Cinacalcet in the management of primary hyperparathyroidism

Abstract

Parathyroidectomy is currently the only curative treatment for primary hyperparathyroidism (PHPT). There are few alternative treatment options in patients who are ineligible for, or unwilling to undergo, surgery and those in whom parathyroidectomy has failed. Current options include the recently approved drug cinacalcet. Cinacalcet is an allosteric modulator of the calciumsensing receptor, acting to sensitize this receptor to extracellular calcium. Cinacalcet has been found to be effective in reducing or normalizing serum calcium levels in several groups of PHPT patients, including those with mild-to-moderate PHPT, intractable disease, parathyroid carcinoma and multiple endocrine neoplasia Type 1. Cinacalcet slightly reduces parathyroid hormone levels and has no effect on bone mineral density. Cinacalcet is well tolerated when used at low doses, but side effects are not uncommon when relatively high doses are needed to control hypercalcemia. The current evidence indicates that cinacalcet may be of benefit in a wide spectrum of PHPT severities, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. It is presently unknown how much of the biochemical benefit of cinacalcet treatment translates into a clinical benefit, particularly in patients with mild-to-moderate hypercalcemia. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT. Keywords: calcium-sensing receptor • hypercalcemia • parathyroid carcinoma • persistent primary hyperparathyroidism Cinacalcet in the management of primary hyperparathyroidism Expert Rev.

Cinacalcet in the management of primary hyperparathyroidism: post marketing experience of an Italian multicentre group

“…In the latter group, cinacalcet can be an alternative treatment option for those patients who have persistent or recurrent PHPT after PTx. Whether cinacalcet might be considered a first‐line treatment in MEN1‐associated PHPT remains to be investigated, but appears to be a rather common choice in this survey.…”

“…Cinacalcet hydrochloride is an allosteric modulator of the calcium sensing receptor, which sensitizes the receptor to the extracellular calcium concentration, leading to a decrease in the synthesis and secretion of PTH . Cinacalcet has been shown to decrease and often normalize serum calcium in a wide spectrum of patients with PHPT including parathyroid carcinoma and Multiple Endocrine Neoplasia type 1 (MEN 1) .…”

“…Cinacalcet hydrochloride is an allosteric modulator of the calcium sensing receptor, which sensitizes the receptor to the extracellular calcium concentration, leading to a decrease in the synthesis and secretion of PTH. 4,5 Cinacalcet has been shown to decrease and often normalize serum calcium in a wide spectrum of patients with PHPT 6-10 including parathyroid carcinoma and Multiple Endocrine Neoplasia type 1 (MEN 1). [10][11][12][13] Cinacalcet has recently been approved in Europe and USA for the management of moderate-to-severe hypercalcaemia in patients with PHPT who are unable to undergo parathyroidectomy.…”

Medical Management of Primary Hyperparathyroidism

“…66 Cinacalcet has been extensively developed in humans. 71 The peak plasma concentration after an oral dose is attained after 2-6 hours 72 and the bioavailability increases if cinacalcet is administered concomitantly with a high-fat meal. 72 Cinacalcet is metabolized in the liver via the cytochrome P450 system.…”