Pharmacology Update

Cinacalcet HCL (Sensipar) Tablets

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The first of a class of calcimimetics has been approved by the FDA for the treatment of hyperparathyroidism associated with renal failure and in patients with parathyroid cancer. This new class of drug inhibits parathyroid hormone secretion and reduces serum calcium levels.1 Cinacalcet is a second-generation calcimimetic and is marketed as SensiparTM by Amgen.

Indications

Cinacalcet is indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis (CKP) and for the treatment of hypercalcemia in patients with parathyroid carcinoma.2

Dosage

The recommended starting dose is 30 mg twice daily. The dose should be titrated at every 2-4 week intervals up to 90 mg 4 times a day as needed to normalize the serum calcium level. The sequence of dose titration should be 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg 3 or 4 times daily. Tablets should be taken whole (ie, not divided). No dosage adjustment is required in patients with renal impairment.2 Food increases the bioavailability of cinacalcet. Serum calcium should be measured within 1 week after starting therapy or after a dosage change. Monthly serum calcium levels, phosphorus levels, and intact parathyroid levels should be measured after a stable dose has been established. Intact parathyroid hormone should be measured 1 to 4 months after initiation or dose adjustment and every 1 to 3 months thereafter.2 In patients with moderate to severe hepatic dysfunction laboratory parameters should be monitored closely.

Cinacalcet is available as 30 mg, 60 mg, and 90 mg tablets.

Potential Advantages

Cinacalcet is the first in a class of calcimimetics and has the ability to significantly reduce levels of circulating parathyroid hormone without causing hypercalcemia and hyperphosphatemia but rather improves calcium-phosphorus homeostasis.

Potential Disadvantages

Cinacalcet is a substrate of CYP3A4. Parathyroid hormone and calcium levels should be monitored if a strong inhibitor of CYP3A4 (eg, erythromycin, itraconazole, ketoconazole) is added, discontinued or given concomitantly.2 Most common side effects are nausea (31% vs 19% for placebo) and vomiting (27% vs 15%). In clinical trials two-thirds of patients developed at least one serum calcium level of < 8.4 mg/dL.2

Comments

Cinacalcet is the first oral calcimimetic agent. It works by increasing the sensitivity of the calcium-sensing receptor on the parathyroid cells. This enhances sensitivity to circulating serum calcium levels and decreasing PTH secretion. The efficacy of cinacalcet was established in three 6-month, double-blind, placebo-controlled trials in patients with secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.2,3 A total of 665 patients were on drug and 471 on placebo. Most patients (93%) were on phosphorus binders and 66% were on vitamin D sterols (eg, calcitriol). The primary end point was intact parathyroid hormone (iPTH) < 250 pg/mL and secondary end points were calcium × phosphorus ion product, serum calcium levels and phosphorus levels. The median dose of cinacalet was 90 mg. Thirty-five to 46% of patients achieved iPTH < 250 pg/mL compared to 4-7% for placebo. About one-third (28-35%) of patients achieved iPTH < 250 pg/mL and Ca × P ion product of < 55 mg2/dL2. Serum calcium was reduced by 6.8%, serum phosphorus by 8.4% and bone-specific alkaline phosphatase by a median of 35%.3 Disease severity, duration of dialysis, and administration of vitamin D sterols did not appear to affect the efficacy of cinacalcet. CKD patients not on dialysis have not been adequately studied. The effects of cinacalcet therapy on clinical outcomes have not been evaluated. Cinacalcet appears to be well tolerated.

A small number of patients (n = 10) with parathyroid carcinoma have been studied. None were able to achieve normal serum calcium levels.

The cost of cinacalcet is about $8 per 30 mg. A starting dose of 30 mg twice daily for a month would be about $500.

Clinical Implications

Secondary hyperparathyroidism is common in patients with chronic renal disease on dialysis. This can lead to metastatic calcification (eg, coronary arteries) and increased mortality risk.4,5 Current therapy for secondary hyperparathyroidism due to chronic renal disease is dietary modification, phosphate binders, and vitamin D sterols. However this often leads to hypercalcemia and hyperphosphatemia. Cinacalcet reduces parathyroid hormone and improves calcium phosphorus homeostasis representing an important therapeutic addition.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Block GA. Kidney Int Suppl. 2003;87:S131-S136.

2. Sensipar Product Information. Amgen Inc, March, 2003.

3. Block GA, et al. N Engl J Med. 2004;350:1516-1525.

4. Goodman WG. N Engl J Med. 2000;342:1478-1483.

5. Block GA. Am J Kidney Dis. 1998:31:607-614.