Paricalcitol

Approved Indications:

• Secondary hyperparathyroidism (sHPT) in:
• Adults with chronic kidney disease (CKD) on dialysis (CKD Stage 5).
• Pediatric patients aged ≥10 years on dialysis.
• Adults with CKD Stages 3 and 4 not yet on dialysis.

Clinically Accepted Off-Label Uses:

• Prevention of progression of sHPT in early-stage CKD.
• Adjunct therapy in patients with vitamin D-resistant rickets (investigational).
• Management of parathyroid hyperplasia in renal transplant patients (limited evidence).

Route of Administration: Oral or Intravenous (IV)

Adults with CKD on Dialysis (IV):

• Initial dose: 0.04 to 0.1 mcg/kg (based on dry weight) administered as a bolus injection no more than every other day, not more than three times a week.
• Example: 70 kg adult = 2.8 to 7 mcg IV dose after dialysis.
• Dose titration based on PTH, calcium, and phosphorus levels.

Adults with CKD Stages 3 or 4 (Oral):

• Initial dose: 1 mcg once daily or 2 mcg every other day.
• Dose adjustment every 2 to 4 weeks based on iPTH, calcium, and phosphorus.

Pediatric Patients ≥10 Years (Dialysis):

• Oral dose: 0.04 to 0.1 mcg/kg three times a week.
• IV dose: Same range based on weight, administered after dialysis.

Elderly: No specific dose adjustments required; monitor biochemical parameters closely.

Hepatic Impairment: Use with caution; no formal adjustment guidelines, but monitoring is essential.

Renal Impairment (non-dialysis): Use lower starting dose; dose adjustment based on biochemical response.

Paricalcitol is a synthetic analog of vitamin D that selectively activates the vitamin D receptor (VDR) in the parathyroid gland. It reduces parathyroid hormone (PTH) synthesis and secretion by inhibiting gene transcription of PTH. Unlike calcitriol, paricalcitol has less calcemic activity, thereby reducing the risk of hypercalcemia. It modulates calcium and phosphate homeostasis by enhancing their intestinal absorption and regulating bone turnover, helping to manage mineral imbalance in CKD patients.

• Absorption (Oral): Bioavailability ~72%.
• Time to Peak Concentration: 3–5 hours (oral); ~5–15 minutes (IV).
• Distribution: Volume of distribution ~17 L; protein binding >99.8%.
• Metabolism: Hepatically metabolized via CYP3A4 and CYP24 to inactive metabolites.
• Half-Life: ~14 to 20 hours (oral); 5–7 hours (IV).
• Excretion: Primarily via feces (~74%), with ~16% via urine.
• Steady-State: Achieved within 7–14 days with repeated dosing.

• Pregnancy Category (FDA): Category C
• Animal studies show fetal toxicity at high doses; human data are lacking.
• Use only if potential benefit justifies the risk.
• Lactation:
• Unknown if paricalcitol is excreted in human milk.
• Vitamin D analogs may affect calcium metabolism in nursing infants.
• Use with caution during breastfeeding; monitor infant for signs of hypercalcemia.

• Primary Class: Vitamin D Analog
• Subclass: Selective Vitamin D Receptor Activator (VDRA)

• Hypersensitivity to paricalcitol or any of its excipients.
• Hypercalcemia (serum calcium above normal range).
• Vitamin D toxicity.
• Severe hepatic impairment without close monitoring.

• Hypercalcemia & Hyperphosphatemia: Frequent monitoring of serum calcium, phosphorus, and PTH is necessary.
• Adynamic Bone Disease: Avoid excessive suppression of PTH.
• Drug Accumulation in Hepatic Dysfunction: Use caution in patients with moderate to severe liver disease.
• Interactions with CYP3A4 inhibitors: May increase paricalcitol levels—monitor closely.
• Risk of Digitalis Toxicity: Hypercalcemia increases sensitivity to digitalis.

Monitoring Required:

• iPTH, serum calcium, phosphate, and Ca×P product—at least monthly during titration.

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, diarrhea, constipation.
• Metabolic: Hypercalcemia, hyperphosphatemia.
• General: Headache, dizziness, edema.

Less Common/Serious Side Effects:

• Pruritus
• Hypersensitivity reactions (rash, angioedema)
• Increased liver enzymes
• Cardiac arrhythmias (from elevated calcium)

Rare Adverse Effects:

• Adynamic bone disease (with prolonged PTH suppression)
• Seizures (in patients with severe hypercalcemia)

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase paricalcitol exposure.
• CYP3A4 Inducers (e.g., rifampin): May reduce efficacy.
• Thiazide diuretics: May increase risk of hypercalcemia.
• Calcium supplements or phosphate binders: Use cautiously to avoid mineral imbalance.
• Digoxin: Risk of arrhythmias increases with hypercalcemia; monitor ECG and electrolytes.

• KDIGO 2023 Guidelines: Recommend individualized use of vitamin D analogs in patients with progressive sHPT and CKD Stages 3–5, avoiding over-suppression of PTH.
• FDA Label Update (2022): Emphasized the importance of frequent calcium and phosphate monitoring, especially when co-administered with other vitamin D products.
• EMA Advisory: Reiterated that excessive suppression of iPTH may contribute to adynamic bone disease—target moderate PTH reduction.

• Oral Capsules:
• Store at 20°C to 25°C (68°F to 77°F).
• Excursions permitted between 15°C and 30°C.
• Protect from moisture and heat.
• Keep in original container.
• Parenteral Solution (IV):
• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light.
• Do not freeze.
• Discard unused portion after opening (single-dose vial).