Paricalcitol (Monograph)

Brand name: Zemplar
Drug class: Vitamin D
ATC class: A11CC
VA class: VT509
Chemical name: (1α,3β,7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1α,3β,25-triol
Molecular formula: C₂₇H₄₄O₃
CAS number: 131918-61-1

Medically reviewed by Drugs.com on Feb 1, 2024. Written by ASHP.

Introduction

A synthetic vitamin D analog.^{110 111 112 113 117}

Uses for Paricalcitol

Secondary Hyperparathyroidism

IV paricalcitol used for prevention and treatment of secondary hyperparathyroidism associated with stage 5 chronic kidney disease (CKD).¹¹⁰

Oral paricalcitol used for prevention and treatment of secondary hyperparathyroidism associated with stage 3 or 4 CKD or stage 5 CHD requiring hemodialysis or peritoneal dialysis.¹¹⁷

Paricalcitol Dosage and Administration

General

• Individualize dosage according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum concentrations of calcium and phosphorus.^{110 111 113 117} Nephrology experts currently recommend using individual values for serum calcium and phosphorus (evaluated together) instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.^{126 128}

• Closely monitor serum calcium and phosphorus concentrations during therapy.^{110 117} (See Patient Monitoring under Cautions.)

Administration

Oral Administration

Administer orally once daily or 3 times weekly without regard to meals.¹¹⁷

If paricalcitol is administered 3 times weekly, administer no more frequently than every other day.¹¹⁷

IV Administration

Administer by direct IV injection at any time during dialysis, no more frequently than every other day.¹¹⁰

Dosage

Nephrology experts currently state that optimal iPTH concentration for predialysis patients with stage 3a (eGFR 45–59 mL/minute per 1.73 m²) to stage 5 (eGFR <15 mL/minute per 1.73 m²) CKD is unknown, but modest elevations may represent an appropriate adaptive response to declining renal function.^{128 129}

For patients with stage 5 CKD undergoing dialysis, some experts suggest maintaining iPTH concentrations within a range of approximately 2–9 times the assay's ULN (may correspond to range of approximately 130–600 pg/mL for commercial assays¹³⁰ ).¹²⁸ PTH assays exhibit substantial variability; previously recommended range of 150–300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer available.^{126 130 131}

Avoid oversuppression of PTH, which may increase risk of adynamic bone disease.^{126 131}

Pediatric Patients

Secondary Hyperparathyroidism

Stage 3 or 4 CKD

Oral

Pediatric patients 10–16 years of age: Initial dosage of 1 mcg 3 times weekly.¹¹⁷

Individualize dosage based on iPTH concentration and serum calcium and phosphorus concentrations to maintain iPTH concentration within the target range.¹¹⁷

May increase dosage in increments of 1 mcg 3 times weekly (i.e., from 1 mcg 3 times weekly to 2 mcg 3 times weekly) at intervals of 4 weeks.¹¹⁷

May decrease dose by 1 mcg at any time during therapy.¹¹⁷

If patient is receiving 1 mcg 3 times weekly and requires dosage reduction, withhold therapy as needed and resume when appropriate.¹¹⁷

If hypercalcemia is observed, reduce dosage or withhold therapy until the concentration has normalized.¹¹⁷

Stage 5 CKD (Dialysis)

Oral

Pediatric patients 10–16 years of age: Manufacturer recommends calculating initial dose (in mcg) by dividing baseline iPTH concentration (in pg/mL) by 120.¹¹⁷ Round calculated dose down to nearest whole number and administer 3 times weekly.¹¹⁷

Individualize dosage based on iPTH concentration and serum calcium and phosphorus concentrations to maintain iPTH concentration within the target range.¹¹⁷

May increase dosage in increments of 1 mcg 3 times weekly (i.e., from 1 mcg 3 times weekly to 2 mcg 3 times weekly) at intervals of 4 weeks.¹¹⁷

May decrease dose by 2 mcg at any time during therapy.¹¹⁷

If patient is receiving 1 or 2 mcg 3 times weekly and requires dosage reduction, withhold therapy as needed and resume when appropriate.¹¹⁷

If hypercalcemia is observed, reduce dosage or withhold therapy until the concentration has normalized.¹¹⁷

IV

Children and adolescents 5–19 years of age: In one study, initial dosage was 0.04 mcg/kg 3 times weekly if iPTH concentration <500 pg/mL or 0.08 mcg/kg 3 times weekly if iPTH concentration ≥500 pg/mL.¹¹⁰

