Introduction
Paricap Capsule 1 mcg is a synthetic vitamin D analog. Paricap Capsule 1 mcg has been used to reduce parathyroid hormone levels. Paricap Capsule 1 mcg is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure.
Uses
Paricap Capsule 1 mcg is a vitamin D analog used to treat hyperparathyroidism associated with stage 3 or greater chronic kidney disease.
For treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4
Associated Conditions
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).
Mechanism of Action
Paricap Capsule 1 mcg 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.
Absorption
Well absorbed
Volume of Distribution
- 30.8 ± 7.5 L [CKD Stage 5-HD]
- 34.9 ± 9.5 L [CKD Stage 5-PD]
- 23.8 L [healthy subjects]
Protein Binding
99.8% (bound to plasma proteins)
Route of Elimination
Paricap Capsule 1 mcg is excreted primarily by hepatobiliary excretion.
Half Life
4 to 6 hours
Clearance
- 1.49 +/- 0.60 L/h [chronic kidney disease Stage 5 with hemodialysis]
- 1.54 +/- 0.95 L/h [chronic kidney disease Stage 5with peritoneal dialysis]
Food Interactions
- Avoid antacids. Avoid taking aluminum-containing antacids chronically with paricalcitol as there is an increased risk of aluminum toxicity.
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4, and paricalcitol metabolism is mediated partially through CYP3A4; therefore, grapefruit may increase paricalcitol serum levels.
- Take with or without food.
Dosage
Initial Dose: Recommended Paricap Capsule 1 mcg 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
- Daily Dose: 2 mcg
- Three Times a Week Dose*: 4 mcg
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
- Daily Dose: Maintain dose
- Three Times a Week Dose*: Maintain dose
- Daily Dose: Decrease dose by 1 mcg
- Three Times a Week Dose*: Decrease dose by 2 mcg
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 Paricap Capsule 1 mcg 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 Paricap Capsule 1 mcg dose based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range. Every 4 weeks, each administered Paricap Capsule 1 mcg 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. Paricap Capsule 1 mcg 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 Paricap Capsule 1 mcg 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 Paricap Capsule 1 mcg 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. Paricap Capsule 1 mcg 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 Paricap Capsule 1 mcg, during dose titration periods and during co-administration with strong CYP3A inhibitors. If hypercalcemia is observed, the dose of Paricap Capsule 1 mcg should be reduced or withheld until these parameters are normalized.
