PARICLAR INJECTION

Indications

• Prevention of secondary hyperparathyroidism associated with chronic kidney disease
• Treatment of secondary hyperparathyroidism in patients undergoing hemodialysis

Dosage

Children: Refer to the BNF for Children for specific dosing information in pediatric patients, as this will depend on the child's age and weight.

Adults: Refer to the product literature for specific dosing recommendations, as it may vary based on the patient's condition and response.

Mechanism of action

Paricalcitol exerts its effects by binding to the vitamin D receptor (VDR), leading to the selective activation of vitamin D responsive pathways. This activity results in the inhibition of PTH synthesis and secretion, thereby lowering elevated PTH levels commonly associated with secondary hyperparathyroidism.

Pharmacodynamics

Secondary hyperparathyroidism occurs due to insufficient levels of active vitamin D, resulting in elevated PTH levels. Paricalcitol helps restore balance by activating VDRs found in the parathyroid gland, intestine, kidney, and bone, which are vital for calcium and phosphorus homeostasis. In chronic kidney disease, impaired vitamin D activation leads to decreased levels of 1,25(OH)2 D3 and elevated PTH, which Paricalcitol aims to correct.

Pharmacokinetics

Paricalcitol is well-absorbed following oral administration. It undergoes hepatic metabolism and is primarily excreted in the urine. The pharmacokinetics can be influenced by factors such as renal function and concurrent medications that may alter vitamin D metabolism.

Adverse effects

• Electrolyte imbalance
• Weight gain
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Fatigue

Interactions

• cobicistat+paricalcitol: Unknown (increases exposure)
• idelalisib+paricalcitol: Unknown (increases exposure)

Precautions

• Monitor calcium and phosphorus levels during treatment
• Assess renal function before initiation
• Adjust dose in patients with hepatic impairment
• Use caution in patients with a history of hypercalcemia or hyperphosphatemia

Pregnancy

Paricalcitol is classified as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether paricalcitol is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Capsules
• Oral suspension
• Oral solution
• Solution for injection

Mechanism of action

Paricalcitol is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D2) and the A (19-nor) ring. Preclinical andin 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 is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D2) and the A (19-nor) ring. Preclinical and in vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the vitamin D receptor (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.

Pharmacodynamics

Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin and from dietary intake. Vitamin D requires two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR). The endogenous VDR activator, calcitriol [1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone. In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis.1 Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy. An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL).