Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Preclinical and in vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.

Chronic Kidney Disease Stages 3 and 4: Paricalcitol capsules are indicated in adults and pediatric patients 10 years of age and older for the prevention and treatment of secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD) Stages 3 and 4.

Chronic Kidney Disease Stage 5: Paricalcitol capsules are indicated in adults and pediatric patients 10 years of age and older for the prevention and treatment of secondary hyperparathyroidism associated with CKD Stage 5 in patients on hemodialysis (HD) or peritoneal dialysis (PD).

Pharmacology

Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Preclinical and in vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.

The initial dose of this capsule for CKD stage 3 and 4 patients is based on baseline intact parathyroid hormone (iPTH) levels.

Baseline intact parathyroid hormone (iPTH) Level: <500 pg/ml

• Daily Dose: 1 mcg
• Daily Dose: 2 mcg

Baseline intact parathyroid hormone (iPTH) Level: >500 pg/ml

• Daily Dose: 2 mcg
• Daily Dose: 4 mcg

Paricalcitol capsules should not be given to patients with evidence of hypercalcemia or vitamin D toxicity.

The most common adverse reactions (>5% and more frequent than placebo) include diarrhea, nasopharyngitis, dizziness, vomiting, hypertension, hypersensitivity, nausea, and edema.

Hypercalcemia: Excessive administration of paricalcitol capsules can cause over suppression of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease. Prescription-based doses of vitamin D and its derivatives should be withheld during paricalcitol treatment.

Digitalis toxicity: Potentiated by hypercalcemia of any cause. Use caution when paricalcitol capsules are prescribed concomitantly with digitalis compounds.

Laboratory tests: Monitor serum calcium, serum phosphorus, and serum or plasma iPTH during initial dosing or following any dose adjustment. Paricalcitol capsules may increase serum creatinine and therefore decrease the estimated GFR (eGFR).

Aluminum overload and toxicity: Avoid excessive use of aluminum-containing compounds.

Pregnancy & Lactation

Limited data with paricalcitol capsules in pregnant women are insufficient to inform a drug- associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with chronic kidney disease in pregnancy. In animal reproduction studies, slightly increased embryofetal loss was observed in pregnant rats and rabbits administered paricalcitol intravenously during the period of organogenesis at doses 2 and 0.5 times, respectively, the maximum recommended human dose (MRHD). Adverse reproductive outcomes were observed at doses that caused maternal toxicity. There is no information available on the presence of paricalcitol in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production.