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Paricalcitol

Pronunciation: (pah-ri-KAL-si-tole)
Class: Vitamin

Trade Names:
Zemplar
- capsules 1 mcg
- capsules 2 mcg
- capsules 4 mcg
- injection 2 mcg/mL
- injection 5 mcg/mL

Pharmacology

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Synthetic analog of calcitriol, the metabolically active form of vitamin D. Binds to vitamin D receptor, which results in selective activation of vitamin D responsive pathways; reduces parathyroid hormone (PTH) levels by inhibiting PTH synthesis and secretion.

Pharmacokinetics

Absorption

Well absorbed after oral administration; bioavailability is approximately 72%. T _max is 3 h. Food delays rate but not extent of absorption.

Distribution

Protein binding is more than 99.8%. Vd is 44 to 46 L (oral dose; chronic kidney disease [CKD] stage 3 to 4) and 31 to 35 L (IV dose; CKD stage 5).

Metabolism

Extensively metabolized by multiple hepatic and nonhepatic enzymes, including CYP3A4.

Elimination

Eliminated primarily by biliary excretion; approximately 63% recovered in feces following IV dose and 70% following oral dose (2% as unchanged drug), 18% to 19% in urine. The t _½ is about 17 h (CKD stage 3); 20 h (CKD stage 4); 13.9 h (CKD stage 5-hemodialysis); and 15.4 h (CKD stage 5-peritoneal dialysis).

Indications and Usage

Prevention and treatment of secondary hyperparathyroidism associated with chronic CKD stage 3 and 4 (oral), and stage 5 (IV).

Contraindications

Evidence of vitamin D toxicity; hypercalcemia; hypersensitivity to any component of the product.

Dosage and Administration

Patients 5 yr of age and older

IV Initial : 0.04 to 0.1 mcg/kg no more frequently than every other day during dialysis. Increase dose by 2 to 4 mcg at 2- to 4-wk intervals if satisfactory response is not observed. Doses may need to be decreased as PTH levels decrease. Dose titration : The following dose titrations are suggested: PTH level decreased less than 30%, is the same, or is increasing: increase dose; PTH level decreased 30% to 60%: maintain dose; PTH level decreased more than 60%: decrease dose; PTH level is 1.5 to 3 times upper limit of normal: maintain dose.

Adults

PO Initial : Based on baseline intact parathyroid hormone (iPTH) levels. If baseline iPTH less than 500 pg/mL: 1 mcg daily or 2 mcg 3 times/wk; if baseline iPTH more than 500 pg/mL: 2 mcg daily or 4 mcg 3 times/wk. Dose titration : The following dose titrations are suggested at 2- to 4-wk intervals: iPTH level decreased less than 30%, is the same, or is increasing: increase dose by 1 mcg daily or 2 mcg 3 times/wk; iPTH level decreased 30% to 60%: maintain dose; iPTH level decreased more than 60% or iPTH is less than 60 pg/mL: decrease dose by 1 mcg daily or 2 mcg 3 times/wk. If patient is taking the lowest dose on the daily regimen and a dose reduction is needed, the dose can be decreased to 1 mcg 3 times/wk.

General Advice

Injection
For IV bolus administration only. Not for intradermal, subcutaneous, IM, IV infusion, or intra-arterial administration.
Do not administer if solution is discolored, cloudy, or contains particulate matter.
Discard any unused portion. Do not save for future use.

Oral
Administer without regard to meals. Administer with food if GI upset occurs.
When using 3 times/wk schedule, administer prescribed dose no more than every other day.

Storage/Stability

Store capsules and injection at controlled room temperature (59° to 86°F).

Drug Interactions

Digitalis compounds

Digitalis toxicity is potentiated by hypercalcemia of any cause; therefore, use paricalcitol with caution in patients receiving a digitalis compound.

Drugs that impair absorption of fat-soluble vitamins (eg, cholestyramine)

Paricalcitol absorption may be impaired, decreasing the efficacy.

