How often can the dose of Zemplar (paricalcitol) be increased in a patient with chronic kidney disease (CKD) being treated for secondary hyperparathyroidism?

Zemplar (Paricalcitol) Dose Titration Frequency

Zemplar dose can be increased every 2 to 4 weeks in adults with CKD stages 3-4, and every 4 weeks in pediatric patients and CKD stage 5 patients, based on iPTH response and serum calcium/phosphorus levels. 1

Adult Dosing Adjustment Schedule

CKD Stages 3-4 (Non-Dialysis)

• The FDA label specifies dose adjustments at 2 to 4 week intervals for adults with CKD stages 3-4, with increases of 1 mcg daily or 2 mcg three times weekly when iPTH remains unchanged, increases, or decreases by less than 30% from baseline 1
• Doses should be maintained when iPTH decreases by 30-60% from baseline, and decreased by 1 mcg daily or 2 mcg three times weekly when iPTH drops more than 60% or falls below 60 pg/mL 1
• Clinical trial data demonstrate that a mean 30% reduction in iPTH occurs by week 3 of treatment, with statistically significant decreases observed after just 1 week 2

CKD Stage 5 (Dialysis)

• For dialysis patients, the FDA recommends individualized dose titration based on the formula: Dose (mcg) = most recent iPTH level (pg/mL) ÷ 80 1
• The label does not specify a minimum interval between dose changes for stage 5 CKD, but monitoring should occur at least weekly during initial titration, with dose adjustments of 2-4 mcg when serum calcium is elevated 1
• In situations where iPTH, calcium, or phosphorus monitoring occurs less frequently than once per week, a more conservative titration ratio (iPTH ÷ 100) is warranted 1

Pediatric Dosing Adjustment Schedule (Ages 10-16)

CKD Stages 3-4

• Every 4 weeks, each administered dose may be increased in 1 mcg increments while maintaining the three times per week regimen (e.g., from 1 mcg to 2 mcg three times weekly) 1
• Doses may be decreased by 1 mcg at any time based on iPTH, calcium, and phosphorus levels 1

CKD Stage 5

• Every 4 weeks, doses may be increased in 1 mcg increments for pediatric dialysis patients, maintaining three times weekly administration 1
• Doses may be decreased by 2 mcg at any time, with treatment stopped if reduction is needed while receiving 1-2 mcg three times weekly 1

Critical Monitoring Requirements

• Serum calcium and phosphorus must be monitored closely after initiation, during all dose titration periods, and during co-administration with strong CYP3A inhibitors 1
• The American Journal of Kidney Diseases recommends checking calcium and phosphorus every 2 weeks in the first month after initiation 3
• Monthly monitoring of calcium, phosphorus, and PTH is required for the first 3 months, then every 3 months thereafter 3

Common Pitfalls to Avoid

• Never increase doses more frequently than every 2-4 weeks in adults or every 4 weeks in pediatrics, as PTH suppression is delayed and premature escalation causes hypercalcemia 4
• Do not initiate or increase paricalcitol when serum calcium exceeds 9.5 mg/dL or phosphorus exceeds 4.6 mg/dL, as this worsens vascular calcification 3, 4
• Severe hyperparathyroidism (PTH >800 pg/mL) requires both higher doses and longer treatment duration (12-24 weeks) to achieve suppression due to downregulated vitamin D receptors in nodular parathyroid glands 4
• Research demonstrates that despite aggressive paricalcitol therapy, severe secondary hyperparathyroidism remains frequent in some populations, particularly when dietary and medication compliance is suboptimal 5