Paricalcitol: Uses, Dosage, Side Effects & Warnings

Uses

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 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.

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 ) Do not inject Paricalcitol Injection directly into a vein ( 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. ( 2.3 ) Suspend or decrease the dose for persistent abnormally low intact PTH or serum calcium consistently above the normal range. ( 2.3 ) 2.1 Important Administration Information Ensure serum calcium is not above the upper limit of normal before initiating treatment [see Warnings and Precautions (5.1) ] . Administer Paricalcitol Injection intravenously through a hemodialysis vascular access port at any time during dialysis. Do not inject Paricalcitol Injection directly into a vein. Inspect Paricalcitol Injection visually prior to administration; the solution should appear clear and colorless. Do not use if the solution is not clear or particles are present. Discard unused portion of 2 mcg/mL and 5 mcg/mL single-dose vials. 2.2 Starting Dose and Dose Titration in Adults Initiate Paricalcitol Injection as an intravenous bolus dose of 0.04 mcg/kg to 0.1 mcg/kg (2.8 mcg to 7 mcg) no more frequently than every other day at any time during dialysis. Target the maintenance dose of Paricalcitol Injection to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits. Monitor serum calcium frequently (e.g., twice weekly) and intact PTH levels every 2 to 4 weeks after initiation of therapy or dose adjustment. Titrate the dose of Paricalcitol Injection based on intact PTH (see Table 1). Prior to raising the dose, ensure serum calcium is within normal limits. The maximum daily adult dose is 0.24 mcg/kg. Suspend or decrease the dose if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease [see Warnings and Precautions (5.3) ] or if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia [see Warnings and Precautions (5.1) ] . If dose suspension is necessary, restart at a reduced dose after laboratory values have normalized. Table 1: Recommended Paricalcitol Injection Adult Dose Titration Based Upon intact PTH Intact PTH Level At Follow-up Visit Dosage Adjustment Above target and intact PTH increased Increase* by 2 mcg to 4 mcg every 2 to 4 weeks Above target and intact PTH decreased by less than 30% Increase* by 2 mcg to 4 mcg every 2 to 4 weeks Above target and intact PTH decreased by 30% to 60% No Change Above target and intact PTH decreased by more than 60% Decrease per clinical judgement At target and intact PTH stable No Change * The maximum daily adult dose is 0.24 mcg/kg 2.3 Starting Dose and Dose Titration for Pediatric Patients 5 Years of Age and Above 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 Administer Paricalcitol Injection three times per week, no more frequently than every other day, at any time during dialysis. Target the maintenance dose of Paricalcitol Injection to intact PTH levels within the desired therapeutic range and serum calcium within normal limits. Monitor serum calcium frequently (e.g., twice weekly) and intact PTH levels every 2 to 4 weeks after initiation of therapy or dose adjustment. Titrate the dose of Paricalcitol Injection based on intact PTH (see Table 2). Prior to raising the dose, ensure serum calcium is within normal limits. Suspend or decrease the dose if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease [see Warnings and Precautions (5.3) ] or if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia [see Warnings and Precautions (5.1) ] . If dose suspension is necessary, restart at a reduced dose after laboratory values have normalized. Table 2: Recommended Paricalcitol Injection Pediatric Dose Titration Based Upon intact PTH – Patients 5 years of age and older Intact PTH Level At Follow-up Visit Dosage Adjustment Above target and intact PTH decreased by less than 30% Increase by 0.04 mcg/kg every 2 to 4 weeks Intact PTH 150 pg/mL or greater and decreased by 30% to 60% No Change Intact PTH less than 150 pg/mL or decreased by more than 60% Decrease by 0.04 mcg/kg weekly, or by 50% if decreased dose equals zero 2.4 Drug Interactions that May Require Dosage Adjustments of Paricalcitol Injection Increased monitoring of serum calcium and dose adjustment of Paricalcitol Injection may be necessary when given concomitantly with drugs that may increase the risk of hypercalcemia [see Drug Interactions (7) ] .