Dosage in this study was adjusted in increments of 0.04 mcg/kg based on serum concentrations of iPTH, calcium, and calcium times serum phosphorus product (Ca × P).¹¹⁰ Mean dose was 4.6 mcg (range: 0.8–9.6 mcg).¹¹⁰

Adults

Secondary Hyperparathyroidism

Stage 3 or 4 CKD

Oral

If baseline iPTH concentration is ≤500 pg/mL, manufacturer recommends initial dosage of 1 mcg once daily or 2 mcg 3 times weekly.¹¹⁷ If baseline iPTH concentration is >500 pg/mL, initial dosage of 2 mcg once daily or 4 mcg 3 times weekly.¹¹⁷

Adjust dosage at 2- to 4-week intervals based on iPTH response.¹¹⁷

Manufacturer recommends maintaining current dosage if decrease in iPTH concentration from baseline is ≥30% but ≤60%.¹¹⁷

If response is inadequate (i.e., iPTH concentration increases, remains unchanged, or is reduced by <30% from baseline), manufacturer recommends increasing dosage in increments of 1 mcg daily (e.g., from 1 mcg daily to 2 mcg daily) or 2 mcg 3 times weekly (e.g., from 2 mcg 3 times weekly to 4 mcg 3 times weekly).¹¹⁷

If iPTH concentration is decreased from baseline by >60% or declines to a value of <60 pg/mL, manufacturer recommends decreasing dosage by 1 mcg daily or by 2 mcg 3 times weekly.¹¹⁷

If patient is receiving dosage of 1 mcg once daily and requires dosage reduction, reduce dosage to 1 mcg 3 times weekly; if further reduction is needed, withhold the drug as needed and reinitiate therapy at a lower dosage by altering dosing interval.¹¹⁷

If hypercalcemia is observed, reduce dosage or withhold therapy until the concentration has normalized.¹¹⁷

Stage 5 CKD (Dialysis)

Oral

Manufacturer recommends calculating initial dose (in mcg) by dividing baseline iPTH concentration (in pg/mL) by 80; administer calculated dose 3 times weekly.¹¹⁷

To minimize risk of hypercalcemia, initiate therapy only if adjusted baseline serum calcium concentration is ≤9.5 mg/dL.¹¹⁷

Individualize dosage based on iPTH, serum calcium, and serum phosphorus concentrations.¹¹⁷ Manufacturer recommends calculating new dose (in mcg) by dividing most recent iPTH concentration (in pg/mL) by 80.¹¹⁷

If hypercalcemia is observed, reduce dosage or withhold therapy until the concentration has normalized.¹¹⁷ If serum calcium concentrations are elevated, decrease dose by 2–4 mcg.¹¹⁷

As iPTH concentration approaches target range, small individualized dose adjustments may be necessary to achieve a stable iPTH concentration.¹¹⁷

In situations where iPTH, calcium, or phosphorus is monitored less frequently than once weekly, manufacturer states that a more modest initial and dose-titration ratio (e.g., iPTH concentration divided by 100) may be appropriate.¹¹⁷

IV

Initial dosage of 0.04–0.1 mcg/kg (2.8–7 mcg) at dialysis (no more often than every other day).¹¹⁰

Manufacturer recommends adjusting dosage at 2- to 4-week intervals with the goal of reducing iPTH concentration to no more than 1.5–3 times ULN.¹¹⁰

Manufacturer recommends maintaining current dosage if decrease in iPTH concentration from baseline is ≥30% but ≤60% or if iPTH concentration is 1.5–3 times the ULN.¹¹⁰

If response is inadequate (i.e., iPTH concentration increases, remains unchanged, or is reduced by <30% from baseline), manufacturer recommends increasing dose by 2–4 mcg per dose at 2- to 4-week intervals.¹¹⁰

If iPTH concentration is decreased from baseline by >60%, reduce dosage.¹¹⁰

If serum calcium (in mg/dL) times serum phosphorus (in mg/dL) product (Ca × P) is >75, reduce or withhold dosage immediately until parameters are normalized; reinitiate drug at a lower dosage. ¹¹⁰

In patients receiving a calcium-containing phosphate binder, dosage of the phosphate binder may be reduced or withheld; alternatively, the patient can be switched to a non-calcium-containing phosphate binder.¹¹⁰

Special Populations

Hepatic Impairment

Mild to moderate hepatic impairment: Dosage adjustment not required.^{110 117} (See Hepatic Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations.^{110 117} (See Geriatric Use under Cautions.)

