PARICALCITOL injection

Страна: САЩ

Език: английски

Източник: NLM (National Library of Medicine)

Активна съставка:

PARICALCITOL (UNII: 6702D36OG5) (PARICALCITOL - UNII:6702D36OG5)

Предлага се от:

Amneal Pharmaceuticals LLC

INN (Международно Name):

PARICALCITOL

Композиция:

PARICALCITOL 2 ug in 1 mL

Начин на приложение:

INTRAVENOUS

Вид предписание :

PRESCRIPTION DRUG

Терапевтични показания:

Paricalcitol injection is indicated for the prevention and treatment of secondary hyperparathyroidism in patients 5 years of age and older with chronic kidney disease (CKD) on dialysis. Paricalcitol injection is contraindicated in patients with: - Hypercalcemia [see Warnings and Precautions (5.1)] - Vitamin D toxicity [see Warnings and Precautions (5.1)] - Known hypersensitivity to paricalcitol or any of the inactive ingredients in paricalcitol injection. Hypersensitivity adverse reactions have been reported [e.g., angioedema (including laryngeal edema) and urticaria] [see Adverse Reactions (6.2)] . Risk Summary Limited data with paricalcitol in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with chronic kidney disease in pregnancy (see Clinical Considerations) . In animal reproduction studies, slightly increased embryofetal loss was observed in pregnant rats and rabbits administered paricalcitol intravenously during the period of organogenesis at doses 2 and 0.5 times, respectively, a human dose of 14 mcg (equivalent to 0.24 mcg/kg), based on body surface area (mg/m2 ). Adverse reproductive outcomes were observed at doses that caused maternal toxicity (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Chronic kidney disease in pregnancy increases the risk for maternal hypertension and preeclampsia, miscarriage, preterm delivery, polyhydramnios, still birth, and low birth weight infants. Data Animal Data Pregnant rats and rabbits were treated with paricalcitol by once-daily intravenous injection during the period of organogenesis (in rats, from gestation day (GD) 6 to 17; in rabbits, from GD 6 to 18). Rats were dosed at 0, 0.3, 1 or 3 mcg/kg/day and rabbits at 0, 0.03, 0.1 or 0.3 mcg/kg/day, representing up to 2 or 0.5 times, respectively, a human dose of 0.24 mcg/kg, based on body surface area (mg/m2 ). Slightly decreased fetal viability was observed in both studies at the highest doses representing 2 and 0.5 times, respectively, a human dose of 0.24 mcg/kg, in the presence of maternal toxicity (decreased body weight and food consumption). Pregnant rats were administered paricalcitol by intravenous injection three times per week at doses of 0, 0.3, 3 or 20 mcg/kg/day throughout gestation, parturition and lactation (GD 6 to lactation day (LD) 20) representing exposures up to 13 times a human dose of 0.24 mcg/kg. A small increase in stillbirths and pup deaths from parturition to LD 4 were observed at the high dose when compared to the control group (9.2% versus 3.3% in controls) at 13 times a human dose of 0.24 mcg/kg, which occurred at a maternally toxic dose known to cause hypercalcemia in rats. Surviving pups were not adversely affected; body weight gains, developmental landmarks, reflex ontogeny, learning indices, and locomotor activity were all within normal parameters. F1 reproductive capacity was unaffected. Risk Summary There is no information available on the presence of paricalcitol in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. Studies in rats have shown that paricalcitol and/or its metabolites are present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk (see Data) . Infants exposed to paricalcitol through breast milk should be monitored for signs and symptoms of hypercalcemia (see Clinical Considerations) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for paricalcitol and any potential adverse effects on the breast-fed child from paricalcitol or from the underlying maternal condition. Clinical Considerations Infants exposed to paricalcitol through breast milk should be monitored for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation and weight loss. Monitoring of serum calcium in the infant should be considered. Data Following a single oral administration of 20 mcg/kg of radioactive [3 H] paricalcitol to lactating rats, the concentrations of total radioactivity was determined. Lower levels of total radioactivity were present in the milk compared to that in the plasma of the dams indicating that low levels of [3 H] paricalcitol and/or its metabolites are secreted into milk. Exposure of the pups to [3 H] paricalcitol through milk was confirmed by the presence of radioactive material in the pups’ stomachs. The safety and efficacy of paricalcitol for the prevention and treatment of secondary hyperparathyroidism associated with CKD have been established in pediatric patients 5 years of age and older with CKD on dialysis. Use of paricalcitol in pediatric patients 5 years of age and older is supported by evidence from an adequate and well-controlled study in 29 patients, 5 to 19 years of age, with CKD on hemodialysis [see Clinical Studies (14)] . The safety and efficacy of paricalcitol have not been established in pediatric patients less than 5 years old. Clinical studies of paricalcitol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the 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 or cardiac function, and of concomitant disease or other drug therapy. The pharmacokinetics of paricalcitol were studied in patients with mild and moderate hepatic impairment and were similar to that of patients with normal hepatic function. No dose adjustment is required in patients with mild or moderate hepatic function. Paricalcitol has not been studied in patients with severe hepatic impairment.