Dosage forms and strengths

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) multiple-dose vial Paricalcitol Injection is available as : Injection: 2 mcg/mL single-dose vial Injection: 5 mcg/mL single-dose vial Injection: 10 mcg/2 mL (5 mcg/mL) multiple-dose vial

Contraindications

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) ] . Hypercalcemia ( 4 ) Vitamin D toxicity ( 4 ) Known hypersensitivity to paricalcitol or any other inactive ingredient. ( 4 )

Warnings and precautions

Hypercalcemia: Can occur during treatment with Paricalcitol Injection and can lead to cardiac arrhythmias and seizures. Severe hypercalcemia may require emergency attention. The risk may be increased when Paricalcitol Injection is used concomitantly with high dose calcium preparations, thiazide diuretics, or vitamin D compounds. Inform patients about symptoms of hypercalcemia and monitor serum calcium prior to initiation and during treatment and adjust dose accordingly ( 2 , 5.1 ). Digitalis Toxicity: Risk increases with hypercalcemia. In patients using digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity. Monitor more frequently when initiating or adjusting the dose of Paricalcitol Injection ( 5.2 ). Adynamic Bone Disease: May develop and increase risk of fractures if intact PTH levels are suppressed to abnormally low levels. Monitor intact PTH levels and adjust dose if needed ( 5.3 ). 5.1 Hypercalcemia Hypercalcemia may occur during Paricalcitol Injection treatment. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart [see Warnings and Precautions (5.2) ] . Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency attention. Hypercalcemia may be exacerbated by concomitant administration of high doses of calcium-containing preparations, thiazide diuretics, or other vitamin D compounds [see Drug Interactions (7) ] . In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Patients with a history of hypercalcemia prior to initiating therapy may be at increased risk for development of hypercalcemia with Paricalcitol Injection. In these circumstances, frequent serum calcium monitoring and Paricalcitol Injection dose adjustments may be required. When initiating Paricalcitol Injection or adjusting Paricalcitol Injection dose, measure serum calcium frequently (e.g., twice weekly). Once a maintenance dose has been established, measure serum calcium at least monthly. If hypercalcemia occurs, reduce the dose or discontinue Paricalcitol Injection until serum calcium is normal [see Dosage and Administration (2.2 , 2.3 )] . Inform patients about the symptoms of elevated calcium (feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) and instruct them to report new or worsening symptoms when they occur. 5.2 Digitalis Toxicity Paricalcitol Injection can cause hypercalcemia [see Warnings and Precautions (5.1) ] which increases the risk of digitalis toxicity. In patients using Paricalcitol Injection concomitantly with digitalis compounds, monitor serum calcium and patients for signs and symptoms of digitalis toxicity. Increase the frequency of monitoring when initiating or adjusting the dose of Paricalcitol Injection [see Drug Interactions (7) ] . 5.3 Adynamic Bone Disease Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by Paricalcitol Injection to abnormally low levels. Monitor intact PTH levels to avoid over suppression and adjust Paricalcitol Injection dose, if needed [see Dosage and Administration (2.2 , 2.3 )] .

