From the Guidelines
Cinacalcet and paricalcitol are effective treatments for hyperparathyroidism, but their use should be guided by the most recent and highest-quality evidence, which suggests that cinacalcet provides small absolute benefits for parathyroidectomy, but has little or no effect on all-cause mortality, and is commonly associated with nausea and vomiting 1.
Mechanism of Action
Cinacalcet is a calcimimetic that binds to calcium-sensing receptors on the parathyroid gland, making them more sensitive to calcium in the bloodstream, thereby reducing parathyroid hormone (PTH) production and secretion. Paricalcitol, on the other hand, is a vitamin D analog that binds to vitamin D receptors in the parathyroid gland, directly suppressing PTH gene transcription and reducing PTH production.
Dosage and Administration
Typical dosing of cinacalcet starts at 30mg once daily, which can be titrated upward every 2-4 weeks to a maximum of 180mg daily based on PTH levels. Paricalcitol is typically dosed at 1-2 mcg daily or 2-5 mcg three times weekly for oral therapy, or 0.04-0.1 mcg/kg intravenously during dialysis.
Monitoring and Side Effects
Both medications help normalize calcium-phosphorus balance in the body, but they can cause hypocalcemia, so regular monitoring of calcium, phosphorus, and PTH levels is essential. Cinacalcet may cause nausea and vomiting, while paricalcitol carries less risk of hypercalcemia compared to traditional vitamin D supplements.
Clinical Guidelines
The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines suggest that cinacalcet, calcitriol, or vitamin D analogues, or a combination of these, may be used to lower PTH levels in patients with chronic kidney disease (CKD) stage G5D, but the evidence is not strong enough to recommend one treatment over another 1.
Key Considerations
When deciding between cinacalcet and paricalcitol, it is essential to consider the individual patient's needs, including their PTH levels, calcium and phosphorus levels, and any potential side effects or interactions with other medications. Additionally, the cost and availability of these medications may vary, and should be taken into account when making treatment decisions.
From the FDA Drug Label
Cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis The recommended starting oral dose of cinacalcet tablets is 30 mg once daily. Serum calcium and serum phosphorus should be measured within 1 week and intact parathyroid hormone (iPTH) should be measured 1 to 4 weeks after initiation or dose adjustment of cinacalcet tablets Cinacalcet tablets can be used alone or in combination with vitamin D sterols and/or phosphate binders
Cinacalcet works by reducing parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism. The medication is administered orally and should be taken with food or shortly after a meal. The starting dose is 30 mg once daily, and the dose can be titrated every 2 to 4 weeks to target iPTH levels of 150 to 300 pg/mL. Key points about cinacalcet and paricalcitol use in hyperparathyroidism include:
- Cinacalcet can be used alone or in combination with vitamin D sterols and/or phosphate binders.
- Paricalcitol is a type of vitamin D sterol that can be used in combination with cinacalcet to manage secondary hyperparathyroidism.
- The use of cinacalcet and paricalcitol should be monitored closely to avoid hypocalcemia and other potential side effects 2
From the Research
Mechanism of Action
- Cinacalcet and paricalcitol are two medications used to treat secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) 3, 4, 5, 6, 7.
- Cinacalcet is a calcimimetic that activates the calcium-sensing receptor (CaR) on the parathyroid gland, reducing parathyroid hormone (PTH) secretion 5.
- Paricalcitol is a vitamin D receptor activator that decreases PTH secretion and helps maintain calcium and phosphorus balance 3, 4, 6, 7.
Efficacy Comparison
- A meta-analysis comparing paricalcitol and cinacalcet found no significant difference in their efficacy in reducing PTH levels, but cinacalcet was more effective in reducing serum calcium levels 3.
- A retrospective observational study found that paricalcitol administered intravenously was more effective in reducing iPTH levels than cinacalcet or a combination of both 4.
- Another study found that cinacalcet and paricalcitol had similar effects on bone metabolism, but cinacalcet induced hypocalcemia and hyperphosphatemia in uremic rats 5.
Clinical Outcomes
- A long-term study found that a titration protocol for cinacalcet and paricalcitol improved bone metabolism and disease outcomes in hemodialysis patients, with significant reductions in serum calcium, phosphorus, and PTH levels 6.
- The IMPACT SHPT study aimed to compare the safety and efficacy of paricalcitol and cinacalcet in patients receiving haemodialysis, with a primary endpoint of achieving a mean iPTH value of 150-300 pg/mL during Weeks 21-28 of treatment 7.