Paricalcitol

PARICALCITOL- paricalcitol injection, solution
Accord Healthcare, Inc.

1 INDICATIONS AND USAGE

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

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)] .
• Increased monitoring of both serum calcium and intact PTH as well as dose adjustment of Paricalcitol Injection may be necessary when given concomitantly with strong CYP3A inhibitors [see Drug Interactions (7)] .

3 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

4 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)] .