Complete SPL Sections#
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
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.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Injection: clear, colorless solution available as follows: 2 mcg/mL single-dose vial 5 mcg/mL single-dose vial 10 mcg/2 mL (5 mcg/mL) single-dose vial 10 mcg/2 mL (5 mcg/mL) multiple-dose vial
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
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) ] .
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
The following serious adverse reactions are described below and elsewhere in the labeling: Hypercalcemia [see Warnings and Precautions (5.1) ] Adynamic Bone Disease [see Warnings and Precautions (5.3) ]
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
Table 4 includes clinically significant drug interactions with paricalcitol. Table 4: Clinically Significant Drug Interactions with Paricalcitol Drugs that May Increase the risk of Hypercalcemia Clinical Impact Concomitant administration of high doses of calcium-containing preparations or other vitamin D compounds may increase the risk of hypercalcemia. Thiazide diuretics are known to induce hypercalcemia by reducing excretion of calcium in the urine. Examples Calcium-containing products, other vitamin D compounds or thiazide diuretics Intervention Monitor calcium more frequently and adjust paricalcitol dose as needed [see Warnings and Precautions (5.1) ] . Digitalis Compounds Clinical Impact Paricalcitol can cause hypercalcemia which can potentiate the risk of digitalis toxicity. Intervention Monitor patients for signs and symptoms of digitalis toxicity and increase frequency of serum calcium monitoring when initiating or adjusting the dose of paricalcitol in patients receiving digitalis compounds [see Warnings and Precautions (5.2) ] . Strong CYP3A Inhibitors Clinical Impact Paricalcitol is partially metabolized by CYP3A. Exposure of paricalcitol will increase upon co-administration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . Examples Boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, and voriconazole Intervention If a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor, dose adjustment of paricalcitol may be necessary. Monitor intact PTH and serum calcium concentrations closely.
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
Overdosage of paricalcitol may lead to hypercalcemia, hypercalciuria, and hyperphosphatemia [see Warnings and Precautions (5.1) ] . The treatment of acute overdosage should consist of supportive measures and discontinuation of drug administration. Serum calcium levels should be measured until normal. Paricalcitol is not significantly removed by dialysis.
11 DESCRIPTION
DESCRIPTION SECTION
Paricalcitol, USP is a synthetically manufactured active vitamin D analog. It is a white to almost white powder chemically designated as (1α,3β,7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1,3,25-triol and has the following structural formula: Molecular formula is C 27 H 44 O 3 . Molecular weight is 416.64 g/mol. Paricalcitol injection, USP is a sterile, aqueous solution for intravenous use. Each mL contains paricalcitol USP, 2 mcg or 5 mcg and the following inactive ingredients: alcohol, 20% (v/v) and propylene glycol, 30% (v/v).
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
Adult Studies in CKD on Dialysis Three 12-week, placebo-controlled studies were conducted in 78 patients with CKD on hemodialysis. In these studies, patients ranged in age from 22 to 90 years, 51% were males, 13% were Caucasian, 79% were African-American, and 8% were Hispanic. The most common causes of renal failure were hypertension and diabetes. The dose of paricalcitol was started at 0.04 mcg/kg 3 times per week intravenously. The dose was increased by 0.04 mcg/kg every 2 weeks until intact PTH levels were decreased at least 30% from baseline or a fifth escalation brought the dose to 0.24 mcg/kg, or intact PTH fell to less than 100 pg/mL, or the Ca × P product was greater than 75 within any 2 week period, or serum calcium became greater than 11.5 mg/dL at any time. Patients treated with paricalcitol achieved a mean intact PTH reduction of 30% within 6 weeks. The results from these studies are as follows: Table 6: Mean Changes from Baseline to Final Evaluation in intact PTH, Alkaline Phosphatase, Phosphorus and Calcium × Phosphorus Product in Adult Patients with CKD on Dialysis in Three 12-Week Placebo-Controlled Studies Group (No. of Pts.) Baseline Mean (Range) Mean (SE) Change From Baseline to Final Evaluation intact PTH (pg/mL) Paricalcitol (n = 40) 783 (291 to 2,076) -379 (43.7) placebo (n = 38) 745 (320 to 1,671) -69.6 (44.8) Alkaline Phosphatase (U/L) Paricalcitol (n = 31) 150 (40 to 600) -41.5 (10.6) placebo (n = 34) 169 (56 to 911) +2.6 (10.1) Phosphorus (mg/dL) Paricalcitol (n = 40) 5.8 (3.7 to 10.2) +0.47 (0.3) placebo (n = 38) 6.0 (2.8 to 8.8) -0.47 (0.3) Calcium × Phosphorus Product Paricalcitol (n = 40) 54 (32 to 106) +7.9 (2.2) placebo (n = 38) 54 (26 to 77) -3.9 (2.3) Pediatric Study in CKD on Dialysis Paricalcitol was evaluated in a 12-week randomized, double-blind, placebo-controlled study of 29 pediatric patients, aged 5 to 19 years, with CKD on hemodialysis; nearly all had received some form of vitamin D prior to the study. Of the 29 patients, 76% were male, 52% were Caucasian and 45% were African-American. The initial dose of paricalcitol was 0.04 mcg/kg 3 times per week, based on baseline intact PTH level of less than 500 pg/mL, or 0.08 mcg/kg 3 times per week, based on baseline intact PTH level of 500 pg/mL or greater. The dose of paricalcitol was adjusted in 0.04 mcg/kg increments based on the levels of serum intact PTH, calcium and Ca × P. The mean baseline levels of intact PTH were 841 pg/mL for the 15 paricalcitol-treated patients and 740 pg/mL for the 14 placebo-treated patients. The mean dose of paricalcitol administered was 4.6 mcg (range: 0.8 mcg to 9.6 mcg). Sixty-seven percent of the paricalcitol-treated patients and 14% of the placebo-treated patients completed the trial. Seventy-one percent of the placebo-treated patients discontinued due to excessive elevations in intact PTH levels, as defined by 2 consecutive intact PTH levels greater than 700 pg/mL and greater than baseline after 4 weeks of treatment. The primary efficacy analysis demonstrated that 60% of paricalcitol-treated patients and 21% of placebo-treated patients achieved two consecutive greater than or equal to 30% reductions from baseline in intact PTH.
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
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.
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Hypercalcemia Advise patients to contact a health care provider if they develop symptoms of elevated calcium (e.g. feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) [see Warnings and Precautions (5.1) ] . Monitoring Inform patients that they will need routine monitoring of laboratory parameters such as calcium and intact PTH while receiving paricalcitol injection. Inform patients that more frequent monitoring is necessary during the initiation of therapy, following dose changes or when potentially interacting medications are started or discontinued [see Dosage and Administration (2) , Drug Interactions (7) ] . Drug Interactions Advise patients to inform their physician of all medications, including prescription and nonprescription drugs, and supplements they are taking. Advise patients to also inform their physician that they are receiving paricalcitol injection if a new medication is prescribed [see Drug Interactions (7) ] . Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Ahmedabad 382213, INDIA Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 03-2024-03
PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 70121-1033-1 Paricalcitol injection, USP 2 mcg/mL Rx only Vial Label Amneal Pharmaceuticals LLC NDC 70121-1033-7 Paricalcitol injection, USP 2 mcg/mL Rx only Carton Label 10 x 1 mL Single-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1033-5 Paricalcitol injection, USP 2 mcg/mL Rx only Carton Label 25 x 1 mL Single-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1034-1 Paricalcitol injection, USP 5 mcg/mL Rx only Vial Label Amneal Pharmaceuticals LLC NDC 70121-1034-7 Paricalcitol injection, USP 5 mcg/mL Rx only Carton Label 10 x 1 mL Single-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1034-5 Paricalcitol injection, USP 5 mcg/mL Rx only Carton Label 25 x 1 mL Single-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1035-1 Paricalcitol injection, USP 10 mcg/2 mL Rx only Vial Label Amneal Pharmaceuticals LLC NDC 70121-1035-7 Paricalcitol injection, USP 10 mcg/2 mL Rx only Carton Label 10 x 2 mL Single-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1035-5 Paricalcitol injection, USP 10 mcg/2 mL Carton Label 25 x 2 mL Single-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1036-1 Paricalcitol injection, USP 10 mcg/2 mL Rx only Multiple-Dose Vial Label Amneal Pharmaceuticals LLC NDC 70121-1036-7 Paricalcitol injection, USP 10 mcg/2 mL Rx only Carton Label 10 x 2 mL Multiple-Dose Vials Amneal Pharmaceuticals LLC NDC 70121-1036-5 Paricalcitol injection, USP 10 mcg/2 mL Rx only Carton Label 25 x 2 mL Multiple-Dose Vials Amneal Pharmaceuticals LLC