Side effects

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) ] The most common adverse reactions (> 5% and more frequent than placebo) are nausea, vomiting and edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The safety of Paricalcitol Injection has been established from adequate and well-controlled studies of another paricalcitol injection product [see Clinical Studies (14) ] . Below is a display of the adverse reactions of paricalcitol injection in these adequate and well-controlled studies. Four placebo-controlled, double-blind, multicenter studies were conducted in 113 patients (51% male, 10% Caucasian, 81% African-American and 9% Hispanic, ranging in age from 18 to 90 years). Sixty-two patients were exposed to paricalcitol injection and the average dose at the end of treatment was 0.12 mcg/kg/dose with a mean number of 55 days of dosing across the studies. Discontinuation of therapy due to any adverse reaction occurred in 6.5% of patients treated with paricalcitol injection and 2.0% of patients treated with placebo. Adverse reactions occurring with greater frequency in the paricalcitol injection group and at a frequency of 2% or greater are presented in Table 3. Table 3: Adverse Reactions Occurring at a Rate of 2% or Greater in Patients with CKD on Dialysis in Four Placebo-Controlled Studies Adverse Reaction Placebo (n = 51) % Paricalcitol Injection (n = 62) % Nausea 8 13 Vomiting 6 8 Edema 0 7 Gastrointestinal Hemorrhage 2 5 Chills 2 5 Pyrexia 2 5 Pneumonia 0 5 Sepsis 2 5 Influenza 4 5 Arthralgia 4 5 Palpitations 0 3 Dry Mouth 2 3 Malaise 0 3 Other Adverse Reactions The following adverse reactions occurred in less than 2% of the paricalcitol injection treated patients in the above mentioned studies and in additional double-blind, active-controlled and open-label studies: Blood and Lymphatic System Disorders: Anemia, lymphadenopathy Cardiac Disorders: Arrhythmia, atrial flutter, irregular heart rate, cardiac arrest, chest discomfort, chest pain, edema peripheral Ear and Labyrinth Disorders: Ear discomfort Endocrine Disorders: Hypoparathyroidism Eye Disorders: Conjunctivitis, glaucoma, ocular hyperemia Gastrointestinal Disorders: Abdominal discomfort, constipation, diarrhea, dysphagia, gastritis, intestinal ischemia, rectal hemorrhage General Disorders: Asthenia, condition aggravated, fatigue, feeling abnormal, pain, swelling Infections: Nasopharyngitis, upper respiratory tract infection, vaginal infection Injection site reactions: Injection site extravasation, injection site pain Laboratory abnormalities: Hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, increased aspartate aminotransferase, prolonged bleeding time Metabolism and Nutrition Disorders: Decreased appetite, thirst, decreased weight Musculoskeletal and Connective Tissue Disorders: Joint stiffness, muscle twitching, myalgia Neoplasms Benign, Malignant and Unspecified: Breast cancer Nervous System Disorders: Cerebrovascular accident, dizziness, dysgeusia, headache, hypoesthesia, myoclonus, paresthesia, syncope, unresponsive to stimuli, gait disturbance Psychiatric Disorders: Agitation, confusional state, delirium, insomnia, nervousness, restlessness Reproductive System and Breast Disorders: Breast pain, erectile dysfunction Respiratory, Thoracic and Mediastinal Disorders: Cough, dyspnea, orthopnea, pulmonary edema, wheezing Skin and Subcutaneous Tissue Disorders: Alopecia, blister, hirsutism, night sweats, rash pruritic, pruritus, skin burning sensation Vascular Disorders: Hypertension, hypotension 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Paricalcitol Injection. 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. Allergic reactions, such as rash, urticaria, and angioedema (including laryngeal edema) have been reported.

Drug interactions

Table 4 includes clinically significant drug interactions with Paricalcitol Injection. Table 4: Clinically Significant Drug Interactions with Paricalcitol Injection 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 Injection dose as needed [see Warnings and Precautions (5.1) ] . Digitalis Compounds Clinical Impact Paricalcitol Injection 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 Injection in patients receiving digitalis compounds [see Warnings and Precautions (5.2) ] . Strong CYP3A Inhibitors Clinical Impact Paricalcitol Injection is partially metabolized by CYP3A. Exposure of Paricalcitol Injection will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . Examples Clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole Intervention If a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor, dose adjustment of Paricalcitol Injection may be necessary. Monitor intact PTH and serum calcium concentrations closely. Strong CYP3A Inhibitors: Co-administration with strong CYP3A inhibitors (e.g., ketoconazole) increases Paricalcitol Injection exposure. Dose adjustment may be necessary. Closely monitor intact PTH and serum calcium. ( 2.4 , 7 )

Use in specific populations

8.1 Pregnancy Risk Summary Limited data with Paricalcitol Injection 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/m 2 ). 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/m 2 ). 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. 8.2 Lactation 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 Injection 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 Injection and any potential adverse effects on the breast-fed child from Paricalcitol Injection or from the underlying maternal condition. Clinical Considerations Infants exposed to Paricalcitol Injection 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. 8.4 Pediatric Use The safety and efficacy of Paricalcitol Injection 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 Injection for this indication is supported by evidence from an adequate and well-controlled study of another paricalcitol injection product in 29 patients, 5 to 19 years of age, with CKD on hemodialysis [see Clinical Studies (14) ] . The safety and efficacy of Paricalcitol Injection have not been established in pediatric patients less than 5 years old. 8.5 Geriatric Use Clinical studies of paricalcitol injection 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. 8.6 Hepatic Impairment 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 Injection has not been studied in patients with severe hepatic impairment.

Pregnancy

8.1 Pregnancy Risk Summary Limited data with Paricalcitol Injection 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/m 2 ). 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/m 2 ). 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.

