Class: Vitamin D
- Capsules, oral 1 mcg
- Capsules, oral 2 mcg
- Capsules, oral 4 mcg
- Injection, solution 2 mcg/mL
- Injection, solution 5 mcg/mL
Synthetic analog of calcitriol, the metabolically active form of vitamin D. Binds to the vitamin D receptor, which results in selective activation of vitamin D responsive pathways; reduces parathyroid hormone (PTH) levels by inhibiting PTH synthesis and secretion.
Bioavailability ranges from 72% to 86%. Food delays T max by about 2 h.
Protein binding is more than 99.8%. Vd is 44 to 46 L (oral dose in chronic kidney disease stage 3 to 4) and 31 to 35 L (IV dose in chronic kidney disease stage 5).
Extensively metabolized by multiple hepatic and nonhepatic enzymes, including CYP3A4.
Eliminated primarily by biliary excretion; approximately 63% recovered in feces following IV dose and 70% following oral dose (2% as unchanged drug), and 18% to 19% in urine. The half-life is about 17 h (chronic kidney disease stage 3), 20 h (chronic kidney disease stage 4), 13.9 h (chronic kidney disease stage 5 and hemodialysis), and 15.4 to 17.7 h (chronic kidney disease stage 5 and peritoneal dialysis).
Special PopulationsRenal Function Impairment
Hemodialysis procedure has essentially no effect on paricalcitol elimination. However, compared with healthy subjects, stage 5 chronic kidney disease subjects showed a decreased Cl and increased half-life.Hepatic Function Impairment
The pharmacokinetics of unbound paricalcitol were similar across the range of hepatic function evaluated in this study. The influence of severe hepatic impairment on the pharmacokinetics of paricalcitol has not been evaluated.Elderly
The pharmacokinetics of paricalcitol have not been investigated in patients older than 65 y.Children
The pharmacokinetics of paricalcitol have not been investigated in patients younger than 18 y.Gender
The pharmacokinetics of paricalcitol were gender independent.
Indications and Usage
Prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4 (oral only), and stage 5.
Vitamin D toxicity; hypercalcemia; hypersensitivity to any component of the product.
Dosage and AdministrationSecondary Hyperparathyroidism Associated With Chronic Kidney Disease Stages 3 and 4
PO The initial dose is based on baseline intact parathyroid hormone (iPTH) levels. If baseline iPTH is less than 500 pg/mL: 1 mcg daily or 2 mcg 3 times per week; if baseline iPTH is more than 500 pg/mL: 2 mcg daily or 4 mcg 3 times per week.Dose titration
PO 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 per week.iPTH level decreased 30% to 60%
Maintain dose.iPTH level decreased more than 60% or iPTH less than 60 pg/mL
Decrease dose by 1 mcg daily or 2 mcg 3 times per week.Dosage adjustment
PO If hypercalcemia or an elevated calcium-phosphorus product (Ca P) is observed, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. If the patient is taking the lowest dose on the daily regimen and a dose reduction is needed, the dosage can be decreased to 1 mcg 3 times per week. If a further dosage reduction is needed, withhold dose as needed and restart at a lower dosing frequency.Secondary Hyperparathyroidism Associated With Chronic Kidney Disease Stage 5
PO The initial dose is based on a baseline iPTH level/80 and is administered 3 times weekly. Base subsequent dosing on iPTH, serum calcium, and phosphorus levels.Dosage adjustment
PO As iPTH approaches target range, small individual dose adjustments may be necessary. In situations where monitoring of iPTH, calcium, or phosphorus occurs less frequently than once per week, a more modest initial dose titration ratio (eg, iPTH/100) may be warranted. If calcium or Ca P are elevated, decrease dose by 2 to 4 mcg lower than that calculated by the most recent iPTH/80. If further dose adjustment is required, reduce or withhold dose until these parameters are normalized.Adults and Children (5 y and older) Initial
IV 0.04 to 0.1 mcg/kg no more frequently than every other day during dialysis.Dose titration
IV Increase dose by 2 to 4 mcg at 2- to 4-wk intervals if satisfactory response is not observed. 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 ULN
Maintain dose.Dosage adjustment
IV Doses may need to be decreased as PTH levels decrease. If an elevated calcium level or a Ca P product greater than 75 is noted, the drug should be immediately reduced or interrupted until these parameters are normalized. Then reinstate paricalcitol at a lower dose.
- For IV bolus administration only. Not for intradermal, subcutaneous, IM, IV infusion, or intra-arterial administration.
- Do not administer if solution is discolored or cloudy, or contains particulate matter.
- Administer without regard to meals. When using the 3 times per week schedule, administer the prescribed dose no more than every other day.
Store between 59° and 86°F. After initial vial use, the contents of the multidose vial remain stable for up to 7 days when stored at room temperature. Discard unused portion.