Strong inhibitors of CYP3A4 (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)

Paricalcitol plasma concentrations may be elevated, increasing the risk of toxicity.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiomyopathy, CHF, hypertension, hypotension, MI, palpitation, postural hypotension, syncope (at least 2%).

CNS

Asthenia, depression, dizziness, headache, insomnia, light-headedness, neuropathy, vertigo (at least 2%).

Dermatologic

Pruritus, rash, skin hypertrophy, skin ulcer, vesiculobullous rash (at least 2%).

EENT

Amblyopia, epistaxis, pharyngitis, retinal disorder, rhinitis (at least 2%).

GI

Constipation, diarrhea, dry mouth, dyspepsia, gastritis, gastroenteritis, GI bleeding, nausea, rectal disorder, vomiting (at least 2%); taste perversion (postmarketing).

Genitourinary

Abnormal kidney function, UTI (at least 2%).

Hematologic-Lymphatic

Ecchymosis, hypervolemia (at least 2%).

Metabolic-Nutritional

Acidosis, dehydration, edema, gout, hyperkalemia, hyperphosphatemia, hypoglycemia, hypokalemia, uremia (at least 2%).

Musculoskeletal

Arthritis, back pain, leg cramps, myalgia (at least 2%).

Respiratory

Bronchitis, increased cough, pneumonia, sinusitis (at least 2%).

Miscellaneous

Abdominal pain, accidental injury, allergic reaction, bacterial infection, chest pain, chills, cyst, feeling unwell, fever, flu syndrome, fungal infection, infection, pain, sepsis, viral infection (at least 2%); allergic reactions including facial and oral edema, pruritus, rash, urticaria (postmarketing).

Precautions

Monitor

Injection

Monitor serum calcium and phosphorous levels closely (eg, twice weekly) during dose adjustments and at least monthly once maintenance dose is established. Reduce dose or interrupt therapy if clinically significant hypercalcemia or a Ca × P product more than 75 is noted. Measure serum or plasma PTH using iPTH assay q 3 mo.

Oral

Monitor serum calcium, serum phosphorous, and serum or plasma iPTH at least q 2 wk for 3 mo after initiating therapy or following dose adjustments, then monthly for 3 mo, and q 3 mo thereafter. Closely monitor serum calcium and iPTH levels during coadministration of strong CYP3A inhibitors.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy of injection not established for patients younger than 5 yr of age. Safety and efficacy of capsules not established.

Elderly

No differences in safety and efficacy observed between patients older than 65 years of age and younger patients.

Supplemental vitamin D

To avoid hypercalcemia, withhold pharmacologic doses of vitamin D and its derivatives during treatment with paricalcitol.

Overdosage

Symptoms

Hypercalcemia, hypercalciuria, hyperphosphatemia, oversuppression of parathyroid hormone.

Patient Information

Caution patient to take exactly as prescribed and not to change the dose or stop taking unless advised by health care provider.
Instruct patient to carefully follow the phosphorous-restricted diet and calcium supplementation instructions given to them by health care provider.
Advise patient to take phosphorous-binding agents exactly as prescribed by health care provider.
Instruct dialysis patient to avoid using any magnesium-containing products (eg, antacids).
Instruct patient to immediately notify health care provider if any signs or symptoms of hypercalcemia occur (eg, appetite loss, constipation, drowsiness, dry mouth, headache, metallic taste, muscle and/or bone pain, nausea, vomiting, weakness).

Injection
Advise patient or caregiver that medication will be prepared and administered by health care provider during hemodialysis session.

Oral
Advise patient or caregiver to read patient information leaflet before starting therapy, and to reread and check for new information each time the medication is refilled.
Advise patient to take prescribed dose without regard to meals, but to take with food if GI upset occurs.
Caution patient not to change the dose or stop taking unless advised by health care provider.