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Zemplar

Generic Name: Paricalcitol
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

Medically reviewed by Drugs.com. Last updated on Feb 11, 2019.

Introduction

A synthetic vitamin D analog.110 111 112 113 117

Uses for Zemplar

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

Zemplar 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.)

Cautions for Zemplar

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 Scr 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

Interactions for Zemplar

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

Drug or Food

Interaction

Comments

Antifungals, azoles (itraconazole, ketoconazole, posaconazole, voriconazole)

Possible increased plasma paricalcitol concentrations110 117

Ketoconazole: Increased paricalcitol AUC and half-life110 117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing therapy with a potent CYP3A4 inhibitor117

Bile acid sequestrants cholestyramine, colestipol)

Intestinal absorption of paricalcitol may be decreased117 d

Allow as long a time interval as possible between ingestion of paricalcitol and bile acid sequestrant117 d

Cholestyramine: Administer oral paricalcitol >1 hour before or 4–6 hours after cholestyramine (or at longest possible interval)117

Cardiac glycosides

Possible cardiac arrhythmiasd

Use concomitantly with caution110 117 d

Clarithromycin

Possible increased plasma paricalcitol concentrations110 117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing clarithromycin therapy117

Conivaptan

Possible increased plasma paricalcitol concentrations117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing conivaptan therapy 117

Grapefruit juice

Possible increased plasma paricalcitol concentrations117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing use of a potent CYP3A4 inhibitor117

HIV protease inhibitors (atazanavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir)

Possible increased plasma paricalcitol concentrations110 117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing therapy with an HIV protease inhibitor117

Mineral oil

May interfere with intestinal absorption of vitamin D analogs117 d

Administer oral paricalcitol >1 hour before or 4–6 hours after mineral oil (or at longest possible interval)117

Nefazodone

Possible increased plasma paricalcitol concentrations110 117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing nefazodone therapy117

Omeprazole

No apparent effect on paricalcitol pharmacokinetics110 117

Telithromycin

Possible increased plasma paricalcitol concentrations110 117

Dosage adjustment of paricalcitol may be needed117

Closely monitor iPTH and serum calcium concentrations when initiating or discontinuing telithromycin therapy117

Thiazide diuretics

Possible increased risk of hypercalcemia110 117

Zemplar 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

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

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 characterized by increased PTH concentrations110 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 Appears to be as effective as calcitriol in suppressing PTH secretion.

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

Paricalcitol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

1 mcg*

Paricalcitol Capsules

Zemplar

AbbVie

2 mcg*

Paricalcitol Capsules

Zemplar

AbbVie

4 mcg*

Paricalcitol Capsules

Parenteral

Injection, for IV use only

2 mcg/mL*

Paricalcitol Injection

Zemplar

AbbVie

5 mcg/mL*

Paricalcitol Injection

Zemplar

AbbVie

AHFS DI Essentials™. © Copyright 2019, Selected Revisions February 11, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

110. AbbVie Inc. Zemplar (paricalcitol) injection prescribing information. North Chicago, IL; 2013 Jan.

111. Goldenberg MM. Paricalcitol, a new agent for the management of secondary hyperparathyroidism in patients undergoing chronic renal dialysis. Clin Ther. 1999; 21:432-41. http://www.ncbi.nlm.nih.gov/pubmed/10321413?dopt=AbstractPlus

112. Slatopolsky E, Finch J, Ritter C et al. A new analog of calcitriol, 19- nor-1,25-(OH)2D2 suppresses parathyroid hormone secretion in uremic rats in the absence of hypercalcemia. Am J Kidney Dis. 1995; 26:852-60. http://www.ncbi.nlm.nih.gov/pubmed/7485144?dopt=AbstractPlus

113. Martin KJ, Gonzalez EA, Gellens M et al. 19-nor-1-α-25-dihydroxyvitamin D2(paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol. 1998; 9:1427-32. http://www.ncbi.nlm.nih.gov/pubmed/9697664?dopt=AbstractPlus

116. Abbott, Abbott Park, IL: Personal communication.

117. AbbVie Inc. Zemplar (paricalcitol) capsules prescribing information. North Chicago, IL; 2016 Oct.

126. Kidney Disease: Improving Global Outcomes (KDIGO) CKD–MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease—mineral and bone disorder (CKD–MBD). Kidney Int. 2009; 76 (Suppl 113): S1–S130.

128. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease—mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017; 7:1-59.

129. Isakova T, Nickolas TL, Denburg M et al. KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. 2017; 70:737-751. http://www.ncbi.nlm.nih.gov/pubmed/28941764?dopt=AbstractPlus

130. Uhlig K, Berns JS, Kestenbaum B et al. KDOQI US commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. 2010; 55:773-99. http://www.ncbi.nlm.nih.gov/pubmed/20363541?dopt=AbstractPlus

131. Bover J, Ureña P, Ruiz-García C et al. Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism. Clin J Am Soc Nephrol. 2016; 11:161-74. http://www.ncbi.nlm.nih.gov/pubmed/26224878?dopt=AbstractPlus

d. AHFS Drug Information. McEvoy GK, ed. Vitamin D Analogs General Statement. Bethesda, MD: American Society of Health-Systems Pharmacists.

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