Drug InteractionsAluminum-containing products (eg, antacids, phosphate binders)
Long-term coadministration is not recommended as increased blood levels of aluminum and aluminum bone toxicity may occur.Digitalis compounds
Digitalis toxicity is potentiated by hypercalcemia of any cause; therefore, use paricalcitol with caution in patients receiving a digitalis compound.Disulfiram, metronidazole
Paricalcitol capsules and injection contain alcohol. Coadministration may produce acute alcohol intolerance. Avoid coadministration.Drugs that impair absorption of fat-soluble vitamins (eg, cholestyramine, mineral oil)
Oral paricalcitol absorption may be impaired, decreasing the efficacy.Phosphate or calcium
High intake of calcium and phosphate with paricalcitol may cause hypercalcemia. Monitor closely and individualize paricalcitol dosage titration.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. Monitor iPTH and serum calcium concentrations if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor. Adjust paricalcitol dosage as needed.
Hypertension (7%); hypotension (5%); palpitation, syncope (3%); arrhythmia, atrial flutter, cardiac arrest, cerebrovascular accident, heart rate irregular (less than 2%).
Dizziness (7%); headache, insomnia, vertigo (5%); anxiety, depression, fatigue, malaise (3%); abnormal feeling, agitation, asthenia, confusional state, delirium, dysgeusia, gait disturbance, hypoesthesia, myoclonus, nervousness, paresthesia, restlessness, unresponsive to stimuli (less than 2%).
Rash (4%); pruritus, skin ulcer (3%); acne, alopecia, blister, hirsutism, night sweats, rash pruritic, pruritus, skin burning sensation, urticaria (less than 2%).
Conjunctivitis, ear discomfort, glaucoma, ocular hyperemia (less than 2%).
Hyperparathyroidism, hypoparathyroidism (less than 2%).
Nausea (13%); diarrhea (12%); vomiting (8%); constipation, GI bleeding (5%); abdominal discomfort (4%); dry mouth, gastroenteritis (3%); decreased appetite, dysphagia, gastritis, gastroesophageal reflux disease, intestinal ischemia, rectal hemorrhage, weight decreased (less than 2%).
Chronic renal failure, UTI (3%); breast cancer, breast pain and tenderness, erectile dysfunction, vaginal infection (less than 2%).
Anemia, lymphadenopathy (less than 2%).
Allergic reactions including angioedema, laryngeal edema, rash, urticaria (postmarketing).
Injection-site extravasation, injection-site pain (less than 2%).
Edema (7%); fluid overload (5%); dehydration, hypoglycemia, peripheral edema (3%); hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, thirst (less than 2%).
Arthralgia, arthritis (5%); back pain, muscle spasms (3%); joint stiffness, muscle twitching, myalgia (less than 2%).
Nasopharyngitis (8%); pneumonia (5%); oropharyngeal pain (4%); cough, sinusitis (3%); dyspnea, orthopnea, pulmonary edema, upper respiratory tract infection, wheezing (less than 2%).
Viral infection (8%); hypersensitivity (6%); chills, influenza, peritonitis, pyrexia, sepsis (5%); pain (4%); chest pain, fungal infection, infection (3%); bleeding time prolonged, chest discomfort, hepatic enzymes abnormal, swelling (less than 2%).
Monitor serum calcium and phosphorous levels closely (eg, twice weekly) during dose adjustments and at least monthly once maintenance dose is established. Measure serum or plasma PTH using iPTH assay every 3 mo.Oral
Monitor serum calcium, serum phosphorous, and serum or plasma iPTH at least every 2 wk for 3 mo after initiating therapy or following dose adjustments, then monthly for 3 mo, and every 3 mo thereafter. Closely monitor serum calcium and iPTH levels during coadministration of strong CYP3A inhibitors.
Category C .
Safety and efficacy of injection not established for patients younger than 5 y. Safety and efficacy of capsules not established.
Oversuppression of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease may occur with excessive administration.
Hypercalcemia, hypercalciuria, hyperphosphatemia, oversuppression of PTH.
- Caution patients to take this medicine exactly as prescribed and not to change the dose or stop taking unless advised by their health care provider.
- Instruct patients to carefully follow the phosphorous-restricted diet and calcium supplementation instructions given to them by their health care provider.
- Advise patients to take phosphorous-binding agents exactly as prescribed by their health care provider.
- Instruct dialysis patients to avoid using any magnesium-containing products (eg, antacids).
- Instruct patients to immediately notify their health care provider if any signs or symptoms of hypercalcemia occur (eg, appetite loss, constipation, difficulty thinking clearly, drowsiness, dry mouth, feeling tired, headache, increased thirst, increased urination, metallic taste, muscle and/or bone pain, nausea, vomiting, weakness, weight loss).
- Advise patients or caregivers that medication will be prepared and administered by a health care provider during a hemodialysis session.
- Advise patients to take prescribed dose without regard to meals, but to take with food if GI upset occurs.
- Caution patients not to change the dose or stop taking unless advised by their health care provider.
Copyright © 2009 Wolters Kluwer Health.