Каталог на резюме:

Paricalcitol injection, USP is supplied as a sterile, clear, colorless, aqueous solution for intravenous injection. It is available as follows: 2 mcg/ mL (1 mL) (Each 1 mL single-dose vial contains 2 mcg of paricalcitol, USP) 1 mL Single-Dose Vial                                   NDC 70121-1033-1 25 Vials in a Carton                                        NDC 70121-1033-5 10 Vials in a Carton                                        NDC 70121-1033-7 5 mcg/ mL (1 mL) (Each 1 mL single-dose vial contains 5 mcg of paricalcitol, USP) 1 mL Single-Dose Vial                                   NDC 70121-1034-1 25 Vials in a Carton                                        NDC 70121-1034-5 10 Vials in a Carton                                        NDC 70121-1034-7 10 mcg/2 mL (5 mcg/mL) (2 mL) (Each 2 mL single-dose vial contains 10 mcg of paricalcitol, USP) 2 mL Single-Dose Vial                                   NDC 70121-1035-1 25 Vials in a Carton                                        NDC 70121-1035-5 10 Vials in a Carton                                        NDC 70121-1035-7 10 mcg/2 mL (5 mcg/mL) (2 mL) (Each 2 mL multiple-dose vial contains 10 mcg of paricalcitol, USP) 2 mL Multiple-Dose Vial                                NDC 70121-1036-1 25 Vials in a Carton                                        NDC 70121-1036-5 10 Vials in a Carton                                        NDC 70121-1036-7 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Discard any unused portion of the single-dose vial after use. The contents of the multiple-dose vial remain stable up to seven days after initial use when stored at controlled room temperature.

Статус Оторизация:

Abbreviated New Drug Application

Данни за продукта

PARICALCITOL- PARICALCITOL INJECTION
AMNEAL PHARMACEUTICALS LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PARICALCITOL INJECTION
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
PARICALCITOL INJECTION.
PARICALCITOL INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1998
INDICATIONS AND USAGE
Paricalcitol injection is a vitamin D analog indicated for the
prevention and treatment of secondary
hyperparathyroidism in patients 5 years of age and older with chronic
kidney disease on dialysis. (1)
DOSAGE AND ADMINISTRATION
Ensure serum calcium is not above the upper limit of normal before
initiating. (2.1)
Administer paricalcitol injection intravenously through a hemodialysis
vascular access at any time
during dialysis. (2.1)
Adult Dose:
Initiate at 0.04 mcg/kg to 0.1 mcg/kg (2.8 mcg to 7 mcg) no more
frequently than every other day.
(2.2)
Target maintenance dose to intact parathyroid hormone (PTH) levels
within the desired therapeutic
range and serum calcium within normal limits. (2.2)
Monitor serum calcium frequently (e.g., twice weekly) and intact PTH
levels every 2 to 4 weeks after
dose initiation or adjustment. (2.2)
See Table 1 in the full prescribing information for titration
recommendations based upon intact PTH
levels. (2.2)
Suspend or decrease the dose for persistent abnormally low intact PTH
or serum calcium consistently
above the normal range. (2.2)
Pediatric Dose:
Initiate paricalcitol injection as an intravenous bolus dose of:
0.04 mcg/kg if baseline intact PTH is less than 500 pg/mL, or
0.08 mcg/kg if baseline intact PTH is 500 pg/mL or greater. (2.3)
Target maintenance dose to intact PTH levels within the desired
therapeutic range and serum calcium
within normal limits. (2.3)
Monitor serum calcium frequently (e.g., twice weekly) and intact PTH
levels every 2 to 4 weeks after
dose initiation or adjustment. (2.3)
See Table 2 in the full prescribing information for titration
recommendations based upon intact PTH
levels.