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

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

Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Preclinical and in vitro studies have shown that its biological effects are mediated through binding to the vitamin D receptor (VDR), leading to selective activation of vitamin D–responsive pathways. Both vitamin D and paricalcitol reduce parathyroid hormone (PTH) levels by inhibiting its 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 mcg. 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.

• Strong CYP3A inhibitors such as ketoconazole may increase the exposure of paricalcitol. These combinations should be used with caution.
• Cholestyramine and mineral oil may reduce the intestinal absorption of paricalcitol if taken together. Therefore, paricalcitol capsules should be taken at least 1 hour before or 4–6 hours after cholestyramine or mineral oil administration.

Paricalcitol capsules are contraindicated in patients with evidence of hypercalcemia or vitamin D toxicity.

Since clinical studies are conducted under varying conditions, the incidence of adverse reactions observed in trials may not directly reflect those seen in clinical practice or when compared with other drugs.

Pregnancy: Limited data in pregnant women are insufficient to determine drug-associated risks of major birth defects or miscarriage. CKD during pregnancy itself carries risks for both mother and fetus. Animal studies showed slightly increased embryofetal loss in pregnant rats and rabbits when paricalcitol was given intravenously during organogenesis at doses 2 and 0.5 times the maximum recommended human dose (MRHD), respectively. These effects occurred at maternally toxic doses. The background risk of major birth defects and miscarriage in this population is unknown. In the general U.S. population, the estimated risk of major birth defects is 2–4% and miscarriage is 15–20%.

Lactation: There is no available information on the presence of paricalcitol in human breast milk or its effects on the breastfed infant or milk production. Animal studies show that paricalcitol and/or its metabolites are present in rat milk, but animal data may not reliably predict human milk levels. Due to the potential risk of serious adverse effects such as hypercalcemia in infants, breastfeeding is not recommended during treatment with Paricalcitol.

Hypercalcemia: Excess vitamin D or its metabolites due to overdose may lead to severe progressive hypercalcemia requiring emergency treatment. Acute hypercalcemia may worsen cardiac arrhythmias, seizures, and may enhance the effect of digitalis. Long-term hypercalcemia may cause generalized vascular and soft tissue calcification.

Concomitant use of high-dose calcium supplements or thiazide diuretics with Paricalcitol may increase the risk of hypercalcemia. High intake of calcium and phosphate with vitamin D compounds may cause abnormal serum levels, requiring frequent monitoring and individual dose adjustment. Patients should be informed about symptoms of high calcium levels, including fatigue, difficulty concentrating, loss of appetite, nausea, vomiting, constipation, increased thirst, frequent urination, and weight loss. Additional vitamin D preparations should be avoided during Paricalcitol therapy to prevent hypercalcemia.

Digitalis Toxicity: Hypercalcemia from any cause may increase digitalis toxicity. Caution is required when Paricalcitol is used with digitalis medications.

Pediatric Use: Safety and effectiveness of Paricalcitol capsules have been established in children aged 10–16 years for prevention and treatment of secondary hyperparathyroidism in CKD stages 3, 4, and 5. Evidence is supported by adult studies, a 12-week randomized controlled trial in pediatric CKD stages 3–4, and a 12-week open-label study in pediatric CKD stage 5 patients on dialysis. Pharmacokinetics in stage 5 pediatric patients are similar to those in stages 3 and 4.

Geriatric Use: In clinical studies, a significant proportion of patients were aged 65 years and older. No major differences in safety or effectiveness were observed between elderly and younger patients, although increased sensitivity in some older individuals cannot be excluded.

Excessive use of Paricalcitol capsules may result in hypercalcemia, hypercalciuria, hyperphosphatemia, and excessive suppression of PTH. Treatment includes supportive care. If recently ingested, emesis or gastric lavage may be considered. Mineral oil may help eliminate the drug if it has passed into the intestine. Serum electrolytes (especially calcium), urinary calcium excretion, and ECG monitoring are required. In patients on digitalis, close monitoring is essential. Calcium supplements should be stopped and a low-calcium diet initiated. Due to the short duration of action, further treatment is usually not required. In persistent severe hypercalcemia, therapies such as phosphates, corticosteroids, or forced diuresis may be used. Paricalcitol is not effectively removed by dialysis.

Thyroid drugs & hormones

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