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3/9/2004

FDA Approves First Calcimimetic

Cheryl A. Thompson

Amgen Inc. and the Food and Drug Administration (FDA) announced yesterday that cinacalcet, also known as Sensipar (PDF), had been approved to treat the hyperparathyroidism that typically develops in patients with chronic kidney disease who are receiving dialysis.

Described by FDA as the first calcimimetic approved for use in the United States, cinacalcet decreases the level of parathyroid hormone in the blood and, consequently, the amount of the calcium-phosphorus product that is responsible for the deposition of calcium in various tissues.

Cinacalcet, according to Amgen, increases the ability of the parathyroid glands' calcium-sensing receptors to respond to extracellular calcium. The glands' increased sensitivity to extracellular calcium leads to the secretion of less parathyroid hormone, which then results in lower levels of calcium in the blood.

FDA also approved the marketing of cinacalcet for the treatment of hypercalcemia in patients with parathyroid cancer.

For dialysis patients with hyperparathyroidism caused by chronic kidney disease, the FDA-approved labeling recommends a starting dosage of cinacalcet 30 mg once daily with food or soon after a meal. Dosage adjustments should be made on the basis of the blood concentration of intact parathyroid hormone but should not lead to a dosage exceeding 180 mg once daily. The goal, according to cinacalcet's labeling, is to maintain an intact parathyroid hormone concentration of 150-300 pg/mL, which is the level recommended by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative, a program supported by an educational grant from Amgen. Use of cinacalcet in these patients does not preclude therapy with a vitamin D sterol (such as calcitriol, paricalcitol, or doxercalciferol) and a phosphate-binding agent (such as calcium acetate, calcium carbonate, or aluminum hydroxide). If, during cinacalcet therapy, the serum calcium concentration drops below the normal range, patients should receive a calcium supplement, a calcium-based phosphate-binding agent, or a vitamin D sterol; cinacalcet therapy may be temporarily stopped if necessary.

Patients with parathyroid cancer should start cinacalcet therapy at a dosage of 30 mg twice daily. The FDA-approved labeling recommends adjusting the cinacalcet dosage every two to four weeks to bring the serum calcium concentration into the normal range, 8.4-10.6 mg/dL. A maximum dosage of 90 mg four times daily is mentioned, although it may be insufficient to normalize the serum calcium of patients with parathyroid cancer; none of the 10 patients described in the labeling had a normal serum calcium concentration during the clinical study.

Because cinacalcet is metabolized in part by cytochrome P-450 isoenzyme 3A4 (CYP3A4), the product's labeling notes that the drug's dosage may need adjustment if a strong inhibitor of CYP3A4, such as ketoconazole, is also given. Such therapy also warrants close monitoring of intact parathyroid hormone and calcium concentrations.

According to Amgen, the most commonly reported adverse effects of cinacalcet therapy are nausea and vomiting.

Company spokeswoman Kelly Stoddard said Sensipar, in 30-, 60-, and 90-mg tablets, will be shipped to drug wholesalers in the next few weeks and should be available in pharmacies within six weeks.