Pediatric use

8.4 Pediatric Use The safety and efficacy of Paricalcitol Injection 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 Injection for this indication is supported by evidence from an adequate and well-controlled study of another paricalcitol injection product in 29 patients, 5 to 19 years of age, with CKD on hemodialysis [see Clinical Studies (14) ] . The safety and efficacy of Paricalcitol Injection have not been established in pediatric patients less than 5 years old.

Geriatric use

8.5 Geriatric Use Clinical studies of paricalcitol injection 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.

Overdosage

Overdosage of Paricalcitol Injection 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.

Description

Paricalcitol, USP, is a synthetically manufactured active vitamin D analog. It is a white powder chemically designated as 19-nor-1α,3β,25-trihydroxy-9,10-secoergosta-5(Z),7(E),22(E)-triene and has the following structural formula: Molecular formula is C 27 H 44 O 3 . Molecular weight is 416.64. Paricalcitol Injection is a sterile, clear, colorless, aqueous solution for intravenous use. Each mL contains paricalcitol, 2 mcg or 5 mcg and the following inactive ingredients: alcohol, 35% (v/v) and propylene glycol, 30% (v/v). 1

Mechanism of action

12.1 Mechanism of Action Paricalcitol is a synthetic, biologically active vitamin D 2 analog. Preclinical and in vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the vitamin D receptor (VDR), which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce PTH levels by inhibiting PTH synthesis and secretion.

How supplied

Paricalcitol Injection is a clear, colorless solution available as follows: Table 7. Paricalcitol Injection Presentations – Carton of 1 vial Total Strength per Total Volume Strength per mL Total Vial Volume and Vial Type NDC 2 mcg/mL 2 mcg/mL 1 mL single-dose vial 16729-310-63 5 mcg/mL 5 mcg/mL 1 mL single-dose vial 16729-311-63 10 mcg/2 mL 5 mcg/mL 2 mL multiple-dose vial 16729-311-30 Table 8. Paricalcitol Injection Presentations – Carton of 25 vials Total Strength per Total Volume Strength per mL Total Vial Volume and Vial Type NDC 2 mcg/mL 2 mcg/mL 1 mL single-dose vial 16729-310-08 5 mcg/mL 5 mcg/mL 1 mL single-dose vial 16729-311-08 10 mcg/2 mL 5 mcg/mL 2 mL multiple-dose vial 16729-311-93 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Excursions permitted between 15° to 30°C (59° to 86°F). Discard unused portion of the single-dose vial. The opened (in use) multiple-dose vial should be stored at room temperature 20°C to 25°C (68° to 77°F) and protected from light. Discard seven days after opening.

Patient information

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 For: Accord Healthcare, Inc., 8041 Arco Corporate Drive, Suite 200, Raleigh, NC 27617, USA. Manufactured By: Intas Pharmaceuticals Limited, Plot No. : 457, 458, Village – Matoda, Bavla Road, Ta.- Sanand, Dist. Ahmedabad - 382 210, India. 10 0246 2 6027315 Issued December, 2023

Active ingredients

Paricalcitol in 35 products

Paricalcitol NDC products (35)