Related/similar drugs

cinacalcet, Sensipar, Hectorol, doxercalciferol, Zemplar

Cautions for Paricalcitol

Contraindications

• Hypercalcemia.^{110 117}

• Evidence of vitamin D toxicity.^{110 117}

• Known hypersensitivity to paricalcitol or any ingredient in the formulation.¹¹⁰

Warnings/Precautions

Excessive Use

Excessive doses of vitamin D analogs (e.g., paricalcitol) may result in excessive suppression of PTH concentrations, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease.^{110 117}

Hypercalcemia

Progressive hypercalcemia resulting from vitamin D overdosage may require emergency treatment measures.^{110 117} If clinically important hypercalcemia develops, reduce or withhold paricalcitol therapy immediately, withdraw calcium supplements, administer a low-calcium diet, and monitor closely for changes in fluid and electrolyte balance and ECG (especially in those receiving a cardiac glycoside).¹¹⁰

Acute hypercalcemia may increase risk of cardiac arrhythmias and seizures, and potentiate toxic effects of cardiac glycosides.^{110 117}

Chronic hypercalcemia increases risk of soft-tissue calcification, including vascular calcification.^{110 117}

Concomitant use of high dosages of calcium or thiazide diuretics increases risk of hypercalcemia; high intake of calcium and phosphates may necessitate frequent patient monitoring and individualized dosage titration.^{110 117}

Do not use prescription-based doses of vitamin D and its analogs during paricalcitol therapy.^{110 117}

Cardiac Glycoside Toxicity

Hypercalcemia increases risk of cardiac glycoside toxicity; use concomitantly with caution.^{110 117} (See Specific Drugs and Foods under Interactions.)

Patient Monitoring

In patients receiving oral paricalcitol, monitor serum calcium, serum phosphorus, and serum or plasma iPTH concentrations at least every 2 weeks for 3 months after initiation of therapy or following any dosage adjustment, then monthly for 3 months, and every 3 months thereafter.¹¹⁷

In patients with stage 5 CKD receiving IV paricalcitol, monitor serum calcium and phosphorus concentrations frequently (e.g., twice weekly) during initial dosage adjustment and after subsequent dosage adjustments; once dosage has been established, monitor at least monthly.¹¹⁰ Monitor serum or plasma iPTH concentrations every 3 months; more frequent monitoring may be required during dosage adjustments.¹¹⁰

Predialysis Patients

Vitamin D analogs (e.g., paricalcitol, calcitriol) may increase S_cr and therefore decrease eGFR in predialysis patients.¹¹⁷

Aluminum Toxicity

Avoid long-term concomitant use of aluminum-containing preparations (e.g., antacids, phosphate binders); risk of increased blood aluminum concentrations and aluminum bone toxicity.^{110 117}

Specific Populations

Pregnancy

Category C.¹¹⁰

Limited data on paricalcitol use in pregnant women.¹¹⁷

Slight increase in embryofetal loss observed in animals; increased stillbirths and newborn mortality observed in animals at maternally toxic doses.^{110 117}

CKD increases maternal risk for hypertension, spontaneous abortion, preterm labor, and preeclampsia and increases fetal risk for intrauterine growth restriction, prematurity, polyhydramnios, stillbirth, and low birth weight.¹¹⁷

Lactation

Distributed into milk in rats;^{110 117} not known whether paricalcitol distributes into human milk, affects milk production, or affects nursing infants.^{110 117}

Avoid nursing during paricalcitol therapy.^{110 117}

Pediatric Use

Safety and efficacy of oral paricalcitol not established in pediatric patients <10 years of age. ¹¹⁷

Safety and efficacy of IV paricalcitol not established in pediatric patients <5 years of age.¹¹⁰

Geriatric Use

No substantial differences in safety and efficacy in those ≥65 years of age relative to younger adults,^{110 117} but increased sensitivity cannot be ruled out.¹¹⁷

Hepatic Impairment

Not studied in patients with severe hepatic impairment.^{110 117}

Mild or moderate hepatic impairment does not alter pharmacokinetics.^{110 117}

Common Adverse Effects

Oral administration in patients with stage 3 or 4 CKD: Diarrhea,¹¹⁷ hypertension,¹¹⁷ viral infection,¹¹⁷ edema,¹¹⁷ hypersensitivity,¹¹⁷ nausea,¹¹⁷ arthritis,¹¹⁷ dizziness,¹¹⁷ headache,¹¹⁷ hypotension,¹¹⁷ vertigo,¹¹⁷ vomiting.¹¹⁷

