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.

Paricalcitol capsules may be taken without regard to food. Chronic Kidney Disease (CKD) Stages 3 and 4 in Adults: Administration of Paricalcitol soft gel capsules orally once daily or three times a week. When dosing three times weekly, do not administer more frequently than every other day.

Initial Dose: Recommended Paricalcitol Starting Dose Based Upon Baseline PTH Level-

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

• Daily Dose: 1 mcg
• Three Times a Week Dose*: 2 mcg

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

• Daily Dose: 2 mcg
• Three Times a Week Dose*: 4 mcg

Dose Titration: Recommended Paricalcitol Dose Titration Base upon IPTH Level-

IPTH Level Relative to Baseline: The same, increased or decreased by less than 30%

• Daily Dose: Increase dose by 1 mcg
• Three Times a Week Dose*: Increase dose by 2 mcg

IPTH Level Relative to Baseline: Decreased by more than or equal to 30% and less than or equal to 60%

• Daily Dose: Maintain dose
• Three Times a Week Dose*: Maintain dose

IPTH Level Relative to Baseline: Decreased by more than 60% or iPTH less than 60 pg/ml

• Daily Dose: Decrease dose by 1 mcg
• Three Times a Week Dose*: Decrease dose by 2 mcg

*To be administered not more often than every other day.

If a patient is taking the lowest dose, 1 mcg, on the daily regimen and a dose reduction is needed, the dose can be decreased to 1 mcg three times a week. If a further dose reduction is required, the drug should be withheld as needed and restarted at a lower dosing frequency.

Chronic Kidney Disease Stage 5 in Adults:

Initial Dose: Administer the dose of Paricalcitol capsules orally three times a week, no more frequently than every other day based upon the following formula: Dose (micrograms) baseline PTH (Pg/ml) divided by 80. Treat patients only after their baseline serum calcium has been adjusted to 9.5 mg/dL or lower to minimize the risk of hypercalcemia.

Dose Titration: Individualize and titrate Paricalcitol dose based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range. Every 4 weeks, each administered Paricalcitol dose may be increased in 1 mcg increments, maintaining the three times per week regimen (e.g., Increase from 1 mcg three times per week to 2 mcg three times per week), At any time, each administered dose may be decreased by 1 mcg. Paricalcitol may be stopped if the patient requires reduction while receiving 1 mcg three times per week, resuming when appropriate.

CKD Stage 5 Initial Dose-

Administer the dose of Paricalcitol capsules orally three times a week, no more frequently than every other day based upon the following formula:Dose* (micrograms) = baseline iPTH (pg/mL) divided by 120 ( Round down to the nearest whole number )

Dose Titration: Subsequent dosing should be individualized and based on IPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range. Every 4 weeks, each administered Paricalcitol dose may be increased in 1 mcg increments, maintaining the three times per week regimen (e.g., increase from 1 mcg three times per week to 2 mcg three times per week). At any time, each administered dose may be decreased by 2 meg. Paricalcitol may be stopped if the patient requires reduction while receiving 2 mcg three times per week or 1 mcg three times per week, resuming when appropriate.

Monitoring: Monitor serum calcium and phosphorus levels closely after initiation of Paricalcitol, during dose titration periods and during co-administration with strong CYP3A inhibitors. If hypercalcemia is observed, the dose of Paricalcitol should be reduced or withheld until these parameters are normalized.

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

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Pregnancy: 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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation: 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. Studies in rats have shown that paricalcitol and/or its metabolites are present in the milk of lactating rats; however, due to specifies-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. Because of the potential for serious adverse reactions, including hypercalcemia in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Paricalcitol.

Hypercalcemia: Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention Acute hypercalcemia may exacerbate tendencies for cardiac arrhythmias and seizures and may potentiate the action of digitalis. Chronic hypercalcemia can lead to generalized vascular calcification and others soft tissue calcification Concomitant administration of high doses of calcium-containing preparations or thiazide diuretics with Paricalcitol may increase the risk of hypercalcemia, High intake of calcium and phosphate concomitant with vitamin D compounds may lead to serum abnormalities requiring more frequent patient monitoring and individualized dose titration. Patients also should be informed about the symptoms of elevated calcium, which include feeling tired, difficulty in thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss. Prescription-based doses of vitamin D and its derivatives should be withheld during Paricalcitol treatment to avoid hypercalcemia.

Digitalis Toxicity: Digitalis toxicity is potentiated by hypercalcemia of any cause. Use caution when Paricalcitol capsules are prescribed concomitantly with digitalis compounds.

Pediatric Use: The safety and effectiveness of Paricalcitol capsules have been established in pediatric patients 10 to 16 years of age for the prevention and treatment of secondary hyperparathyroidism associated with Stage 3, 4, and 5 CKD. Use of Paricalcitol capsules in this age group is supported by evidence from adequate and well controlled studies in adults with CKD, a 12 week double-blind placebo-controlled randomized multicenter study in 36 pediatric patients 10 to 16 years of age with CKD Stages 3 and 4, and safety data from a 12-week open-label single-arm multicenter study in 13 pediatric patients 10 to 16 years of age with CKD Stage 5 receiving peritoneal dialysis or hemodialysis. The pharmacokinetics of paricalcitol in Stage 5 CKD pediatric patients appear to be similar to those observed in Stage 3 and 4 pediatric patients.

Geriatric Use: Of the total number in = 220) of CKD Stages 3 and 4 patients in clinical studies of Paricalcitol capsules, 49% were age 65 and over, while 17% were age 75 and over. Of the total number in-88) of CKD Stage 5 patients in the pivotal study of Paricalcitol capsules, 28% were age 65 and over, while 6% were age 75 and over. No overall differences in safety and effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Excessive administration of Paricalcitol capsules can cause hypercalcemia, hypercalciuria, and hyperphosphatemia, and over suppression of PTH. The treatment of acute overdosage of Paricalcitol capsules should consist of general supportive measures. If drug ingestion is discovered within a relatively short time, induction of emesis or gastric lavage may be of benefit in preventing further absorption. If the drug has passed through the stomach, the administration of mineral oil may promote its fecal elimination. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion, and assessment of electrocardio graphic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and institution of a low-calcium diet are also indicated in accidental overdosage. Due to the relatively short duration of the pharmacological action of paricalcitol, further measures are probably unnecessary. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered depending on the patient’s underlying condition. These include the use of drugs such as phosphates and corticosteroids, as well as measures to induce an appropriate forced diuresis. Paricalcitol is not significantly removed by dialysis.

Store below 30°C in dry place, protected from light. Keep out of children's reach.