NDC	Strength & form	Labeler	Type
65162-822	Paricalcitol 1 ug/1 Capsule	Amneal Pharmaceuticals LLC	ANDA
65162-823	Paricalcitol 2 ug/1 Capsule	Amneal Pharmaceuticals LLC	ANDA
70121-1036	Paricalcitol 10 ug/2mL Injection	Amneal Pharmaceuticals LLC	ANDA
70121-1035	Paricalcitol 10 ug/2mL Injection	Amneal Pharmaceuticals LLC	ANDA
70121-1034	Paricalcitol 5 ug/mL Injection	Amneal Pharmaceuticals LLC	ANDA
70121-1033	Paricalcitol 2 ug/mL Injection	Amneal Pharmaceuticals LLC	ANDA
65162-824	Paricalcitol 4 ug/1 Capsule	Amneal Pharmaceuticals LLC	ANDA
65862-938	Paricalcitol 4 ug/1 Capsule, Liquid Filled	Aurobindo Pharma Limited	ANDA
65862-936	Paricalcitol 1 ug/1 Capsule, Liquid Filled	Aurobindo Pharma Limited	ANDA
65862-937	Paricalcitol 2 ug/1 Capsule, Liquid Filled	Aurobindo Pharma Limited	ANDA
69452-145	Paricalcitol 1 ug/1 Capsule	Bionpharma Inc.	ANDA
69452-146	Paricalcitol 2 ug/1 Capsule	Bionpharma Inc.	ANDA
69452-147	Paricalcitol 4 ug/1 Capsule	Bionpharma Inc.	ANDA
72162-1915	Paricalcitol 1 ug/1 Capsule	Bryant Ranch Prepack	ANDA
63629-2452	Paricalcitol 1 ug/1 Capsule	Bryant Ranch Prepack	ANDA
63629-2453	Paricalcitol 2 ug/1 Capsule	Bryant Ranch Prepack	ANDA
72162-1916	Paricalcitol 2 ug/1 Capsule	Bryant Ranch Prepack	ANDA
55111-663	Paricalcitol 1 ug/1 Capsule, Liquid Filled	Dr. Reddy's Laboratories Limited	ANDA
55111-664	Paricalcitol 2 ug/1 Capsule, Liquid Filled	Dr. Reddy's Laboratories Limited	ANDA
55111-665	Paricalcitol 4 ug/1 Capsule, Liquid Filled	Dr. Reddy's Laboratories Limited	ANDA
55150-215	Paricalcitol 10 ug/2mL Injection	Eugia US LLC	ANDA
55150-214	Paricalcitol 10 ug/2mL Injection	Eugia US LLC	ANDA
55150-213	Paricalcitol 5 ug/mL Injection	Eugia US LLC	ANDA
55150-212	Paricalcitol 2 ug/mL Injection	Eugia US LLC	ANDA
25000-017	Paricalcitol 4 ug/1 Capsule, Liquid Filled	MARKSANS PHARMA LIMITED	ANDA
25000-014	Paricalcitol 2 ug/1 Capsule, Liquid Filled	MARKSANS PHARMA LIMITED	ANDA
25000-012	Paricalcitol 1 ug/1 Capsule, Liquid Filled	MARKSANS PHARMA LIMITED	ANDA
49483-689	Paricalcitol 4 ug/1 Capsule, Liquid Filled	TIME CAP LABORATORIES, INC	ANDA
49483-688	Paricalcitol 2 ug/1 Capsule, Liquid Filled	TIME CAP LABORATORIES, INC	ANDA
49483-687	Paricalcitol 1 ug/1 Capsule, Liquid Filled	TIME CAP LABORATORIES, INC	ANDA
16729-311	Paricalcitol 5 ug/mL Injection, Solution	Accord Healthcare, Inc.	NDA
16729-310	Paricalcitol 2 ug/mL Injection, Solution	Accord Healthcare, Inc.	NDA
0143-9596	Paricalcitol 5 ug/mL Injection	West-Ward Pharmaceuticals Corp	NDA
0143-9625	Paricalcitol 2 ug/mL Injection	West-Ward Pharmaceuticals Corp	NDA
0143-9624	Paricalcitol 5 ug/mL Injection	West-Ward Pharmaceuticals Corp	NDA

Paricalcitol recalls

D-0719-2016 Feb 24, 2016 · Class III · Terminated
Failed Tablet/Capsule Specifications: Product recalled due to reports of breakage and leakage of Paricalcitol capsules.
D-0720-2016 Feb 24, 2016 · Class III · Terminated
Failed Tablet/Capsule Specifications: Product recalled due to reports of breakage and leakage of Paricalcitol capsules.
D-0721-2016 Feb 24, 2016 · Class III · Terminated
Failed Tablet/Capsule Specifications: Product recalled due to reports of breakage and leakage of Paricalcitol capsules.

Frequently asked questions

What is Paricalcitol used for?

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 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.

What are the side effects of Paricalcitol?

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) ] The most common adverse reactions (> 5% and more frequent than placebo) are nausea, vomiting and edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at… See the full label for the complete list.

Who makes Paricalcitol?

Paricalcitol is listed by 10 labelers in the FDA NDC directory, including Amneal Pharmaceuticals LLC, Aurobindo Pharma Limited, Bionpharma Inc., Bryant Ranch Prepack.

Has Paricalcitol been recalled?

The FDA enforcement database lists 3 recalls for Paricalcitol, most recently D-0719-2016 (class iii): Failed Tablet/Capsule Specifications: Product recalled due to reports of breakage and leakage of Paricalcitol capsules.