Oral administration in patients with stage 5 CKD: Diarrhea,¹¹⁷ nasopharyngitis,¹¹⁷ dizziness,¹¹⁷ vomiting,¹¹⁷ constipation,¹¹⁷ fluid overload,¹¹⁷ insomnia,¹¹⁷ peritonitis.¹¹⁷

IV administration in patients with stage 5 CKD: Nausea,¹¹⁰ vomiting,¹¹⁰ edema,¹¹⁰ arthralgia,¹¹⁰ chills,¹¹⁰ GI hemorrhage,¹¹⁰ influenza,¹¹⁰ pneumonia,¹¹⁰ pyrexia,¹¹⁰ sepsis.¹¹⁰

Drug Interactions

Partially metabolized by CYP3A.^{110 117}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potent CYP3A inhibitors: Potential pharmacokinetic interaction (increased plasma paricalcitol concentrations).^{110 117}

CYP substrates: Does not appear to inhibit clearance of drugs metabolized by CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A, or induce clearance of drugs metabolized by CYP isoenzymes 2B6, 2C9, or 3A.¹¹⁰

Specific Drugs and Foods

Paricalcitol Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; absolute bioavailability is about 72–86%.¹¹⁷

Food

High-fat meal increased time to peak plasma concentration of paricalcitol capsules by about 2 hours but did not affect AUC or peak concentration.¹¹⁷

Special Populations

Hemodialysis does not appear to affect plasma concentrations.^{110 e h}

Distribution

Distributed into milk in rats; not known whether distributed into human milk.^{110 117}

Plasma Protein Binding

≥99.8%.^{110 117}

Elimination

Metabolism

Extensively metabolized (about 98%) by multiple hepatic and nonhepatic enzymes (e.g., CYP24, CYP3A4, uridine diphosphate-glucuronosyltransferase [UGT] 1A4).^{110 117 i}

Elimination Route

Paricalcitol and its metabolites eliminated principally in feces via biliary excretion.^{110 117}

Excreted in feces mainly (about 63–70%) as metabolites (2% as unchanged drug), and in urine as metabolites (18–19%).^{110 117}

Half-Life

In healthy individuals: 4–7 hours.^{110 117}

Special Populations

Pharmacokinetic profile of oral paricalcitol in patients with stage 5 CKD undergoing hemodialysis or peritoneal dialysis similar to that in patients with stage 3 or 4 CKD.¹¹⁷

Half-life following oral administration: 14–20 hours in patients with stage 3 or 4 CKD or stage 5 CKD undergoing hemodialysis or peritoneal dialysis.¹¹⁷

Half-life following IV administration: 13.9 hours in patients with stage 5 CKD undergoing hemodialysis and 15.4 hours in those with stage 5 CKD undergoing peritoneal dialysis.¹¹⁰

Mild or moderate hepatic impairment does not alter pharmacokinetics.^{110 117}

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).¹¹⁷

Parenteral

Injection

25°C (may be exposed to 15–30°C).¹¹⁰

Multidose vial: Stable at room temperature for up to 7 days after initial use.¹¹⁰

Actions

• A synthetic vitamin D analog of calcitriol (the metabolically active form of vitamin D).^{110 111 112 113 117}

• In patients with CKD, decreased metabolic activation of vitamin D in the kidneys results in secondary hyperparathyroidism,^{117 a b c} characterized by increased PTH concentrations^{110 117} and disturbances in calcium and phosphorus homeostasis.^{110 117} These effects may affect bone turnover rate and may result in renal osteodystrophy.^{110 117 d}

• Biologic actions of paricalcitol are mediated through binding of the vitamin D receptor, which results in selective activation of vitamin D responsive pathways.^{110 117}

• Paricalcitol reduces serum or plasma PTH concentrations in patients with CKD.^{110 117 e f} Appears to be as effective as calcitriol in suppressing PTH secretion.^{b e f g}

Advice to Patients

• Importance of adherence to diet and calcium supplementation regimen.^{110 117}

• Importance that patients with CKD use appropriate types of phosphate-binding compounds to control serum phosphate concentrations; importance of avoiding excessive use of aluminum-containing compounds.^{110 117}

• Importance of laboratory monitoring (e.g., serum calcium, phosphorus, and iPTH) during paricalcitol therapy.^{110 117}

• Importance of reporting potential manifestations of hypercalcemia (e.g., tiredness, difficulty thinking, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, weight loss).^{110 117}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and dietary or herbal supplements.^{110 117}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{110 117}

• Importance of informing patients of other important precautionary information.^{110 117} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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