Cinacalcet

Cinacalcet is a prescription drug used for the treatment of secondary hyperparathyroidism (high parathyroid hormone levels) in people with chronic kidney disease on dialysis. It is also used for the treatment of high blood calcium levels in patients with parathyroid carcinoma. The Food and Drug Administration approved cinacalcet on March 9, 2004.

Structure of cinacalcet Source: Wikimedia Commons

Sensipar package Source: Amgen

Other Names

• Cinacalcet is marketed under the name Sensipar by Amgen and is sold under the brand name Mimpara in Europe.

Uses

Cinacalcet is used to reduce the levels of circulating parathyroid hormone (PTH) in secondary hyperparathyroidism. The elevated levels of PTH seen in this condition result from low calcium levels (hypocalcemia). The condition occurs in people with kidney disease who are receiving dialysis.^[1]

Cinacalcet is also used to reduce excessively high calcium levels in the blood (hypercalcemia) in people with parathyroid carcinoma.^[2] This type of cancer is rare and results in excessive secretion of PTH.

How Cinacalcet is Taken

Cinacalcet is available in 30-mg, 60-mg, and 90-mg tablets. For secondary hyperparathyroidism, the starting dose is 30 mg once daily. For parathyroid carcinoma, the starting dose is 30 mg taken twice daily. Doses may be increased thereafter for either condition depending on PTH levels.

How Cinacalcet Works

Secondary hyperparathyroidism and parathyroid carcinoma are both characterized by elevated levels of PTH in the blood. Parathyroid hormone is released from the parathyroid glands, which are adjacent to (para-) the thyroid gland in the neck. The main role of PTH is to increase blood calcium levels; it works on bone to mobilize mineralized calcium, on the kidney to reduce the amount of calcium lost in the urine, and (indirectly) on the gut to improve calcium absorption from the diet. Elevated levels of PTH can weaken the bone and increase the risk of fractures; high blood calcium levels can also interfere with normal functioning of the nervous and muscular systems.

The goals of treatment of secondary hyperparathyroidism and parathyroid carcinoma are to lower levels of PTH, prevent bone disease, and reduce the risk of complications due to elevated calcium and phosphorus levels.

Cinacalcet works in the parathyroid gland to reduce the amount of PTH released in response to calcium. Cinacalcet acts like calcium (that is, it acts as a calcimimetic) and signals the chief cells to reduce hormone secretion.^[3]

How the Body Affects Cinacalcet

Peak circulating levels of cinacalcet are achieved between two and six hours after dose administration. Cinacalcet is metabolized by enzymes in the liver called CYP3A4, CYP2D6 and CYP1A2. Approximately 80% of the dose is excreted in the urine and 15% is excreted in the feces.

Because cinacalcet is primarily metabolized by the liver, excretion of the drug in people with liver disease is reduced. Data have shown that circulating levels of cinacalcet are increased two to four times in people with liver damage.

Side Effects

The most common side effects of cinacalcet are nausea and vomiting.

Risks and Precautions

Cinacalcet can lower levels of circulating calcium to dangerously low levels. Low calcium levels can cause abnormal sensations, cramping, convulsions, and muscle pain or spasms.

Weakening of bone strength, called adynamic bone disease, may develop during treatment with cinacalcet because of excessively low parathyroid hormone. People with adynamic bone disease have a tendency to develop more fractures and accumulate calcium in blood vessel walls.

People with liver impairment may need lower doses of cinacalcet because of metabolism by the liver.

Drug Interactions

Cinacalcet has been shown to interact with the following drugs:

• Ketoconazole (Nizoral)
• Desipramine (Norpramin)
• Amitriptyline (Endep)

Research

Three clinical studies of similar design were conducted in patients with chronic kidney disease on dialysis. A total of 665 patients received Cinacalcet and 471 patients received placebo.^[4] All three studies showed that Cinacalcet reduced parathyroid hormone, phosphorous, and calcium levels.

References

1. ↑ Block GA, Martin KJ, de Francisco AL, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med. 2004 Apr 8;350(15):1516-25. Abstract | Full Text | PDF
2. ↑ Silverberg SJ, Rubin MR, Faiman C, et al. Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab. 2007 Oct;92(10):3803-8. Abstract | Full Text | PDF
3. ↑ Dong BJ. Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. Abstract
4. ↑ Food and Drug Administration Web site. Sensipar (cinacalcet HCl) Tablets. PDF

External Links

FDA: Patient Information Sheet