At what levels of hypercalcemia and elevated Parathyroid Hormone (PTH) should I start Cinacalcet (Cinacalcet hydrochloride)?

From the Guidelines

Cinacalcet should be initiated when PTH levels reach 85 pmol/L (corresponding to 802 pg/mL) in patients with secondary hyperparathyroidism who are refractory to other treatments and surgery is contraindicated, as recommended by the National Institute for Health and Care Excellence guideline 1. The decision to start cinacalcet is based on PTH levels rather than serum calcium levels, as PTH is a more sensitive indicator of clinically relevant secondary hyperparathyroidism, especially in patients who have undergone bariatric surgery or have chronic kidney disease on dialysis.

• Key considerations for initiating cinacalcet include:
  • PTH levels above 85 pmol/L (802 pg/mL)
  • Refractoriness to standard therapy, including dietary modification, phosphate binders, and vitamin D supplementation
  • Contraindication to surgery
• It is essential to monitor PTH and calcium levels regularly during cinacalcet treatment, as the medication can cause hypocalcemia as a side effect.
• Cinacalcet works by increasing the sensitivity of calcium-sensing receptors on parathyroid glands, thereby reducing PTH secretion and subsequently lowering serum calcium levels 1.
• The standard starting dose of cinacalcet is typically 30 mg once daily, which can be titrated every 2-4 weeks based on PTH and calcium levels, with potential increases to 60 mg, 90 mg, and up to a maximum of 180 mg daily if needed.
• Common side effects of cinacalcet include nausea, vomiting, and hypocalcemia, so careful monitoring is essential, especially during the initial treatment phase.

From the FDA Drug Label

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 should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH levels of 150 to 300 pg/mL.

The starting dose of Cinacalcet should be 30 mg once daily, with serum calcium and serum phosphorus measured within 1 week, and intact parathyroid hormone (iPTH) measured 1 to 4 weeks after initiation. The goal is to target iPTH levels of 150 to 300 pg/mL.

• Key points to consider when starting Cinacalcet:
  • Serum calcium levels should be monitored frequently
  • iPTH levels should be assessed no earlier than 12 hours after dosing with Cinacalcet
  • Dose titration should occur no more frequently than every 2 to 4 weeks 2

From the Research

Initiation of Cinacalcet for Hypercalcemia and Elevated PTH

To determine the appropriate levels of hypercalcemia and elevated Parathyroid Hormone (PTH) for initiating Cinacalcet, we must consider the clinical guidelines and study results.

• The study 3 suggests that Cinacalcet can be initiated in patients with secondary hyperparathyroidism and PTH levels ≥ 300 pg/ml.
• Additionally, the dose of Cinacalcet can be escalated to a maximum of 180 mg once daily if PTH concentrations remain > 250 pg/ml 3.
• However, there is no specific mention of the exact calcium levels at which Cinacalcet should be initiated in the provided studies.
• It is essential to note that Cinacalcet is typically used in patients with chronic kidney disease on dialysis, and its use in other patient populations may vary 4, 5.
• The management of secondary hyperparathyroidism involves suppressing PTH to normal levels with active vitamin D therapy and phosphate binders, and Cinacalcet may be considered in certain cases 5.

Key Considerations

• PTH levels ≥ 300 pg/ml may be a suitable threshold for initiating Cinacalcet in patients with secondary hyperparathyroidism 3.
• The dose of Cinacalcet can be adjusted based on PTH concentrations, with a maximum daily dose of 180 mg 3.
• Calcium levels should be monitored closely during Cinacalcet treatment, as the drug can lower serum calcium concentrations 3, 6.
• Cinacalcet is generally well-tolerated, but asymptomatic blood calcium reduction is a common adverse event 6.