAJOR CHANGES
Warnings and Precautions, Ophthalmic Adverse Reactions (5.5) 7/2019
INDICATIONS AND USAGE
Calcipotriene and betamethasone dipropionate topical suspension is a
combination of calcipotriene, a
vitamin D analog, and betamethasone dipropionate, a corticosteroid,
indicated for the topical treatment of
plaque psoriasis of the scalp in patients 12 years and older and
plaque psoriasis of the scalp and body in
patients age 18 years and older. (1)
DOSAGE AND ADMINISTRATION
Shake bottle before use. (2)
Apply calcipotriene and betamethasone dipropionate topical suspension
to affected areas on the scalp
and body once daily for up to 8 weeks. Discontinue therapy when
control is achieved. (2)
Patients age 12 to 17 years should not use more than 60 grams per
week. (2)
Adult patients should not use more than 100 grams per week. (2)
Do not use with occlusive dressings unless directed by a healthcare
provider. (2)
Avoid use on the face, groin, or axillae, or if skin atrophy is
present at the treatment site. (2)
Not for oral, ophthalmic, or intravaginal use. (2)
DOSAGE FORMS AND STRENGTHS
Topical Suspension: 0.005%/0.064% - each gram of calcipotriene and
betamethasone dipropionate topical
suspension contains 50 mcg of calcipotriene and 0.643 mg of
betamethasone dipropionate. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
_Hypercalcemia and Hypercalciuria:_ Hypercalcemia and hypercalciuria
have been reported. If either
occurs, discontinue until parameters of